[Link].

org/CR Review

1,2,3-Triazole and Its Analogues: New Surrogates for Diazo

Compounds
Monalisa Akter,† Kavuri Rupa,† and Pazhamalai Anbarasan*

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ABSTRACT: Readily accessible and shelf-stable 1,2,3-triazole and its analogues such as
pyridotriazole, triazoloindole, benzotriazole, and thiadiazole exist in equilibrium with their
ring-opened isomers, viz., diazo compounds. These ring-opened isomers could be trapped
by various metal catalysts (e.g., Rh, Pd, Cu, Co, Ag, etc.) to generate the corresponding
metal carbenoids with extrusion of nitrogen. As a consequence, these unique N-heterocycles
facilitate access to a realm of N-containing complex structural motifs of biological
importance through denitrogenative transformations such as transannulations, insertions,
ylide formation, and rearrangements by trapping of the metal carbenoids with a diverse
range of coupling partners (e.g., alkenes, alkynes, nitriles, carbo/heterocycles, X−H/C−X
bonds, etc.). Hence, suitably substituted triazole derivatives have emerged as efficient
surrogates of diazo compounds for the generation of reactive metal carbenoids during the
past decades. In this comprehensive review, we aim to discuss in detail the remarkable advancement in their synthesis and synthetic
applications.

CONTENTS 5.6.5. Cycloaddition Followed by Rearrange-

ment 13159
1. Introduction 13109 5.7. Miscellaneous 13160
2. Historical Perspective 13110 5.8. Applications in Total Syntheses of Natural
3. Synthesis of 1,2,3-Triazoles 13111 Products 13165
4. Synthesis of Thiadiazoles and Analogues of 1,2,3- 6. Denitrogenative Transannulations of Thiadia-
Triazoles 13112 zoles 13168
5. Denitrogenative Transformations of Triazoles 13113 7. Denitrogenative Transformations of Pyridotria-
5.1. Transannulations with Triple Bonds (C�N/ zoles 13170
C�C) 13113 7.1. Transannulations 13170
5.2. Transannulations with Double Bonds (C�C/ 7.2. Insertions into X−H Bonds 13173
C�X) 13115 7.3. Miscellaneous 13176
5.3. Transannulations with Carbo/Heterocycles 13127 8. Denitrogenative Transformations of Triazoloin-
5.4. Insertions into C−H/X−H Bonds 13134 doles 13179
5.4.1. C−H Insertions 13135 8.1. Transannulations 13179
5.4.2. N−H Insertions 13142 8.2. Insertions into X−H/C−X Bonds 13181
5.4.3. O−H Insertions 13143 8.3. Miscellaneous 13184
5.4.4. B−H Insertion 13150 9. Denitrogenative Transformations of Benzotria-
5.5. Insertions into C−X/X−X Bonds 13150 zoles 13186
5.5.1. C−X Insertions 13150 9.1. Transannulations 13186
5.5.2. X−X Insertions 13154 9.2. Miscellaneous 13191
5.6. Rearrangements 13154 10. Summary and Outlook 13193
5.6.1. Rearrangements Involving a 1,2-H/Alkyl
Shift 13154
5.6.2. Rearrangements Involving Generation
Received: November 30, 2021
of Azadienes 13155
Published: July 19, 2022
5.6.3. Rearrangements Involving Generation
of Ylides 13156
5.6.4. Rearrangements Involving Formation of
Ketenimines 13158

© 2022 American Chemical Society [Link]

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Figure 1. Classification and various diazo and non-diazo precursors of metal carbenoids.

Figure 2. Structures of 1,2,3-triazole and its analogues.

Author Information 13194 suitable metal catalysts.4,5 Several synthetic routes are available
Corresponding Author 13194 for the synthesis of diazo compounds, such as diazotization of
Authors 13194 primary amines, base-catalyzed diazo transfer from azide to
Author Contributions 13194 activated alkane, and oxidation of tosyl hydrazones. Alter-
Notes 13194 natively, metal carbenoids can also be generated from various
Biographies 13194 non-diazo precursors, such as alkynes, cyclopropanes, cyclo-
Acknowledgments 13194 heptatrienes, etc., in the presence of transition metal catalysts,
Abbreviations 13194 and most of them inherently possess structural constraints.5
References 13195 Most recently, enormous efforts have been devoted to finding
suitable replacements for the diazo compounds, which are toxic
and explosive and have low thermal stability.
1. INTRODUCTION As a consequence, readily accessible N-heterocycles such as
triazole 1.1 (Figure 2) have emerged as shelf-stable and safe-to-
Metal carbenes or carbenoid complexes are versatile reactive
handle new surrogates of diazo compounds 1.2, in which the
intermediates in organic synthesis.1 Because of their high
diazo can be generated in situ under mild conditions and trapped
reactivity, they initiate cascade sequences that lead to the
by suitable transition metal catalysts for the formation of metal
generation of complex structural molecules of biological
interest.2 For instance, they undergo various transformations carbenoids 1.3 (Scheme 1). These approaches afford access to a
such as insertion reactions, cycloaddition reactions, ylide new class of diazo compounds, viz., α-diazoimines (carbenes,
formation followed by rearrangement, etc. Transition metal viz., azavinyl carbenes), which cannot be accessed through
carbenoids have been classified into three major classes on the traditional methods. Notably, nitrogen-based heterocycles do
basis of the substituents attached to the carbenoid carbon:
acceptor, acceptor−acceptor, and donor−acceptor carbenoids Scheme 1. Formation of Metal Carbenoids from Triazoles
(Figure 1).3 Among these, acceptor and donor−acceptor
carbenoids have demonstrated excellent chemoselectivity and
hence have found wide application in organic synthesis.
Traditionally, metal carbenoids have been exclusively synthe-
sized from several diazo-based precursors in the presence of
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not require any additional coupling partner for generation of Scheme 2. Photolytic Denitrogenative Transformation of 1-
metal carbenoids. Arylbenzotriazoles
In this context, Gevorgyan, Fokin, and co-workers trapped the
chain isomer of pyridotriazole and N-sulfonyl-1,2,3-triazole (i.e.,
the α-diazoimine intermediate) with a Rh(II) catalyst with
concomitant extrusion of nitrogen and generated a rhodium
azavinyl carbenoid.6,7 Generally, this synthetic method gen-
erates donor−acceptor metal carbenoids, which undergo various
denitrogenative transformations with suitable coupling partners
(e.g., alkene, alkyne, nitrile, carbonyl, etc.) to form diverse N-
heterocyclic compounds (NHCs) of biological importance.
Importantly, N-sulfonyl-1,2,3-triazoles are easily accessible
through Cu(I)-catalyzed azide−alkyne cycloaddition
(CuAAC). Consequently, a wide range of N-sulfonyl-1,2,3-
triazoles and their analogues such as pyridotriazoles and
triazoloindoles have been extensively employed as diazo intact, except for the Dimroth rearrangement of 5-amino-1,2,3-
surrogates in the synthesis of variety of (hetero)cyclic triazoles.30,31 This rearrangement involves a ring−chain isomer-
compounds. The presence of an imino group next to the ism phenomenon based on an equilibrium between the triazole
rhodium carbenoid facilitates the construction of various ring and an α-diazoimine intermediate (Scheme 3). Several
nitrogen-containing heterocyclic compounds. The efficiency of
this methodology relies on its atom-economical, single-step, and Scheme 3. Dimroth Rearrangement and Related Ring−Chain
waste-free transformations, releasing molecular nitrogen as the Isomerism of 1,2,3-Triazoles
byproduct exclusively. Simultaneously, denitrogenative trans-
formations of benzotriazoles, which would generate diazonium
salts instead of diazoimines, also have been developed
significantly in past years.
Overall, remarkable developments in denitrogenative trans-
formations of various triazoles to afford valuable (hetero)cyclic
compounds have been observed in past decades. These
transformations have been reviewed before, mostly through
minireviews that are either specific to the diazo surrogate or
selective to the product formed.8−15 In this comprehensive
review, we discuss all of the denitrogenative transformations of
various triazole derivatives reported until the end of 2020. The
discussions are divided on the basis of the different N-
heterocycles, and in each section the developments are discussed
in terms of the types of reactions.

2. HISTORICAL PERSPECTIVE
For a long time, easily accessible 1,2,3-triazoles displaying a
broad spectrum of biological activities have been extensively
employed in biochemistry, medicinal chemistry, and materials
science.16−20 Historically, benzotriazoles have long been
established as versatile synthetic auxiliaries through the research groups studied this phenomenon exclusively. In 1965,
pioneering works of the Katritzky group in the 1990s.21 Grünanger and co-workers32 attempted to prepare 5-ethoxy-1H-
However, the denitrogenative ring-opening chemistry of 1,2,3-triazole from the reaction of ethoxyethyne and tosyl azide
benzotriazoles was still in its infancy. In this context, in 1896 at room temperature (Scheme 3). Surprisingly, the isolated
Graebe and Ullmann disclosed the first photolytic denitrogena- product appeared to be the corresponding ring-opened α-
tive transformation of 1-phenylbenzotriazole 2.1, which diazoimine isomer. In 1970, Harmon and co-workers33 also
afforded the corresponding carbazoles 2.2 (Scheme 2).22 observed a similar equilibrium while studying the reaction of
Mechanistically, 1,3-diradical 2.3 is generated upon pyrolysis sulfonyl azides with α-(N,N-diethylamino)alkynes at room
and then converted into 1,5-diradical 2.4. Finally, the carbazole temperature (Scheme 3). They confirmed the existence of these
is obtained through intramolecular cyclization 2.5 followed by tautomeric forms by NMR and IR spectroscopy. Moreover, α-
aromatization. This synthesis was a breakthrough in the ring- diazoamidines were obtained as the only products in case of α-
opening chemistry of benzotriazoles. Besides 1-phenylbenzo- (N,N-diethylamino)alkynes.
triazoles, benzotriazoles containing other aromatic rings at N1 Hermes and Marsh34 documented that 1H-1,2,3-triazole-1-
also undergo similar transformations effectively.23−28 Con- carbonitrile also exists in equilibrium with its ring-opened
sequently, this strategy has been widely employed in various isomer under thermal conditions (Scheme 4). Subsequently,
organic syntheses.29 However, its applicability in other synthetic Habraken and co-workers35 also witnessed a similar equilibrium
transformations was unexplored for decades. in the case of 1-nitro-1H-1,2,3-benzotriazole (Scheme 4). Later,
On the other hand, the heterocyclic unit of triazole was ring−chain isomerism of various substituted 1,2,3-triazoles was
considered to be significantly robust, and many functionaliza- also reported by Bakulev and co-workers.36−38 All of these
tions were documented around the triazole that keep the core reports emphasized that the position of the equilibrium is highly
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Scheme 4. Ring−Chain Isomerism of 1,2,3-Triazoles have seen exponential growth in the past decade. All of the
reported denitrogenative transformations are discussed in detail
elsewhere in this review.

3. SYNTHESIS OF 1,2,3-TRIAZOLES
Generally, N-sulfonyl-1,2,3-triazoles 6.2 could be synthesized
via the sulfonylation of corresponding N-H-1,2,3-triazoles 6.1
with sulfonyl chlorides (Scheme 6). However, the formation of

Scheme 6. Synthesis of N-Sulfonyl-1,2,3-triazoles

influenced by the nature of the substituents surrounding the

ring. Notably, when a strongly electron-withdrawing substituent
such as a sulfonyl group is present at N1, an electron-donating
substituent at C5 of the 1,2,3-triazole pushes the equilibrium
toward the ring-opened structure, i.e., the α-diazoimine
intermediate. The groups of Gevorgyan and Fokin first utilized
this phenomenon to generate metallocarbenes and demon-
strated their important synthetic utilities. Trapping of the α-
diazoimine intermediate with metal catalysts such as Rh(II)
catalysts generates the corresponding azavinyl carbenes, in
which the highly electrophilic carbene carbon and highly
nucleophilic sulfonylimine nitrogen are the key attributes for
its 1,3-dipolar nature.
In 2007, Gevorgyan and co-workers6 first demonstrated the mixtures of products 6.2 and 6.3 is major drawback that
formation of Rh−azavinyl carbene from 7-chloropyridotriazole significantly reduces the efficiency and applicability.40 Alter-
(5.1, R = Cl) by trapping of the formed carbene through a Si−H natively, CuAAC has emerged as the most effective and reliable
insertion reaction (Scheme 5). In this experiment, only 7- click reaction, giving facile access to a wide range of 1,4-
disubstituted triazoles 6.6 from terminal alkynes 6.4 and azides
Scheme 5. Rh(II)-Catalyzed Functionalization of 7- 6.5 (Scheme 6).41,42 The efficiency of this reaction relies on its
Chloropyridotriazole and 1,2,3-Triazoles significantly high regioselectivity and its high yields compared
with the traditional Huisgen cycloaddition. However, the
reaction of terminal alkynes with sulfonyl azides leads to the
formation of various secondary products 6.8 instead of the
desired triazoles via the generation of ketenimine intermediate
6.7.43,44
In 2007, Chang, Fokin, and co-workers demonstrated the first
Cu(I)-catalyzed selective synthesis of 4-substituted N-sulfonyl-
1,2,3-triazoles from the corresponding terminal alkynes and
sulfonyl azides using CuI and a stoichiometric amount of the
base 2,6-dimethylpyridine (Scheme 7).45,46 Subsequently, Fu
and co-workers47 developed an efficient and inexpensive
catalytic system using the combination of CuBr and thioanisole
in water medium. This system afforded N-sulfonyl-1,2,3-

Scheme 7. Copper-Catalyzed Synthesis of 1,2,3-Triazoles

chloropyridotriazole reacted smoothly to give the product 5.3;

pyridotriazole (5.1, R = H) did not react. Thus, it was evident
that 7-halo-substituted pyridotriazoles can be exploited as
efficient Rh carbenoid precursors. Subsequently, Fokin and
Gevorgyan39 demonstrated a rhodium-catalyzed denitrogena-
tive transannulation of N-sulfonyl-1,2,3-triazoles 5.4 with
nitriles 5.5 to afford various substituted imidazoles 5.6 in
good to excellent yields.
After the initial finding by the groups of Gevorgyan and Fokin,
denitrogenative transformations of N-heterocycles involving
insertion, cycloaddition, rearrangement, ring expansion, etc.
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triazoles in high yields at room temperature. It was emphasized Scheme 9. Synthesis of Multisubstituted 1,2,3-Triazoles
that the addition of sulfur-containing ligands stabilizes the
triazole ring by inhibiting the cleavage of the N1−N2 bond.
Later, the group of Pérez48 accomplished the synthesis of N-
sulfonyltriazoles using the well-defined copper complex
[Tpm*,BrCu(NCCH3)]BF4. On the other hand, on the basis
of the influence of sulfur ligands in copper catalysis, Raushel and
Fokin49 employed Cu(I)−thiophene-2-carboxylate (CuTC)
complexes as catalysts under mild conditions for the more
efficient synthesis of N-sulfonyltriazoles. In 2011, Hu and co-
workers50 reported a high-selectivity controlled synthesis of N-
sulfonyltriazoles that uses the combination of copper(II) acetate
monohydrate and 2-aminophenol. Interestingly, 2-aminophenol
was exploited as a ligand as well as a reductant to avoid the use of
expensive Cu(OAc)2 as the catalyst. By this method, the first
1,2,3-triazole bearing two electron-withdrawing groups was accomplished through sequential KOH-promoted HBr elimi-
synthesized successfully. In 2018, Cazin and co-workers51 nation from the vinyl bromide and copper-catalyzed [3 + 2]
exploited Cu(I)−NHC complexes for the selective preparation cycloaddition of the resulting alkyne 9.2 with azide. Sub-
of 4-substituted N-sulfonyl-1,2,3-triazoles under click reaction sequently, Ma and co-workers57 prepared 5-sulfamido-N-
conditions. sulfonyl-1,2,3-triazoles in high yields and regioselectivity
All of these above-mentioned methods were limited to the through Cu-catalyzed cycloaddition of sulfonyl azides 9.5 and
selective synthesis of 1,4-disubstituted triazoles. Croatt and co- terminal alkynes 9.4 in the presence of LiOtBu.
workers52 accomplished the synthesis of 5-substituted N-
sulfonyl-1,2,3-triazoles from the corresponding terminal alkynes 4. SYNTHESIS OF THIADIAZOLES AND ANALOGUES
8.1 and sulfonyl azides 8.2 using a strong base such as n-BuLi OF 1,2,3-TRIAZOLES
(Scheme 8). Additionally, various 1,4,5-trisubstituted triazoles In 1955, Hard and Mori developed an efficient synthesis of 1,2,3-
thiadiazoles from the reaction of acylhydrazones and thionyl
Scheme 8. Synthesis of 4,5-Disubstituted N-Sulfonyl-1,2,3- chloride (Scheme 10).58 This strategy appeared to be the most
triazoles
Scheme 10. Synthesis of 1,2,3-Thiadiazoles

commonly utilized method for the synthesis of a variety of

thiadiazoles. Thiadiazoles could also be synthesized from the
reaction of diazo compounds and Lawesson’s reagent.59
Most commonly, pyridotriazoles 11.2 are synthesized from
the corresponding hydrazones 11.1 of 2-pyridylcarboxaldehydes
or ketones by oxidation (Scheme 11).60,61 Some hydrazones
8.3 were also prepared through incorporation of suitable afford corresponding pyridotriazoles when boiled in methanol in
electrophiles in 4-lithio-1,5-disubstituted triazole formed in the presence of air. However, most hydrazones require a suitable
the reaction mixture. Subsequently, Wang and co-workers oxidizing agent such as nickel peroxide, potassium ferrocyanide
developed an enamine-catalyzed strategy to synthesize 4,5- and bicarbonate, air and a copper(II) salt, manganese dioxide, or
disubstituted triazoles 8.6 from carbonyl compounds 8.5 and (diacetoxyiodo)benzene. In the case of sensitive substrates,
various azides 8.4.53,54 Recently, Anbarasan and co-workers55 pyridotriazoles can be synthesized from tosyl hydrazones of 2-
synthesized a wide range of 4,5-disubstituted N-sulfonyl-1,2,3- pyridylcarboxaldehydes or ketones by treatment with base,
triazoles 8.9 in good yields with excellent regioselectivity from usually morpholine. In 2006, Deady and Devine developed an
substituted 1,3-dicarbonyl compounds 8.7 and sulfonyl azides alternative method to access pyridotriazoles 11.6 from amino-
8.8 through enamine cycloaddition employing proline as a naphthyridinone 11.3 (Scheme 11).62 In fluoroboric acid,
catalyst. compound 11.3 formed diazonium salt 11.4 upon treatment
In 2016, Zhang and co-workers56 reported the synthesis of 4- with aqueous sodium nitrite. Then the salt was suspended in
substituted N-sulfonyl-1,2,3-triazoles 9.3 from (Z)-arylvinyl water and treated with sodium hydroxide to furnish the
bromides 9.1 and sulfonyl azides (Scheme 9). The synthesis was triazolopyrido aldehyde as a white solid.
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Scheme 11. Synthesis of Pyridotriazoles Scheme 13. Synthesis of Benzotriazole Derivatives

5. DENITROGENATIVE TRANSFORMATIONS OF
TRIAZOLES
5.1. Transannulations with Triple Bonds (C�N/C�C)
As mentioned earlier (section 2, Scheme 5), in 2008 Fokin and
co-workers39 demonstrated a rhodium-catalyzed denitrogena-
tive transannulation of N-sulfonyl-1,2,3-triazoles with nitriles to
afford various substituted imidazoles in good to excellent yields.
Optimization of the reaction conditions emphasized that
electron-rich rhodium(II) octanoate and Rh2(S-DOSP)4 are
more effective catalysts compared with electron-deficient
Rh2(O2CCF3)4 and Rh2(O2CC3F7)4. The transformation can
be carried out following two procedures: (i) irradiation of the
triazoles and nitriles in chloroform solvent with a microwave
sensitizer at 140 °C for 15 min and (ii) conventional heating of
the reaction mixture at 80 °C for 12−24 h in 1,2-dichloroethane
solvent. Eventually, a one-pot, two-step synthesis of imidazoles
was achieved with terminal alkynes 14.1, tosyl azide 14.2, and
nitriles 14.3 (Scheme 14). Mechanistically, in path A,

Scheme 14. Rh(II)-Catalyzed Transannulation of N-Sulfonyl-

In 2014, Lu and Wang developed a copper-catalyzed tandem 1,2,3-triazoles with Nitriles
process for the synthesis of triazoloindoles 12.2 from alkyne
substrates 12.1 and sulfonyl azides (Scheme 12).63 A diverse

Scheme 12. Synthesis of Diverse Substituted Triazoloindoles

range of 3-diazoindolin-2-imines 12.3 were synthesized in

excellent yields. This tandem process involves amine-group- nucleophilic attack of nitrile 14.3 on Rh carbenoid 14.5
stabilized CuAAC and a subsequent C−N coupling reaction. followed by cyclization results in the formation of zwitterion
The same group reported an efficient catalyst-free synthesis of 3- 14.6, which upon subsequent metal loss furnishes imidazole
diazoindolin-2-imines 12.6 and their application in the synthesis 14.4. According to path B, a 1,3 Rh shift in ylide 14.7 leads to Rh
of 2,3-diaminoindoles.64 Indoles containing alkyl, allyl, and carbenoid 14.8, which upon cyclization followed by reductive
benzyl substituents at N1 and electron-donating substituents on elimination affords the desired product.
the phenyl ring reacted smoothly to give the 3-diazoindolin-2- Subsequently, Fokin and Zibinsky reported Rh(II)-catalyzed
imines in good yields. However, a significant drop in the yield transformations of N-(1,2,4-triazolyl)-substituted 1,2,3-triazoles
was observed in the presence of electron-withdrawing groups on 15.1 with nitriles and alkenes to synthesize imidazoles 15.2 and
the phenyl ring. In the case of 1,2-dimethyl- and 1-methyl-2- cyclopropanes 15.3, respectively (Scheme 15).65 Interestingly,
phenylindoles, the corresponding 3-aminoindoles were ob- N1-substituted 1,2,4-triazolyl was shown to facilitate the ring−
tained. chain isomerism of the triazole, similar to a sulfonyl moiety. The
Mostly, benzotriazole derivatives are prepared by functional- reaction of N-(1,2,4-triazolyl)-substituted 1,2,3-triazole and
ization of the corresponding simple benzotriazole (BtH) alkene in the presence of 1 mol % Rh2-(S-NTTL)4 in CHCl3
(Scheme 13).21 In general, the Bt group can be introduced at 65 °C followed by reduction of the formed imine with NaBH4
into a compound by either substitutions or additions, as shown afforded the cyclopropane with high enantio- and diastereose-
below. lectivity, whereas imidazoles were synthesized in good yields by
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Scheme 15. Rh(II)-Catalyzed Transformations of N-(1,2,4- quently, they utilized the synthesized azide to prepare N-
Triazolyl)-Substituted 1,2,3-Triazoles (bromotetrafluoroethyl)-1,2,3-triazoles through azide−alkyne
cycloaddition. The synthetic utility of these triazoles was
demonstrated by the synthesis of imidazoles, oxazoles, thiazoles,
ketamides, and β-enamido triflates under rhodium catalysis.
In 2018, Xu and Li reported the BF3·OEt2-promoted synthesis
of imidazoles from N-sulfonyl-1,2,3-triazoles and nitriles in the
absence of a rhodium catalyst (Scheme 19).70 Numerous
substituted triazoles afforded the corresponding imidazoles in
up to 99% yield under the optimized conditions. Nitriles were
exploited as both the solvent and reagent. Notably, aromatic
nitriles were found to be less reactive than acetonitrile towards
this transformation.
Murakami and co-workers disclosed the synthesis of
reacting the triazoles with aliphatic and aromatic nitriles in the polysubstituted pyrroles 20.3 through nickel(0)/phosphine-
presence of Rh2(esp)4 as the catalyst in 1,2-DCE at 80 °C. catalyzed denitrogenative coupling of N-sulfonyl-1,2,3-triazoles
In 2015, Lee and co-workers66 developed a facile method for
20.1 with internal alkynes 20.2 (Scheme 20).71 The best results
the synthesis of 2-bromo-1-sulfonyl imidazoles 16.2 via
were obtained in the presence of the Lewis acid AlPh3 as an
rhodium-catalyzed transannulation of N-sulfonyl-1,2,3-triazoles
additive. Although unsymmetrical internal alkynes gave mixtures
16.1 with cyanogen bromide (Scheme 16). Various substituted
of pyrroles regioisomers, terminal alkynes did not afford the
triazoles afforded the desired products regardless of electronic
desired products, presumably because of rapid self-oligomeriza-
and steric effects. Importantly, this protocol was utilized for the
synthesis of 2-arylated and 2-alkynylated imidazoles 16.3 and tion. According to the proposed mechanism, the chain isomer of
16.4 from 2-bromoimidazoles 16.2 through Sonogashira and triazole was trapped by nickel catalyst to produce α-imino nickel
Suzuki coupling, respectively. carbenoid 20.4, which was proposed to exist in equilibrium with
Similarly, they also synthesized N-imidazolyl sulfoximines azanickelacycle 20.5. Insertion of alkyne into the azanickelacycle
17.4 from triazoles 17.1 and N-cyanosulfoximines 17.2 followed by reductive elimination affords pyrrole along with
(Scheme 17).67 One-pot N-imidazolylation of N-sulfonyl- regeneration of the catalyst.
1,2,3-triazoles was achieved by the use of terminal alkynes, To overcome the poor reactivity of terminal alkynes, in 2011
tosyl azide, and N-cyanosulfoximines. This one-pot reaction Chattopadhyay and Gevorgyan72 developed the rhodium/
involves Cu-catalyzed [3 + 2] cycloaddition followed by Rh- silver-cocatalyzed synthesis of 1,2,4-trisubstituted pyrroles
catalyzed transannulation of triazole with N-cyanosulfoximines. from N-sulfonyl-1,2,3-triazoles and terminal alkynes (Scheme
According to a plausible mechanism, nucleophilic attack of the 21). Experimental data indicated that the silver salt is necessary
N-cyanosulfoximine on the α-imino Rh carbenoid provides for this reaction. The authors ruled out paths B and C on the
zwitterionic intermediate 17.3. Then intramolecular cyclization basis of deuterium labeling experiments. Even though the exact
through attack of the imine nitrogen on the electrophilic center role of the silver salt was unclear, it presumably acts as a Lewis
of the nitrilium ion furnishes the imidazole derivative. acid by coordinating to the imine nitrogen to make the Rh
Beier and co-workers68 reported the rhodium-catalyzed carbene more electrophilic.
transannulation of N-perfluoroalkyl-1,2,3-triazoles with nitriles, Shi and Gevorgyan73 successfully synthesized fused pyrroles
vinyl ethers, and phenyl isocyanate to synthesize N-perfluor- 22.4 and spiro compounds from alkynyl triazoles 22.1 via
oalkyl-substituted five-membered heterocycles (Scheme 18). N- alkyne−carbene metathesis (Scheme 22). Mechanistically, the
Perfluoroalkyl-1,2,3-triazoles were synthesized by CuAAC. alkynyl triazole in the presence of the Rh catalyst first produces
Notably, the best results were obtained when the reaction imino Rh carbene 22.2, which undergoes carbene−alkyne
mixture was heated at 140 °C under microwave conditions metathesis to form the new Rh carbene intermediate 22.3.
instead of conventional heating. Experimental data emphasized Subsequently, nucleophilic attack of the imine nitrogen on Rh-
that N-(perfluoroalkyl)triazoles are less reactive than N- carbene followed by tautomerization produces the fused pyrrole
sulfonyltriazoles. In continuation of their work, they also in excellent yield.
synthesized 1-azido-2-bromo-1,1,2,2-tetrafluoroethane from Li and co-workers74 developed a Rh(III)-catalyzed [3 + 2]/[5
1,2-dibromotetrafluoroethane and sodium azide.69 Subse- + 2] annulation of 4-aryl-N-sulfonyl-1,2,3-triazoles 23.1 with

Scheme 16. Synthesis of 2-Bromo-1-sulfonyl Imidazoles and Their Utilization

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Scheme 17. Synthesis of N-Imidazolyl Sulfoximines from Triazoles and N-Cyanosulfoximines

Scheme 18. Rhodium-Catalyzed Transannulation of N- Scheme 21. Rhodium/Silver-Cocatalyzed Synthesis of 1,2,4-

Perfluoroalkyl-1,2,3-triazoles Trisubstituted Pyrroles

Scheme 19. Lewis Acid-Catalyzed Synthesis of Imidazoles

Scheme 20. Nickel(0)/Phosphine-Catalyzed

Transannulation of N-Sulfonyl-1,2,3-triazoles
H activation. Finally, the products 23.12 and 23.13 are
generated from 23.11 with the aid of Cu(OAc)2 and H2O.
Subsequently, the same group converted 4-(2-ethynylaryl)-N-
sulfonyl-1,2,3-triazoles 24.1 to various functionalized isoquino-
lines 24.2 using a silver catalyst (Scheme 24).76 Surprisingly, Rh
catalysts did not afford the desired products, and Cu catalysts
showed lower catalytic activity. In the product, the sulfonate can
be replaced with acetate, benzoate, or halides by the use of acetic
acid, benzoic acid, or halide nucleophiles, respectively.
Mechanistically, in the Ag carbenoid, Ag coordinates to the
alkyne to enhance its electrophilicity. Then cyclization of
intermediate 24.3 in the presence of water leads to the formation
of intermediate 24.4, which upon second cyclization with TsOH
gives intermediate 24.5. Finally, intermediate 24.5 undergoes
ring opening and protonation to afford the desired product.
5.2. Transannulations with Double Bonds (C�C/C�X)
Similar to alkynes and nitriles, substituted alkenes and carbonyl
internal alkynes 23.2 through a dual C(sp2)−H bond activation derivatives have been efficiently employed as coupling partners
strategy (Scheme 23). Notably, experimental results indicated in denitrogenative transannulations of suitably substituted
that AgSbF6 and the Cu oxidant play key roles in this triazoles. For the first time, in 2009 Fokin and co-workers
transformation along with Rh catalyst. Li and Liao proposed a disclosed a highly diastereo- and enantioselective synthesis of
possible mechanism based on DFT mechanistic studies.75 chiral cyclopropanes by the Rh-catalyzed transannulation of N-
Initially, the activated Rh(III) catalyst 23.4 generates Rh sulfonyl-1,2,3-triazoles with substituted styrenes (Scheme 25).77
carbenoid 23.5, and subsequent addition of diphenylacetylene A reaction of 4-aryl-N-sulfonyl-1,2,3-triazoles with styrenes in
(23.6) produces zwitterionic intermediate 23.7. Then electro- the presence of Rh2(S-NTTL)4 in 1,2-dichoroethane at 65 °C
philic cyclization of the aryl ring with the electrophilic center and subsequent addition of K2CO3 in wet MeOH provided
furnishes the first [3 + 2]-annulated product 23.8. Next, a cyclopropane carboxaldehydes in excellent yields and enantio-
second annulation with alkyne 23.6 leads to the formation of selectivities. Importantly, trans-methylstyrene gave the tetrasub-
Cp*Rh(H)-coordinated intermediate 23.10, which immedi- stituted cyclopropane with excellent enantioselectivity, whereas
ately undergoes trans addition to form the corresponding cis-methylstyrene produced almost racemic product.
intermediate 23.11. Alternatively, the second annulation could Subsequently, they proposed an alternative pathway for the
also proceed through the formation of intermediate 23.9 via C− generation of Rh azavinyl carbenes from NH-triazoles 26.1
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Scheme 22. Rh-Catalyzed Synthesis of Fused Pyrroles from Alkynyl Triazoles

Scheme 23. Rh(III)-Catalyzed [3 + 2]/[5 + 2] Annulation of Scheme 25. Stereoselective Synthesis of Chiral
4-Aryl-N-sulfonyl-1,2,3-triazoles Cyclopropanes

Scheme 26. Synthesis of Chiral Cyclopropane Carbaldehydes

Scheme 24. Silver-Catalyzed Synthesis of Various

Functionalized Isoquinolines

In 2012, Alford and Davies introduced new donor/acceptor

carbenes derived from 4-(N-phthalimido)-N-sulfonyl-1,2,3-
triazole 27.2, in which the donor group is a protected amine
(Scheme 27).80 The carbene readily reacts with terminal and
internal alkenes 27.3 in the absence of rhodium catalyst to form
phthalimide-substituted cyclopropane carboxaldehyde deriva-

Scheme 27. Synthesis of Phthalimide-Substituted

Cyclopropane Carboxaldehydes

through in situ sulfonylation by triflic anhydride in the presence

of a pyridine base (Scheme 26).78 Subsequent addition of
Rh2(S-NTTL)4 followed by styrenes 26.2 produced cyclo-
propane carbaldehydes 26.3 in good yields with excellent
diastereo- and enantioselectivities, regardless of treatment with
wet MeOH. Similarly, in 2011, cyclopropane derivative 26.7 was
synthesized diastereo- and enantioselectively from N-sulfamoyl-
1,2,3-triazole 26.6, which had been synthesized from sulfamoyl
azide 26.4 and terminal alkyne 26.5 using a Cu(I) catalyst and
styrene.79
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tives 27.4. These derivatives were converted to α-amino acids Scheme 30. Rh-Catalyzed Asymmetric Trimerization of N-
27.5 through a sequence of reactions. Methanesulfonyl-4-(4-vinylphenyl)-1,2,3-triazoles
Subsequently, Davies and co-workers synthesized 2,3-fused
pyrroles and substituted indoles starting from 4-alkenyl-N-tosyl-
1,2,3-triazoles 28.1, which were synthesized from cyclic ketones
in three steps (Scheme 28).81 Heating of 4-alkenyl-N-tosyl-

Scheme 28. Synthesis of 2,3-Fused Pyrroles and Substituted

Indoles

H/D atoms on the benzene rings of the title compound afforded

enantiopure hydrocarbons, and the absolute configuration was
confirmed by vibrational circular dichroism (VCD) spectrosco-
py. They also reported the first example of the synthesis of chiral
hydrocarbon molecules in which the chirality is due to an
asymmetrical arrangement of 12C/13C, and their absolute
configurations were assigned using the VCD technique.84
Subsequently, they extended this study to the synthesis of chiral
macrocycles from vinylthiophene-substituted triazole.85 The
selectivity of the trimeric macrocyclic compound formation
depends on the 2,4-substitution pattern of the thiophene. The
reaction of 4-(N-mesyltriazolyl)-2-vinylthiophene with
1,2,3-triazoles 28.1 in the presence of Rh2(esp)4 generates Rh2[(S)-NTTL]4 catalyst afforded the 1S,2S trimeric macro-
rhodium-stabilized imino carbene intermediate 28.3, which cycle as the major product with >99% ee, whereas, 2-(N-
participate in a 4π electrocyclization to form pyrrolylium cations mesyltriazolyl)-4-vinylthiophene in the presence of Rh2[(S)-
28.4, after which aromatization and protonation furnish 2,3- NTTL]4 gave the other enantiomer of the trimeric macrocycle
fused pyrroles 28.2. The one-pot reaction starting from alkynes with similar enantioselectivity. Deformylation of these products
gave good yields of up to 90% starting from triazoles. stereospecifically using RhCl(PPh3)3 furnished optically active
Additionally, 2,3-fused pyrrole products were oxidized to chiral macrocyclic hydrocarbons. The observed electronic
substituted indoles in good to excellent yields using DDQ. circular dichroism (ECD) spectra of these compounds were in
Pan and Xu synthesized azabicyclo[4.1.0]/[5.1.0]- good agreement with density functional theory calculations.
carbaldehydes via intramolecular Rh-catalyzed denitrogenative Subsequently, they also reported86 the synthesis of syntheti-
cyclopropanation of N-allyl- or N-homoallyl-tethered triazoles cally useful boryl-substituted cyclopropylmethanamines 31.3
(Scheme 29).82 Rh2(OAc)4 was found to be the best catalyst for with excellent diastereo- and enantioselectivities through the
this transformation. This protocol was utilized in the synthesis of reaction of N-mesyl-1,2,3-triazoles 31.1 and pinacol allylboro-
the antidepressant agent GSK1360707 (see Scheme 200). nate (31.2) using chiral Rh2[S-NTTL]4 as the catalyst (Scheme
31). Oxidation of boryl-substituted cyclopropylmethanamine
Scheme 29. Rh-Catalyzed Denitrogenative Cyclopropanation 31.4 with NaBO3·4H2O gave the corresponding cyclopropyl-
of Alkene-Tethered Triazoles methanol 31.5, and alkyl/arylcyclopropanes 31.6 were synthe-
sized through Suzuki−Miyaura cross-coupling.
The groups of Volla87 and Shi88 individually reported the
synthesis of benzofurans 32.2 and cyclopropa[cd]indoles 32.3
through intramolecular cyclopropanation of alkenes from
triazole 32.1 containing a tethered cyclohexadienone group in
which an O or N atom is present in the linker (Scheme 32).
Mechanistically, the Rh-bound iminocarbenoid intermediate
32.4 is initially formed from triazole 32.1 and the Rh catalyst.
However, its subsequent reactions proposed by the two groups
are different. The Volla group proposed intramolecular
cyclopropanation of the iminocarbenoid with the olefin to
afford tricyclic compound 32.5 as the next step. The formed
tricyclic compound was proposed to take different paths
depending on the linker atom. In the presence of the N linker
Miura and Murakami reported an asymmetric trimerization of atom, the imine immediately was hydrolyzed to the
N-methanesulfonyl-4-(4-vinylphenyl)-1,2,3-triazole to form C3- carbaldehyde to produce cyclopropa[cd]indole 32.3 (path A).
symmetric triangular macrocycles in the presence of the chiral On the other hand, when an O atom was employed as the linker
Rh catalyst Rh2[(S)-NTTL]4 (Scheme 30).83 Experimental atom, opening of the cyclopropane ring gives intermediate 32.8,
results declared that each repetition of the enantioselective which upon intramolecular nucleophilic addition affords
cyclopropanation step intensified the enantiopurity of the final benzofuran derivatives 32.2. Alternatively, the Shi group
product to get the enantiopure triangular macrocycle, which is a proposed that the carbenoid undergoes a 1,2-H shift, resulting
chiral building block in the fields of supramolecular chemistry in the formation of intermediate 32.6, which undergoes oxy-
and metal−organic frameworks. The asymmetric distribution of Cope rearrangement to form 1,4-diketone intermediate 32.7.
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Scheme 31. Synthesis of Boryl-Substituted Cyclopropylmethanamines

Scheme 32. Synthesis of Benzofurans and Cyclopropa[cd]indoles

Scheme 33. Synthesis of 2,3-Fused Pyrroles and Substituted Indoles

Isomerization of intermediate 32.7 provides 32.8, which upon Davies and co-workers reported the synthesis of 2,3-fused
intramolecular nucleophilic attack gives intermediate 32.9. pyrroles and substituted indoles from 4-cycloalkenyltriazoles via
Finally, benzofurans are obtained by loss of a water molecule. intramolecular electrocyclization (Scheme 33).89 4-Alkenyl-N-
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sulfonyl-1,2,3-triazoles were synthesized from the correspond- tial [2 + 1] cycloaddition of intermediate 35.3 to provide
ing ketones in three steps: vinyl triflate formation, Kumada-type intermediate 35.4. Then [3,3]-aza-Cope rearrangement of
coupling, and Cu(I)-catalyzed [3 + 2] cycloaddition. Moreover, intermediate 35.4 furnishes the desired product through six-
the formation of the 2,3-fused pyrrole in the one-pot reaction membered transition state 35.5. Notably, in the absence of the
starting from the alkyne was more efficient than the sequential Rh catalyst in chloroform solvent at 140 °C, the diene-tethered
triazole isolation method. Furthermore, utility of this one-pot triazole gave an unexpected [4.4.0]bicyclic heterocycle in 50%
synthesis of 2,3-fused pyrroles was explored by the synthesis of yield, presumably via a ketenimine intermediate. Similar
the steroid skeletons of 5-cholestan-3-one and nootkatone. observations were made by the groups of Tang92 and Shen93
Notably, treatment of the electrocyclized product with an for the synthesis of fused 2,5-dihydroazepines through intra-
oxidizing agent such as DDQ in the same pot afforded various molecular Rh-catalyzed [4 + 3] cycloaddition of dienyltriazoles.
substituted indoles in good to excellent yields. Tang and co-workers94 disclosed the divergent synthesis of
Similarly, Parr and Davies disclosed the synthesis of 2,5-dihydroazepines 36.3, 36.7, and 36.11 and dihydropyrroles
cycloheptadienes 34.3 from 4-alkenyltriazoles 34.1 by a tandem 36.5, 36.8, and 36.10 by intermolecular Rh-catalyzed aza-[4 +
Rh-catalyzed formal [4 + 3] cycloaddition with dienes 34.2 3]/[3 + 2] cycloadditions of N-sulfonyl-1,2,3-triazoles 36.1 and
(Scheme 34).90 The reaction of 4-cyclohexenyl-N-sulfonyl- 1,3-dienes 36.2, 36.4, 36.6, and 36.9 (Scheme 36). The reaction
of readily available triazoles with 1,3-dienes in the presence of 1
Scheme 34. Synthesis of Cycloheptadienes from 4- mol % Rh2(Oct)4 at 140 °C for 12 h afforded dihydropyrroles
Alkenyltriazoles exclusively, whereas irradiation at 120 °C under microwave
condition for 5−10 min with the addition of 4 Å molecular sieves
gave the dihydroazepines as the major products. On the basis of
the isolation of a cyclopropane intermediate, a possible
mechanism was proposed. First, the α-imino Rh carbene
intermediate couples with the diene to form the cyclo-
propylaldimine intermediate, aza-Cope rearrangement of
which affords the dihydroazepine. On the other hand,
cyclopropylimine rearrangement of the cyclopropylaldimine
intermediate gives the dihydropyrrole derivative. In addition to
the conditions, the reaction outcome depends on the
substitution and geometry of the diene. For example, trans-
annulation of triazoles 36.1 with (Z)-1-aryl-1,3-dienes 36.2
afforded aza-[4 + 3] cycloaddition adducts 36.3, whereas aza-[3
+ 2] cycloadducts 36.5 were obtained from (E)-1-aryl-1,3-
dienes 36.4. Along with aryl-substituted dienes, various alkyl-
substituted dienes 36.9 also afforded the desired products 36.10
1,2,3-triazole with 1,3-butadiene in 1,2-DCE at 60 °C in the and 36.11 in good to high yields.
presence of Rh2(S-NTTL)4 gave the corresponding cyclo- Similarly, Motornov and Beier disclosed a chemo- and
heptadiene in excellent yield with good diastereo- and regioselective aza-[4 + 3] transannulation of N-perfluoroalkyl-
enantioselectivity. The application of this approach was 1,2,3-triazoles with 1,3-dienes to form N-perfluoroalkyl-
exemplified by the synthesis of chiral fused tetrahydroindole substituted azepines.95 N-Perfluoroalkyl-substituted azepinone
34.6 in 94% overall yield. derivatives were obtained when 2-trimethylsilyloxybutadiene
On the other hand, Sarpong and co-workers91 developed the was employed. Transannulation of N-(perfluoroalkyl)triazoles
synthesis of fused azepine derivatives 35.2 from diene-tethered with unsymmetrical 2-aryl-1,3-dienes gave regioselective 4,6-
triazoles 35.1 (Scheme 35). Various substituted dienyltriazoles disubstituted dihydroazepines exclusively.
reacted smoothly to afford fused dihydroazepines as a single In a continuation of that study, Lee and co-workers reported a
diastereomer in good yields. The proposed mechanism for the catalyst-controlled divergent aza-[4 + 3]/aza-[3 + 2] annulation
Rh(II)-catalyzed formation of dihydroazepine involves sequen- of iminocarbenes with 1,3-dienes to form dihydroazepines and
dihydropyrroles (Scheme 37).96 Electron-rich Rh2(Oct)4 was
Scheme 35. Synthesis of Fused Azepine Derivatives more efficient than electron-deficient rhodium catalysts such as
Rh2(tfa)4 and Rh2(pfb)4 for the generation of dihydropyrroles,
whereas, Rh2(S-PTAD)4 gave good yields of dihydroazepines.
Furthermore, the one-pot synthesis of the desired products was
achieved using terminal alkynes, sulfonyl azides, and 1,3-dienes
along with Cu(I) thiophene 2-carboxylate and rhodium catalyst.
Notably, the stereochemistry of the diene did not affect the
efficiency of the product formation.
In 2014, Fokin and co-workers97 reported the catalytic
synthesis of enantioenriched 2,3-dihydropyrroles from NH-
1,2,3-triazoles and electron-rich olefins (Scheme 38). The
reaction involves a cascade sequence of Rh-catalyzed formation
of cyclopropyl-N-triflylimine from in situ-generated N-triflyl
triazole, which immediately rearranges to the 2,3-dihydropyr-
role. Interestingly, racemic cyclopropyl-N-triflylimine gave the
enantioenriched 2,3-dihydropyrrole in the presence of a chiral
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Scheme 36. Synthesis of Various 2,5-Dihydroazepines and Dihydropyrroles

Scheme 37. Catalyst-Controlled Divergent Aza-[4 + 3]/Aza-[3 + 2] Annulation of Triazoles

Scheme 38. Synthesis of Enantioenriched 2,3- Scheme 39. Asymmetric Synthesis of Piperidine-Fused trans-
Dihydropyrroles from NH-1,2,3-Triazoles Cycloalkenes

Brønsted acid. This developed methodology gave access to the

synthesis of chiral cyclic amines, amino acid analogues, and that was a crystalline solid, and its single-crystal X-ray analysis
complex polycyclic architectures found in natural products and proved the absolute stereochemistry of the trans-alkene.
pharmaceutically useful compounds. Furthermore, piperidine-fused trans-cycloalkenes were also
The asymmetric synthesis of piperidine-fused trans-cyclo- prepared by a one-pot three-component reaction of terminal
alkenes through a two-step cascade reaction of methylenecy- alkynes, tosyl azide, and methylenecyclopropane with copper
clopropanes and N-sulfonyl-1,2,3-triazoles was reported by and rhodium catalysts.
Miura and Murakami (Scheme 39).98 The cascade reaction Lee and co-workers demonstrated an efficient method for the
comprises enantioselective cyclopropanation of the methylene- synthesis of substituted pyrroles from triazoles and alkenyl alkyl
cyclopropane with the α-imino Rh carbenoid followed by ethers (Scheme 40).99 The transformation was achieved in one
skeletal rearrangement. The driving force for the skeletal pot by employing terminal alkynes, tosyl azide, and alkenyl alkyl
rearrangement is probably ring strain of the spirocyclic ethers. The reaction proceeds through the initial formation of
compound. The cycloalkene was treated with trans- the 2,3-dihydropyrroline and subsequent alcohol elimination to
PtCl2(2,4,6-collidine)(η2-ethylene) to form a Pt(II) complex afford the desired product.
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Scheme 40. Rh(II)-Catalyzed Synthesis of Substituted Scheme 42. Synthesis of 3-Pyrrolin-2-one Derivatives
Pyrroles

Rajasekar and Anbarasan demonstrated a regioselective

method for the synthesis of mono-, di-, and trisubstituted
pyrroles via the rhodium-catalyzed transannulation of N-
sulfonyl-1,2,3-triazoles with vinyl ethers (Scheme 43).102 The

Scheme 43. Regioselective Synthesis of Mono-, Di-, and

Trisubstituted Pyrroles
They also demonstrated the Rh-catalyzed transannulation of
N-sulfonyl-1,2,3-triazoles 41.1 with 2,3-dihydrofurans and 3,4-
dihydro-2H-pyrans 41.2 to form tetrahydrofuranodihydro-
pyrroles and tetrahydropyranodihydropyrroles 41.6 with high
diastereoselectivity (Scheme 41).100 According to the proposed

Scheme 41. Rh-Catalyzed Transannulation of N-Sulfonyl-

1,2,3-triazoles with Electron-Rich Alkenes

mechanism, the in situ-generated α-imino carbenoid gives Rh- [3 + 2] cycloaddition of the α-imino rhodium carbenoid with
bound zwitterionic intermediate 41.3 through nucleophilic the vinyl ether followed by alcohol elimination furnishes the
attack of the coupling partner. Next, addition of the imine pyrrole. Numerous substituted pyrroles were synthesized by
nitrogen to the oxonium carbon affords the desired product employing various substituted triazoles and vinyl ethers.
through ring closure. Alternatively, [2 + 1] cycloaddition of the Treatment of triazoles with cyclic ethers afforded bicyclic
carbenoid with the olefin gives cycloalkoxycyclopropyl imine compounds in good yields under the standard reaction
41.4, which further undergoes cyclopropane ring opening to conditions. The two-step synthesis of 3,4-dianisylpyrrole,
give intermediate 41.5. Finally, intermediate 41.5 furnishes the which is the key intermediate for the synthesis of the antitumor
desired product upon ring closure. agent neolamellarin A, emphasized the importance of this
Li and co-workers reported the rhodium-catalyzed denitro- methodology. Similarly, Tang and co-workers103 also reported
genative reaction of N-sulfonyl-1,2,3-triazoles with ketene silyl the synthesis of highly substituted N-heterocycles from N-
acetals for the synthesis of 3-pyrrolin-2-one derivatives (Scheme sulfonyl-1,2,3-triazoles and silyl or alkyl enol ethers. Employ-
42).101 Among various catalysts, Rh2(OAc)4 emerged as a ment of silyl ketene acetals as coupling partners for trans-
suitable catalyst for this transformation, and a wide range of annulation of triazoles afforded 3-pyrrolin-2-ones, which are a
substituted 3-pyrrolin-2-ones were synthesized from the key structural element in various bioactive molecules.
corresponding triazoles and ketene silyl acetals. Of note, Miura and Murakami developed the Ni(0)-catalyzed
hydrogenation of 3-pyrrolin-2-ones gave the corresponding γ- regiocontrolled synthesis of polysubstituted pyrroles 44.5
lactams in good yields. Moreover, this method was used to from terminal alkynes 44.1, sulfonyl azides 44.2, and allenes
synthesize a key bilirubin intermediate. 44.4 through the formation of N-sulfonyltriazoles 44.3 (Scheme
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44).104 The reaction of allenes with imino Ni carbenoids Scheme 46. Synthesis of α,β,γ,δ-Unsaturated Imines from
generates 3-methylene-2,3-dihydropyrroles, which are readily Triazoles and Allenes

Scheme 44. Ni(0)-Catalyzed Regiocontrolled Synthesis of

Polysubstituted Pyrroles

Immediately, the imine nitrogen abstracts the allylic hydrogen

with skeletal rearrangement to afford ring-opened enamine
product 46.5. Subsequent 1,5-H migration via a six-membered
cyclic transition state produces the α,β,γ,δ-unsaturated imine.
Alcaide and Almendros described the regiodivergent
reactivity of N-sulfonyl-1,2,3-triazoles 47.1 with allenols 47.2
and allenones 47.4 to form 2-pyrrolines 47.3 and 6-oxohexa-2,4-
dienals 47.5, respectively (Scheme 47).107 Mechanistically,

Scheme 47. Synthesis of 2-Pyrrolines and 6-Oxohexa-2,4-

dienals
converted to pyrroles in the presence of p-toluenesulfonic acid
by transposition. On the other hand, addition of other
electrophilic reagents such as Eschenmoser’s salt, diethyl
ketomalonate, and diethyl azodicarboxylate to the reaction
mixture afforded the corresponding pyrroles 44.6−44.8 via the
Alder-ene reaction. Interestingly, cyclic allene 44.10 also
participated in this transformation with triazole 44.9 to produce
3-methylene-2,3-dihydropyrrole 44.11 in moderate yield.
Likewise, Schultz and Sarpong105 reported the synthesis of
3,4-fused pyrroles from allenyl alkynes (Scheme 45). The

Scheme 45. Synthesis of 3,4-Fused Pyrroles from Triazoles

and Allenyl Alkynes

reaction involves the Cu(I)-catalyzed synthesis of the N-

sulfonyl-1,2,3-triazole followed by Rh-catalyzed intramolecular
annulation of the allene with the N-sulfonyl-1,2,3-triazole to
afford the 3,4-fused pyrrole. The natural product cyclo-
prodigiosin was synthesized by applying this method (see
Scheme 195). Besides, 2-substituted 3,4-fused pyrroles can be
successfully used as starting materials for peroxynitrite scavenger
synthesis.
In 2015, Miura and Murakami synthesized α,β,γ,δ-unsatu- nucleophilic addition of the internal double bond of cumulene
rated imines (1-azatrienes) 46.3 from triazoles 46.1 and allenes to α-imino rhodium(II) carbenoid 47.6 gives zwitterionic
46.2 (Scheme 46).106 They found that Rh2[(S)-TCPTTL]4 was intermediate 47.7, which upon azacyclization affords 2-pyrro-
the best catalyst for this transformation. At first, alkylidenecy- lines 47.3. However, upon replacement of the allenol with an
clopropyl methanimine 46.4 is obtained from the Rh carbene allenone, the terminal double bond of the allenone attacks the
with the less hindered side of the allene double bond. electrophilic rhodium(II) carbenoid to form zwitterionic
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intermediate 47.8. This undergoes a 1,2-hydride shift to form with cyclic silyl dienol ethers 50.2 to form various functionalized
another zwitterion, intermediate 47.9, which is rapidly hydroindolones 50.4 (Scheme 50).110 The synthetic applic-
converted to 1,6-dicarbonyl derivative 47.5. ability of the present protocol was demonstrated by the synthesis
In 2016, Kang and co-workers108 developed a facile method of the 5,11-methanomorphanthridine framework, which is
for the synthesis of polycyclic spiroindolines 48.2 by Rh(II)- extensively found in montanine-type Amaryllidaceae alkaloids.
catalyzed dearomatizing annulation of tryptamine-derived Additionally, synthetically valuable bicyclo[3.3.1]alkenone
sulfonyltriazoles 48.1 (Scheme 48). Various substituted trypt- derivatives and pyrrolidine-ring-containing bicyclic indole
compounds have been synthesized by utilizing this strategy.
Scheme 48. Rh(II)-Catalyzed Dearomatizing Annulation of Jiang and Shi111 developed a convenient method for the
Tryptamine-Derived Sulfonyltriazoles synthesis of indoles 51.4 and C3-functionalized indoles 51.3
containing N-dihydropyrrole from N-vinylindoles 51.2 and
triazoles 51.1 (Scheme 51). The reaction of 1 equiv of the N-
vinylindole with 0.5 equiv of the triazole in the presence of
Rh2(esp)2 at 80 °C afforded the indole-containing N-
dihydropyrrole derivative. The use of 2.5 equiv of triazole
followed by in situ reduction afforded the C3-functionalized
indole containing the N-dihydropyrrole. A broad range of
substituted triazoles and N-vinylindoles smoothly underwent
this transformation to give the corresponding products in good
to excellent yields. Further transformations of the products gave
different synthetically useful compounds.
Carbonyl compounds and their derivatives are vital synthetic
equivalents that offer multiheteroatom-containing heterocycles
under annulation conditions with α-imino carbenes. In 2013,
Zibinsky and Fokin112 demonstrated transannulation of N-
sulfonyl-1,2,3-triazoles 52.1 with aldehydes 52.2 to form
amine-tethered sulfonyltriazoles gave the corresponding poly- oxazolines 52.3 with high enantioselectivity at ambient
cyclic spiroindolines in good to excellent yields. The substituent temperature (Scheme 52). Screening of different catalysts
on the indole nitrogen plays a key role in this transformation: revealed that Rh2[(S)-NTTL]4 was the best catalyst for this
better results were obtained through employment of electron- annulation. In some cases, because of the lability of the C−O
donating groups on the indole nitrogen, whereas sluggish bond, ring opening of the N,O-aminals occurred to form acyclic
reactions were observed with electron-withdrawing groups such compounds. Notably, aliphatic aldehydes and 4-alkyl-substi-
as tosyl and mesyl. The product was obtained in 55% yield with tuted triazoles failed to give oxazolines because of the formation
46.6% ee in the presence of a chiral dirhodium catalyst such as of unwanted side products. Additionally, transannulation of
Rh2(S-BNP)4. triazoles 52.1 with aldimines 52.4 produced substituted
Bi and co-workers reported the Rh/Ag binary metal-catalyzed imidazoles 52.5 through a cyclization−elimination sequence.
transannulation of N-sulfonyl-1,2,3-triazoles with vinyl azides Thus, the reaction mixture of triazole, aldimine and Rh2(OPiv)4
49.2 and 49.4, which afforded important classes of azo- in CHCl3 was heated to 120 °C for 5−10 min and then treated
heterocycles such as pyrroles 49.3 and 2H-pyrazines 49.5, with DBU for an additional 1 min to afford imidazoles in good
respectively (Scheme 49).109 A combination of Rh2(Oct)4 and yields.
AgO2CCF3 worked well for this transannulation. Of note, the Furthermore, Miura and Murakami disclosed the Rh-
reaction of α-acyl internal vinyl azides with triazoles gave 2H- catalyzed transannulation of N-sulfonyl-1,2,3-triazoles 53.1
pyrazines, whereas simple vinyl azides produced pyrroles. with α,β-unsaturated aldehydes 53.2 for the diastereoselective
Although the role of the Ag salt was not clear, the authors synthesis of trans-2,3-disubstituted 2,3-dihydropyrroles 53.3
believed that it acts as a Lewis acid in the reaction. In the pyrrole (Scheme 53).113 Both the E and Z isomers of the α,β-
synthesis, the azide group acts as the leaving group, but in the unsaturated aldehydes furnished the trans-2,3-disubstituted
case of 2H-pyrazines, N2 of the azide acts as the leaving group to dihydropyrroles in high yields. On the basis of intermediate
form the azirine, which participates in the reaction as the active isolation and 1H NMR studies, the mechanism shown at the
substrate. bottom of Scheme 53 was proposed. Initially, reaction of the
Li and Zhai reported a Rh-catalyzed [3 + 2] cycloaddition of aldehyde with the imino carbene gives intermediate 53.4, which
imino carbenes derived from N-sulfonyl-1,2,3-triazoles 50.1 undergoes cyclization to provide oxazoline 53.5. Because of the

Scheme 49. Rh/Ag Binary Metal-Catalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles

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Scheme 50. Rh-Catalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles with Silyl Dienol Ethers

Scheme 51. Rh(II)-Catalyzed Transannulation of Triazoles of dihydropyrroles was also achieved employing terminal
with N-Vinylindoles alkynes, tosyl azide, and α,β-unsaturated aldehydes in the
presence of CuTC and a rhodium catalyst. Notably, this
transformation was limited to α,β-unsaturated aldehydes only.
In 2020, Li and Xu synthesized 2,5-diaryl-substituted oxazoles
54.3 and 54.5 via Rh-catalyzed denitrogenative transannulation
of N-sulfonyl triazoles 54.1 with aryl aldehydes 54.2 and 54.4,
respectively (Scheme 54).114 Various substituted oxazoles were

Scheme 54. Synthesis of 2,5-Diaryl-Substituted Oxazoles

Scheme 52. Transannulation of N-Sulfonyl-1,2,3-triazoles

with Aldehydes and Aldimines

Scheme 53. Rh-Catalyzed Transannulation of N-Sulfonyl-

1,2,3-triazoles with α,β-Unsaturated Aldehydes accessed from readily available triazoles and arylaldehydes. The
reaction was carried out at a higher temperature (120 °C) to
help with the elimination of sulfinic acid. Aliphatic aldehydes did
not afford the desired products. Additionally, natural products
such as balsoxin and texamine were synthesized in one step in
85% and 79% yield, respectively.
Wang and co-workers115 obtained polysubstituted dihydro-
pyrroles and pyrroles from N-sulfonyltriazoles 55.1 and both
cyclic 55.2 and acyclic α,β-unsaturated ketones 55.4 (Scheme
55). Among various catalysts examined, Rh2(S-PTV)4 emerged
as the best catalyst for this transformation. Employment of 2-
benzylidenebenzofuran-3(2H)-one as the substrate afforded
trans-2,3-dihydro-1H-benzofuro[3,2-b]pyrrole. Importantly,
electron-rich α,β-unsaturated ketones are more efficient toward
this transformation.
labile nature of the C−O bond, the oxazoline opens to give Gong and Yang116 reported Rh-catalyzed tandem reactions of
zwitterion 53.6, which upon cyclization gives dihydropyrrole 2-triazolylbenzaldehydes and 2-triazolylaryl alkyl ketones 56.1
53.3. On the other hand, a one-pot three-component synthesis with alcohols 56.2 and water to form dihydroisobenzofurans
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Scheme 55. Transannulation of N-Sulfonyltriazoles with α,β- Scheme 57. Diastereoselective Synthesis of the
Unsaturated Ketones Oxabicyclo[2.2.1]heptene Core

56.3 and indanones 56.4, respectively (Scheme 56). Although

there were some electronic effects on the product formation,
various substituted triazoles gave the corresponding products in Scheme 58. Synthesis of Aza-Bridged Benzodioxepine
good yields. According to the proposed mechanism, intra- Derivatives from Carbonyltriazoles
molecular nucleophilic addition of the carbonyl oxygen to the
electrophilic carbenoid forms oxonium intermediates 56.5. At
this stage, nucleophilic addition of the alcohol furnishes the
dihydroisobenzofurans through the formation of intermediates
56.6. On the other hand, addition of water to the oxonium
intermediates forms hydroxylrhodium species 56.7, and
subsequent ring opening to give intermediates 56.8 followed
by ring closure affords the indanones, which are important
building blocks in medicinal chemistry.
In continuation of their study, Gong and Yang developed a
method for the diastereoselective synthesis of oxabicyclo[2.2.1]-
heptene-containing polycyclic compounds (Scheme 57).117
Various substituted polycyclic ring systems bearing an
oxabicyclo[2.2.1]heptene core were synthesized successfully.
The conversion involves tandem intramolecular carbonyl attack
on the carbenoid to form the five-membered carbonyl ylide
followed by inter/intramolecular [3 + 2] dipolar cycloaddition
with alkynes and alkenes. Notably, employment of Rh2(S-
DOSP)4 furnished the polycyclic compound in 86% yield with
83% ee.
Tang and Shi developed the Rh-catalyzed intramolecular
transannulation of carbonyltriazoles 58.1 to synthesize aza- [b][1,5]oxazecin and 2,5-epoxybenzo[f ][1,4]oxazepine deriva-
bridged benzodioxepine derivatives 58.2 (Scheme 58).118 The tives.
reaction showed a broad substrate scope and tolerance to many 2,5-Disubstituted thiazoles were successfully synthesized via
valuable functional groups with various electronic and steric transannulation of N-sulfonyl-1,2,3-triazoles with thionoesters
substituents. The proposed mechanism involves the formation in up to 99% yield by Miura and Murakami (Scheme 59).119
of cyclic carbonyl ylide 58.4 followed by ring opening to afford Heating of a chloroform solution of the triazole and thionoester
zwitterion 58.5 and cyclization through the formation of for 1 h at 70 °C in the presence of Rh2(OPiv)4 afforded the
intermediate 58.6. Furthermore, applications of this trans- substituted thiazoline, and subsequent addition of acidic silica
formation were explored by the synthesis of 2,8-epiminobenzo- gel furnished the 2,5-disubstituted thiazole by alkyl sulfonate

Scheme 56. Rh(II)-Catalyzed Synthesis of Dihydroisobenzofurans and Indanones

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Scheme 59. Transannulation of N-Sulfonyl-1,2,3-triazoles corresponding 6-alkoxypiperidin-3-one in 82% yield with 97%
with Thionoesters ee.
Li and co-workers synthesized multifunctionalized 2-carbon-
ylpyrroles 63.3 via rhodium-catalyzed transannulation of N-
sulfonyl-1,2,3-triazoles 63.1 with 1,3-diketones 63.2 (Scheme
63).123 A series of multisubstituted 2-carbonylpyrroles were
synthesized efficiently in up to 94% yield from readily available
starting materials under mild conditions. When benzoylacetone
derivatives were used as trapping reagents for azavinyl rhodium
carbenoids, the corresponding pyrrole products were obtained
elimination. The synthetic utility of the present protocol was regioselectively. Mechanistically, nucleophilic attack of the enol
explored in the late-stage transformation of biorelated isomer of 63.2 on Rh carbenoid 63.4 gives zwitterionic
derivatives and the highly selective synthesis of oligomeric intermediate 63.5. Subsequent addition−elimination reactions
arylene compounds. provide intermediate 63.7 through 63.6. Next, aldol reaction of
Li and co-workers120 isolated multisubstituted furans from the
63.7 generates intermediate 63.8, which upon aromatization
reaction of carbonyl-tethered N-sulfonyl-1,2,3-triazoles via
furnishes the desired product.
intramolecular trapping of an α-imino rhodium carbenoid by
Similarly, Zhang and Bi124 disclosed substrate-controlled
carbonyl compounds and subsequent aromatization (Scheme
reactions of sulfonyltriazoles with 1,3-diketones to form pyrroles
60). A wide range of functionalized polysubstituted furans were
and fused pyrroles (Scheme 64). Employment of acyclic
synthesized in up to 92% yield. The applicability of this
symmetrical 1,3-diketones afforded polysubstituted pyrroles
transformation was explored by the conversion of a propargyl-
via O−H insertion-cum-condensation. Interestingly, in the case
tethered furan to a phenol derivative through gold-catalyzed
rearrangement. of unsymmetrical diketones, the pyrrole derivatives were
Fu and co-workers demonstrated the Rh-catalyzed trans- obtained with excellent regioselectivity. Furthermore, cyclic
annulation of aldehyde-tethered triazoles 61.1 with electron- ketones gave fused pyrroles via C−H insertion-cum-condensa-
rich aromatic nucleophiles 61.2 to furnish 6-substituted tion. However, the reaction of 2-substituted 1,3-diketones with
piperidin-3-ones 61.3 (Scheme 61).121 The reaction affords N-sulfonyl-1,2,3-triazoles furnished exclusively α-amino ke-
the trans diastereomer of the 5,6-disubstituted piperidin-3-one tones.
exclusively in good yield. The proposed mechanism begins with In 2013, Chuprakov, Kwok, and Fokin125 disclosed the
trapping of the in situ-generated α-imino rhodium carbene by synthesis of imidazolones 65.4 and thiazoles 65.7 from
the carbonyl oxygen to form oxonium ylide 61.5. Nucleophilic denitrogenative transannulations of N-mesyl-1,2,3-triazoles
addition of aromatic nucleophile 61.2 to oxonium ylide 61.5 65.1 with isocyanates 65.2 and isothiocyanates 65.5, respec-
produces zwitterion 61.6, which upon proton release gives tively, at room temperature in up to 99% yield (Scheme 65).
rhodium-bound anionic intermediate 61.7. Then Lewis acid Among various Rh(II) catalysts examined, Rh2(S-NTTL)4
coordination to the oxygen atom and simultaneous reaction of emerged as the optimal catalyst for this reaction, and a wide
the aromatic ring facilitates C−O bond cleavage to give range of imidazolones and thiazoles were synthesized in good to
zwitterion 61.9. Nucleophilic addition of nitrogen to the excellent yields. The synthesis of imidazolones 65.4 from
benzylic carbon with release of the Rh catalyst followed by triazoles and isocyanates involves the formation of intermediates
hydrolysis furnishes the desired product 61.11. Alternatively, 65.3 through nucleophilic attack on the electrophilic carbenoid,
demetalation of intermediate 61.7 followed by 1,4-migration followed by cyclization. However, in the case of isothiocyanates,
would furnish the product. sulfur attacks the carbenoid to produce intermediates 65.6, and
Similarly, Bi and Fu122 disclosed the synthesis of 6- subsequent cyclization affords thiazoles 65.7.
alkoxypiperidin-3-ones from the reaction of aliphatic alde- Li and co-workers reported a Rh(II)/cobaloxime(III) dual
hyde-tethered N-sulfonyl-1,2,3-triazoles with alcohols (Scheme catalytic system to promote tandem reactions of benzamide-
62). The reaction proceeds through intramolecular trapping of tethered triazoles to afford biologically important spiroinda-
the α-imino Rh carbenoid by the carbonyl group to form an nones with high diastereoselectivity (Scheme 66).126 The
oxonium intermediate. Then nucleophilic attack of alcohol on cascade involves an α-imino Rh carbene-initiated Pictet−
the oxonium intermediate furnishes a tetrahydrofuran derivative Spengler-type cyclization followed by a cobaloxime-promoted
that upon subsequent skeletal rearrangement affords the 6- intramolecular Mannich-type reaction. This methodology gave
alkoxypiperidin-3-one. Importantly, enantioenriched 6-alkox- facile access to a wide range of substituted spiroindanones in
ypiperidin-3-ones were obtained by the use of chiral alcohols. good yields. Moreover, replacement of the indole fragment in
For example, the use of (+)-menthol led to the formation of the the substrates did not give the desired products.

Scheme 60. Synthesis of Multisubstituted Furans

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Scheme 61. Synthesis of 6-Substituted Piperidin-3-ones from Aldehyde-Tethered Triazoles

Scheme 62. Synthesis of 6-Alkoxypiperidin-3-ones In 2013, Spangler and Davies127 accomplished the synthesis of
enantioenriched pyrroloindolines via [3 + 2] annulation of α-
imino carbenoids (generated in situ from N-sulfonyl-1,2,3-
triazoles) with indoles (Scheme 67). A variety of aryl-substituted
pyrroloindolines were obtained with high enantioselectivity in
good yields using Rh2(S-PTAD)4 as a catalyst. Moreover, the
reaction of indole with 1-tosyl-1,2,3-triazoles did not afford the
corresponding pyrroloindolines, which suggested that the
Scheme 63. Transannulation of N-Sulfonyl-1,2,3-triazoles reaction is sensitive to steric effects.
with 1,3-Diketones Tang and Shi synthesized various polycyclic indolines 68.3
and azepino[4,5-b]indoles 68.5 in moderate to high yields from
the corresponding indolyltriazoles 68.1 using Rh2(S-PTTL)4
(Scheme 68).128 Suitably substituted indolyltriazoles can
undergo [3 + 2] cycloaddition followed by ring expansion (in
the case of protected indoles) or C−H functionalization (in the
case of nonprotected indoles), resulting in the formation of
indolines 68.3 or azepine derivatives 68.5, respectively. The C−
H functionalization involves a Friedel−Crafts reaction via the
formation of intermediate 68.4. Among various rhodium
catalysts, chiral Rh2(S-PTTL)4 emerged as an efficient catalyst
for the synthesis of polycyclic indolines, whereas Rh2(Piv)4
along with Cu(OAc)2 as an additive gave the C−H-function-
alized products in good yields. A hydrogen-bonding interaction
may exist between the indole NH and the imine group, which
could stabilize intermediate 68.4. Upon addition of Cu(OAc)2,
the interaction between Cu and the imine becomes even
stronger to stabilize this intermediate, furnishing product 68.5
with higher selectivity. Interestingly, oxygen-tethered trypto-
pholtriazole also afforded the corresponding spiro compounds.
Subsequently, Fu and Davies129 reported the synthesis of
tetrahydrocarbolines 68.7 and polycyclic spiroindolines 68.8,
5.3. Transannulations with Carbo/Heterocycles depending on the substitution of the indole nitrogen, via
Carbo/heterocycles are widely present structural subunits in rhodium(II)-catalyzed intramolecular annulations of indolyl-
many therapeutically important molecules and in materials and pyrrolyl-tethered N-sulfonyl-1,2,3-triazoles 68.6.
science. Selective functionalization of them would offer an Miura and Murakami130 disclosed the intramolecular [3 + 2]
elegant approach that would find applications in various fields. annulation of α-imino carbenoids with aryl rings to obtain 3,4-
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Scheme 64. Substrate-Controlled Synthesis of (Fused) Pyrroles

Scheme 65. Transannulations of N-Mesyl-1,2,3-triazoles with Treatment of pyrrolyl and indolyl triazoles with Rh2(Oct)4 in
Isocyanates and Isothiocyanates 1,2-DCE at 80 °C for 2 h followed by addition of NaBH3CN
furnished the desired products. Moreover, the synthesis of the
tetracyclic [1,4]diazepino[4,5-a]indole skeleton from indolyl
azepines was accomplished.
Shi and co-workers132 reported the synthesis of 3-methylene-
2,3-dihydrobenzofurans 71.2 and 3-methylene-2,3-dihydroin-
doles 71.7 from aryl-tethered triazoles 71.1 and 71.6,
respectively, through intramolecular annulation of the aromatic
rings with the N-sulfonyl-1,2,3-triazole moiety (Scheme 71).
During the synthesis of 3-methylene-2,3-dihydroindoles 71.6,
the formation of side products via β-H elimination and 1,2-H
shift was suppressed by addition of LiCl to the reaction mixture.
On the basis of control experiments and kinetic studies, the
mechanism shown in Scheme 71was proposed. Friedel−Crafts-
type nucleophilic attack on the Rh carbenoid gives zwitterionic
intermediate 71.3. Next, elimination of Rh(II) and cleavage of
fused indole skeletons (Scheme 69). Herein, α-imino Rh the C−O bond generates acrolein imine 71.4 and its resonance
carbenoid 69.4 was exploited as a 1,3-dipole equivalent. structure 71.5, which affords the desired product through a 1,2-
According to the possible mechanism, triazole 69.1 was first addition.
converted into α-imino Rh carbenoid 69.4, which was attacked In 2017, Xu and co-workers developed the [8 + 3]
by the phenyl nucleophile in 6-exo mode to form zwitterionic cycloaddition of 8-azaheptafulvenes with N-sulfonyl-1,2,3-
intermediate 69.5, which was further cyclized to give the 3,4- triazoles to form cyclohepta[b]pyrazines (Scheme 72).133
fused indole by release of the rhodium catalyst for the next Herein, the in situ-generated α-imino Rh carbenoid intermediate
catalytic cycle. The one-pot synthesis gave facile access to was exploited as a three-carbon ([3C]) synthon. The reaction
tricyclic 3,4-fused dihydroindoles starting from simple 5-aryl-1- worked efficiently in the presence of Zn(OTf)2 as an additive,
alkynes. The synthetic utility of this methodology was explored where it might act as a Lewis acid to activate the dissociation of
by the synthesis of Uhle’s ketone, which has been often utilized rhodium from the rhodium carbene complex. Moreover, 4-alkyl-
in the synthesis of ergot alkaloids (see Scheme 196). substituted N-sulfonyl-1,2,3-triazoles did not afford the desired
Later, Tang and Shi synthesized biologically and pharmaceuti- products, presumably because of decomposition of the rhodium
cally important N-bridgehead azepine skeletons from pyrrolyl/ carbene complex during the reaction.
indolyl-tethered triazoles via intramolecular C−H functionaliza- Dehaen and co-workers converted bis(1,2,3-triazoles) into
tion of pyrrole and indole rings at C2 (Scheme 70).131 polycyclic 3,4-fused dihydroindoles in a single step via a Rh(II)-

Scheme 66. Diastereoselective Synthesis of Spiroindanones

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Scheme 67. Enantioselective Synthesis of Pyrroloindolines

Scheme 68. Synthesis of Various Polycyclic N-Heterocycles Scheme 70. Synthesis of N-Bridgehead Azepine Skeletons

Scheme 71. Synthesis of 3-Methylene-2,3-

dihydrobenzofurans and 3-Methylene-2,3-dihydroindoles

Scheme 69. Intramolecular [3 + 2]-annulation of α-imino

carbenoids with aryl rings

Scheme 72. [8 + 3] Cycloaddition of 8-Azaheptafulvenes with

N-Sulfonyl-1,2,3-triazoles

with MnO2 afforded the corresponding 3,4-fused indole

alkaloids in excellent yields. Additionally, heterocyclic dibenzo-
furan-containing bis(1,2,3-triazoles) also underwent [3 + 2]
catalyzed intramolecular dearomatizing [3 + 2] annulation annulation to afford the corresponding polyheterocyclic
reaction (Scheme 73).134 Oxidation of 3,4-fused dihydroindoles products in good yields.
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Scheme 73. Synthesis of Polycyclic 3,4-Fused Dihydroindoles Scheme 75. Denitrogenative Transformations of N-Sulfonyl-
from Bis(1,2,3-triazoles) 1,2,3-triazoles with 2H-Azirines

Novikov and co-workers disclosed the stereoselective syn-

thesis of 1-(2-aminovinyl)indoles from N-sulfonyl-1,2,3-tria-
zoles and 2,2-diaryl-2H-azirines (Scheme 74).135 The cascade
reaction involves the initial formation of 1,4-diazahexa-1,3,5-
trienes from α-imino Rh carbenoids and 2,2-diaryl-substituted
2H-azirines, which rapidly cyclize to form 2,2-diaryl-1-sulfonyl-
1,2-dihydropyrazines. Subsequent isomerization affords ther-
mally stable 1-(2-aminovinyl)indoles. DFT calculations sup-
ported this cascade sequence for the formation of the product.
The synthesis of 1,3′-biindole derivatives from 1-(2-
aminovinyl)indoles by the Ullmann reaction emphasizes the
importance of this protocol.
Lee and co-workers136 developed an approach for the
synthesis of pyrazines from N-sulfonyl-1,2,3-triazoles and 2H-
azirines via dihydropyrazines (Scheme 75). Later, Tang and co-
workers137 disclosed substrate-controlled [3 + 2] and [3 + 3]
cycloadditions of N-tosyl-1,2,3-triazoles with 2H-azirines to
form 3-aminopyrroles and 1,2-dihydropyrazines, respectively. rhodium catalyst did not afford the piperazine scaffold. Instead,
Importantly, in the [3 + 2] cycloaddition, the azavinyl carbene pyridine derivatives 76.4 were formed from aziridinium ylide
serves as a [2C] synthon and the 2H-azirine serves as an aza- species 76.3 via cheletropic extrusion.
[3C] synthon. Similarly, Tang and Shi reported the Rh-catalyzed In 2013, Davies and co-workers developed an approach for
denitrogenative [3 + 2] cycloaddition of triazoles with 2H- the synthesis of highly functionalized pyrroles by rhodium-
azirines to form polysubstituted pyrroles.138 The synthetic catalyzed transannulation of N-sulfonyl-1,2,3-triazoles with 2,5-
utility of this methodology was explored by the synthesis of dimethylfurans (Scheme 77).140 Many of the unsymmetrical
URB447 and one of the key intermediates of Lipitor. 2,5-disubstituted furans gave mixtures of regioisomers of
Fernández and Schomaker139 explored aziridine ring pyrroles. Numerous Rh catalysts were tested, and Rh2(S-
expansions with α-imino Rh carbenes to form dehydropiper- DOSP)4 emerged as the optimal catalyst, affording the pyrroles
azines in good yields with high diastereoselectivity (Scheme 76). in up to 99% yield. The reaction involves the attack of C3 of
According to computational studies, the nitrogen atom in furan 77.3 on α-imino carbenoid 77.2 to give intermediate 77.4.
aziridine ring 76.1 first attacks the rhodium α-imino carbene of Subsequent nucleophilic attack of the N atom of the imine
triazole 76.5 to generate ylide intermediate 76.6. Subsequent moiety on the resultant oxocarbenium 77.4 produces hemi-
cyclization involving ring opening of the aziridine furnishes the aminal 77.5. Opening of the furan ring generates carbocation
desired product 76.7. On the other hand, treatment of intermediate 77.6, which is then aromatized to pyrrole 77.7 by
pyridotriazoles 76.2 with aziridines 76.1 in the presence of the deprotonation.

Scheme 74. Stereoselective Synthesis of 1-(2-Aminovinyl)indoles

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Scheme 76. Rh-Catalyzed Synthesis of Dehydropiperazines and Pyridine Derivatives

Scheme 77. Transannulation of N-Sulfonyl-1,2,3-triazoles imines and 1,2-dihydropyridines, respectively. Interestingly,

with 2,5-Dimethylfurans pyridine-mediated isomerization of open-chain penta-2,4-dien-
1-imines under heating afforded the corresponding cyclic 1,2-
dihydropyridines. Hence, the one-pot synthesis of 1,2-
dihydropyridines was accomplished by the use of Rh2(esp)4 as
the catalyst and pyridine as an additive.
Tang and co-workers reported the Rh-catalyzed formal [3 +
2] cycloaddition of N-sulfonyl-1,2,3-triazoles 79.1 with
isoxazoles 79.2 to form polysubstituted 3-aminopyrroles 79.3
(Scheme 79).142 Herein, N-sulfonyl-1,2,3-triazoles were ex-
ploited as [2C] synthons instead of the usual aza-[3C] synthons.
Mechanistically, isoxazole 79.2 attacks azavinyl Rh-carbenoid
79.4 to form isoxazolium intermediate 79.5, which then
undergoes sequential ring opening with cleavage of the N−O

Scheme 79. [3 + 2] Cycloaddition of N-Sulfonyl-1,2,3-

triazoles with Isoxazoles

Subsequently, Miura and Murakami141 utilized 2-(siloxy)-

furans as coupling partners for azavinyl rhodium carbenoids
derived from N-sulfonyl-1,2,3-triazoles to synthesize open-chain
penta-2,4-dien-1-imines and cyclic 1,2-dihydropyridines
(Scheme 78). Notably, the product selectivity depends on the
ligands surrounding the Rh(II). Thus, Rh2[S-NTTL]4 and
Rh2(esp)4 efficiently delivered open-chain penta-2,4-dien-1-

Scheme 78. Denitrogenative Transformations of N-Sulfonyl-

1,2,3-triazoles with 2-(Siloxy)furans

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bond to form azatriene 79.6. Next, 5-exo-trig cyclization of the Wang and Chen145 reported ring opening of styrene oxide
azatriene produces zwitterionic intermediate 79.7, which then derivatives 82.2 with α-imino Rh carbenoids 82.4 to form 3,4-
undergoes proton transfer followed by tautomerization to dihydro-2H-1,4-oxazines 82.3 (Scheme 82). A solution of N-
deliver polysubstituted 3-aminopyrroles 79.3. Eventually, they
successfully demonstrated a sequential one-pot synthesis of Scheme 82. Rh(II)-Catalyzed Ring Opening of Styrene
polysubstituted 3-aminopyrroles starting from the correspond- Oxides with Triazoles
ing terminal alkynes and sulfonyl azides.
In continuation to their work, the Tang group also disclosed
the synthesis of quinazolines by Rh-catalyzed denitrogenative
transannulation of N-sulfonyl-1,2,3-triazoles with 2,1-benzisox-
azoles through formal aza-[4 + 2] cycloaddition (Scheme
80).143 Interestingly, in this transformation, the azavinyl

Scheme 80. Rh-Catalyzed Synthesis of Various Quinazolines

and Imidazoles

sulfonyl-1,2,3-triazole 82.1 and styrene oxide 82.2 in DCE

solvent was heated to 120 °C for 1 h in the presence of Rh2(S-
NTTL)4 or Rh2(S-PTV)4 to obtain the desired product in
moderate yield. The transformation involves the formation of
oxonium ylide intermediate 82.5 and opening of the oxide ring.
Subsequent nucleophilic attack of the imine nitrogen on
benzylic cation 82.6 affords 3,4-dihydro-2H-1,4-oxazines.
However, this transformation is limited to substituted styrene
carbenes derived from N-sulfonyl-1,2,3-triazoles are exploited
oxides only.
as aza-[2C] synthons in the aza-[4 + 2] cycloaddition. Various
Likewise, Lee and co-workers disclosed the substrate-
2,1-benzisoxazoles reacted smoothly to give corresponding
controlled synthesis of 1,4-oxazepines and 1,4-oxazines from
quinazolines. On the other hand, the use of 1,2-benzisoxazoles in
N-sulfonyl-1,2,3-triazoles and glycidols (Scheme 83).146 The
place of 2,1-benzisoxazoles afforded imidazoles through a formal
tandem sequential reaction consists of 1,3-insertion of the imino
[3 + 2] cycloaddition with N-sulfonyl-1,2,3-triazoles.
carbenoid into the O−H bond of the glycidol followed by
Novikov and co-workers synthesized fully substituted 5-
Mg(OtBu)2-induced epoxide ring opening. The epoxide ring
sulfonamidoimidazoles through rhodium-catalyzed transannu-
opening depends on the substitution of the glycidol: substituted
lation of N-sulfonyl-1,2,3-triazoles with 1,2,4-oxadiazole de-
glycidols furnished seven-membered oxazepine derivatives
rivatives (Scheme 81).144 Among various catalysts, Rh2(OPiv)4
selectively, while unsubstituted glycidols afforded six-membered
oxazine derivatives.
Scheme 81. Synthesis of Substituted 5- Shen and Xu147 demonstrated a regioselective synthesis of
Sulfonamidoimidazoles 3,4-dihydro-2H-1,4-thiazines through ring opening of thiiranes
with α-imino rhodium carbenoids, which were generated in situ
from triazoles in the presence of Rh2(esp)2 (Scheme 84). The
reaction features a formal [3 + 3] cycloaddition of the imino
rhodium carbenoid intermediate with the thiirane. Importantly,
alkyl thiiranes did not afford the desired dihydro-1,4-thiazines.
Notably, in this transformation acetic acid was exploited as an
additive that presumably enhances the electrophilicity of the
rhodium carbene through hydrogen bonding between the imino
nitrogen and the acetic acid proton.
Lacour and co-workers disclosed transannulations of N-
sulfonyl-1,2,3-triazoles with 1,3-dioxolane and 1,3-dioxane to
form eight-membered dioxazocines and nine-membered
emerged as the most efficient catalyst for these reactions, and dioxazonines, respectively (Scheme 85).148 Herein, 1,3-
numerous imidazole derivatives were synthesized in up to 98% dioxolane and 1,3-dioxane were exploited as both solvents and
yield using a series of 1,2,4-oxadiazoles and 1-sulfonyl-1,2,3- reagents. Treatment of triazoles with Rh2(OAc)4 at 100 °C for 5
triazoles regardless of steric and electronic effects. These h in 1,3-dioxolane or 1,3-dioxane gave the corresponding
reactions involve initial nucleophilic attack of the 1,2,4- products with high regioselectivity in up to 92% yield. Moreover,
oxadiazole on the carbenoid to form the ylide intermediate employment of tetrahydrofuran as both the solvent and reagent
and subsequent ring opening and 5-exo-trig cyclization of the in this transformation afforded the corresponding eight-
formed 1,3,6-triazahexatriene intermediate to afford the 5- membered-ring products, which decomposed during isolation
sulfonamidoimidazole. The reaction worked effectively on a by column chromatography.
gram scale and gave the corresponding 5-sulfonamidoimidazole Similarly, Beller and co-workers149 reported the synthesis of
in 84% yield. nine-membered 1,3,5,7-trioxazonines 86.3 through ring ex-
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Scheme 83. Substrate-Controlled Synthesis of 1,4-Oxazepines and 1,4-Oxazines

Scheme 84. Regioselective Synthesis of 3,4-Dihydro-2H-1,4- simplified from a two-stage procedure to a one-pot multi-
thiazines component procedure.
Later, Bao and co-workers disclosed the transannulation of N-
sulfonyl-1,2,3-triazoles 87.1 with 1,3,5-triazinanes 87.2 to
produce octahydro-1H-purine derivatives 87.3 (Scheme
87).150 Except 4-alkyl-substituted 1-sulfonyl-1,2,3-triazoles,

Scheme 87. Transannulation of N-Sulfonyl-1,2,3-triazoles

with 1,3,5-Triazinanes
Scheme 85. Transannulations of N-Sulfonyl-1,2,3-triazoles
with Dioxolanes and Dioxanes

pansion of 1,3,5-trioxanes 86.2 with azavinyl rhodium

carbenoids 86.4 (Scheme 86). The reaction involves the initial
rhodium-assisted formation of oxonium ylide 86.5 and
subsequent trioxanyl ring opening of 86.5 followed by ring
closure of the formed oxocarbenium ion 86.6 to furnish the
desired nine-membered ring. Interestingly, this procedure was

Scheme 86. Synthesis of Nine-Membered 1,3,5,7-

Trioxazonines

various substituted triazoles underwent the transformation

smoothly with 1,3,5-triazinanes to afford octahydro-1H-purine
derivatives. On the basis of DFT computational study, authors
proposed a mechanism involving the generation of rhodium-
bound azavinyl carbenoid 87.4. Nucleophilic addition of 1,3,5-
triazinane 87.2 to carbenoid 87.4 produces adduct 87.6 via
open-chain zwitterionic intermediate 87.5. Subsequent intra-
molecular nucleophilic attack affords bicyclic intermediate 87.7,
which undergoes ring opening and closure to furnish the desired
product.
Lee and Lee151 accomplished the synthesis of 3a,7a-
dihydroindoles from N-sulfonyl-1,2,3-triazoles and alkylbenzene
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derivatives via rhodium-catalyzed intermolecular [3 + 2] furnishes the pyridine derivative. On the other hand, employ-
cycloaddition (Scheme 88). Triazoles were treated with ment of homofurfurylamine as the starting material gave the
desired product along with a significant amount of the
Scheme 88. Synthesis of 3a,7a-Dihydroindoles corresponding pyrrole derivative.
Novikov and co-workers154 developed the synthesis of
pyrroles and pyrazines via the Rh(II)-catalyzed reaction of
1,2,3-triazoles with isoxazoles (Scheme 90). Initially, in the
presence of Rh2(OPiv)4, the reaction of phenylisoxazole with
triazole in α,α,α-trifluorotoluene (TFT) solvent produced a
mixture of pyrrole and pyrazine products in almost equal
amounts. Screening of the reaction conditions revealed that the
reaction in dilute solution promotes the formation of the
dihydropyrazine selectively, emphasizing that the formation of
the pyrrole involves an intermolecular process. Eventually,
running the reaction in refluxing toluene was found to be the
optimal condition for the selective formation of pyrazine
derivatives, whereas the reaction in chloroform led to the
alkylbenzenes in the presence of Rh2(esp)2 at 70 °C under preferential formation of pyrroles.
microwave conditions for 30 min to furnish 3a,7a-dihydroin- Lacour and co-workers155,156 prepared a series of polycyclic
doles. Herein, the alkylbenzene serves as both the reagent and indoline−benzodiazepines 91.3 in a single step through Rh(II)-
the solvent. Similarly, Davies and co-workers also reported the catalyzed reaction of Tröger bases (TBs) 91.2 with N-sulfonyl-
synthesis of regioisomers of alkyl-substituted 3a,7a-dihydroin- 1,2,3-triazoles 91.1 (Scheme 91). Mechanistically, in the
doles along with the products of formal C−H functionalization presence of Rh catalyst, the α-imino carbene generated from
of 4-phthalimido-N-methanesulfonyl-1,2,3-triazoles and alkyl- triazole 91.1 reacts with TB 91.2 to produce ylide intermediate
substituted benzene derivatives under catalyst-free condi- 91.4. Then a cascade of aminal opening, aza-Mannich, Friedel−
tions.152 On the basis of DFT calculations, the tandem reaction Crafts, Grob, and cyclization steps leads to the formation of
sequence features cyclopropanation, 6π electrocyclization, 6π triaza polycycle 91.9. Diversely substituted TBs reacted with
electrocyclic ring opening, and 3,5-sigmatropic rearrangement. several triazoles to afford the desired heterocycles in low to high
Notably, heating of alkyl-fused dihydroindoles led to the yields. The lowest yield was obtained in the case of the dimethyl-
formation of the C−H functionalization product through ring substituted TB, which might be due to the strain created by the
opening. methyl groups in immediate proximity to the central bicyclic
Uchuskin and Hashmi153 explored an intramolecular trans- core. Recently, in their extended study, these synthesized
annulation of furan-tethered N-sulfonyl-1,2,3-triazoles 89.1 to benzodiazepinoindoles 91.3 were derivatized to obtain the
form 2-formyl- and 2-acetylpyridine building blocks 89.2 corresponding chiral hemicyanine fluorophores 91.11 in two
(Scheme 89). This protocol was utilized to synthesize various steps.157 The photophysical properties of these hemicyanines
were then studied exclusively, and the chiroptical properties
Scheme 89. Intramolecular Transannulation of Furan- were studied using ECD and VCD.
Tethered N-Sulfonyl-1,2,3-triazoles Very recently, the same group reported the single-step
preparation of hexahydropyrazinoindoles 92.3 through a
Rh(II)-catalyzed cascade reaction of N-sulfonyl-1,2,3-triazoles
92.1 and imidazolidines 92.2 (Scheme 92).158 This cascade also
involves sequential carbene generation, ylide formation, [1,2]-
Stevens, and Friedel−Crafts reactions. Interestingly, treatment
of triazoles 92.6 with unsymmetrical imidazolidines 92.7 led to
the unprecedented formation of eight-membered hexahydro-
1,3,6-triazocines 92.8, in contrast to the symmetrical imidazo-
lidines. Additionally, tetrahydropyrazinoindoles 92.4 were
synthesized from 92.3, and their subsequent functionalization
was accomplished via an oxidative C−C bond-forming reaction
to obtain compounds 92.5.
5.4. Insertions into C−H/X−H Bonds
Similar to the reaction of unsaturated multiple bonds, reactions
functionalized heterocyclic compounds such as indolizine of C−H, X−H, and C−X bonds with carbenoids are also
derivatives. Moreover, the one-pot synthesis of 2-formyl- and witnessed in the literature significantly. In this context, α-imino
2-acetylpyridine derivatives was achieved starting from easily rhodium carbenoids can be inserted into C−H, X−H, and C−X
accessible (furan-2-ylmethyl)propargyl amines. In this trans- bonds via 1,1- or 1,3-insertion because of the unique reactivity of
formation, the azavinyl Rh carbenoid intermediate participates the imino carbenes. Nonpolar bonds like C−H undergo 1,1-
in a sequence of domino reactions, as shown in Scheme 89. insertion with rhodium azavinyl carbenoids via a concerted
Intramolecular attack of the azavinyl Rh carbenoid on the furan process involving a three-membered transition state. On the
followed by furan ring opening affords azatriene intermediate other hand, polar bonds like X−H involve initial ylide formation
89.4, and electrocyclization of 89.4 followed by oxidation with azavinyl rhodium carbenoids followed by intramolecular
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Scheme 90. Synthesis of Pyrroles and Pyrazines

Scheme 91. Synthesis of Polycyclic Indoline−Benzodiazepines

proton abstraction to give the corresponding enamides, which In 2015, Kang and co-workers160 developed a rhodium-
constitutes a formal 1,3-insertion. catalyzed cascade approach towards the synthesis of benzofur-
5.4.1. C−H Insertions. [Link]. C(sp3)−H Insertions. In ans from suitably substituted N-sulfonyl-1,2,3-triazoles (Scheme
2011, Fokin and co-workers reported a highly efficient 94). The transformation involves sequential rhodium-catalyzed
enantioselective C−H insertion of azavinyl rhodium carbenoids C(sp3)−H insertion and copper-catalyzed aerobic oxidation. A
into unactivated alkanes using a chiral rhodium catalyst (Scheme one-pot synthesis was also achieved by employing benzyloxyaryl
93).159 To isolate the product, the formed imine intermediates triazoles, dirhodium(II)tetraoctanoate, CuTC, and molecular
were reduced to mesyl-protected amines using sodium sieves in toluene at 100 °C under O2. The authors stated that the
borohydride or lithium aluminum hydride. Hydrolysis of the one-pot method starting from the terminal alkyne was more
imine intermediates to the corresponding carbaldehydes gave convenient for benzofuran synthesis. Besides, indole derivatives
racemic mixtures because of the presence of presumably an were also prepared successfully by this strategy. Similarly, Wang
acidic proton at the stereocenter. In this protocol, the α-imino and Chen disclosed an efficient method for the synthesis of 2,3-
rhodium carbenoids insert into tertiary C−H bonds preferably disubstituted dihydrobenzofurans and benzofurans via the
compared with secondary C−H bonds. intramolecular C(sp3)−H insertion reaction of α-imino
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Scheme 92. Synthesis of Hexahydropyrazinoindoles and Hexahydro-1,3,6-triazocines

Scheme 93. Rh(II)-Catalyzed Enantioselective C−H rhodium carbenes generated from N-sulfonyl-1,2,3-triazoles in
Insertion of Triazoles good to excellent yields.161 Experimental data indicated that
primary C−H bonds are much more inert than secondary and
benzyl C−H bonds.
Sarpong and co-workers demonstrated the stereodivergent
synthesis of saturated 2,3-disubstituted tetrahydrofuran com-
pounds through intramolecular azavinyl carbene insertion into
ethereal C(sp3)−H bonds (Scheme 95).162 The sterically
hindered Rh2(tpa)4 catalyst afforded the cis product with high
diastereoselectivity, whereas Rh2(OAc)4 in the presence of 2-
picoline provided the trans diastereomer in high yield.
Additionally, fused N-heterotricycles were synthesized from
the resulting products through intramolecular C−N bond-
forming processes such as C−H amination and the Pictet−
Spengler reaction. Addition of Grignard to the crude imine
intermediate obtained from C−H insertion afforded a
Scheme 94. Synthesis of Benzofurans and tetrahydrofuran possessing three contiguous stereocenters.
Dihydrobenzofurans The homologated substrate under this reaction condition
afforded the tetrahydrofuran in 43% yield instead of the
expected tetrahydropyran, presumably as a result of the
generation of a stable five-membered oxonium ylide and
subsequent [1,2]-alkyl shift sequence.
Similarly, Urabe and co-workers163 successfully synthesized
various functionalized cyclic products such as pyrrolidines,
tetrahydrofurans, and cyclopentane from triazoles 96.1 having
an N-protected benzylamine, ether, and alkyl moiety,
respectively, in good yields through carbene insertion into the
benzylic C−H bond (Scheme 96). Since sulfonyl imines are
moisture-sensitive, the crude product 96.2 was reduced in situ
with LiAlH4 to get 2,3-disubstituted pyrrole derivative 96.3. The
stereoselective formation of the cis-2,3-disubstituted pyrrole was
rationalized through six-membered transition state 96.5, where
the sterically demanding [Rh] portion occupies the pseudoe-
quatorial position while the R2 group is located at the
pseudoaxial position to minimize the steric repulsion against
the neighboring bulky N-sulfonyl group, as shown in Scheme 96.
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Scheme 95. Synthesis of Saturated 2,3-Disubstituted Tetrahydrofurans

Scheme 96. Synthesis of Various Substituted Pyrrolidines

Davies and co-workers accomplished enantioselective allylic/ Scheme 97. Enantioselective C(sp3)−H Bond
benzylic C(sp3)−H bond functionalization at room temperature Functionalization
via insertion of azavinyl rhodium carbenes derived from N-
sulfonyl-1,2,3-triazoles 97.1 in the presence of Rh2(S-NTTL)4
(Scheme 97).164 The carbene preferentially inserted into tertiary
C−H bonds over primary and secondary C−H bonds,
furnishing the desired products in good yields with moderate
enantioselectivity. In their extended work, they demonstrated
the utility of allylic C−H bond-functionalized products in the
formation of highly diversified β-arylpyrrolidines 97.8.165 A
sequence of allylic C(sp3)−H functionalization, imine reduc-
tion, ozonolysis, and reduction with triethylsilane/BF3·OEt2
furnished the desired pyrrolidines with retention of the
asymmetric induction achieved during C−H bond functional-
ization. Additionally, they expanded this methodology to the
regio- and stereoselective synthesis of C(sp3)−H-functionalized
silanes 97.12 and 97.13 by employing cyclic and acyclic silanes
97.9 and 97.10, respectively.166 Functionalization occurred
regioselectively at the position β to silicon irrespective of
primary, secondary, and tertiary C(sp3)−H bonds as a result of
the β-silyl effect.
Recently, Davies and co-workers disclosed the synthesis of a
variety of δ-functionalized allyl silyl ethers with high diastereo-
and enantioselectivity (Scheme 98).167 The reaction proceeds
through insertion of the Rh-bound azavinyl carbene into the δ-
C−H bond of β,γ-unsaturated silyl ethers. Interestingly, chiral
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Scheme 98. Stereoselective Synthesis of Various δ- Scheme 100. Aminoacylation of Indoles and Pyrroles
Functionalized Allyl Silyl Ethers

Rh2(S-NTTL)4 completely controls the regioselectivity for the Scheme 101. Diastereoselective N-
less preferred allylic C−H bond over the electronically more Sulfonylaminoalkenylation of Azulenes
preferred allylic ethereal C−H bond. The synthetic utility of this
developed method was demonstrated by the synthesis of 3,4-
disubstituted L-proline derivatives, which are a basic scaffold
found in biologically active compounds.
Shen and Xu168 and Gong and Yang169 individually reported
an efficient method for the synthesis of N-substituted 2-
arylindole-3-carbaldehydes/imines through Rh-catalyzed C−H
functionalization of N-alkyl-N-benzylanilin-2-yltriazoles
(Scheme 99). This method involves tandem rhodium carbene

Scheme 99. Syntheses of N-Substituted 2-Arylindole-3-

carbaldehydes/imines

at 60 °C for 2−12 h under air was found to produce the N-

sulfonylaminoalkenylated products. Since the azulene was found
to be sensitive to the Cu catalyst, the desired product was
synthesized via a three-component semi-one-pot method.
Arylacetylenes and tosyl azides were treated with CuTC in
DCE at 50 °C, and then the newly formed N-tosyltriazole-
containing reaction mixture was filtered through a short pad of
silica, after which the crude material was subjected to the
optimized reaction conditions along with azulenes to produce
insertion into the benzylic C(sp3)−H bond and oxygen- the N-sulfonylaminoalkenylated products in good yields with
mediated oxidative aromatization and affords functionalized excellent diastereoselectivity.
indole derivatives in good to excellent yields. Furthermore, this Lin and co-workers converted triazole-tethered anilines to 3-
method was successfully expanded to the synthesis of 2,3- indolylimines and indole-3-carboxaldehydes using a rhodium
disubstituted benzofurans from benzyl phenol-based triazoles. catalyst (Scheme 102).172 A precipitation technique was used to
[Link]. C(sp2)−H Insertions. Subsequently, Alford and purify the product 3-indolylimine because of the poor stability of
Davies demonstrated an effective method for aminoacylation the imine derivative under traditional silica gel column
of indoles and pyrroles at C3 and C2, respectively, without using chromatography. Subsequently, the same group also reported
any catalysts (Scheme 100).170 A mixture of 4-alkoxy-N- the synthesis of substituted 3-methylene-2,3-dihydrobenzofur-
sulfonyltriazole and pyrrole/indole was heated to 80 °C under ans and 3-methylbenzofurans from 4-(aryloxymethyl)-N-tosyl-
microwave irradiation in 1,2-dichloroethane for 15 min and then 1H-1,2,3-triazoles through insertion of the Rh carbenoid
treated with Amberlyst 15 to hydrolyze the resultant enol ether intermediate into the C−H bond.173 Similarly, Xu and Shen
in situ. In the case of C3-substituted indoles, the dearomatized [3 synthesized acridones from N-aryl-2-(N-sulfonyl-1,2,3-triazol-4-
+ 2] annulation product was obtained instead of the possible C2- yl)anilines through a cascade reaction involving C−H insertion
acylated product. A one-pot, three-step procedure was of the rhodium carbene into the N-aryl ring followed by
developed that employed the ynol ether, the indole, and mesyl oxidative cleavage.174
azide along with CuTC followed by addition of Amberlyst 15. Anbarasan and co-workers reported the rhodium-catalyzed
In 2014, Lee and Park reported an efficient diastereoselective regioselective synthesis of 2,2-diarylenamides from the corre-
N-sulfonylaminoalkenylation at C1 of azulenes with N-sulfonyl- sponding N-sulfonyl-1,2,3-triazoles and N,N-disubstituted ani-
1,2,3-triazoles in excellent yields of up to 96% (Scheme 101).171 lines (Scheme 103).175 According to the proposed mechanism,
After screening of the reaction conditions, treatment of triazole addition of the arene to the electrophilic metal carbene through
with azulene in the presence of 1 mol % Rh2(Oct)4 in 1,2-DCE the assistance of the nitrogen lone pair produces the zwitterion-
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Scheme 102. Denitrogenative Transformations of Triazole-Tethered Aniline Derivatives

Scheme 103. C−H Insertions of N-Sulfonyl-1,2,3-triazoles Scheme 104. Synthesis of Fluorenes and Benzofulvenes
with N,N-Disubstituted Anilines and Anisoles

type intermediate, which upon subsequent proton loss and

rearomatization gives the enamide product. They demonstrated
the utility of this methodology by synthesizing pharmaceutically through Rh-catalyzed transannulation of arylethenyl triazoles
important N-heterocyclic systems such as indole and tetrahy- 104.6.178 The formation of the Z isomer was explained by the
droisoquinoline derivatives. Similarly, Lee and co-workers favorable hydrogen bonding between the N−H and the CO2Et
synthesized 4-methoxyaryl enamine compounds from N- group.
sulfonyl-1,2,3-triazoles and anisoles through azavinyl carbenoid Miura and Murakami demonstrated the regioselective
insertion into the C−H bond.176 insertion of α-imino rhodium carbenoids into C−H bonds of
Subsequently, Lee and co-workers converted 4-biaryl- monosubstituted and 1,2-disubstituted indoles at C3 (Scheme
substituted N-sulfonyl-1,2,3-triazoles 104.1 into fluorenes 105).179 Subsequently, Chen and co-workers disclosed a
104.2 through Rh-catalyzed denitrogenative cyclization in 5- regioselective 1,3-insertion reaction of rhodium carbenoids
exo mode (Scheme 104).177 According to the proposed into C−H bonds of simple indoles to synthesize structurally
mechanism, intramolecular nucleophilic addition of the aryl diverse 2-indolylenamides in good to excellent yields.180 The
group in 5-exo mode to the in situ-formed electrophilic carbene utility of the developed method was demonstrated by the
center of 104.3 forms Rh-bound zwitterionic intermediate synthesis of tryptamine and 3,3′-biindole derivatives of bio-
104.4. Rearomatization followed by protoderhodation produces logical importance. Notably, 2-methoxythiophene also success-
the desired fluorenes 104.2. Subsequently, the same group fully produced insertion products under the same reaction
synthesized a wide range of functionalized benzofulvenes 104.7 conditions.
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Scheme 105. Regioselective 1,3-Insertion Reactions of of the intermediate by deprotonation furnishes the 3-enamido-
Triazoles with Indole Derivatives 9H-carbazoles.
Later, Dawande and co-workers183 synthesized a wide range
of C3-enamido-functionalized indolizines 108.3 from N-
sulfonyl-1,2,3-triazoles 108.1 and indolizines 108.2 (Scheme
108). The utility of the protocol was explored by the synthesis of

Scheme 108. Synthesis of C3-Enamido-Functionalized

Indolizines and 1,3-Bis(enamido)indolizine Derivatives

Independently, Anbarasan and co-workers successfully

isolated various tryptamine derivatives in up to 95% yield
from substituted indoles by the use of terminal alkynes and
sulfonyl azides as readily accessible aminoethylating agents
(Scheme 106).181 The reaction involves sequential CuAAC,

Scheme 106. Synthesis of Tryptamine Derivatives

1,3-bis(enamido)indolizine derivative 108.6. Notably, pyrrolo-

[1,2-a]quinoline gave the C1-functionalized product under
optimal reaction conditions.
Rajasekar and Anbarasan disclosed the synthesis of dihydro-β-
carbolines 109.3 and dihydroisoquinolines 109.5 via C−H
rhodium-catalyzed C−H insertion, and reduction employing functionalization followed by base-mediated intramolecular aza-
Na(CN)BH3. Moreover, the utility of the cascade approach was Michael addition of Michael acceptor-tethered indole and
demonstrated in the synthesis of dihydro-β-carbolines and aniline derivatives 109.2 and 109.4, respectively (Scheme
tryptolines, which are pivotal scaffolds in drug discovery. They 109).184 Treatment of suitably substituted indoles/anilines in
extended the developed methodology to related pyrrole the presence of 2 mol % Rh2(OAc)4 in 1,2-DCE at 100 °C for 8 h
derivatives. However, pyrroles afforded the corresponding followed by addition of 2 equiv of triethylamine and heating of
aminoethylated pyrroles in lower yields. the reaction mixture at the same temperature for 14 h furnished
In 2017, Yoo and co-workers demonstrated an efficient the desired products. Importantly, one-pot conversion of
method for regioselective C3 functionalization of 9H-carbazoles alkynes and azides to dihydro-β-carbolines was also demon-
through insertion of in situ-generated α-imino rhodium strated. Furthermore, the enantioselective synthesis of sub-
carbenoids (Scheme 107).182 9H-Carbazoles substituted with stituted β-carbolines 109.8 via rhodium(II)/chiral squaramide
relay catalysis was disclosed.185 When a chiral squaramide
Scheme 107. Regioselective C3 Functionalizations of Various catalyst was employed instead of triethylamine, an enantiose-
9H-Carbazoles lective aza-Michael reaction occurred through the hydrogen-
bonding interaction between the squaramide and ketone.
Various substituted β-carbolines were obtained in excellent
yields and enantioselectivities.
In 2016, Tang and Zou demonstrated an approach for the
synthesis of various functionalized tetrahydro-β-carbolines
110.2 through a rhodium-catalyzed denitrogenative trans-
formation of indole-tethered triazoles 110.1 (Scheme 110).186
Substitution of the indole at C4 decreased the product yield for
steric reasons. Of note, other heterocyclic compounds, i.e.,
pyrrole and 1H-pyrrolo[2,3-b]pyridine-tethered triazoles,
underwent this transformation to afford the corresponding
products. The potential utility of the present reaction was
demonstrated by the synthesis of oxopropaline-G, a naturally
electron-withdrawing groups at nitrogen such as p-toluenesul- occurring β-carboline alkaloid. Likewise, Kang and co-work-
fonyl (Ts), tert-butoxycarbonyl (Boc), and carboxybenzyl (Cbz) ers187 synthesized pyranoindoles 110.4 in up to 93% yield from
did not afford the desired products. A possible mechanism for indole-tethered triazoles 110.3 having an oxygen linkage. In
this transformation involves initial formation of the electrophilic order to explore the synthetic utility of the reaction, an
α-imino rhodium(II) carbenoid, after which nucleophilic oxepinoindole derivative was synthesized. Formation of the
addition of the C3 atom of the carbazole to the electrophilic product was explained by two possible paths. In path A, Friedel−
carbenoid gives the zwitterionic intermediate. Rearomatization Crafts-like alkylation at C3 of the indole with the α-imino
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Scheme 109. Synthesis of Various Dihydro-β-carbolines and Dihydroisoquinolines

Scheme 110. Synthesis of Various Functionalized Tetrahydro-β-carbolines

rhodium carbenoid in 110.5 and subsequent loss of the rhodium In 2017, Miura and Murakami disclosed the selective
catalyst and intermolecular proton transfer from C3 of the functionalization of aromatic C(sp2)−H bonds in the presence
indole ring to the nitrogen atom in the enamine would afford the of benzylic C(sp3)−H bonds by acceptor−acceptor carbenoids
desired product 110.4. Alternatively, in path B, intramolecular derived from 4-acyl-N-sulfonyl-1,2,3-triazole and a rhodium
cyclopropanation of the indole C2−C3 bond followed by ring catalyst (Scheme 111).188 4-Acyl-N-sulfonyl-1,2,3-triazole was
expansion and intermolecular proton transfer would furnish the prepared from but-3-yn-2-ol and mesyl azide via Cu-catalyzed
desired product through intermediate 110.8. 1,3-dipolar cycloaddition reaction and subsequent Dess−Martin
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Scheme 111. Selective Functionalization of Aromatic Scheme 113. Synthesis of Diverse Bisfunctionalized (Z)-
C(sp2)−H Bonds Olefins

oxidation of the hydroxyl group of the resulting triazole. The

reactivity of 4-acyl-N-sulfonyl-1,2,3-triazole was different from
that of 4-aryl-N-sulfonyl-1,2,3-triazole because the latter was selectivity in the reactions of carbamates and amides toward
shown to preferentially undergo benzylic C−H functionalization Rh(II) azavinyl carbenes with the aid of computational
under similar reaction conditions. studies.192
Li and co-workers189 reported C−C coupling reactions of Lee and co-workers synthesized imidazolines from triazoles
various arenes (i.e., N-pyridylisoquinolones and N-pyrimidiny- through a sequential cascade of α-imino carbene insertion into
lindoles) with electron-deficient carbenoids derived from 4-acyl- the N−H bond of the β-enamino ester followed by enamine−
N-sulfonyl-1,2,3-triazole and [RhCp*Cl2]2/AgSbF6 as the imine tautomerization and conjugate addition (Scheme 114).193
catalyst via C−H activation (Scheme 112). The reaction When α-substituted enamines were employed, the imidazolines
were obtained as single diastereomers.
Scheme 112. Syntheses of Various Olefinated Indole and
Isoquinoline Derivatives Scheme 114. Synthesis of Imidazolines from Triazoles

Lee and Yoo successfully isolated potent antibiotic hetero-

biaryls from 9H-carbazoles and triazoles (Scheme 115).194 The
furnished various olefinated indole and isoquinoline derivatives. reaction involves two steps: (1) insertion of the Rh carbenoid
Unfortunately, N-pyridyl-2-pyridone did not afford any C−C- into the N−H bond of the carbazole to produce the enamine and
coupled product under the above reaction condition. (2) Pd-catalyzed regioselective oxidative C−N coupling of the
Importantly, a wide range of functionalized isoquinolines were resultant enamine. Notably, when nonsymmetrical carbazoles
synthesized from benzimidates and 4-acyl-1-sulfonyltriazoles by were used, atropisomers of enamines were formed because of the
a cascade reaction involving Rh(III)-catalyzed C−C coupling restricted rotation about the C−N bond. Subsequently, Shang
followed by cyclization in the presence of Zn(OAc)2, and then and co-workers195 demonstrated 1,3-insertion of α-imino
reduction with NaBH4. The utility of the present protocol was rhodium carbenoids into the N−H bonds of N-arylglycine
explored by the synthesis of various complex structures. Wu and esters or diarylamines to afford various substituted enamines.
Hou studied the detailed mechanism of the Rh(III)-catalyzed Anbarasan and co-workers196 disclosed an efficient diaster-
ortho functionalization of diverse arenes with 4-acyl-N-sulfonyl- eoselective synthesis of 2,2,3,3-tetrasubstituted indolines 116.3
1,2,3-triazoles by DFT calculations.190 via carbenylative amination of o-vinylanilines 116.2 with
5.4.2. N−H Insertions. In 2014, Fokin and co-workers191 iminocarbenes derived from N-sulfonyl-1,2,3-triazoles 116.1
reported a regio- and stereoselective 1,3-insertion of azavinyl (Scheme 116). According to a possible mechanism, reaction of
carbenes into N−H and O−H bonds of various amides, the rhodium carbenoid with the o-vinylaniline generates
alcohols, and carboxylic acids to afford a wide range of ammonium-type ylide 116.5, and a subsequent 1,3-Rh shift
bisfunctionalized (Z)-olefins (Scheme 113). The consistent produces zwitterion 116.6. Protonation of 116.6 followed by an
formation of (Z)-enamides indicates that the insertion reaction intramolecular aza-ene reaction affords indoline derivative
operates through the ylide formation. Various propargylic 116.3. The reaction affords excellent cis diastereoselectivity,
alcohols afforded the corresponding allene products through a presumably due to a well-organized chairlike transition state
cascade sequence of O−H insertion followed by [3,3]- during ene cyclization. The utility of the present protocol was
sigmatropic rearrangement. Further transformations of these explored by the synthesis of imidazoindolines 116.4 via
densely functionalized (Z)-enamide products furnished valuable reduction followed by oxidative cyclization.
heterocyclic compounds and building blocks amenable to Beier and co-workers introduced a facile method for the
further derivatization. Zou and Bao explained the chemo- synthesis of 2-perfluoroalkylimidazoles 117.2 and 2-perfluor-
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Scheme 115. Synthesis of C−N-Coupled Heterobiaryls and Substituted Enamines

Scheme 116. Diastereoselective Synthesis of 2,2,3,3-Tetrasubstituted Indolines

oalkyloxazoles 117.3 from rhodium-catalyzed denitrogenative products via β-hydride elimination, slightly basic reaction
transannulation of N-perfluoroalkyl-1,2,3-triazoles 117.1 with conditions were used.
tert-butyl carbamates and water, respectively (Scheme 117).197 Subsequently, the same group accomplished the synthesis of
According to the proposed mechanism, imino Rh carbenoid α-allyl-α-amino ketones 119.4 from terminal alkynes 119.1,
intermediate 117.5 was generated and inserted into the O−H/ tosyl azide (119.2), and allyl alcohol (119.3) through a dual
N−H bond of the corresponding coupling partners to afford catalytic transformation in one pot (Scheme 119).199 The one-
enamine-type intermediates 117.6 and 117.10. Subsequent HF pot process involves Cu(I)-catalyzed cycloaddition of tosyl
elimination followed by cyclization of resultant iminoyl fluorides azide and the terminal alkyne to afford the triazole at room
117.7 and 117.12 furnished three-membered azirines 117.9 and temperature. Mechanistically, the resultant triazole 119.5 reacts
117.14 with elimination of another molecule of HF. Finally, the with alcohol 119.3 in the presence of the Rh catalyst to furnish
desired products 117.2 and 117.3 were obtained via ring- zwitterion intermediate 119.8 via addition to carbenoid
expansion reactions. Alternatively, the use of a large excess of intermediate 119.7, and upon proton transfer 119.8 produces
water gave the corresponding α-aminoketone derivatives 117.4. (Z)-allyl vinyl ether 119.9. Finally, a Claisen-type [3,3]-
5.4.3. O−H Insertions. In 2012, Murakami and co-workers sigmatropic rearrangement via six-membered chairlike tran-
reported an efficient method for the synthesis of α-amino sition state 119.10 gives the desired product 119.4. Employ-
ketones through α-imino rhodium carbenoid insertion into the ment of propargyl alcohol instead of allyl alcohol afforded α-
O−H bond of water (Scheme 118).198 The reaction proceeds allenyl-substituted α-amino ketone. The synthetic utility of the
when N-sulfonyltriazoles, water, and Rh2(Oct)4 are heated to α-allyl-α-amino ketones was explored by the synthesis of 3,4-
140 °C in a microwave for 15 min to afford the desired products. dehydropiperidines. Importantly, (−)-α-conhydrine was syn-
Regioselective 1,2-aminohydroxylation of terminal alkynes was thesized in nine steps starting from the alkyne using this
achieved in one pot by CuTC-catalyzed cycloaddition of azide protocol.200
with alkyne followed by Rh-catalyzed carbenoid insertion into In 2014, Miura and Murakami201 introduced a new method to
the O−H bond of water. To suppress the formation of side synthesize syn-α-amino-β-oxy ketones 120.6 from terminal
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Scheme 117. Syntheses of 2-Perfluoroalkylimidazoles and 2-Perfluoroalkyloxazoles

Scheme 118. Synthesis of Various α-Amino Ketones from 1,2,3-Triazoles

Scheme 119. Synthesis of α-Allyl-α-amino Ketones Scheme 120. Diastereoselective Synthesis of syn-α-Amino-β-
oxy Ketones

α-aminosilyl enol ethers 120.4 afforded α-amino-β-oxy ketones

alkynes 120.1 via the formation of triazoles in two steps 120.6 with excellent syn selectivity. Herein, the aldol
(Scheme 120). In the first step, Z-selective α-aminosilyl enol condensation occurs through transition states 120.7 and
ethers 120.4 were synthesized from triazoles (which were 120.8, which involve chelation of Ti(IV) with the oxygen of
generated in situ via alkyne−azide cycloaddition) and tert- aldehyde 120.5 and the nitrogen of α-aminosilyl enol ether
butyldimethylsilanol 120.3. Next, upon treatment with 120.4. Transition state 120.8 is favored over 120.7 because the
aldehydes 120.5 under TiCl4-mediated Mukaiyama conditions, R3 group of the aldehyde is anti to the α-amino group of 120.4 in
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120.8, which leads to the formation of syn product 120.6 from 122.6, and then Grob fragmentation followed by isomerization
the corresponding (Z)-α-aminosilyl enol ethers 120.4. furnishes the indigo analogue 122.3.
The same group developed a one-pot, multistep process for Subsequently, Yu and Deng disclosed a facile method for the
the synthesis of 2,5-dihydropyrroles 121.4 starting from alkynes divergent synthesis of 3,5,6-trisubstituted- and 3,6-disubsti-
121.1, sulfonyl azides 121.2, and propargylic alcohols 121.3 tuted-1,2,4-triazines from triazoles and N-acylhydrazones via an
catalyzed by copper, rhodium, and gold catalysts (Scheme unexpected Rh azavinyl carbene insertion into the O−H bond of
121).202 The transformation consists of three steps. The first the hydroxy tautomer of the N-acylhydrazones (Scheme
123).205 The synthesis of 3,6-disubstituted-1,2,4-triazines
Scheme 121. One-Pot Multistep Synthesis of 2,5-
Dihydropyrroles Scheme 123. Divergent Synthesis of Di- and Trisubstituted
1,2,4-Triazines

step is generation of the N-sulfonyl-1,2,3-triazole from the

terminal alkyne and tosyl azide in the presence of copper(I)
thiophene-2-carboxylate. In the second step, Rh2(OPiv)4 is
added to the resultant triazole mixture to prompt O−H insertion
and subsequent sigmatropic rearrangement. Finally, the
resulting α-allenyl-α-amino ketones 121.7 are cyclized to 2,5-
dihydropyrroles 121.4 in the presence of a gold catalyst.
Notably, in the case of enantiomerically pure α-substituted
propargyl alcohol, the stereochemistry of the chiral carbon was
retained in the product.
Yu and Deng203 and Volla204 individually reported the involves O−H insertion and hydrolysis followed by condensa-
synthesis of indigo analogues by rhodium-catalyzed trans- tion, and addition of p-TsOH to the reaction mixture afforded
formations of secondary amides (i.e., isatins 122.2) with N- the products in good yields. On the other hand, addition of base
sulfonyl-1,2,3-triazoles 122.1 (Scheme 122). Screening of and oxidizing agent as additives improved the yield of 3,5,6-
trisubstituted-1,2,4-triazines. Furthermore, the 3,5,6-trisubsti-
Scheme 122. Synthesis of Indigo Analogues tuted-1,2,4-triazine products were transformed to structurally
important azaheterocycles such as pyridines or pyridazinone-
fused triazines in excellent yields by hydrazine condensation and
inverse-electron-demand Diels−Alder reactions.
Lee and co-workers disclosed a regio- and stereoselective
synthesis of γ-oxo-β-amino esters from terminal alkynes, tosyl
azide, and γ-hydroxy-α,β-unsaturated esters (Scheme 124).206
The reaction proceeds through sequential tandem catalysis

Scheme 124. Synthesis of γ-Oxo-β-amino Esters and α-

Methylene-δ-oxo-γ-amino Esters

various Rh(II) catalysts indicated that Rh2(Oct)4 is the best-

performing catalyst for this transformation. The practical
viability of this transformation was proved by the gram-scale
reaction, which afforded the corresponding product in 86%
yield. On the basis of control experiments, the authors proposed
a possible mechanism in which the initially formed α-imino
rhodium carbenoid reacts with the hydroxy isomer of the isatin
to produce O−H inserted intermediate 122.4. Subsequent
intramolecular rearrangement forms aziridine intermediate
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involving copper-catalyzed triazole synthesis, rhodium-catalyzed Scheme 126. Synthesis of 2,5-Epoxybenzo[f ][1,4]oxazepine
O−H insertion, and [3,3]-sigmatropic rearrangement. More-
over, this protocol works well with γ-hydroxy enones for
regioselective incorporation of amine and vinyl functionalities
onto the 1,4-diketone backbone. The synthetic utility of the
produced α-vinyl-γ-oxo-β-amino ester was demonstrated by the
synthesis of a polysubstituted γ-lactone. The present tandem
process worked smoothly for a gram-scale reaction, affording the
desired product in 93% yield with >99:1 dr. Similarly,
employment of α-methylene-δ-oxo-γ-amino esters instead of
γ-hydroxy-α,β-unsaturated esters in the denitrogenative func-
tionalization of N-sulfonyltriazoles afforded α-methylene-δ-oxo-
γ-amino esters in good yields.207
Seo and Lee reported the Rh(II)-catalyzed regioselective
functionalization of O−H and C−O bonds of tropolone (125.2)
with N-sulfonyl-1,2,3-triazoles 125.1 for the synthesis of 2-
functionalized aminotropones 125.3 (Scheme 125).208 The

Scheme 125. Regioselective Functionalization of Tropolone

Scheme 127. Reaction of N-Sulfonyl-1,2,3-triazoles with
Benzyl Alcohols

ether intermediate follwed by a rhodium-induced [1,3]-alkyl

shift to give the α-amino ketone. High diastereo- and
enantioselectivities were achieved in the case of chiral benzylic
alcohols. Notably, the synthetic utility of the present protocol
was demonstrated by the cyclization of α-amino ketones to
1,2,3,4-tetrahydroisoquinolines, which are privileged structures
reaction involves the Rh-catalyzed insertion of the imino in many biological and medicinal compounds.
carbene into the O−H bond of tropolone to give 125.5 and Zhao and Song reported a convenient approach for the
subsequent intramolecular 1,8-addition of 125.5 and rearrange- synthesis of polysubstituted furans from furfuryl alcohols and N-
ment of 125.6. The developed reaction was successfully sulfonyl triazoles through insertion of the α-imino rhodium
extended to a one-pot tandem reaction from terminal alkynes carbene into the O−H bond of the furfuryl alcohol followed by
employing Cu(I) and Rh(II) catalysts. [3,3]-sigmatropic rearrangement (Scheme 128).212
Li and co-workers disclosed the formation of 2,5-epoxybenzo-
[f ][1,4]oxazepines 126.3 from readily available salicylaldehydes Scheme 128. Synthesis of Polysubstituted Furans
126.1 and triazoles 126.2 in the presence of a rhodium catalyst
(Scheme 126).209 They proposed two possible reaction paths
for the formation of the complex structures. Path A involves
initial insertion of Rh-bound imino carbene 126.4 into the O−H
bond to give 126.5, subsequent stepwise [3 + 2] cycloaddition,
and a 1,2-hydride shift, leading to the formation of the desired
product. Alternatively, in path B, formal [3 + 2] cycloaddition of
α-imino rhodium carbene 126.4 with aldehyde 126.1 would Volla and co-workers213 demonstrated a method for the
produce oxazoline 126.7, and subsequent intramolecular synthesis of biologically interesting 5-aminooxadiazoles 129.3
hydroalkoxylation would then afford 2,5-epoxybenzo[f ][1,4]- and 2-aminobenzoxazinones 129.5 from readily available
oxazepine 126.3. On the basis of computational studies, Bao and oxadiazolones 129.2 and isatoic anhydrides 129.4, respectively
co-workers suggested that path B is the more feasible path for (Scheme 129). Mechanistically, the reaction to form 2-
this reaction.210 Notably, upon hydrolysis of the 2,5- aminobenzoxazinones 129.5 involves initial 1,3-insertion of
epoxybenzo[f ][1,4]oxazepine with 2 M HCl, the corresponding the α-imino rhodium carbenoid into the O−H bond of the
α-amino ketone and salicylaldehyde were recovered in 70% and hydroxyl tautomer of the isatoic anhydride to form intermediate
68% yield, respectively. 129.6. Then intramolecular nucleophilic addition produces
Bi and co-workers211 demonstrated a tandem reaction of N- spiro-oxazole 129.7, after which ring opening and keto−enol
sulfonyl-1,2,3-triazoles and benzyl alcohols to synthesize α- tautomerization form 129.5. To explore the synthetic utility of
functionalized α-amino ketones (Scheme 127). They proposed this method, further transformations of 2-aminobenzoxazinones
a mechanism involving α-imino rhodium carbenoid insertion to biologically important frameworks like imidazo-fused
into the O−H bond of the benzylic alcohol to form the vinyl benzoxazinones and imidazolones were demonstrated.
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Scheme 129. Synthesis of 2-Aminobenzoxazinones and 5-Aminooxadiazoles

Alcaide and Almendros described the divergent reactivity of 4- H insertion/symmetric [1,3]-rearrangement from triazoles
aryl-N-sulfonyl-1,2,3-triazoles and 4-acyl-N-sulfonyl-1,2,3-tria- 132.1 and benzyl alcohols 132.2 catalyzed by the rhodium salt
zoles toward allenols (Scheme 130).214 They demonstrated that and chiral N,N′-dioxide−indium(III) complex 132.5. Accord-
ing to the proposed mechanism, initial insertion of the
Scheme 130. Synthesis of 3-Methylene-5,6-dioxo-hept-1- rhodium(II)-stabilized imino carbene into the O−H bond of
enyl-4-amine Derivatives the benzylic alcohol generates (Z)-α-amino enol ether 132.4.
Here, chiral N,N′-dioxide−indium(III) complex 132.5 coor-
dinates to the oxygen atom of the enol ether and cleaves the O−
Bn bond to form ion-pair intermediate 132.6 containing the
benzyl cation species and its enolate counterpart. The Si face of
the enolate is blocked by the 2,4,6-triisopropylphenyl group of
the ligand, resulting in the predominant Re-face addition to the
benzyl cation, as shown in Scheme 132.
Yu and Deng disclosed a novel method for the synthesis of
the chemoselectivity can be switched from carbon to oxygen by 3,4-fused pyrroles 133.3 from triazoles 133.1 and Morita−
replacing an aryl group with an acyl group in the rhodium- Baylis−Hillman (MBH) adducts 133.2 via a four-step cascade
catalyzed reactions of 4-substituted-N-sulfonyl-1,2,3-triazoles sequence (Scheme 133).217 Various substituted triazoles and
with allenols. DFT calculations declared that because of the MBH adducts gave the corresponding fused pyrrole derivatives
greater electrophilicity of the acceptor/acceptor rhodium in good yields. According to the proposed mechanism, the
carbenoid derived from the 4-acyl-N-sulfonyl-1,2,3-triazole, initially N-sulfonyl-1,2,3-triazole 133.1 reacts with the Rh(II)
the allenol O−H bond inserted into carbenoid first, followed catalyst to generate the α-imino rhodium carbene, which inserts
by a [3,3]-sigmatropic rearrangement to afford the 3-methylene- into the O−H bond of the MBH adduct to form an isomeric
5,6-dioxo-hept-1-enyl-4-amine derivative. mixture of enamide intermediates 133.5. Then the intra-
In 2018, Feng and co-workers215 disclosed a tandem reaction molecular [3,3]-sigmatropic rearrangement and subsequent
of N-sulfonyl-1,2,3-triazoles 131.1 with allyl alcohol esters 131.2 intramolecular cyclization followed by oxidation of the
and 131.4 employing bimetallic relay catalytic systems (Scheme intermediate under basic conditions affords the desired product
131). The tandem reaction involves an achiral rhodium- 133.3.
catalyzed insertion and a chiral N,N′-dioxide−indium(III) Anbarasan and co-workers218 synthesized substituted naph-
complex-catalyzed asymmetric Claisen rearrangement, which thofurans and benzofurans through a cascade reaction of
affords either γ-oxo-β-amino esters 131.3 or δ-oxo-γ-amino rhodium azavinyl carbenes with β-naphthols (Scheme 134).
esters 131.5 in high yields with good to excellent diastereo- and The cascade reaction involves insertion of the rhodium azavinyl
enantioselectivities. The chiral induction for rearrangement was carbene into the O−H bond to provide intermediate 134.5,
explained through the bidentate binding of the allyl vinyl ether subsequent Yb-catalyzed annulative C−C bond formation in
intermediate to In(III) with oxygen atoms of both the tosyl 134.5, and concomitant air oxidation of intermediate 134.7.
group and ester group, after which the enantioselective Claisen- Various substituted naphthofuran derivatives were synthesized
type [3,3]-sigmatropic rearrangement proceeds via six-mem- in good to excellent yields. Furthermore, the synthesis of
bered chairlike transition state 131.9 to give the desired product important polyheteroaromatic compounds was accomplished
in excellent yield with high diastereo- and enantioselectivity. successfully.
Subsequently, they expanded the applications of this strategy Volla and co-workers reported an efficient Rh(II)-catalyzed
for the highly enantioselective construction of α-amino ketones cascade transannulation of N-sulfonyl-1,2,3-triazoles 135.2 with
132.3 (Scheme 132).216 The reaction proceeds via catalytic O− vinyl benzoxazinones 135.1 for the synthesis of structurally
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Scheme 131. Synthesis of γ-Oxo-β-amino Esters and δ-Oxo-γ-amino Esters

Scheme 132. Enantioselective Synthesis of α-Amino Ketones

diverse tricyclic 2-imidazolones 135.3 in moderate to good 135.4 from triazole 135.2 and vinyl benzoxazinone 135.1 and
yields with excellent diastereoselectivity (Scheme 135).219 The subsequent Rh(II)-catalyzed ring opening followed by intra-
reaction proceeds through the initial formation of intermediate molecular nucleophilic addition of amide to the carbonyl group
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Scheme 133. Synthesis of 3,4-Fused Pyrroles lyzed insertion of α-imino rhodium carbenes into the O−H
bond of H2O followed by intramolecular Michael addition
(Scheme 136). A wide range of functionalized 2-amino-
indanones were synthesized in good yields with good trans
diastereoselectivity. Notably, epimerization occurred during
isolation of the product indanone, which led to the poor
diastereoselectivity of the isolated product.
Stewart and co-workers221 demonstrated a facile method for
the synthesis of 2,6-substituted dihydro-2H-1,4-oxazines from
α-imino rhodium carbenoids and halohydrins under basic
conditions (Scheme 137). The reaction proceeds through 1,3-
insertion of the carbene into the O−H bond of the halohydrin
and subsequent intramolecular nucleophilic displacement. The
synthetic utility of the reaction was explored by the synthesis of
the antimicrobial natural product (±)-chelonin C.
Scheme 134. Synthesis of Substituted Naphthofurans and Majireck and co-workers222 disclosed the Rh-catalyzed
Benzofurans intramolecular cyclization of triazole-tethered benzyl alcohols
to form N-(2-alkoxyvinyl)sulfonamide frameworks (Scheme
138). Moreover, they converted the N-(2-alkoxyvinyl)-
sulfonamides to phenethylamine derivatives and substituted
phthalan derivatives using simple synthetic transformations.
Interestingly, reductive ring opening of phthalan with Red-Al
afforded phenethylamine, which represents an anti-Markovni-
kov hydroamination of a terminal aryl alkyne.
In 2020, Xu and Li synthesized α-(2-hydroxyphenyl)-α-
amino ketones 139.3 from N-sulfonyl-1,2,3-triazoles 139.1 and
benzoquinone-derived alcohols 139.2 (Scheme 139).223 The
cascade involves sequential generation of the Rh carbene, 1,3-
insertion into the O−H bond, Claisen rearrangement, and
aromatization. Although Rh2(esp)2, Rh2(Adc)4, and Rh2(OPiv)4
worked well for this transformation, other Rh catalysts such as
Rh2(dpf)4, Rh2(OAc)4, and Rh2(tfa)4 led to decomposition of
the triazole. Notably, 4-alkyl-N-sulfonyl-1,2,3-triazole did not
afford the desired product under the optimized reaction
conditions. Alcohols possessing various alkyl substituents
afforded the corresponding products effectively. However,
substituents (e.g., Me) at the β-position of the alcohol
suppressed the reaction because of steric hindrance. One-step
conversion of the α-(2-hydroxyphenyl)-α-amino ketones to
bioactive compounds such as benzoxazinones and 3-amino-
to generate intermediate 135.6. Finally, diastereoselective allylic benzofuran was achieved.
etherification furnishes the desired product 135.3. In 2016, Chen, Huang, and co-workers224 developed the
Xing et al.220 converted Michael acceptor-tethered triazoles synthesis of polysubstituted 3-aminofurans through a dual-
into 2-aminoindanones diastereoselectively via rhodium-cata- catalytic tandem reaction of N-sulfonyl-1,2,3-triazoles with

Scheme 135. Transannulation of N-Sulfonyl-1,2,3-triazoles with Vinylbenzoxazinones

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Scheme 136. Synthesis of 2-Aminoindanones from Michael Acceptor-Tethered Triazoles

Scheme 137. Synthesis of 2,6-Substituted Dihydro-2H-1,4- Scheme 139. Synthesis of α-(2-Hydroxyphenyl)-α-Amino

oxazines Ketones

propargylic alcohols (Scheme 140). The tandem reaction

involves Rh-catalyzed O−H insertion at the azavinyl carbene,
thermal propargyl-Claisen rearrangement, and gold-catalyzed
intramolecular cyclization. Various propargylic alcohols reacted
smoothly to afford the corresponding 3-aminofurans in high
yields. However, the applicability of this strategy was limited to
simple propargylic alcohols, as an initial attempt with an α-
substituted propargylic alcohol led to the formation of
dihydropyrrole following previously reported protocol of
Murakami.202
5.4.4. B−H Insertion. Miura and Murakami reported a syn-
selective aza-aldol reaction of boron azaenolates 141.2
generated from N-sulfonyl-1,2,3-triazoles 141.1 and 9-BBN
(Scheme 141).225 The formation of the aldol product could be
Scheme 140. Synthesis of Polysubstituted 3-Aminofurans
explained in terms of the formation of enolate 141.2 in the
presence of Rh2(OPiv)4 and its subsequent reaction with the
aldehyde via six-membered transition state 141.3. Furthermore,
DIBAL-H was added to the reaction mixture to isolate more
stable products, and the corresponding reduced products 141.5
were obtained with a syn/anti ratio of greater than 95:5.
5.5. Insertions into C−X/X−X Bonds
5.5.1. C−X Insertions. Insertion of carbenoids into C−X
bonds rapidly increases the complexity in a single step. Most
often, these transformations involve the initial formation of
ylides with Lewis basic “X” followed by concomitant reaction/
rearrangement. Xu and Shen converted 4-N-allylarylpropylami-
no-N-sulfonyl triazoles 142.1 into tricyclic benzopyrrolizidinyl smoothly to furnish the desired products in good yields. On the
sulfonamides 142.2 in one-pot (Scheme 142). 226 The other hand, hydrolysis of intermediate 142.6 could result in the
conversion involves intramolecular trapping of rhodium carbene formation of compound 142.3.
142.4 with the arylamino nitrogen and [2,3] or [1,2] In 2013, Murakami and co-workers227 reported the sequential
rearrangement to give 2-allylpyrrolidinyl-2-carbimine inter- one-pot transformation of terminal alkynes, tosyl azide, and
mediate 142.6, which subsequently undergoes copper-catalyzed allylic sulfides to accomplish the synthesis of α-allyl-α-
aza-Friedel−Crafts cyclization to furnish the desired product sulfanylimines (Scheme 143). The transformation starts with
142.2. A variety of triazoles underwent the transformation CuAAC and carbenoid formation, after which nucleophilic

Scheme 138. Intramolecular Cyclization of Triazole-Tethered Benzyl Alcohols

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Scheme 141. Syn-Selective Aza-Aldol Reaction of In Situ-Generated Boron Azaenolates

Scheme 142. One-Pot Synthesis of Tricyclic Benzopyrrolizidinyl Sulfonamides

Scheme 143. Synthesis of Functionalized α-Allyl-α- sigmatropic rearrangement, probably for steric reasons. At the
sulfanylimines same time, Yadagiri and Anbarasan228 also reported a similar
transformation of N-sulfonyl-1,2,3-triazoles and allylic sulfides.
Subsequently, Miura and Murakami229 demonstrated the
regio- and stereoselective α-imino rhodium carbene insertion
into thioesters 144.2 for the synthesis of β-sulfanyl enamides
144.4 in good yields (Scheme 144). The reaction proceeds

Scheme 144. Synthesis of β-Sulfanyl Enamides

through nucleophilic addition of the sulfur atom of the thioester

addition of the allylic sulfide to the α-imino rhodium carbenoid to the Rh carbenoid carbon atom to give intermediate 144.3 and
induces a Doyle−Kirmse reaction to afford the rearranged subsequent intramolecular migration of the acyl group from the
product. A wide range of functionalized α-allyl-α-sulfanylimines sulfur atom to the imino nitrogen atom. Experimental data
were synthesized in good to excellent yields. When a γ- indicated that the sulfenylation reaction occurred preferentially
disubstituted allylic sulfide was used, a direct SN2 reaction over the O−H and N−H insertion reactions. The synthetic
occurred at the imino nitrogen in preference to [2,3]- utility of the present reaction was explored by the synthesis of
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medium-sized lactams 144.7 containing a vinylsulfanyl moiety Rh2(dpf)4 did not afford any product. A wide range of
starting from thiolactams 144.6 by a ring expansion reaction. thiochromones provided the corresponding multifunctionalized
Koenigs and co-workers reported the Rh-catalyzed enamine benzothiazonines in good to excellent yields. Surprisingly, no
homologation of cyclopropylmethyl sulfides, i.e., formal desired product was obtained from the corresponding oxygen
homologation of a C−S bond with an enamine fragment analogues (chromones) and nitrogen analogues (quinolin-
(Scheme 145).230 DFT calculations emphasized that the 4(1H)-ones), and the triazole was decomposed over a period.
reaction proceeds through the formation of a free ylide Boyer232 disclosed the Rh-catalyzed denitrogenative trans-
intermediate. formation of allyl/propargylic ether-tethered 5-substituted and
4,5-disubstituted N-sulfonyl-1,2,3-triazoles 147.2 to dihydrofur-
Scheme 145. Rh-Catalyzed Enamine Homologation of an-3-imines 147.6 (Scheme 147). The proposed mechanism
Cyclopropylmethyl Sulfides involves initial formation of rhodium carbenoid 147.4, and then
the ethereal oxygen atom attacks the electrophilic center of the
carbenoid to form oxonium species 147.5, which undergoes
[2,3]-sigmatropic rearrangement to produce the desired
product 147.6. Propargylic ether-tethered triazoles under this
transformation afforded allene dihydrofuran-3-imines as a result
of [2,3]-sigmatropic rearrangement. Additionally, the natural
product (+)-petromyroxol was synthesized in nine steps in an
Recently, Xu and Li accomplished the synthesis of overall yield of 20%.233
benzothiazonines 146.3 through the Rh-catalyzed reaction of Similarly, Boyer converted 4-(γ-allyloxy)- and 4-(γ-propargy-
N-sulfonyl-1,2,3-triazoles 146.1 with thiochromones 146.2 loxy)-pendent N-sulfonyl-1,2,3-triazoles to tetrahydrofurans in
(Scheme 146).231 Mechanistically, nucleophilic addition of excellent yields and diastereoselectivity (Scheme 148).234 The
Scheme 146. Synthesis of Benzothiazonines Scheme 148. Diastereoselective Synthesis of
Tetrahydrofurans

reaction features onium ion formation followed by [2,3]-

sigmatropic rearrangement. A variety of tetrahydrofuran
derivatives were successfully synthesized in up to 98% yield
sulfur in thiochromone 146.2 to the Rh carbenoid generates with >20:1 dr. However, the imine group in the product was
sulfur ylide 146.4. Subsequent intramolecular Michael addition converted into the corresponding aldehyde, sulfonamide, 1,3-
of 146.4 followed by ring opening of 146.5 furnishes the desired dithiane, or spiro group.
product 146.3. Screening of several Rh catalysts indicated In 2014, Yang and co-workers developed the stereoselective
Rh2(OAc)4 to be the optimal catalyst, whereas Rh2(tfa)4 and synthesis of oxaspirocycles from N-sulfonyl-1,2,3-triazoles in

Scheme 147. Synthesis of Dihydrofuran-3-imines

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good to excellent yields (Scheme 149).235 In this trans- Scheme 151. Synthesis of N-Allyl (Z)-Amino Vinyl
formation, the initial formation of the imine product involves Carboxylates and Ethers

Scheme 149. Stereoselective Synthesis of Oxaspirocycles

a similar type of mechanism as reported by Boyer.232

Subsequent Grignard reaction followed by ring-closing meta-
thesis (RCM) in the presence of Grubbs second-generation
catalyst furnishes the desired type I product, whereas Grignard
reaction followed by allylation and RCM affords the type II
product. Importantly, this methodology was utilized in the total In 2017, Lacour and co-workers reported the synthesis of
syntheses of two natural products (see Scheme 199). macrocycles from oxetanes and N-sulfonyl-1,2,3-triazoles using
Tang and Shi accomplished the synthesis of alkylideneph- a rhodium catalyst (Scheme 152).238 2-Imino tetrahydrofurans
thalan and alkylidenethiophthalan derivatives via Rh-catalyzed
cyclization of ester- and thioester-containing N-sulfonyl-1,2,3- Scheme 152. Synthesis of Macrocycles from Oxetanes and N-
triazoles, respectively (Scheme 150).236 Moreover, upon Sulfonyl-1,2,3-triazoles

Scheme 150. Synthesis of Alkylidenephthalan and

Alkylidenethiophthalan Derivatives

ozonolysis these alkylidenephthalans were converted to and 13- and 15-membered-ring azamacrocycles were synthe-
phthalides (i.e., 3H-isobenzofuran-1-ones), which are frequently sized via formal [1 + 4], [5 + 4 + 4] and [3 + 4 + 4 + 4]
found in natural products and exhibit a broad spectrum of condensations of α-imino carbenes and oxetanes depending on
biological activities. Notably, phosphoryl groups also were found the oxetane concentration. For instance, under dilute con-
to be migrating groups, like acyl groups. ditions, the [1 + 4] condensation product was obtained. At a
Lee and co-workers237 disclosed Pd(0)/Rh(II) dual-catalytic high concentration of oxetane, 15-azamacrocycles were
incorporation of both the allyl and counteranion of allyl obtained via formal [3 + 4 + 4 + 4] condensations of an α-
carboxylates/carbonates 151.2/151.4 into α-imino Rh(II) imino carbene and three oxetanes. On the other hand, alkyl
carbenoids 151.6 derived from N-sulfonyl-1,2,3-triazoles sulfonyl triazoles afforded 13-membered heterocycles by the
151.1 (Scheme 151). A wide range of N-allyl (Z)-amino vinyl reaction of two oxetanes and the involvement of the S�O bond
carboxylates 151.3 and ethers 151.5 were synthesized regardless of the sulfonylimine as an intramolecular nucleophile.
of steric and electronic effects. In this catalysis, Pd(0) activates In 2019, Shi and co-workers239 successfully synthesized 1-
allylic substrate 151.4 to generate π-allyl Pd(II) complex 151.8 azaspiro[5.5]undecane derivatives 153.4 from 4-methoxycyclo-
and liberate the counteranion 151.7. The resulting counteranion hexa-2,5-dienone-containing N-sulfonyl-1,2,3-triazoles 153.1
151.7 acts as a nucleophile and attacks electrophilic rhodium via oxonium ylide intermediates 153.3 (Scheme 153). Notably,
carbenoid 151.6 to form Pd/Rh-associated zwitterionic substitution at the β-position of the carbonyl was not tolerated in
intermediate 151.10, in which the Pd(II) species coordinates this transformation. According to the possible mechanism, the
with both the counteranion and the imine nitrogen in the same α-imino rhodium carbenoid is trapped by the methoxy group to
plane to afford the desired product 151.5. produce oxonium ylide 153.3. Subsequent intramolecular
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Scheme 153. Synthesis of 1-Azaspiro[5.5]undecane triazole 154.1 generates nickel azavinyl carbene 154.5, which
Derivatives upon further rearrangement produces nickel-bound ketenimine
intermediate 154.6. Subsequent nucleophilic attack of phos-
phorous acid 154.7 on ketenimine intermediate 154.6 produces
zwitterionic intermediate 154.8. Finally, proton transfer
followed by Ni catalyst extrusion via reductive elimination
gives the desired product 154.3.
5.5.2. X−X Insertions. In 2015, Fu and co-workers
disclosed transformations of N-sulfonyl-1,2,3-triazoles through
rhodium-catalyzed denitrogenative thioacetalization with diaryl
nucleophilic attack to cleave the C−O bond produces the disulfides (Scheme 155).241 Initially, the triazole is converted
desired spiro compound 153.4. into the Rh-bound imino carbene, and then the sulfur
Jiang and co-workers explored the 1,2-insertion of H- nucleophile of the diaryl disulfide attacks the carbenoid to
phosphine oxides 154.2 into azavinyl carbenes via nickel- form an ylide-type intermediate, which is further converted into
bound ketenimine intermediate 154.6 to form α-amino- the thioacetalized product. The synthesized thioacetalized
vinylphosphoryl derivatives 154.3 (Scheme 154).240 Ni(cod)2 products were converted into various useful products through
hydrolysis, reduction, and umpolung reactions and deprotec-
Scheme 154. Synthesis of α-Aminovinylphosphoryl tion.
Derivatives 5.6. Rearrangements
5.6.1. Rearrangements Involving a 1,2-H/Alkyl Shift.
Suitably substituted N-sulfonyl-1,2,3-triazoles can undergo
rearrangements in the presence of transition metal catalysts to
afford diverse functionalized molecules. In 2012, Miura and
Murakami synthesized enaminones from 1-(N-sulfonyl-1,2,3-
triazol-4-yl)alkanols via intramolecular 1,2-hydride or alkyl
migration (Scheme 156).242 The rearranged products were

Scheme 156. Synthesis of Enaminones from 1-(N-Sulfonyl-

1,2,3-triazol-4-yl)alkanols

obtained upon treatment of the triazoles with 0.5 mol %

was found to be the best catalyst for this conversion among Rh2(OAc)4 in chloroform at 140 °C under microwave
various catalysts examined, including Rh-, Ni-, and Cu-based irradiation for 15 min. Initially, an α-imino rhodium carbenoid
catalysts. A possible mechanism for this transformation was is generated. Then the electron pushing effect of the hydroxyl
proposed on the basis of DFT calculations and deuterium group facilitates the 1,2-migration of hydride ion (or alkyl) to
labeling experiments. At first, in the presence of the Ni catalyst, the electrophilic carbenoid, leading to the formation of the

Scheme 155. Denitrogenative Thioacetalization of N-Sulfonyl-1,2,3-triazoles

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corresponding enaminones. This reaction was applicable to both Scheme 159. Synthesis of S-Containing Tetrahydropyridine
symmetric and asymmetric tertiary alcohols. In the case of Derivatives
asymmetric alcohols, mixtures of products were obtained
through migration of both substituents. Moreover, cyclic tertiary
alcohols gave ring expansion products under the standard
reaction conditions.
Tang and co-workers243 synthesized highly substituted
cyclobutene derivatives from ring expansion of 4-cyclo-
propane-substituted N-sulfonyl-1,2,3-triazoles, which involves
formal 1,2-migration of the alkyl group (Scheme 157). After

Scheme 157. Synthesis of Highly Substituted Cyclobutene

Derivatives

Independently, Yadagiri and Anbarasan246 also reported a

similar cascade reaction of thio-tethered N-sulfonyl-1,2,3-
triazoles to afford a wide range of (fused) tetrahydropyridines,
tricyclic and (bridged) bicyclic compounds, and cyclohexenes
along with tetrahydropyridines in good to excellent yields
(Scheme 160). The synthesis of these diverse (hetero)cyclic
compounds was accomplished through in situ trapping of the 1-
screening of reaction conditions, silver triflate was found to be azadiene intermediate with various external dienophiles such as
the most efficient catalyst to achieve high regioselectivity. alkyne, alkene, (cyclic) diene, enol ether, enamine, and ketene
Subsequently, treatment of cyclopropyl acetylenes with tosyl S,S-acetal. Additionally, a one-pot conversion of propargyl
azides in the presence of both CuTc and AgOTf catalysts sulfides to (fused) tetrahydropyridines was achieved through the
afforded cyclobutenes with aldehyde or sulfonamide function- effective integration of copper and rhodium catalysts.
ality in good yields and regioselectivity. In 2017, Xu and Li reported the synthesis of highly substituted
5.6.2. Rearrangements Involving Generation of dihydropyridine derivatives by a tandem reaction of 4-(1-
Azadienes. In 2012, Fokin and co-workers reported the Rh- acetoxyallyl)-N-sulfonyl-1,2,3-triazoles (Scheme 161).247 The
catalyzed rearrangement of various 4-substituted N-sulfonyl- key step in this conversion is the 1,2-acetoxy migration, which
1,2,3-triazoles (Scheme 158).244 N-Sulfonyltriazoles bearing a provides a penta-2,4-diene-1-imine intermediate. Then electro-
cyclic ring closure of the intermediate leads to the formation of
Scheme 158. Rh-Catalyzed Rearrangement of N-Sulfonyl- the 1,2-dihydropyridine in up to 90% yield. Additionally, the
1,2,3-triazoles potential of this strategy was demonstrated by various
transformations of the dihydropyridine products.
Later, Xu and Li expanded this methodology to intermo-
lecular reactions. They reacted (N-tosyl-1,2,3-triazol-4-yl)-
methyl acetates 162.1 with different coupling partners such as
alkyl vinyl ethers 162.2 and various substituted indoles 162.5 in
the presence of a rhodium catalyst (Scheme 162).248,249 These
reactions afforded piperidines 162.4 and pyrido[2,3-b]indole
derivatives 162.6 through aza-Diels−Alder reaction of the in
situ-generated aza-1,3-dienes 162.3. Simultaneously, they ex-
plored the reaction between benzoxy-tethered N-sulfonyl-1,2,3-
triazoles 162.7 and indoles 162.8, which afforded cyclopenta-
[b]indoles 162.9 in good to moderate yields.250 The reaction
involves a Michael addition and subsequent [3 + 2] cyclo-
quaternary center at C4 underwent Rh-catalyzed rearrangement addition in the presence of a weak acid. Excellent functional
to give the corresponding substituted olefins through migration group tolerance and chemoselectivity were achieved. The same
of a substituent from the quaternary carbon to the rhodium group also reported 1,3-migration of the acyloxy group of
azavinyl carbene carbon. 162.10, which furnished highly functionalized cyclopropanes
Shi and co-workers reported a Rh-catalyzed cascade reaction 162.11 in excellent yields.251
of thio-tethered N-sulfonyl-1,2,3-triazoles 159.1 to S-containing In 2019, Xu et al.252 accomplished the synthesis of fused
tetrahydropyridine derivatives 159.2 (Scheme 159).245 The pyrimidine derivatives employing N-sulfonyl-1,2,3-triazoles as
cascade involves intramolecular 1,2-sulfur migration in the in 1-aza-[4C] synthons and 2H-azirines (Scheme 163). The very
situ-generated Rh azavinyl carbene 159.3 followed by an high strain of the 2H-azirine triggers the cyclization, leading to
intermolecular aza-Diels−Alder reaction of the resulting 1- the formation of cyclized products. The fused ring can be
azadiene 159.5. Diversely substituted tetrahydropyridines were opened upon treatment with BF3·OEt2, furnishing the seven-
obtained in up to 94% yield. Besides, unsaturated imines were membered multifunctionalized 1H-1,4-diazepine derivatives.
also synthesized from suitably substituted triazoles under Moreover, 1H-1,4-diazepines were synthesized directly from
identical reaction conditions. triazoles and 2H-azirines in one pot.
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Scheme 160. Synthesis of a Variety of (Hetero)cyclic Compounds

Scheme 161. Synthesis of Highly Substituted Dihydropyridine Derivatives

Scheme 162. Synthesis of Various Functionalized N- Scheme 163. Synthesis of Fused Pyrimidine and 1H-1,4-
Heterocycles Diazepine Derivatives

regioselective nucleophilic addition (1,2- or 1,4-addition).

Michael addition of indoles to the azadienes followed by
reduction produced homotryptamines, whereas 1,2-addition of
1,3,5-trimethoxybenzene to the 1-azadienes afforded allyl-
amines. The synthetic utility of this protocol was demonstrated
by functionalization of the homotryptamines into other
biologically relevant heterocycles.
5.6.3. Rearrangements Involving Generation of Ylides.
In 2016, Li and co-workers254 introduced a facile approach for
the synthesis of 4-bromo-1,2-dihydroisoquinolines (DHIQs)
165.2 from o-benzyl bromide-containing N-sulfonyl-1,2,3-
triazoles 165.1 via bromonium ylide intermediate 165.3
Later, Volla and co-workers253 synthesized homotryptamines (Scheme 165). Mechanistically, bromonium ylide intermediate
and allylamines from N-sulfonyl-1,2,3-triazoles with indoles and 165.3 is formed through intramolecular nucleophilic attack at
1,3,5-trimethoxybenzene, respectively (Scheme 164). The the Rh carbenoid. Then cleavage of the C−Br bond leads to the
reaction involves Rh(II)-catalyzed intramolecular rearrange- formation of benzylic cation 165.4, which can exist in
ment of 1,2,3-triazolyl esters into 1-azadienes followed by equilibrium with intermediate 165.5 by displacement of the
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Scheme 164. Synthesis of Various Homotryptamines and Allylamines

Scheme 165. Synthesis of 4-Bromo-1,2-dihydroisoquinolines Scheme 166. Synthesis of 1,2-dihydroisoquinolines and 2-

aminoindanones

Rh catalyst. Finally, 6π electrocyclic ring closure furnishes the

desired product 165.2. The DHIQs could be readily converted
into 1,2,3,4-tetrahydro-4-bromoisoquinolines or 4-bromoiso-
quinolines by reduction or oxidation, respectively. Since the
DHIQs contained a bromide, several valuable heterocyclic
compounds were synthesized by Sonogashira coupling or Heck rearrangement of 167.6 and 167.7. Experimental results
coupling followed by other transformations. Importantly, 1- indicated that the diastereoselectivity of the product depends
benzylated isoquinolines, which possess important physiological on the indole loading in the reaction mixture, which was
properties, were successfully synthesized. Of note, triazole presumed to be due to π−π stacking interactions between excess
bearing α-H atoms did not afford the corresponding DHIQ indole and the aromatic part of the indole-substituted indanone.
product, but instead, the α,β-unsaturated imine was isolated in The skeletal rearrangement is favored as a result of the electron-
60% yield. rich indole group and the electron-withdrawing sulfonyl moiety.
In 2016, Huang and co-workers255 reported the synthesis of Notably, pyrrole also acts as a nucleophile and affords the
1,2-dihydroisoquinolines 166.2 and 2-aminoindanones 166.3 corresponding product in significant yield.
from skeletal rearrangement of ether-tethered N-sulfonyl 1,2,3- Pal and Volla258 converted 1,2,3-triazolylcarbamates to 4-
triazoles 166.1 using a rhodium catalyst (Scheme 166). aminooxazolidinones via Rh(II)-catalyzed tandem rearrange-
Mechanistically, azavinyl rhodium carbenoid 166.4 is first ment/cyclization (Scheme 168). Additionally, a one-pot
generated from substituted triazole 166.1, and the methoxy procedure was also developed for the synthesis of 4-amino-
group attacks the rhodium carbenoid to form oxonium ylide- oxazolidinones from the corresponding propargyl carbamates
type intermediate 166.5. Ring closure of the benzylic carbon and tosyl azide through sequential CuAAC and Rh2(OAc)4-
center at the nitrogen atom leads to 1,2-dihydroisoquinoline catalyzed triazole transannulation.
166.2. Alternatively, 1,3-[Rh] migration in carbocyclic inter- In 2020, Anbarasan and co-workers reported an efficient
mediate 166.5 followed by skeletal rearrangement affords synthesis of various functionalized enamides 169.3 via a
intermediate 166.8. Subsequent hydrolysis of 166.8 gives 2- Sommelet−Hauser-type rearrangement of sulfur ylides 169.4
aminoindanone 166.3. At the same time, Tang and Shi also (Scheme 169).259 Ylides 169.4 were obtained from α-thioesters
observed a similar skeletal rearrangement.256 169.2 and N-sulfonyl-1,2,3-triazoles 169.1 in the presence of a
In 2017, Gong and Yang257 synthesized indole-substituted rhodium catalyst. Replacement of the α-thioester with an α-
indanones 167.3 from carbonyl-tethered triazole derivatives thioacetyl moiety and α-thio-N,N-diethylamide also afforded
167.1 and indoles 167.2 (Scheme 167). The transformation the corresponding enamide products. According to the
occurs through a tandem reaction involving the Rh-catalyzed proposed mechanism, initially N-sulfonyl-1,2,3-triazole 169.1
denitrogenative formation of oxonium ylide 167.4 followed by is converted into an electrophilic α-imino rhodium carbenoid
nucleophilic addition of indole and subsequent skeletal intermediate in the presence of the rhodium catalyst.
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Scheme 167. Synthesis of Indole-Substituted Indanones

Scheme 168. Synthesis of 4-Aminooxazolidinones

Scheme 169. Synthesis of Various Functionalized Enamides 5.6.4. Rearrangements Involving Formation of Kete-
nimines. In 2013, Croatt and co-workers synthesized and
explored the reactivity of a series of 1,5-disubstituted N-
sulfonyltriazoles 171.1 (Scheme 171).261 Various α-sulfonylni-
triles 171.2 were synthesized from the corresponding triazoles
171.1 via thermolysis and Rh(II)-catalyzed reactions. However,
the applicability of this protocol was limited to 1,5-disubstituted
triazoles only. Later, Li and co-workers262 disclosed the
synthesis of α-sulfonylnitriles 171.4 through a thermal
rearrangement of 1,4-disubstituted triazoles 171.3. A solution
of the 4-substituted N-sulfonyl-1,2,3-triazole in DCE solvent
was heated to 150 °C in a sealed tube to obtain the α-cyano
sulfone. On the basis of several control experiments, the
mechanism was proposed to involve initial production of
ketenimine 171.6 by a tandem ring−chain tautomerization and
1,2-H shift. Then 1,3-sulfonyl migration by homolytic cleavage
of the N−S bond followed by recombination affords the desired
product 171.4. Notably, 5-alkyl-N-sulfonyl-1,2,3-triazoles and
Nucleophilic addition of the sulfur of α-thioester 169.2 to the aliphatic sulfonyl-1,2,3-triazoles did not afford the sulfones
rhodium carbenoid generates sulfur ylide 169.4. Then the acidic under the standard reaction conditions, but 4-alkyl-N-sulfonyl-
proton α to the ester is transferred, producing the new sulfur 1,2,3-triazoles afforded the corresponding sulfones.
ylide 169.6, which upon subsequent aza-[2,3]-sigmatropic Shi and co-workers263 demonstrated a catalyst-free thermally
rearrangement furnishes the enamide 169.3. induced cyclization of sulfide-tethered N-sulfonyl-1,2,3-triazoles
In 2020, Chen and Sun reported the dearomative migratory to form 3-sulfide-substituted isoquinolines and dihydroisoqui-
rearrangement reactions of 2-oxypyridines with α-imino nolines (Scheme 172). The transformation occurred through
rhodium carbenes (Scheme 170).260 The reaction of o- the formation of a ketenimine intermediate followed by sulfide
carboxylic ester-substituted pyridines with N-sulfonyl-1,2,3- attack and subsequent skeletal rearrangement via sulfide
triazoles in the presence of Rh2(OPiv)4 in a 4:1 mixture of migration. Importantly, methoxy and tertiary amide groups
cyclopentane and benzene at 100 °C for 4 h afforded 1,4- were also found to be involved in the migration to afford the
migratory products. Besides, the formation of 1,6-migratory desired product. However, tertiary-amide-tethered aryl alkynes
products was observed in the presence of Rh2(esp)4 at 110 °C in gave 3-amino-substituted 1,2-dihydroisoquinilines in good
the same solvent. Moreover, the use of pyridotriazoles instead of yields in the presence of TsN3, CuCl, and DIPEA. This reaction
N-sulfonyl-1,2,3-triazoles afforded the corresponding rear- tolerates many functional groups and heterocyclic compounds.
ranged products in good to excellent yields. All of these Similarly, Li and co-workers264 also reported the catalyst-free
transformations showed very high functional group tolerance. thermal cyclization of 1-sulfonyl-4-(2-alkenylphenyl)-1,2,3-
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Scheme 170. Dearomative Migratory Rearrangement Reactions of 2-Oxypyridines

Scheme 171. Synthesis of α-Sulfonylnitriles Scheme 172. Synthesis of Substituted Isoquinolines and 2-
Aminonaphthalenes

Scheme 173. Synthesis of N-Acylamidines

triazoles to form 2-aminonaphthalenes via ketenimine inter-
mediates. This reaction gave facile access to various substituted
2-aminonaphthalenes.
5.6.5. Cycloaddition Followed by Rearrangement. Li
and co-workers synthesized N-acylamidines 173.3 from N-
sulfonyl-1,2,3-triazoles 173.1 and nitrosobenzene derivatives
173.2 in good to high yields (Scheme 173).265 The reaction
involves cycloaddition of azavinyl rhodium carbenoid 173.4
with nitrosobenzene derivative 173.2 followed by rearrange-
ment. The authors proposed two possible paths for the
formation of products. In path A, α-imino rhodium carbenoid
173.4 undergoes [2 + 1] cycloaddition with nitrosobenzene
173.2 to give 1,2-oxaziridine 173.5. Subsequent cleavage of the
N−O bond of 173.5 followed by migration of the imino group
affords the desired product 173.3. In path B, the nucleophilic
oxygen of nitrosobenzene 173.2 attacks rhodium carbenoid
173.4, and subsequent cyclization generates 2,3-dihydro-1,2,3-
oxadiazole 173.6, which rearranges to give diaziridine 173.7.
Then ring opening and migration of the acyl group afford N-
acylamidine 173.3.
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5.7. Miscellaneous enamines in excellent yields with high stereoselectivity.

In 2012, Selander and Fokin reported the Rh-catalyzed Additionally, a two-step synthesis of several (hetero)aryl-
transformation of 1,2,3-triazoles into the corresponding chiral substituted indoles was accomplished through subsequent
sulfinylamidines (Scheme 174).266 It involves an unprecedented cyclization of the arylated enamines.
In 2014, Tang and Shi developed a Rh-catalyzed tandem
Scheme 174. Synthesis of Chiral Sulfinylamidines cycloisomerization of methylenecyclopropanes with azavinyl
carbenes to afford highly functionalized polycyclic N-hetero-
cycles 176.2 of biological importance (Scheme 176).268

Scheme 176. Rh-Catalyzed Tandem Cycloisomerization of

Methylenecyclopropanes

enantioselective intramolecular oxygen transfer from sulfur to According to a plausible mechanism, initially azavinyl carbene
carbon in the presence of a chiral Rh(II)−carboxylate catalyst. 176.3 is converted into unsaturated imine 176.5 by electrophilic
The amino substituent at C5 of the 1,2,3-triazole stabilizes the attack of the methylenecyclopropane through 176.4. Then the
ring-opened isomer preferentially and triggers its facile reactivity imine undergoes an intermolecular aza-Diels−Alder reaction to
with the Rh catalyst. Screening of reaction conditions indicated provide the desired polycyclic compound 176.2 with good
Rh2(S-PTAD)4 to be the most efficient catalyst, which afforded stereoselectivity. Experimental data indicated that presence of
the chiral sulfinylamidines in excellent yields with reasonable the strained cyclopropane ring in the substrate is essential to
enantioselectivity. A variety of triazoles underwent the trans- accomplish this tandem reaction.
formation effectively, but the triazole possessing an ortho- Yoo et al. reported the isolation of air-stable azomethine ylides
substituted aryl group at C4 was nearly inactive under the 177.4 via the Rh-catalyzed reaction of pyridines 177.1 and N-
standard reaction conditions. sulfonyl-1,2,3-triazoles 177.3 (Scheme 177).269 The isolated
The Fokin group also demonstrated the synthesis of 2,2-diaryl ylides were successfully utilized in the synthesis of biologically
enamines by arylation of various Rh azavinyl carbenes with active 1,4-diazepine compounds 177.5 through a [5 + 2]
arylboronic acids at room temperature (Scheme 175).267 cycloaddition reaction with activated alkynes 177.2. Eventually,
the multicomponent [5 + 2] cycloaddition reaction was
Scheme 175. Synthesis of Various 2,2-Diaryl Enamines and accomplished in a one-pot manner directly from the triazoles,
Substituted Indoles pyridines, and alkynes.
In 2014, the groups of Lee270 and Murakami271 individually
reported the Rh-catalyzed stereoselective synthesis of cis-
diamino enones 178.3 from 1,2,3-triazoles 178.1 employing
formamides 178.2 as nucleophiles (Scheme 178). A wide variety
of tertiary formamides reacted smoothly with substituted
triazoles to furnish cis-diamino enones in good to excellent
yields in the presence of Rh 2 (OPiv)4 as the catalyst.
Mechanistically, nucleophilic attack of formamide 178.2 on
rhodium carbene 178.4 followed by cyclization leads to the
formation of 2-amino-4-oxazoline derivative 178.5. Subsequent
cleavage of the C−O bond of 178.5 followed by recyclization
gives aziridine intermediate 178.6. Finally, ring opening of
Screening of the reaction conditions emphasized that CaCl2 as aziridine 178.6 and rearrangement afford the desired product
an additive plays a crucial role in the synthesis of arylated 178.3.
enamines through the effective formation of the active arylating At the same time, Yoo and co-workers utilized a similar
species, i.e., the trimeric arylboroxine. Among various Rh(II) strategy for the synthesis of fully substituted enaminones from
complexes, Rh2(S-PTAD)4 emerged as the best-performing N-sulfonyl-1,2,3-triazoles by exploiting tertiary benzamides
catalyst. Numerous arylboronic acids afforded the desired exclusively in the presence of Rh2(esp)4 as the catalyst (Scheme
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Scheme 177. Synthesis of Azomethine Ylides and 1,4-Diazepines

Scheme 178. Rh-Catalyzed Stereoselective Synthesis of cis- Scheme 180. Synthesis of Functionalized β-Amino-α,β-
Diamino Enones unsaturated Ketones

Scheme 181. Synthesis of Various Benzoyl Nitriles

272
179). A wide range of benzamides afforded the desired
enaminones in good to excellent yields with significant

Scheme 179. Synthesis of Fully Substituted Enaminones

regioselectivity. Notably, reduction of the synthesized enami-

nones with NaBH4 led to the formation of sterically less
favorable (Z)-enamides in excellent yields. resulting in a sulfinyl benzoylimine intermediate, and Cope-type
In 2015, Li and co-workers demonstrated the Rh-catalyzed elimination of the sulfinyl group affords the nitrile product
synthesis of functionalized β-amino-α,β-unsaturated ketones exclusively. Additionally, the authors successfully demonstrated
180.3 using 1,2,3-triazoles 180.1 and β-(methylthio)-α,β- the sequential one-pot synthesis of benzoyl nitriles starting from
unsaturated ketones 180.2 (Scheme 180).273 Nucleophilic the corresponding terminal alkynes and sulfonyl azides.
attack of the sulfur of 180.2 on the carbon of azavinyl carbene Li and Zhai reported a Rh-catalyzed dearomative [3 + 2]
180.4 generates sulfur ylide 180.5, and subsequent Michael cycloaddition of indoles triggered by an N-sulfonyl-1,2,3-triazole
addition of the nitrogen leads to the formation of zwitterionic moiety present within the substrates 182.1 (Scheme 182).275
intermediate 180.6. Finally, rearrangement of intermediate This protocol gave access to a wide range of indole alkaloid
180.6 affords the desired unsaturated ketone 180.3. scaffolds 182.3 and 182.4 of biological importance in moderate
Miura and Murakami reported a thermal reaction of 4-(p- to high yields (for more details, see Scheme 201). Initially, six
aminophenyl)-N-sulfonyl-1,2,3-triazoles to furnish benzoyl alkaloid derivatives were prepared from the corresponding
cyanides in up to 90% yield (Scheme 181).274 The reaction indole substrates in the presence of Rh2(Oct)4. However, during
proceeds through intramolecular migration of oxygen from workup the imine resulting from the triazole moiety underwent
sulfur to carbon in the in situ-generated azavinyl carbene, hydrolysis to give stable aldehyde 182.3. To avoid this, before
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Scheme 182. Synthesis of Indole Alkaloid Scaffolds

workup a one-pot reduction of the imine was carried out using formation of the final product 183.2 along with regeneration of
NaBH4, which provided stable secondary sulfonamides 182.4 as the Rh catalyst.
single isomers. In 2016, Yu and co-workers277 demonstrated a Rh-catalyzed
Li and co-workers synthesized 5-iodo-1,2,3,4-tetrahydropyr- tandem reaction of 1,2,3-triazoles 184.1 with salicylaldehydes
idines 183.2 via the Rh-catalyzed tandem reaction of leaving- 184.2 to access 2,5-epoxy-1,4-benzoxazepines 184.3 (Scheme
group-tethered 1,2,3-triazoles 183.1 with sodium iodide 184). Although both Rh2(Oct)4 and Rh2(OPiv)4 were efficient
(Scheme 183).276 Various substituted triazoles reacted
Scheme 184. Synthesis of 2,5-Epoxy-1,4-benzoxazepines
Scheme 183. Synthesis of 5-Iodo-1,2,3,4-tetrahydropyridines

in catalyzing the reaction, Rh2(Oct)4 was chosen as the optimal

catalyst to attain a cost-effective synthetic strategy. Diversely
substituted salicylaldehydes afforded the desired products in
moderate to excellent yields. However, electron-withdrawing
substituents at the ortho or para position of the salicylaldehyde
caused lower yields, probably by decreasing the nucleophilicity
of the hydroxyl group. Product formation occurs through the
formation of [3 + 2] cycloaddition product 184.4 from the
smoothly with NaI in the presence of Rh2(esp)4, leading to aldehyde and rhodium azavinyl carbene. Then sequential ring
the formation of the desired tetrahydropyridine derivatives in opening of 4-oxazoline 184.4, tautomerization, and nucleophilic
low to excellent yields with high functional group tolerance. addition of the hydroxyl group gives the desired product 184.3.
Mechanistically, in path A, alkyl iodide 183.3 is formed through In 2017, Bochet and co-workers278 accomplished the
substitution of OMs with iodide and generates intermediate synthesis of indoles and carbazoles through photolysis of N-
183.4 upon denitrogenation in the presence of the Rh catalyst. aryltriazoles and N-arylbenzotriazoles, respectively (Scheme
Then intramolecular attack of iodine on the carbene carbon 185). In that work, they prepared a library of triazoles that were
affords iodonium ylide 183.5. Finally, cleavage of the C−I bond subjected to UV irradiation for 4 h at 254 nm to obtain the
and intramolecular nucleophilic attack furnish the desired desired indole products. Various trisubstituted triazoles under-
product 183.2. Alternatively, in path B, attack of iodide on in went the transformation, affording moderate to excellent yields.
situ-generated rhodium carbene 183.7 generates intermediate Better results were obtained with triazoles bearing electron-
183.8, and subsequent intramolecular SN2 reaction results in the withdrawing substituents such as ester and cyano groups at C4
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Scheme 185. Photolytic Synthesis of Various Indoles and Scheme 187. Metal-Free Stereospecific Synthesis of (E)-
Carbazoles Monofluoroenamines

Scheme 188. Transannulation of N-Sulfonyl-1,2,3-triazoles

with 2-Hydroxybenzyl Alcohols

and/or C5. Interestingly, photolysis of a regioisomeric mixture

of triazoles furnished single isomers of the corresponding
indoles exclusively.
Xia and Hu reported a Rh-catalyzed multicomponent reaction control experiments, the authors proposed a possible mecha-
employing 1,2,3-triazoles 186.2, C2-substituted indoles 186.1, nism involving attack on the in situ-generated α-imino Rh
and paraformaldehyde (186.3) (Scheme 186).279 In the carbenoid by the o-quinone methide intermediate generated
presence of Rh2(OAc)4, the in situ-generated Rh carbenoid from o-hydroxybenzyl alcohol 188.2 upon elimination of a water
reacts with water to generate amino enol intermediate 186.6. molecule to form a carbonyl ylide intermediate. Subsequent 1,3-
The formed intermediate 186.6 is trapped by vinylimine ion rhodium migration followed by electrocyclization leads to an
186.5, generated from paraformaldehyde and 1,2-disubstituted oxonium intermediate, which upon deprotonation and isomer-
indole 186.1, to afford the desired product 186.4 through 186.7. ization furnishes the desired product 188.3. The potential utility
A broad range of triazoles furnished the corresponding products of this transannulation was explored by the preparation of
in moderate to good yields. Surprisingly, other electrophiles biologically important polyheteroaromatics from benzopyrans.
such as imines, isatin, and aromatic aldehydes could not trap the In 2019, Urabe and co-workers282 prepared sulfonylated
amino enol intermediate. unsaturated piperidines 189.2 via the Rh-catalyzed intra-
Li and co-workers280 reported a metal-free stereospecific molecular cyclization of sulfinate-tethered N-sulfonyl-1,2,3-
synthesis of (E)-monofluoroenamines from 1,2,3-triazoles and triazoles 189.1 (Scheme 189). A wide variety of triazoles
BF3·OEt2 (Scheme 187). Use of TBAF·3H2O as an additive furnished the desired products in good yields. However,
enhanced the yields significantly. Surprisingly, addition of HBF4, substrates containing substituents at the position α to the
which is the source of both fluorine and proton, resulted in a triazole gave significantly decreased yields. According to the
decrease in the yield. Various alkyl- and arylsulfonyl-substituted proposed mechanism, the formation of the observed product
triazoles afforded the desired products in moderate to high was explained through two pathways. In path A, the sulfur atom
yields. The applicability of this protocol was examined in the of the sulfinate reacts with the carbene, resulting in the
synthesis of various fluorine-containing compounds by accom- formation of zwitterionic intermediate 189.4 or 189.5, and
plishing several transformations such as a C−N coupling subsequent intramolecular alkylation of the nitrogen atom gives
reaction, an intramolecular SN2 reaction, and a Michael addition the final product 189.2. In path B, alkylation of the sulfonamide
reaction of the resulting fluorinated products. with the sulfinate generates 189.7, and addition of the released
In 2018, Anbarasan and co-workers281 reported the rhodium- sulfinate anion to rhodium carbenoid 189.8 furnishes the final
catalyzed denitrogenative transannulation of N-sulfonyl-1,2,3- product 189.2.
triazoles 188.1 with 2-hydroxybenzyl alcohols 188.2 to form Beier and co-workers283 accomplished the stereoselective
benzopyrans 188.3 (Scheme 188). On the basis of various synthesis of (Z)-β-enamido triflates or fluorosulfonates from N-

Scheme 186. Multicomponent Reaction of 1,2,3-Triazoles, Indoles, and Paraformaldehyde

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Scheme 189. Synthesis of Sulfonylated Unsaturated Scheme 191. Synthesis of α-Amino Ketones
Piperidines

well-tolerated, but tosyl-substituted triazoles were most efficient

under the standard reaction conditions. Notably, a triazole with
an ortho-substituted phenyl group at C4 could not afford the
desired product, in contrast to its meta- and para-substituted
isomers.
Hong and co-workers285 reported an efficient synthesis of
amidine-based fluorophores from carboxaldehyde-attached
triazoles and arylamines via a 6π electrocyclic ring closure
(Scheme 192). Various catalysts such as Cu-, Pd-, and Rh-based

Scheme 192. Synthesis of Amidine-Based Fluorophores

fluoroalkyltriazoles in the presence of triflic acid or fluorosul-

fonic acid, respectively (Scheme 190). An initial study revealed

Scheme 190. Stereoselective Synthesis of (Z)-β-Enamido

Triflates and Fluorosulfonates

catalysts were examined for the reaction, but only low to

moderate yields were obtained. Delightfully, a remarkable
enhancement in yield was observed in the absence of a catalyst.
A wide variety of arylamines reacted smoothly to furnish the
corresponding cyclic amidines in good to excellent yields with
high functional group tolerance. Besides, some other amines
that when R2 = F, decomposition of the product occurred during such as naphthylamine, 2-aminopyridine, and phenylhydrazine
aqueous workup as a result of the hydrolytic instability of the also afforded the desired products in moderate yields.
NHCF3 moiety in the resulting enamine. As a consequence, a Very recently, Dawande and co-workers286 developed a Rh-
longer-chain perfluoroalkyl group was introduced, which catalyzed domino synthesis of azepino-fused diindoles 193.3
stabilized the product in the form of an enamide through HF from isatin-tethered 1,2,3-triazoles 193.1 and indoles 193.2
elimination from the enamine followed by hydrolysis. (Scheme 193). Various diindoles were synthesized in good to
Experimental data indicated that the reaction proceeds at high yields. Mechanistically, the in situ-generated Rh azavinyl
ambient temperature in the presence of an electron-rich aryl carbene undergoes an intramolecular carbonyl insertion
group in the substrate, whereas in the case of an electron-poor reaction to give carbonyl ylide 193.4. The 1,3-dipolar cyclo-
aryl group, the reaction temperature needs to be raised to 40−60 addition reaction of the resulting carbonyl ylide 193.4 with
°C. Furthermore, the synthetic utility of this method was indole 193.2 affords the adduct 193.5. Then sequential
demonstrated through versatile transformations of vinyl semipinacol rearrangement/ring expansion/oxidation of inter-
sulfonates, including Pd-catalyzed cross-coupling reactions mediate 193.5 affords the desired product 193.3.
such as Suzuki and Sonogashira coupling as well as Pd-catalyzed Kotovshchikov et al.287 demonstrated the efficient synthesis of
alkylation with diethylzinc. thio-substituted benzoxazoles 194.3 via inexpensive copper-
Li and co-workers developed a synthesis of α-amino ketones catalyzed coupling of 5-iodotriazoles 194.1 with thiols (Scheme
from N-sulfonyl-1,2,3-triazoles that involves an intramolecular 194). The readily available complex Cu(Ph3P)3Br was found to
oxygen transfer mechanism (Scheme 191).284 The synthesis was be the optimal catalyst, providing the highest yields with trace
accomplished successfully in the presence of a Rh catalyst such amounts of byproduct formation. A variety of heterocyclic thiols,
as Rh2(OPiv)4 and N-fluorobenzenesulfonimide (NFSI). including thiols with azole groups such as imidazole, 1,2,4-
Absence of NFSI or replacement of NFSI with PIDA, DMP, triazole, tetrazole, oxadiazole, and thiadiazole moieties and
DDQ, or Selectfluor led to decomposition of the triazole azine-derived thiols, reacted efficiently with diversely substituted
without yielding the desired products. During examination of iodotriazoles to furnish the desired products in yields of up to
the substrate scope, it was found that bulky sulfonyl groups were 91%. Interestingly, a selective SH insertion was observed in the
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Scheme 193. Rh-Catalyzed Domino Synthesis of Azepino-Fused Diindoles

Scheme 194. Synthesis of Thiosubstituted Benzoxazoles

Figure 3. Representative examples of natural products and related

scaffolds.

strategy (Scheme 195). At first, allenyl alkyne 195.2 was

prepared from the known alkyne 195.1 in six steps as a mixture
of diastereomers. Next, treatment of the allenyl alkyne with
presence of free NH groups. Herein, iodotriazole 194.4 having a CuTC followed by rhodium octanoate afforded pyrrole 195.3,
hydroxymethyl group at C4 exhibited an unexpected reactivity, which subsequently afforded deprotected pyrrole 195.4 upon
resulting in the formation of product 194.6 exclusively. The OH treatment with LiAlH4. Finally, condensation of pyrrole 195.4
group of the initially formed compound 194.7 readily undergoes
facile substitution due to anchimeric assistance of the azahetero- Scheme 195. Enantioselective Synthesis of (R)-
cycle, providing cationic intermediate 194.8. Finally, nucleo- Cycloprodigiosin
philic ring opening of 194.8 furnishes the final product 194.6.
5.8. Applications in Total Syntheses of Natural Products
As shown by the above discussion, it is worth mentioning that
denitrogenative transformations of various triazoles have
emerged as highly efficient tools for the synthesis of a diverse
range of complex organic molecules. Often, these synthesized
molecules have appeared as key intermediates or precursors of
biologically important natural products (Figure 3).12 Hence,
several research groups have explored the synthetic utility of
triazoles as diazo surrogates in total synthesis as well as structural
modification of various natural products and drug molecules.
In 2013, Schultz and Sarpong reported the synthesis of 3,4-
fused pyrroles from allenyl alkynes (Scheme 45).105 Impor-
tantly, they accomplished the first enantioselective synthesis of
the natural product (R)-cycloprodigiosin (195.6) from the
corresponding chiral alkyne 195.1 by applying their developed
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with 195.5 furnished the desired (R)-cycloprodigiosin in 71% Recently, Li and co-workers290 developed a Rh-catalyzed [4 +
yield. 3] cyclization of triazoles with various indole derivatives. They
In 2014, Miura and Murakami disclosed an intramolecular [3 exploited this strategy in the total synthesis of the azepinoindole
+ 2]-annulation of α-imino carbenoids with aryl rings to obtain alkaloid (±)-aurantioclavine (198.6) in just four steps (Scheme
3,4-fused indole skeletons (Scheme 69).130 This strategy was 198). Reduction of the double bond in 198.3, which was readily
utilized in the synthesis of Uhle’s ketone (196.3), which has obtained from triazole 198.2 and indole 198.1, followed by
been often utilized in the synthesis of various ergot alkaloids hydrazinolysis of phthalimide produced compound 198.4 in one
(Scheme 196). Tricyclic compound 196.2 was synthesized from step using N2H4·H2O. Finally, removal of the amino and tosyl
groups afforded the desired product 198.6.
Scheme 196. Synthesis of Uhle’s Ketone In 2014, Yang and co-workers reported the stereoselective
synthesis of oxaspirocycles from N-sulfonyl-1,2,3-triazoles
(Scheme 149).235 They utilized this strategy in the total
synthesis of two biologically active natural products, (±)-tuber-
ostemospiroline (199.5) and (±)-stemona-lactam R (199.6).
Oxaspirocycle 199.3 obtained from simple 4-substituted triazole
199.1 affords lactone 199.4 in five steps (Scheme 199). Further
methylation of the lactone produces (±)-tuberostemospiroline,
which in turn furnishes (±)-stemona-lactam R in three steps
through functional group interconversion.
arene-tethered triazole 196.1 and produced a ketone upon Subsequently, Pan and Xu reported the synthesis of
treatment with TBAF followed by MnO2. Finally, Uhle’s ketone azabicyclo[4.1.0]/[5.1.0]carboxaldehydes via intramolecular
was obtained through tosyl deprotection with KOH. Rh-catalyzed denitrogenative cyclopropanation of N-allyl- or
Subsequently, Luo and co-workers288 further explored the N-homoallyl-tethered triazoles (Scheme 29).82 In that work,
efficiency of this strategy in the synthesis of the ergot alkaloid they demonstrated the synthesis of the antidepression agent
(+)-lysergol (197.7) and its analogues starting from chiral GSK1360707 (Scheme 200). Triazole 200.3 was obtained from
homopropargylic alcohol 197.1 (Scheme 197). At first, boronic acid 200.1 in four steps and subsequently afforded the
dihydropyrrole 197.2 was synthesized through TBS protection GSK1360707 skeleton 200.6 under standard reaction con-
and subsequent silver-catalyzed cyclization of chiral alcohol ditions in one pot.
197.1 prepared from (R)-Garner’s aldehyde. Then cyclo- In 2016, Li and Zhai reported a Rh-catalyzed dearomative [3
propanation, ring opening of the gem-dibromocyclopropane, + 2] cycloaddition of indoles triggered by an N-sulfonyl-1,2,3-
and a nucleophilic addition process produced tetrahydropyr- triazole moiety (Scheme 182).275 This method was applied to
idine 197.4. Next, alkyne 197.5 was synthesized from 197.4 via the synthesis of various alkaloid derivatives. For example, the
Suzuki coupling and Seyferth−Gilbert homologation. Subse- synthesis of vindoline analogue 201.4 was accomplished in six
quent copper-catalyzed [3 + 2] cycloaddition of 197.5 with tosyl steps from tryptamine derivative 201.1 (Scheme 201).
azide followed by rhodium-catalyzed intramolecular dearoma- Recently, Houk and Li developed the synthesis of bridged
tive [3 + 2] transannulation gave product 197.6. Finally, medium-sized polycyclic ring systems through the intra-
(+)-lysergol was obtained after two steps of protecting group molecular [3 + 2] cycloaddition of triazoles with unactivated
manipulations. Furthermore, the syntheses of (−)-isolysergol alkene moieties.291 They demonstrated the synthetic utility of
and (+)-13-fluorolysergol were also accomplished. Later, Cao this strategy by accomplishing the first asymmetric total
and co-workers289 reported the synthesis of the ergot alkaloid synthesis of nakafuran-8 (202.8) (Scheme 202). First,
(−)-chanoclavine I and an oxygen-substituted ergoline deriva- compound 202.3 was obtained from readily available alkyne
tive using a similar strategy. compound 202.1 and aldehyde 202.2 through an aldol reaction

Scheme 197. Synthesis of (+)-Lysergol

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Scheme 198. Synthesis of (±)-Aurantioclavine

Scheme 199. Synthesis of (±)-Tuberostemospiroline and (±)-Stemona-lactam R

Scheme 200. Synthesis of the Antidepression Agent GSK1360707

followed by various functionalizations in four steps. Next, the compound 202.7. Finally, treatment of compound 202.7 with
alkyne in 202.3 reacted with tosyl azide to afford triazole DIBAL-H furnished the desired product 202.8 in 65% yield.
derivative 202.4. Then [3 + 2] cycloaddition of triazole 202.4 In summary, suitably substituted triazoles have seen
followed by hydrolysis and reduction in one pot produced exponential growth as surrogates of diazo (viz., α-diazoimines)
compound 202.5, which after a series of reactions provided that offer a number of denitrogenative transformations in the
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Scheme 201. Synthesis of a Vindoline Analogue

Scheme 202. Asymmetric Total Synthesis of Nakafuran-8

presence of transition metal catalysts. For instance, trans- 6. DENITROGENATIVE TRANSANNULATIONS OF

annulation of triazoles with a diverse range of coupling partners THIADIAZOLES
such as alkynes, nitriles, heterocycles, etc. in both inter- and Similar to N-sulfonyl-1,2,3-triazoles, recently thiadiazoles were
intramolecular fashion has furnished a large class of nitrogen- also shown to undergo ring−chain isomerism to afford thiavinyl
based heterocyclic systems of high importance. Insertion of metal carbenes in the presence of suitable metal catalysts. In
metal carbenoids into various nonpolar bonds such as C−H 2016, Kurandina and Gevorgyan first demonstrated the
bonds and polar bonds such as N−H and O−H bonds has also synthesis of multisubstituted thiophenes 203.3 through the
been successfully demonstrated. Interestingly, denitrogenative rhodium-catalyzed denitrogenative transannulation of 1,2,3-
thiadiazoles 203.1 with alkynes 203.2 under mild reaction
transformations of triazoles that involve various rearrangement
conditions (Scheme 203).59 Various 1,2,3-thiadiazoles under-
reactions leading to the formation of some unprecedented went the transannulation, providing good to excellent yields
products have been documented recently. Most of these with high regioselectivity (ratio of regioisomers up to >20:1).
rearrangement reactions involve the formation of azadiene and The transformation proceeds through the formation of Rh
ylide intermediates. Importantly, these transformations facilitate thiavinyl carbene 203.4, which is analogous to the previously
stereoselective access to various complex structural motifs of mentioned Rh azavinyl and oxavinyl carbenes. According to the
biological importance. As a consequence, utilizing these proposed mechanism, the denitrogenative reaction of 1,2,3-
denitrogenative transformations as key step, total syntheses of thiadiazole 203.1 with the Rh catalyst generates carbene species
some representative natural products and related scaffolds have 203.4, which can undergo a [2 + 1] cycloaddition (path A) or a
[3 + 2] cycloaddition (path B) with the alkyne to form 203.5 or
also been successfully accomplished. However, most of these
203.7, respectively. Intermediate 203.7 can also be generated
transformations are rather limited to N-sulfonyl-1,2,3-triazoles through nucleophilic attack of the alkyne on the carbene
and rhodium carboxylate-based catalysts. This opens wide space followed by cyclization (path C). Finally, the thiophene is
for future developments and to further widen the scope and find obtained through either cycloisomerization of 203.5 or
applications in other fields. elimination of Rh from intermediate 203.7.
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Scheme 203. Transannulation of 1,2,3-Thiadiazoles with Scheme 205. Synthesis of Dihydrothiophenes and Thiophene
Alkynes Derivatives

phenes were obtained in good to excellent yields with very high

regioselectivity and wide functional group compatibility. In
contrast to the alkynes, here the substituents were exclusively
introduced at the 4-position of the dihydrothiophene ring
instead of the 5-position. Additionally, a one-pot regioselective
synthesis of thiophenes 205.4 was also demonstrated via a
tandem Rh-catalyzed transannulation of thiadiazoles 205.1 with
alkenes 205.2 followed by oxidation with DDQ. Along with
aliphatic alkenes, several styrenes afforded the desired
regioselective thiophenes in high yields ranging from 75 to
96%. Treatment of thiadiazole 205.5 with homoallyl alcohol
Subsequently, Lee and co-workers reported the Rh-catalyzed 205.6, subsequent heating of the reaction mixture for 12 h, and
transannulation of 1,2,3-thiadiazoles with various alkyl, aryl, and treatment with DDQ led to the formation of the product 205.7
heteroaryl nitriles to afford isothiazoles in excellent yields via successive transannulation, lactonization, and oxidation.
(Scheme 204).292 Herein, the unexpected formation of In 2017, Lee and co-workers reported the synthesis of 5,n-
fused bicyclic thiophenes through the Rh-catalyzed intra-
Scheme 204. Transannulation of 1,2,3-Thiadiazoles with molecular transannulation of alkynyl thiadiazoles (Scheme
Nitriles 206).294 A wide range of alkynyl thiadiazoles possessing a

Scheme 206. Synthesis of 5,n-Fused Bicyclic Thiophenes

isothiazole instead of thiazole indicated that the α-thiavinyl

carbene acts as an umpolung 1,3-dipole equivalent, in contrast to
its transannulation with alkynes, i.e., the carbene carbon is
nucleophilic and the α-thiavinyl sulfur is electrophilic in nature. variety of linkers (e.g., esters, amides, or ethers) between the
A mechanism similar to that of the reaction with alkynes was alkynyl group and the thiadiazole ring underwent trans-
proposed. The synthesis of pentaoligomeric arylene compounds annulation to afford diverse fused thiophenes in good to
possessing three benzene rings and two thiazole rings was excellent yields under mild reaction conditions and a shorter
successfully accomplished in good yields by the use of this reaction time of 30 min. Additionally, this method was applied to
strategy. the synthesis of spirocyclic fused thiophenes of biological
Later, the same group described the synthesis of dihydro- importance.
thiophenes 205.3 from 1,2,3-thiadiazoles 205.1 and alkenes Subsequently, the same group demonstrated an intra-
205.2 (Scheme 205).293 Various aliphatic, aromatic, and molecular Rh-catalyzed denitrogenative transannulation of
heteroaromatic alkenes effectively participated in the trans- cyanothiadiazoles to accomplish the synthesis of various bicyclic
annulation of thiadiazoles. Diversely substituted dihydrothio- isothiazoles under mild reaction conditions (Scheme 207).295
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Numerous bi-, tri-, and tetracyclic isothiazoles were synthesized Scheme 209. Synthesis of Various 4H-Thiopyran-4-ones and
in high yields from various cyanothiadiazoles containing ester, 2,3-Dihydro-4H-thiopyran-4-ones
amide, or ether as a linker.

Scheme 207. Synthesis of Various Bicyclic Isothiazoles

Recently, Nishibayashi and Nakajima reported the synthesis

of 1,3-thiophospholes through Rh-catalyzed transannulation of
thiadiazoles with phosphaalkynes (Scheme 208).296 A variety of

Scheme 208. Rh-Catalyzed Synthesis of 1,3-Thiophospholes

obtained through migratory insertion of the hydrido ligand to

the carbenic center. Finally, reductive elimination followed by 6-
endo-trig/dig cyclization furnishes the desired product 209.6.
Additionally, this strategy has been utilized in structural
modification of estrone.
In summary, thiadiazoles, which are analogues of triazoles
containing a sulfur atom at the 1-position, have recently been
identified as potential surrogates for diazo compounds and offer
access to α-diazo thiocarbonyl compounds. Recently, a few
phosphaalkynes reacted with thiadiazoles to afford diverse 1,3- examples of transannulations of thiadiazoles with various
thiophospholes in excellent yields. During screening of the coupling partners such as alkynes, nitriles, phosphaalkynes,
reaction conditions, 1,3-bis(dicyclohexylphosphino)propane etc. have been reported. However, their efficiency in other types
(dcypp) emerged as the optimal ligand. Notably, as in previously of denitrogenative transformations has not yet been explored.
reported transformations, the absence of an ester group at the 4-
position of thiadiazole did not afford the corresponding product 7. DENITROGENATIVE TRANSFORMATIONS OF
at all. PYRIDOTRIAZOLES
In 2019, Yang and Xu developed the Rh-catalyzed synthesis of
As mentioned earlier, the group of Gevorgyan first disclosed the
4H-thiopyran-4-ones and 2,3-dihydro-4H-thiopyran-4-ones via
reactivity of pyridotriazoles in Si−H insertion reactions via
the formation of thioketone intermediates through 1,1-hydro-
generation of the corresponding azavinyl Rh carbenoid (section
acylation of thiadiazoles with alkynyl and alkenyl aldehydes
2). Thereafter, a wide variety of pyridotriazoles, have been
(Scheme 209).297 Optimization of the reaction conditions
synthesized and their reactivity has been explored in various
indicated that the addition of AgSbF6 provided better results
denitrogenative transformations to access diverse polycyclic
under the standard conditions. During substrate screening, it
compounds, which are discussed in this section.
was observed that the efficiency of the transformation is highly
influenced by steric factors, as aldehydes containing bulky 7.1. Transannulations
groups provided significantly lower yields. Importantly, alkenyl For the first time, in 2007 Chuprakov and Gevorgyan developed
aldehydes appeared to be more efficient than alkynyl aldehydes a regiodivergent synthesis of 1,2- and 1,3-disubstituted
even in the absence of the silver salt. Mechanistically, oxidative indolizines through the rearrangement of 3-(2-pyridyl)-
addition of Rh(I) to aldehyde 209.5 generates hydride cyclopropenes, which were generated from transannulation of
intermediate 209.7, which reacts with thiadiazole 209.4 to pyridotriazoles and alkynes in the presence of a Rh(II) catalyst
give carbene complex 209.8. Next, intermediate 209.9 is (Scheme 210).298 These cyclopropenes could undergo a
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Scheme 210. Regiodivergent Synthesis of 1,2- and 1,3- reaction conditions to afford diverse multisubstituted indoli-
Disubstituted Indolizines zines in good yields.
Subsequently, they expanded the application of this trans-
annulation strategy for synthesis of polycyclic indolizines 212.2
via Cu-catalyzed intramolecular transannulation of pyridotria-
zoles 212.1 (Scheme 212).300 Various tri-, tetra-, and
pentacyclic indolizines were synthesized in good yields from
the corresponding pyridotriazoles tethered with terminal
alkynes. It was found that the reaction could also be catalyzed
by Lewis acids such as In(OTf)3 and triisopropylsilyl triflate
(TIPSOTf). According to the Lewis acid mechanism,
intermediate 212.5 could be generated through metalation of
diazo form 212.4 and could subsequently undergo denitroge-
native cyclization to give cationic intermediate 212.6. Finally,
cyclization followed by metal loss would furnish the desired
product 212.3. Alternatively, intermediate 212.7 could be
formed through nucleophilic attack of the diazo carbon on the
Lewis acid-activated triple bond, after which denitrogenation,
aza-Nazarov cyclization, and metal loss would afford the
indolizine product 212.3.
In 2016, Adimurthy and co-workers reported the copper-
catalyzed transannulation of pyridotriazoles 213.1 with benzyl-
amines 213.2 and α-amino acids 213.4 under aerobic conditions
(Scheme 213).301 Diversely substituted benzylamines reacted
with pyridotriazoles to afford imidazopyridines 213.3 in good to
excellent yields. Additionally, several α-amino acids also led to
imidazopyridine derivatives through decarboxylative oxidative
cyclization in high yields. Mechanistically, α-imino diazo
compound 213.5 reacts with the copper catalyst to generate
carbene intermediate 213.6. Migratory insertion of the benzyl-
regioselective rearrangement in the presence of either a Rh(I) or amine at the carbene carbon gives intermediate 213.7, which
Cu(I) catalyst to afford 1,3- or 1,2-disubstituted indolizines, upon oxidative dehydrogenation followed by a single electron
respectively. A variety of indolizines were synthesized in good to transfer (SET) process produces 213.9−213.11. Finally,
excellent yields with high regioselectivity. cyclization of 213.11 and subsequent aromatization furnishes
The previously reported transannulation of pyridotriazoles the desired product 213.3.
was dependent on expensive Rh catalysts. Besides, the presence Subsequently, the same group demonstrated the Lewis acid-
of halogen substitution at C7 and an ester group at C3 of the catalyzed transannulation of pyridotriazoles 214.1 with nitriles
triazole as an activating group were essential for the sufficient 214.3 in the presence of BF3·OEt2 catalyst in a dichloroben-
formation of the ring-opened isomer under the standard zene/dichloroethane mixture (Scheme 214).302 Various pyr-
reaction conditions. Overcoming these limitations, the same idotriazoles underwent the transformation with aromatic as well
group demonstrated an efficient Cu-catalyzed transannulation of as aliphatic nitriles, furnishing the corresponding imidazopyr-
unactivated pyridotriazoles with terminal alkynes to afford idines in good to excellent yields under metal-free conditions.
indolizines (Scheme 211).299 Notably, in contrast to previous Iminodiazo 214.2 generates intermediates 214.5−214.6 upon
methods, along with aryl acetylenes several aliphatic and reaction with BF3·OEt2. Intermediate 214.6 can undergo [3 + 2]
heteroaromatic alkynes reacted smoothly under identical cycloaddition to form 214.7, which upon denitrogenation
followed by elimination of BF3 gives the desired product 214.4
Scheme 211. Transannulation of Unactivated Pyridotriazoles (path A). Alternatively, nucleophilic substitution of 214.6 with
with Terminal Alkynes the nitrile leads to the formation of 214.8, which upon
subsequent cyclization affords the desired product (path B).
Recently, they further extended their study on trans-
annulation of pyridotriazoles 215.1 to accomplish the synthesis
of pyridoindoles 215.3 in the presence of In(OTf)3 as the
catalyst (Scheme 215).303 During the screening of reaction
conditions, it was observed that the use of a stoichiometric
amount of trifluoroacetic acid as an additive significantly
improved the yield. Various arenes such as 2-methoxynaph-
thalene, anthracene, 9-methylanthracene, and 1,3,5-trimethox-
ybenzene reacted smoothly with different pyridotriazoles to
afford the desired pyridoindoles in good to high yields.
According to a plausible mechanism, the indium carbene
generated upon the reaction of pyridotriazole 215.1 with indium
triflate undergoes insertion with 215.2 to produce aza-Nazarov-
type intermediate 215.4. Next, elimination of In(OTf)3 from
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Scheme 212. Synthesis of Polycyclic Indolizines

Scheme 213. Copper-Catalyzed Transannulation of Scheme 214. Lewis Acid-Catalyzed Transannulation of

Pyridotriazoles Pyridotriazoles with Nitriles

Scheme 215. In(OTf)3-Catalyzed Synthesis of Pyridoindoles

215.4 forms biscationic pyridinium tertiary carbocation 215.5,

which leads to the formation of 215.6 via intramolecular C−H
amination. Finally, oxidation of intermediate 215.6 affords the
desired product 215.3.
In 2017, Lee and co-workers304 developed a one-pot, three-
step synthesis of 3-alkenyl indolizines 216.3 through trans-
annulation of pyridotriazoles 216.1 with 1,3-dienes 216.2
(Scheme 216). Various pyridotriazoles underwent the trans-
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Scheme 216. One-Pot, Three-Step Synthesis of 3-Alkenyl Scheme 217. Transannulation of In Situ-Generated
Indolizines Pyridotriazoles with Alkynes

annulation sequence with different 1,3-dienes to afford the

corresponding 3-alkenyl indolizines in good to excellent yields.
The three-step sequence includes Rh-catalyzed [2 + 1]
cycloaddition of the in situ-generated azavinyl carbene with
diene to give cyclopropane 216.4, ring expansion in the presence
of the Pd catalyst to afford 216.5, and oxidation of 216.5 with
MnO2.
Chattopadhyay and co-workers305 reported the first radical
transannulation/cyclopropanation of in situ-generated pyrido-
triazoles 217.7 or 2-(diazomethyl)pyridines 217.8 with alkynes
217.2 using Co(TPP) (217.9) as the catalyst (Scheme 217). Scheme 218. Synthesis of Iminothiazolopyridines and
Various substituted (hetero)aryl and alkyl alkynes participated Oxothiazolopyridines
in the transformation to give the corresponding indolizines in
good to excellent yields. Simultaneously, reaction with various
alkenes 217.4 furnished the corresponding substituted cyclo-
propanes 217.5 in high yields with significant diastereoselectiv-
ity. Mechanistically, the in situ-generated 2-(diazomethyl)-
pyridine 217.8, which exists in equilibrium with pyridotriazole
217.7, is activated by Co(III)-based metalloradical catalyst
217.9 to afford α-Co(III)-pyridyl radical intermediate 217.10.
Dong and co-workers demonstrated a Brønsted acid-
Trapping of intermediate 217.10 by the alkyne produces γ-
mediated transannulation of pyridotriazoles 219.1 with 7-
Co(III)-vinyl radical intermediate 217.11. Finally, indolizine
azaindoles 219.2 (Scheme 219).307 Interestingly, along with
217.3 is obtained via a direct radical-rebound step with
TsOH, AIBN, which is usually used as a radical initiator, could
regeneration of the catalyst.
promote the reaction as an oxidizing agent. Diversely substituted
Very recently, Zhang and Gevorgyan306 also reported a similar
pyridoindoles underwent the [3 + 2] annulation with different
kind of Co(TPP)-catalyzed transannulation of pyridotriazoles
pyridotriazoles to produce the corresponding fused polycyclic
with isothiocyanates and xanthate esters to furnish iminothia-
products in good yields. Mechanistically, TsOH stabilizes
zolopyridines and oxothiazolopyridines, respectively (Scheme
intermediate 219.5/219.6, which upon nucleophilic attack by
218). Various isothiocyanates and xanthates underwent the
pyridoindole 216.2 leads to the formation of zwitterionic
transformation with several halogenated and methylated
intermediate 219.7. Cyclization of intermediate 219.7 through
pyridotriazoles to give the corresponding heterocycles in good
elimination of TsOH and subsequent oxidation of 219.8 with
to excellent yields. Notably, isothiocyanates derived from amino
AIBN afforded the desired pyridoindoloindolizines 219.3.
acids also reacted effectively. Of note, xanthate esters were used
as stable precursors of carbonyl sulfide (OCS), which was 7.2. Insertions into X−H Bonds
obtained via Chugaev elimination, to avoid difficulty in handling In 2014, Gevorgyan and co-workers disclosed a Rh-catalyzed
gaseous OCS. N−H insertion reaction of pyridotriazoles that affords 2-
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Scheme 219. Brønsted Acid-Mediated Transannulation of Scheme 221. Synthesis of Various (2-Pyridyl)alkylamines
Pyridotriazoles

with a series of differently substituted anilines to produce the

corresponding (2-pyridyl)alkylamines 221.3 in good to
excellent yields. The reaction exhibited good chemoselectivity
picolylamine derivatives (Scheme 220).308 In the presence of and high functional group tolerance. According to the proposed
Rh2(esp)2 as the catalyst, a wide range of alkyl, aryl, and alkenyl mechanism, diazo compound 221.4 reacts with water to
produce intermediate 221.5. Nucleophilic attack of the bromide
Scheme 220. Synthesis of 2-Picolylamine Derivatives and ion of TBAB on intermediate 221.5 leads to the formation of
Imidazopyridines 221.6. Finally, alkylation of the aniline with 221.6 and
subsequent deprotonation of 221.7 affords picolylamine
product 221.3.
In 2015, Strassert and Glorius developed a Rh(III)-catalyzed
synthetic methodology to access fluorescent scaffolds 222.3 via
C−H activation of 2-arylpyridines 222.2 employing pyrido-
triazoles 222.1 as coupling partners (Scheme 222).310 In

Scheme 222. Synthesis of Fluorescent Scaffolds via C−H

Activation of 2-Arylpyridines

amides, aliphatic/aromatic amines, and enamines reacted

effectively to furnish the corresponding insertion products in
good to excellent yields. Additionally, an efficient one-pot
synthesis of imidazopyridines was accomplished through the
transannulation of pyridotriazoles with primary amines. This
strategy involves Rh-catalyzed N−H insertion of the amide into
the pyridyl carbene and subsequent Brønsted acid-catalyzed
cyclization of the insertion product. Several imidazopyridines
bearing alkyl, alkenyl, and aryl substituents were obtained in
high yields.
Recently, Alami and Hamze demonstrated a metal-free
C(sp3)−N bond-forming reaction of pyridotriazoles 221.1
with weakly nucleophilic anilines 221.2 using tetrabutylammo-
nium bromide (TBAB) and water as cocatalysts (Scheme
221).309 Various pyridotriazoles underwent the transformation
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Scheme 223. Synthesis of 1,2-Benzothiazines

presence of a Cp*Rh(III) catalyst, various fused fluorophores then reacts with sulfoximine 223.2 to afford intermediate 223.5.
were obtained in excellent yields. The properties of these derived Intermediate 223.6 is formed through electrophilic C−H bond
fluorophore moieties and their metal complexes were exten- cleavage of 223.5 and then reacts with diazo intermediate 223.7
sively studied to demonstrate their potential uses as metal ion to form 223.8. Next, migratory insertion followed by
sensors. Mechanistically, cationic rhodacycle 222.4 is generated protoderhodation produces 223.10. Finally, nucleophilic attack
through coordination of substrate 222.1 with the cationic Rh on pyridyl ester 223.10 and subsequent alcohol elimination
catalyst followed by reversible C−H bond cleavage. Then in situ- from 223.11 afford 1,2-benzothiazines 223.3.
generated diazo intermediate 222.5 reacts with 222.4, resulting Later, Dong and co-workers demonstrated a similar kind of
in the formation of RhIII carbene intermediate 222.6 by loss of
cascade C−H activation/cyclization/elimination strategy to
N2. Intermediate 222.6 undergoes migratory insertion to give
new rhodacycle 222.7. Next, intermediate 222.9 is formed synthesize a variety of 3H-indoles from pyridotriazoles and N-
through protodemetalation of 222.7 followed by nucleophilic phenylbenzimidamides (Scheme 224).312 Diverse 3H-indoles
addition to the activated ester carbonyl of 222.8. Finally, the
product 222.3 is obtained through elimination of alcohol with Scheme 224. Synthesis of a Variety of 3H-Indoles
regeneration of the catalyst. Presumably, the chelation of Rh
between the pyridyl and ester groups in intermediate 222.8
facilitates the nucleophilic cyclization by activating the
carboxylate.
Subsequently, Lee and co-workers311 reported the synthesis
of 1,2-benzothiazines 223.3 via a Rh-catalyzed sequential C−H
activation/cyclization/elimination process using pyridotriazoles
223.1 and S-arylsulfoximines 223.2 (Scheme 223). Several
pyridotriazoles underwent the domino reaction with a diverse
range of sulfoximines to produce the desired 1,2-benzthiazines
in high yields. Mechanistically, Rh(III) complex 223.4 is formed
upon treatment of [Cp*Rh(MeCN)3][SbF6]2 with NaOAc and
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Scheme 225. Rh-Catalyzed C−H Insertion of Pyridotriazoles with N-Acetylsulfonamides

were achieved in moderate to excellent yields through Rh- Finally, 1,2 phosphorus migration of intermediate 226.6
catalyzed C−H activation of the N-phenylbenzimidamide followed by protodemetalation of 226.7 furnishes the
followed by cyclization with the pyridotriazole and subsequent phosphorylated pyridine 226.3.
elimination of ammonia. Very recently, Dehaen and co-workers demonstrated both the
Subsequently, Xu and co-workers313 reported the Rh- synthesis and denitrogenative ring opening of triazoloisoquino-
catalyzed sulfonamide-directed C−H insertion of pyridotria- lines under metal-free conditions (Scheme 227).315 Initially, the
zoles with N-acetylsulfonamides (Scheme 225). Various
benzylpyridyl sulfonamides were prepared in low to good yields Scheme 227. Metal-Free Denitrogenative Ring Opening of
via C−H activation of different sulfonamide derivatives. The Triazoloisoquinolines
transformation occurs following a similar kind of reaction
pathway as described by Lee and co-workers.311
In 2018, Shen et al. reported the Cu-catalyzed synthesis of
phosphorylated pyridines 226.3 through C−P coupling of
pyridotriazoles 226.1 with P(O)H compounds 226.2 (Scheme
226).314 Various P(O)H compounds such as H-phosphonates,

Scheme 226. Cu-Catalyzed Synthesis of Phosphorylated

Pyridines

synthesis of several triazoloisoquinolines was accomplished

from aminoacetaldehyde dimethyl acetal, 4-nitrophenyl azide,
and acetophenones in excellent yields. Subsequently, their acid-
mediated ring opening followed by coupling with various
nucleophiles was achieved to afford the corresponding Nu−H
insertion products. Initially, various (hetero)aromatic nucleo-
philes such as veratrole, thiophene, and naphthalenes reacted in
the presence of HBF4 to give mixtures of two regioisomers.
Subsequently, 1-methylindoles, 1H-indoles, and 9H-carbazoles
were also examined and afforded the desired products in
excellent yields in the presence of triflic acid. Interestingly, polar
nucleophiles such as alcohols, thiols, and amines reacted
smoothly to provide high yields of corresponding inserted
products in the presence of triflic acid.
7.3. Miscellaneous
In 2016, Hong and co-workers demonstrated the Pd-catalyzed
denitrogenative arylation of pyridotriazoles 228.1 using aryl
bromides (Scheme 228).316 By means of this arylation strategy,
H-phosphinates, and secondary H-phosphine oxides underwent substitution at either C3 or C7 of the triazolopyridine was
the transformation to afford the desired products in moderate to achieved from same substrate in the presence of different bases.
high yields. Mechanistically, a Cu(I) species is generated by When K2CO3 was used, a variety of heteroaryl bromides 228.2
reduction of Cu(OAc)2 with the P(O)H compound and then such as thiophenes, pyridines, pyrimidines, benzothiazoles, and
reacts with pyridotriazole 226.1 to give carbene species 226.4. chromones as well as aryl bromides easily reacted to form C3-
Subsequently, Cu carbene intermediate 226.6 is formed through arylated products 228.3. However, in the presence of potassium
coordination of 226.5 (the tautomer of 226.2) with 226.4. tert-butoxide, a wide range of C7-arylated products 228.6 were
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Scheme 228. Pd-Catalyzed Denitrogenative Arylation of Scheme 229. Pd-Catalyzed Functionalization of

Pyridotriazoles Pyridotriazoles

Xu and Hu reported the Rh-catalyzed synthesis of pyridyl-

substituted 2,5-dihydrofurans 230.3 through formal [4 + 1]
cycloaddition of pyridotriazoles 230.1 and propargyl alcohols
230.2 (Scheme 230).319 Different 7-substituted pyridotriazoles

Scheme 230. Rh-Catalyzed Synthesis of Pyridyl-Substituted

obtained exclusively in good to excellent yields. Mechanistically,
2,5-Dihydrofurans
organopalladium species 228.7 is generated through oxidative
addition and reacts with diazo compound 228.8 to form Pd−
carbene complex 228.9. Here, Ni could coordinate to the pyridyl
nitrogen of 228.8 to facilitate Pd−carbene formation. Upon
migratory insertion of the aryl group, intermediate 228.9 gives
alkylpalladium species 228.10. Finally, β-hydride elimination of
228.10 affords the desired product 228.11 with regeneration of
the Pd(0) species.
In 2019, Adimurthy et al. reported the sequential Pd-catalyzed
C−H activation and Ag-catalyzed aerobic oxidation of
pyridotriazoles 229.1 with haloarenes (Scheme 229).317
Iodoarenes reacted more efficiently than chloro- and bromoar-
enes under identical reaction conditions. Mechanistically,
according to path A, first Pd-catalyzed C−H activation of
pyridotriazole 229.1 generates intermediate 229.4 through
oxidative addition followed by reductive elimination. Reaction
of 229.5 with the silver salt at 120 °C gives silver carbene
intermediate 229.6. Then addition of oxygen to 229.6 in the
presence of base generates 229.7. Finally, elimination of the Ag
species furnishes the desired product 229.2. Later, in their
extended study, they reported the acyloxylation of pyrido-
triazoles.318 In the presence of acetic anhydride, various 2-oxo-1- underwent the transformation with a diverse range of propargyl
phenyl-1-(pyridin-2-yl)propyl acetates 229.3 were obtained in alcohols bearing substituted aromatic rings to afford the
good yields through the incorporation of both acetyl and acetoxy corresponding 2,5-dihydrofurans in high yields. In the presence
functionality. The formation of 229.3 could be explained of Rh2(esp)2, the propargyl alcohol reacts with the in situ-
following path B. Initially, Pd carbene intermediate 229.8 is generated Rh carbenoid to afford oxonium ylide 230.4/230.5.
formed through the reaction of 229.5 with the Pd catalyst. Then intramolecular nucleophilic attack of the alkyne species
Intermediate 229.9 is obtained through insertion of Ac2O into followed by deprotonation furnishes the desired cyclized
229.8. Finally, intermediate 229.9 furnishes the desired product product 230.3 via [4 + 1] cycloaddition. Surprisingly, in the
229.3 through metal elimination followed by acyl migration. presence of Cu and Pd catalysts and other dirhodium catalysts
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such as Rh2(OAc)4 and Rh2(Oct)4, the formation of a mixture of Scheme 232. Synthesis of 1-(2-Pyridyl)-2-azabuta-1,3-dienes
[2,3]-sigmatropic rearrangement, O−H insertion, and [4 + 1]
cycloaddition products (e.g., 230.7 and 230.8) was observed.
Shen and co-workers demonstrated the metal-free C−C
cross-coupling of pyridotriazoles 231.1 with boronic acids 231.2
to afford secondary and tertiary pyridines 231.3 (Scheme
231).320 Diversely substituted pyridine derivatives were

Scheme 231. Metal-Free C−C Cross-Coupling of

Pyridotriazoles

Scheme 233. Initial Reactivities of Pyridotriazoles

obtained in high yields from various substituted pyridotriazoles

and aliphatic and (hetero)aromatic boronic acids. Mechanisti-
cally, following path A, heating of pyridotriazole 231.1 with the
boronic acid results 2-picolylboronic acid intermediate 231.6 via
boronate intermediate 231.5. Protodeboronation of 231.6 gives
the desired product 231.3. The reaction can also proceed
through the formation of boroxine from the reactive boronic derivative was treated under UV irradiation, ketene 233.11 was
acid following path B. obtained as the major product, probably as a result of
Very recently, Rostovskii and co-workers321 reported a Rh- fragmentation of the resulting carbene 233.9 through
catalyzed reaction of pyridotriazoles with 2H-azirines to produce intermediate 233.10. However, under thermal conditions, 2-
1-(2-pyridyl)-2-azabuta-1,3-dienes, which upon subsequent 1,6- acylpyridine was formed exclusively through decarbonylation of
electrocyclization furnish non-aromatic pyridopyrazine deriva- the resulting ketene followed by rearrangement. These
tives (Scheme 232). This strategy was also utilized for the observations were well-supported by DFT calculations.
efficient synthesis of 1H-pyrazino[1,2-a]quinoline and 4H- Interestingly, the formation of ylide 233.13 was observed by
benzo[4,5]oxazolo[3,2-a]pyrazine. the Tidwell group in 2007 through intramolecular trapping of
In 1986, Wentrup et al. demonstrated the formation of the formed carbene with tethered nitrogen.327
carbenes 233.2 and 233.4 through photolysis of quinoline- and In 1999, Zimmerman and Ignatchenko328 reported a
isoquinoline-based pyridotriazoles 233.1 and 233.3, respec- photolytic cyclopropanation reaction of pyridotriazole with
tively (Scheme 233).322 In that work, the generation of nitrenes cyclopentadiene (Scheme 234). The in situ-generated carbene
through pyrolysis of these pyridotriazoles was also reported. undergoes a [2 + 1] cycloaddition reaction with cyclopentadiene
Later, Tomioka and co-workers323 observed the formation of that results in the formation of a mixture of exo and endo
ketenes 233.8 upon photolysis of 3-methoxycarbonyl-1,2,3- products.
pyridotriazoles 233.5. The formation of ketene was explained in Recently, Gevorgyan and co-workers329 reported transition-
terms of ring opening of the pyridotriazole to give diazo metal-free light-induced transformations of pyridotriazoles
intermediate 233.6, which undergoes a Wolf rearrangement to 235.1, including arylation, X−H insertion, and cyclopropana-
produce ketene 233.8. Similar ketene products were also tion reactions at room temperature (Scheme 235). First, the
obtained by the Wentrup group.324−326 Interestingly, when ester UV−vis spectroscopy of pyridotriazole was investigated, which
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Scheme 234. Photolytic Cyclopropanation of Pyridotriazole other groups have also reported several denitrogenative
with Cyclopentadiene transformations of triazoloindoles, which are discussed in detail
in this section.
8.1. Transannulations
In 2015, Wang and Lu reported the Rh-catalyzed trans-
annulation of triazoloindoles with furans and dihydrofurans to
afford pyridoindoles and tetrahydrofuropyrroloindoles, respec-
tively (Scheme 236).330 Various unsymmetrical furans such as
Scheme 235. Light-Induced Transformations of
Pyridotriazoles Scheme 236. Rh-Catalyzed Transannulation of
Triazoloindoles

showed an absorption in the 390 nm region. On the basis of this

observation, fruitful conversion of pyridotriazoles into corre-
sponding carbene species upon irradiation was anticipated.
Subsequently, irradiation of unactivated 3-aryl-substituted
pyridotriazoles at 390 nm led to the formation of carbene
species 235.2, which were exploited in the above-mentioned
transformations. Arylation of various pyridotriazoles 235.1 with
a wide variety of arylboronic acids 235.3 resulted in the
formation of the corresponding arylated products 235.4 in good
to excellent yields in the presence of K2CO3. Additionally, 3-
arylpyridotriazoles 235.1 underwent O−H, N−H, and CO2−H
insertion reactions with alcohols, amines, and carboxylic acids,
respectively, providing access to a diverse range of heteroatom- methylfurans, ethylfurans, and methylbenzylfurans reacted
substituted benzylpyridines 235.5 in good yields. Furthermore, smoothly to give the corresponding pyridoindoles in low to
cyclopropanation of pyridotriazoles through [2 + 1] cyclo- moderate yields. The reaction involves nucleophilic attack on
addition with numerous alkenes was also accomplished the Rh carbene carbon by the furan, 6π cycloaddition, and
effectively. Although a wide range of heterocyclic compounds subsequent aromatization to afford the desired product.
were obtained under mild reaction conditions utilizing this Furthermore, the reaction of 3-diazoindolin-2-imines with
strategy, its applicability was limited to 3-aryl-substituted dihydrofurans furnished the corresponding transannulated
pyridotriazoles. products in good yields.
In summary, pyridotriazoles were the first triazole derivatives Li and co-workers331 developed the synthesis of indoloiso-
to be employed as surrogates for diazo compounds and opened quinolines through C−C/C−N coupling of imidates with 3-
new avenues in diazo chemistry. Pyridotriazoles were shown to diazoindolin-2-imine using [RhCp*Cl2]2 and AgSbF6 catalysts
undergo diverse transformations, including transannulations, under mild reaction conditions (Scheme 237). However,
insertions, and so on with various coupling partners in the control experiments emphasized that the use of AgSbF6 is not
presence of either metal catalysts, Lewis acids, or light sources. essential to accomplish the synthesis. Diversely substituted aryl
This strategy provides access to a diverse range of pyridine- imidates smoothly underwent the transformation with different
containing heterocycles, which in turn limits the broader diazo compounds to afford substituted indoloisoquinolines in
application of pyridotriazoles. good to excellent yields. Besides, alkyl ester substrates and
several benzophenone imines also afforded the desired products
8. DENITROGENATIVE TRANSFORMATIONS OF efficiently under identical reaction conditions. Here, the
TRIAZOLOINDOLES corresponding alcohols of the alkyl esters were used as solvents
Because of the growing interest of researchers in finding new to avoid transesterification.
alternatives to existing diazo precursors, the group of Lu and Similarly, Volla and co-workers332 reported an efficient
Wang synthesized and explored the reactivity of various Rh(III)-catalyzed denitrogenative [4 + 2] annulation of 3-
triazoloindoles for the first time in 2014. Subsequently, a few diazoindolin-2-imines with N-methoxybenzamides to access
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Scheme 237. Synthesis of Indoloisoquinolines N1 reacted smoothly with various azirines to give the desired
products in good yields. Mechanistically, nucleophilic addition
of azirine 239.2 to the in situ-generated amidino rhodium
carbene gives intermediate 239.4. C−N bond cleavage via path
A followed by 6π electrocyclic ring closure leads to the formation
of 239.6. Here, 239.6 could also be directly obtained from 239.4
following path B. Finally, desulfonylation of 239.6 affords the
desired product.
Later, Novikov and co-workers also reported the synthesis of
pyrazinoindoles under modified reaction conditions (Scheme
240).334 This strategy avoids the use of tBuOK base. A series of

Scheme 240. Synthesis of Pyrazinoindoles

biologically important indolo[2,3-c]isoquinolin-5-ones in the

presence of [Cp*RhCl2]2 and CsOAc in DCE solvent (Scheme
238). A variety of N-methoxybenzamides reacted with diverse

Scheme 238. Synthesis of Indolo[2,3-c]isoquinolin-5-ones

polysubstituted pyrazinoindoles were synthesized from diazo-

indolin-2-imines and azirines in good to excellent yields.
Additionally, a one-pot synthesis of pyrazinoindoles was
accomplished using the corresponding 5-alkoxyisoxazoles as
precursors of azirines.
In 2017, Wang and co-workers reported a one-pot synthesis of
azepinoindoles 241.3 via a [4 + 3] cycloaddition reaction of 3-
diazoindolin-2-imines 241.1 and 1,3 dienes 241.2 (Scheme
241).335 First, iminyl vinyl cyclopropane 241.7 is generated
triazoloindoles to furnish the desired products in moderate to
good yields. Several deuterium exchange and kinetic studies Scheme 241. Synthesis of Azepinoindoles and
were carried out to understand the mechanism. The product Hexahydroindoloindoles
formation involves C−H activation, Rh carbenoid formation,
and migratory insertion followed by cyclization reactions.
Wang and co-workers demonstrated the Rh-catalyzed syn-
thesis of pyrazinoindoles 239.3 from 3-diazoindolin-2-imines
239.1 and azirines 239.2 in cumene solvent (Scheme 239).333
Diazo compounds bearing various alkyl and aryl substituents at

Scheme 239. Rh-Catalyzed Synthesis of Pyrazinoindoles

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from the corresponding rhodium carbene 241.6 and 1,3-diene doles 242.3, respectively. Mechanistically, in situ-generated Rh
241.2 through a [2 + 1] cycloaddition reaction and subsequently carbene 242.4 undergoes a cyclopropanation reaction with
undergoes a thermal aza-Cope rearrangement to afford the indole 242.2 to give spirocyclic intermediate 242.5. Then
desired azepinoindole 241.3. Diversely substituted 3-diazo- diindole intermediate 242.6 is formed through rearrangement of
indolin-2-imines reacted smoothly with several substituted 242.5 and in the presence of DBU base undergoes an
dienes, resulting in the formation of multisubstituted intramolecular SN2 reaction to afford the desired polycyclic
azepinoindoles in moderate to high yields in the presence of product 242.3.
Rh2(Oct)4 as the catalyst and AgOTf as the cocatalyst. In the 8.2. Insertions into X−H/C−X Bonds
presence of cyclic dienes 241.4, hexahydroindoloindoles 241.5
were obtained exclusively through [3 + 2] cycloaddition. This In 2014, Lu and Wang developed a copper-catalyzed tandem
cycloaddition proceeded through [2 + 1] cycloaddition followed process for synthesis of triazoloindoles from alkynes and sulfonyl
by a 1,3-shift to furnish the desired products. Subsequently, Lee azides (Scheme 12).63 A diverse range of 3-diazoindolin-2-
and co-workers reported similar work with enhanced yields imines were synthesized in excellent yields. Subsequently,
using Rh2(OPiv)4 as the catalyst.336 Multisubstituted azepi- syntheses of various pyrrolo[2,3-b]indoles 243.2 and spirocy-
noindoles were obtained in good to excellent yields from the clopropyl iminoindoles 243.3 were accomplished via [3 + 2] and
corresponding substituted 3-diazoindolin-2-imines and various [2 + 1] cycloadditions of the resulting 3-diazoindolin-2-imines
alkyl- and aryl-substituted dienes. However, cyclic 1,3-dienes 243.1 with alkynes and alkenes, respectively (Scheme 243).
were inactive under the standard reaction conditions, in contrast Besides, arylation of 243.1 with various indoles was achieved
to the previous method. using Rh2(Oct)4 as the catalyst, affording the corresponding
Recently, Wang and Lu demonstrated the one-pot synthesis of 3,3′-biindoles 243.4 and 2,3′-biindoles 243.5 in excellent yields.
a series of diindole derivatives using Rh2(Oct)4 and DBU Later, in their extended study, arylation of 3-diazoindolin-2-
(Scheme 242).337 Various substituted 3-(2-bromoethyl)indoles, imines was accomplished employing 2-arylpyridines, 2-phenyl-
pyrimidines, and 1-phenylpyrazoles as coupling partners
Scheme 242. One-Pot Synthesis of Various Diindole (Scheme 244).338 Several 2-phenylpyridines possessing a
Derivatives methyl group at the ortho position of the phenyl ring afforded
the desired biaryl products in low yields, probably as a result of
steric hindrance. However, electron-withdrawing groups
enhanced the yield by increasing the polarity of the ortho C−
H bond. Besides, pyrimidinyl and pyrazolyl substituents were
utilized as directing groups effectively under identical reaction
conditions. Very recently, they accomplished the arylation of 3-
diazoindolin-2-imines with pyrimidinylindoles using [Cp*Co-
(CO)I2] as the catalyst with AgSbF6 as the cocatalyst.339
The same group reported an efficient catalyst-free synthesis of
3-diazoindolin-2-imines and their application in the synthesis of
2,3-diaminoindoles (Scheme 245).64 Indoles containing alkyl,
allyl, and benzyl substituents at N1 and electron-donating
substituents on the phenyl ring reacted smoothly to give the 3-
diazoindolin-2-imines in good yields. However, a significant
drop in the yield was observed in the presence of electron-
withdrawing groups on the phenyl ring. In the case of 1,2-
3-(3-bromopropyl)indoles, and 3-(4-bromobutyl)indoles 242.2 dimethyl- and 1-methyl-2-phenylindoles, the corresponding 3-
efficiently reacted with different 3-diazoindolin-2-imines 242.1 aminoindoles were obtained. Subsequently, 2,3-diaminoindoles
to afford azepinodiindoles, azocinodiindoles, and azoninodiin- were synthesized in good to excellent yields through the reaction

Scheme 243. Denitrogenative Transformations of Triazoloindoles

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Scheme 244. Synthesis of 3-Aryl-2-aminoindoles and 2,3′-Diindoles

Scheme 245. Synthesis of 2,3-Diaminoindoles Scheme 247. Synthesis of Functionalized Indole Derivatives

of the resulting diazoindolin-2-imines and N-alkylanilines using

Rh2(Oct)4.
They also demonstrated a Cu-catalyzed cascade double
arylation of 3-diazoindolin-2-imines with indoles to afford
symmetrical 3,3-diaryl-2-iminindoles (Scheme 246).340 The
reaction regioselectively occurred at the indole 3-position and
furnished a variety of 3,3-diarylindolin-2-imines in remarkably
high yields. Indoles bearing alkyl, allyl, aryl, and benzyl
substituents at N1 afforded the desired products in the presence
of Cu(OTf)2. However, the desired product formation was not
observed in the presence of electron-withdrawing groups such as
Boc or Ts at N1.
Subsequently, they synthesized a series of diverse heterocyclic Scheme 248. Synthesis of Various 3-Phosphinoindoles
compounds from 3-diazoindolin-2-imines (Scheme 247).341 In
the presence of Rh2(Oct)4, various N,N-dialkylanilines 247.2,
N-alkyl-N-allylanilines 247.4, and N-propargyl-N-alkylanilines
247.6 smoothly reacted with 3-diazoindolin-2-imines 247.1,
resulting in the formation of the corresponding 3-aryl-2-
aminoindoles 247.3, 3-allyl-3-amino-2-iminoindolines 247.5,
and tetrahydro-[1,4]diazepino[2,3-b]indoles 247.7, respec-
tively, in moderate to high yields.
In 2017, Jiang and co-workers reported an efficient copper-
catalyzed P−H insertion reaction of 3-diazoindolin-2-imines
with H-phosphine oxides to access various 3-phosphinoindoles
(Scheme 248).342 Their initial attempts to accomplish the
reaction by employing common catalysts used for the

Scheme 246. Synthesis of Symmetrical 3,3-Diaryl-2-iminindoles

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decomposition of triazoles and diazo compounds, including diaminoindoles furnished the corresponding oxidized products,
Rh2(Oct)4, [Ru(p-cymene)Cl2]2, (η3-C3H5)2Pd2Cl2, and Ni- which upon heating at 90 °C in toluene for 36 h afforded the
(cod)2, all failed. Eventually, Cu(CH3CN)4PF6 appeared to be corresponding cyclized 5H-pyrazino-[2,3-b]indole products.
the optimal catalyst in CHCl3. Various alkyl substituents at N1 Subsequently, they demonstrated the syntheses of 3-allyl-3-
of the indole moiety were compatible with the reaction, arylthioindolin-2-imines and 3-allenyl-3-arylthioindolin-2-
providing the desired products in high yields. However, no imines through the Cu-catalyzed cascade reaction of 3-
insertion product was observed in the case of N-unprotected diazoindolin-2-imines with allyl and propargyl arylsulfides,
substrates. Notably, effective insertion was achieved using respectively (Scheme 251).345 Cu(OTf)2 was found to be the
heterocyclic phosphine oxide along with a variety of phosphine
oxides. Furthermore, a chiral version of this P−H insertion was Scheme 251. Cu-Catalyzed Synthesis of 3-Allyl- and 3-
also accomplished using (1R,2S,5R)-(−)-menthoxyphenylphos- Allenyl-3-arylthioindolin-2-imines
phinate, which furnished several chiral 3-methoxyarylphophi-
noindoles in moderate yields with high diastereoselectivity.
Wang and Lu accomplished the synthesis of 2-amino-3-
(arylthio)indoles via the Rh(II)-catalyzed C−S/C−N coupling
between 3-diazoindolin-2-imines and thioesters (Scheme
249).343 In presence of Rh2(tfa)4, 3-diazoindolin-2-imines

Scheme 249. Synthesis of 2-Amino-3-(arylthio)indoles

optimal catalyst for both types of sulfides. Product formation

involves the generation of the sulfonium ylide from the in situ-
generated copper carbene and subsequent [2,3]-sigmatropic
rearrangement.
In 2019, Chen, Pu, and co-workers346 accomplished the
synthesis of spirocyclic indoline imines 252.3 through the [5 +
1] cycloaddition of 3-diazoindolin-2-imines 252.1 with benzo-
[d]isoxazoles 252.2 using Rh2(esp)2 as the catalyst (Scheme
252). A copper(I) catalyst that previously participated

bearing various substituents at C5 of the indole reacted Scheme 252. Synthesis of Spirocyclic Indoline Imines
smoothly with numerous aryl- and alkyl-substituted cyclic and
acyclic thioesters to afford the desired products in moderate to
high yields. Various substituents such as methoxy, methyl ,and
bromo at the 4-position of S-phenyl ethanethioate were well-
tolerated under the optimized reaction conditions. Additionally,
successful oxidation of the resulting 2-amino-3-(arylthio)-
indoles and removal of the N-sulfonyl group were achieved
using mCPBA and SmI2, respectively.
The same group reported the Rh-catalyzed N−H insertion of
3-diazoindolin-2-imines with β-enamino esters for the synthesis
of 2,3-diaminoindoles (Scheme 250).344 A wide variety of
enamino esters underwent the transformation and afforded 2,3-
diaminoindoles in remarkably high yields, showing high
functional group tolerance. Upon treatment with DDQ in
DCM at room temperature for 30 min, the synthesized 2,3-

Scheme 250. Synthesis of 2,3-Diaminoindoles effectively in Cu carbene formation from 3-diazoindolin-2-

imines was completely inert in this reaction. A wide variety of 3-
diazoindolin-2-imines reacted with various functionalized
benzo[d]isoxazoles to furnish the corresponding spiro-benzo-
[e][1,3]oxazineindoline imine products in low to high yields.
Mechanistically, nucleophilic attack of benzo[d]isoxazole 252.2
on the in situ-generated Rh carbene carbon affords adduct 252.4.
Next, the electronic resonance of this species with the assistance
of the adjacent benzenoid ring produces intermediate 252.5.
Imine intermediate 252.6 is generated through subsequent N−
O bond cleavage of 252.5 with regeneration of the Rh catalyst.
Subsequently, rearomatization of the aryl moiety of 252.6 results
in the formation of phenoxy anion species 252.7, which upon
ring closure furnishes the desired product 252.3.
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Recently, Wang and Lu developed a Pd-catalyzed synthesis of afford a wide range of 3-substituted-4H-chromen-4-ones as the
3-haloindol-2-amines 253.3 from 3-diazoindolin-2-imines major products in moderate to high yields. However, no reaction
253.1 and alkyl halides 253.2 under mild reaction conditions occurred with substrates containing an unprotected indole
(Scheme 253).347 Pd2(dba)3 and K2CO3 were found to be the moiety. Pyridodiindoles and pyrazinodiindoles were isolated as
byproducts in some cases, and their photophysical properties,
Scheme 253. Pd-Catalyzed Synthesis of 3-Haloindol-2- such as luminescence, were also disclosed.
amines Very recently, Lu and Wang reported a Au(I)-catalyzed
cascade oxygen transfer/imine exchange process of 3-
diazoindolin-2-imines and nitrones to afford the corresponding
2-iminoindolin-3-ones (Scheme 255).349 The best results were

Scheme 255. Au(I)-Catalyzed Synthesis of 2-Iminoindolin-3-

ones

obtained in the presence of JohnPhosAu(CH3CN)SbF6 as the

most effective reagent combination during screening of the catalyst and AcOH as an additive in chlorobenzene. However,
reaction conditions. Various 3-diazoindolin-2-imines efficiently the addition of CF3CO2H led to a significant decrease in yield.
reacted with a range of alkyl, allyl, and benzyl bromides, allyl Nitrones bearing both electron-donating and -withdrawing
chlorides, alkyl iodides, α-bromo ketones, and carboxylic esters substituents at the 2- or 4-position of the aniline participated in
to furnish diverse 3-haloindol-2-amines in good to excellent the transformation effectively to provide corresponding
yields. Mechanistically, in path A, reaction of diazo compound products in good to excellent yields. Additionally, the resulting
253.1 with the Pd catalyst generates Pd carbene intermediate 2-iminoindolin-3-ones were converted into the corresponding
253.4, which upon reaction with alkyl halide 253.2 affords 2,3-dihydroquinazolin-4(1H)-one derivatives of medicinal
intermediate 253.5. Finally, 253.5 undergoes an intramolecular importance through a Ag(I)-catalyzed reaction with terminal
SN2 reaction to give the desired product 253.3. Alternatively, in alkynes.
path B, attack of the halide ion on the carbene carbon in 253.4 8.3. Miscellaneous
generates intermediate 253.6, which undergoes an intermolec- In 2016, Wang and Lu reported the Rh-catalyzed denitrogena-
ular SN2 reaction with alkyl halide 253.2 to furnish the final tive transformation of 3-diazoindolin-2-imines with aldehydes
product 253.3. and unsaturated aldehydes (Scheme 256).350 In the presence of
Subsequently, the same group reported the Cu(II)-catalyzed Rh2(HFB)4, a diverse range of aldehydes reacted smoothly with
electrophilic cyclization reaction of o-hydroxyarylenaminones several 3-diazoindolin-2-imines to afford the corresponding 2-
with copper carbenes generated from 3-diazoindolin-2-imines aminomethylene-3-oxoindoles in moderate to good yields.
(Scheme 254).348 Various substituted 3-diazoindolin-2-imines Besides, the reaction of 3-diazoindolin-2-imines with acryl-
underwent a smooth transformation with several enaminones to aldehydes using Rh2(tfa)4 furnished pyranoindoles in low yields

Scheme 254. Synthesis of 3-Substitueted 4H-Chromen-4-ones

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Scheme 256. Synthesis of 2-Aminomethylene-3-Oxoindoles and Pyranoindoles

of up to 36%. Unfortunately, no improvement in the yield was Scheme 258. TfOH-Mediated Synthesis of 3-Aryl-2-
observed when the reaction conditions and substrates were aminoindoles
changed.
Subsequently, the same group reported the Pd-catalyzed
arylation of 3-diazoindolin-2-imines 257.1 with arylboronic
acids 257.2 (Scheme 257).351 The best results were obtained

Scheme 257. Pd-Catalyzed Arylation of 3-Diazoindolin-2-

imines

Subsequently, they further expanded the chemistry of 3-

diazoindolin-2-imines and reported a copper-catalyzed cascade
reaction of 3-diazoindolin-2-imines with 2-(phenylamino)-
ethanols that gave access to spiro[indoline-3,2′-oxazolidin]-2-
imines (Scheme 259).353 The cascade involves sequential Cu
carbene generation, N−H insertion, and C−O coupling
reactions. A wide range of diversely substituted spiro[indoline-
3,2′-oxazolidin]-2-imines were synthesized in good yields with
excellent regio- and diastereoselectivity. The sulfonyl group in
the spiro[indoline-3,2′-oxazolidin]-2-imines could be easily
using the combination of Pd(OAc)2, Et3N, and 70% aqueous removed by treatment with NaOH to afford spiro[indoline-
HClO4 at room temperature. A diverse range of arylboronic 3,2′-oxazolidin]-2-ones.
acids reacted with diazo compounds to give the arylated Subsequently, a Cu-catalyzed synthesis of 3-allyl-2-amino-
products in low to high yields, emphasizing the significant indoles from 3-diazoindolines and allyltrimethylsilane was
influence of the substituents present in the substrates. According accomplished by the same group (Scheme 260).354 Among
to the proposed mechanism, Pd carbene 257.4 is generated first various Cu catalysts examined, Cu(OTf)2 was found to be
upon reaction of 257.1 with Pd(OAc)2. Then the aryl group optimal. Various 3-diazoindolin-2-imines underwent smooth
migrates from the arylboronic acid to the carbene carbon in the reaction with allyltrimethylsilane to give the corresponding allyl-
presence of Et3N, producing intermediate 257.6. Finally, 2-aminoindoles in moderate to high yields. However, in the
palladium migration from the C atom to the N atom in 257.6 presence of a methoxy group at the 5-position of the indole
followed by Pd−H exchange furnishes the desired product moiety, a relatively lower yield was obtained, with the formation
257.3. of more byproducts that were difficult to isolate. Additionally,
Very shortly thereafter, they synthesized a series of 3-aryl-2- the resulting 3-allyl-2-aminoindoles were effectively transformed
aminoindoles through the TfOH-mediated reaction between 3- into the corresponding 3-allyl-3-hydroxylindolin-2-imines and
diazoindolin-2-imines and electron-rich arenes (Scheme 3-allyl-3-fluoroindolin-2-imines through simple synthetic ma-
258).352 Various substituted 3-aryl-2-aminoindoles were nipulations.
synthesized in moderate to excellent yields from substituted 3- Recently, Lu and Wang also accomplished the synthesis of
diazoindolin-2-imines and several thiophenes. Substrates with spiro[imidazolidine-4,3′-indolin]-2′-imines 261.3 via Cu-cata-
electron-withdrawing groups occupying the 5-position of the lyzed formal [2 + 2 + 1] cycloaddition of 3-diazoindolin-2-
indole moiety resulted in the formation of the desired products imines 261.1 and triazines 261.2 (Scheme 261).355 In the
in better yields than those with electron-donating groups. presence of the optimal catalyst, CuOTf·(1/2)C6H6, various
Besides, several benzenes and naphthalenes also afforded the 1,3,5-triaryl-1,3,5-triazines and substituted 3-diazoindolin-2-
corresponding arylation products in up to 98% yield. imines were efficiently converted to the corresponding products
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Scheme 259. Synthesis of Spiro[indoline-3,2′-oxazolidin]-2-imines

Scheme 260. Synthesis of Allylated Indole Derivatives undergoes intramolecular nucleophilic addition to afford the
final product 261.3.
To summarize, triazoloindoles, which are fused analogues of
triazoles, offer access to α-diazoimines and also undergo similar
denitrogenative transformations with suitable coupling partners
in the presence of metal catalysts. As a consequence, the
formation of indole-based complex polycyclic compounds has
been achieved with high selectivity. Nonetheless, their potential
application as diazo surrogates in modern organic synthesis is
still underdeveloped.

9. DENITROGENATIVE TRANSFORMATIONS OF
BENZOTRIAZOLES
Although benzotriazoles were exploited as versatile synthetic
auxiliaries in the 1990s, their denitrogenative transformations
remained underdeveloped for decades. Interestingly, benzo-
triazoles undergo denitrogenative transformations through the
formation of quite different intermediates compared with those
of other triazole derivatives. The presence of the highly aromatic
Scheme 261. Cu-Catalyzed Formal Cycloaddition of 3- benzene ring fused with the triazole moiety could be the cause of
Diazoindolin-2-imines and Triazines their different reaction behavior.
9.1. Transannulations
Typically, most of the denitrogenative transformations of
benzotriazoles were achieved through the generation of a
diradical intermediate under photolysis or pyrolysis conditions.
In 1986, Wender and Cooper reported the synthesis of indole
derivatives 262.2 and 262.4 through photolytic denitrogenative
cyclization of N-vinylbenzotriazoles 262.1 and 262.3, respec-
tively (Scheme 262).356 Subsequently, Storr and co-workers
accomplished a similar synthesis by the use of flash vacuum
pyrolysis (FVP).357 On the other hand, Johnson and co-workers
demonstrated the synthesis of spiro-oxindoles 262.7 through
photolysis of N-vinylbenzotriazoles 262.5.358 The product
formation can be explained in terms of the formation of 2-
cyanoindolenines 262.6, which upon hydrolysis afford the
desired oxindoles.
In 1995, Katritzky and co-workers359 reported the synthesis of
quinazoline derivatives 263.4 from the corresponding benzo-
triazoles 263.1 and formamides 263.2 (Scheme 263). The
reaction involves the formation of enamine intermediate 263.3.
in moderate to high yields. According to the proposed They also reported that a similar intermediate 263.6 could be
mechanism, nucleophilic addition of 1,3,5-triazine-derived obtained through lithiation of 1-benzylbenzotriazole 263.5
formaldimine 261.5 to in situ-generated Cu carbene 261.4 followed by addition of benzonitrile. The formed enamine
furnishes ylide 261.6. After Cu(I) elimination, addition of intermediates undergo sequential ring opening, cyclization, and
another formaldimine generates ylide 261.8. Next, 261.8 rearrangement to furnish the quinazoline products 263.7.
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Scheme 262. Synthesis of Indole and Spiro-oxindole reaction time. In 2017, Bochet and co-workers278 utilized the
Derivatives photochemical Graebe−Ullmann reaction of benzotriazoles
265.8 to synthesize a variety of carbazole derivatives. Addition-
ally, they accomplished the first synthesis of the antimalarial
alkaloid clausenawalline D (265.9).
In 2007, Moyano and co-workers reported the synthesis of
dibenzoazepinones 266.2 through FVP of N-(benzoylmethyl)-
benzotriazoles 266.1 (Scheme 266).364 The product formation
involves loss of hydrogen from the initially formed diradical
species 266.4 and subsequent intramolecular cyclization. Upon
an increase in temperature, decarbonylation from the azepinone
leads to the formation of the aromatized product, phenan-
thridine 266.3. One drawback of this reaction is the formation of
a mixture of products under the standard reaction conditions.
In 2009, Nakamura and co-workers reported the Pd-catalyzed
denitrogenative transannulation of N-aroylbenzotriazoles 267.1
with internal alkynes 267.2 to afford multisubstituted indoles
267.3 (Scheme 267).365 This method avoids the formation of a
stoichiometric amount of halogenic acid byproduct and excess
use of base, in contrast to the Larock indole synthesis. Several
benzotriazoles underwent the transannulation with both
symmetrical and unsymmetrical alkynes to afford good to
moderate yields of indole derivatives under mild reaction
Very shortly thereafter, they also demonstrated an efficient
route for the synthesis of ortho-substituted anilines and conditions. The results obtained by screening of the reaction
heterocycles via the generation of o-imino phenyllithium with differently substituted benzotriazoles emphasized that the
intermediate 264.3 (Scheme 264).360 This strategy avoids the electronic character of the aroyl group present on the
use of an excess amount of base and the formation of byproducts benzotriazole nitrogen has a significant influence on the
arising from N-functionalization of the aniline. Intermediate reaction. Generally, substrates with electron-withdrawing
264.3 is formed through deprotonation of compound 264.1 substituents (e.g., CF3, F, Ac) afforded the desired product in
followed by ring opening and can be trapped by a variety of higher yields compared with those having electron-donating
electrophiles such as ketone, nitrile, halide, ester, and imine to groups (e.g., OMe, Me, Ph). However, in some cases,
afford diverse (hetero)cyclic compounds 264.4−264.9. benzotriazoles possessing electron-withdrawing groups decom-
In 2000, Stevens and co-workers accomplished the synthesis posed under the same reaction conditions. According to the
of pentacyclic acridines 265.2 via thermolysis of suitably proposed mechanism, o-arenediazonium species 267.4 is
substituted benzotriazoles 265.1 in diphenyl ether or triglyme generated upon thermolysis of 267.1. Next, oxidative addition
at significantly high temperatures through the Graebe−Ullmann of 267.4 with Pd(0) gives intermediate 267.5. Finally, reaction
reaction (Scheme 265).361,362 Mechanistically, thermolysis of of alkyne 267.2 with 267.5 followed by reductive elimination
265.1 generates diradical intermediate 265.3, which undergoes furnishes the desired product 267.3.
cyclization followed by aromatization to produce intermediate Subsequently, Kim and Kim366 demonstrated that benzo-
265.5. Intermediate 265.5 tautomerizes to the desired product triazoles 268.1 bearing an unsaturated ketone group at N1 can
265.2. In 2006, Vaquero and co-workers reported the synthesis undergo denitrogenative cyclization to afford substituted
of α-carbolines 265.7 through a modified Graebe−Ullmann indoles 268.2 in the presence of n-Bu3SnH and AIBN as a
reaction using microwave irradiation.363 Various substituted radical initiator (Scheme 268). The reaction proceeds through
carbolines were obtained from benzotriazoles 265.6 and azines the formation of β-(benzotriazol-1-yl)allylic O-stannyl ketyl
bearing a leaving group at C2 in improved yields in a shorter radical intermediate 268.5. Its canonical form 268.6 undergoes

Scheme 263. Synthesis of Quinazoline Derivatives

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Scheme 264. Synthesis of Ortho-Substituted Anilines and Various Heterocycles

Scheme 265. Synthesis of Pentacyclic Acridines, α- Scheme 266. Syntheses of Dibenzoazepinones and
Carbolines, and Carbazoles Phenanthridines

Scheme 267. Pd-Catalyzed Transformation of N-

Aroylbenzotriazoles

ring opening through N2 extrusion, and subsequent ring closure

gives cyclized intermediate 268.8. Next, depending upon the
nature of the substituents, two types of indoles are obtained as
major products. Generally, ketyl radical 268.8 abstracts a
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Scheme 268. Synthesis of Various Substituted Indoles + 2 + 2] cycloaddition reaction in the presence of Pd-
(PhCN)2Cl2 as the catalyst. Moreover, the reaction of
benzotriazoles with terminal alkynes led to the formation of o-
aminostyrenes in good yields in the presence of Pd(dppf)2Cl2 as
the catalyst.
In 2013, Tiwari and co-workers developed an efficient two-
step synthesis of glycoconjugate benzothiazoles 270.2 through a
radical-initiated denitrogenative cyclization of benzotriazolyl
methanethiones 270.1 (Scheme 270).368 This methodology

Scheme 270. Intramolecular Denitrogenative Cyclization of

Benzotriazolyl Methanethiones

hydrogen atom and undergoes hydrolysis to give intermediate

alcohol 268.10, which rapidly undergoes oxidative C−C bond
cleavage to furnish compound 268.2 and aldehyde 268.11.
However, for R1 = tBu, the O-stannyl ketyl radical intermediate
268.8 readily extrudes tert-butyl radical to produce 3-alkylidene-
3H-indoline 268.12, which upon hydrolysis generates com-
pound 268.4. gave facile access to a wide range of 2-O-substituted
In 2018, Tang and co-workers367 reported the Pd-catalyzed benzothiazoles in good yields under mild reaction conditions.
synthesis of 5,6-spiro bicycles and naphthalenes from benzo- Mechanistically, when benzotriazolyl methanethione 270.1 is
triazoles and internal alkynes (Scheme 269). The 5,6-spiro treated with n-Bu3SnH and AIBN under heating or microwave
bicyclic products were obtained through a [2 + 2 + 1] irradiation, intermediate 270.3 is generated via the addition of
cycloaddition reaction in the presence of Pd(tfa)4 as the catalyst. stannanyl radical to the thiocarbonyl sulfur atom. Successive
Notably, the spiro product could readily undergo thermal ring addition of hydrogen radical and subsequent β-scission by
expansion to afford the thermodynamically more stable radical cleavage of the benzotriazole ring then afford biradical
naphthalenes. Naphthalenes were also obtained through a [2 intermediate 270.4. Next, elimination of nitrogen followed by
cyclization via thermally induced oxidation leads to the
Scheme 269. Syntheses of 5,6-Spiro Bicycles, Naphthalenes, aromatized benzothiazole products 270.2. Notably, trialkylsillyl
and o-Aminostyrenes radical can also promote the reaction, but one drawback is the
slower decay of the biradical intermediate because of the
presence of the comparatively stronger Si−S bond in place of the
Sn−S bond.
Later, they improved the applicability of this strategy by
conducting the same synthesis under modified reaction
conditions in which a significantly lower amount of toxic n-
Bu3SnH (0.6 equiv instead of 2.2 equiv) was used.369 However,
an excess amount of NaBH4 was required to regenerate the
active reagent n-Bu3SnH in the reaction mixture. Subsequently,
they synthesized benzothiazoles 270.7 from 1-(1-pyrrolidinylth-
ioxomethyl)-1H-benzotriazoles 270.6 in excellent yield.370
In their extended studies, the toxic n-Bu3SnH was replaced
with a metal-free and less toxic radical initiator such as
(TMS)3SiH371,372 or polymethylhydroxysilane (PMHS),373
which provided the benzothiazoles in good to excellent yields
(Scheme 271). Remarkably, PMHS, a cheap waste product of
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the silicon industry, provided a cost-effective, solvent-free, and Scheme 273. Synthesis of Biphenyl Derivatives and
environmentally benign way to accomplish the synthesis. Dihydropyrrolo[3,4-b]indoles

Scheme 271. Synthesis of Benzothiazoles

The same group also reported the Lewis acid-mediated ring

cleavage of N-acylbenzotriazoles 272.1 to give the correspond-
ing benzoxazoles 272.2 (Scheme 272).374 Various aroylbenzo-

Scheme 272. Lewis Acid-Mediated Synthesis of Benzoxazoles

However, scope of this method was limited to internal alkynes

only.
Subsequently, Glorius et al. reported a similar methodology
for the exclusive synthesis of highly regioselective 2-substituted
indoles using the photocatalyst [Ir(ppy)2(dtbbpy)](PF6) and
blue LEDs in DMSO (Scheme 274).377 Various aromatic

Scheme 274. Regioselective Synthesis of 2-Substituted

triazoles reacted smoothly in the presence of anhydrous AlCl3 Indoles
under mild conditions to afford the desired 2-arylbenzoxazoles
in good to excellent yields. This transformation follows an ionic
mechanism in which AlCl3 initiates the reaction by generating
intermediate 272.3 upon reaction with N-acylbenzotriazole
272.1. The traditional Friedel−Crafts product can be obtained
from 272.3 in the case of aliphatic N-acylbenzotriazoles.
However, in the case of aryl N-acylbenzotriazoles, cyclization
via the formation of carbocation intermediates 272.4 and 272.5
with elimination of N2 affords the oxazole product 272.2.
Typically, the diradical species generated upon photolysis or
pyrolysis of benzotriazoles is trapped by the substituent present
at N1 of the triazole ring. Interestingly, it can also be trapped by
the use of a suitable external electrophile. In 1972, during their
study of photolysis of benzotriazoles, Yonezawa and co-
workers375 observed that biphenyl compound 273.2 was formed
as major product from benzotriazole 273.1 in benzene solvent
(Scheme 273). This indicated the trapping of the diradical terminal alkynes selectively participated in transannulation with
species 273.3 with benzene. In 2014, Al-Jalal and co-workers376 N-aroylbenzotriazoles to furnish 2-substituted indoles in good
demonstrated the photolytic denitrogenative transannulation of to high yields. The authors described a mechanism-based
benzotriazoles with acetylenes and maleimides, which afforded luminescence screening method that showcases how a reaction
the corresponding indoles and dihydropyrrolo[3,4-b]indoles, can be optimized and developed by focusing on only one
respectively. Initial extrusion of nitrogen generates a diradical fundamental step of an overall catalytic cycle. This screening first
intermediate that undergoes a cycloaddition reaction with either demonstrated that N-aroylbenzotriazole can act as an oxidative
alkenes or alkynes. Irradiation of benzotriazole 273.5 and quencher in photocatalytic reactions. Eventually, a mechanism
maleimides 273.6 with a 16 W low-pressure mercury arc lamp was proposed on the basis of Stern−Volmer analysis and
afforded the corresponding dihydropyrrolo[3,4-b]indoles 273.7 determination of quantum yields along with other mechanistic
in 19−38% yield along with Michael adducts. Similarly, experiments. Mechanistically, benzotriazole 274.1 generates
irradiation of benzotriazole and internal alkynes led to the radical anion intermediate 274.4 under irradiation. Then
formation of functionally substituted indoles in 31−37% yield. nitrogen extrusion followed by addition of 274.5 to alkyne
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Scheme 275. Synthesis of 6-Aminophenanthridines

274.2 produces intermediate 274.6, which upon oxidation gives Scheme 276. Carbonylative Transformation of
zwitterionic intermediate 274.7. Finally, 274.7 furnishes the Benzotriazoles to Benzoxazinones
desired product 274.3 through cyclization.
In 2015, Ahmed and co-workers developed a functional
group-induced ring-opening of benzotriazoles 275.3 for the
synthesis of 6-aminophenanthridines 275.4 (Scheme 275).378
In the presence of 2-oxoaldehydes 275.1 and secondary amines
275.2, benzotriazoles 275.3 produce the three-component
intermediates 275.5. The enolic form of these intermediates
undergoes oxo-driven nitrogen extrusion, resulting in the
formation of aryl electrophiles 275.6. Then intermediates
275.6 undergo electrophilic cyclization to provide intermediates
275.7, which immediately produce iminium ion intermediates
275.8 upon oxidation with Cu(II). Finally, rearrangement of
intermediates 275.8 and subsequent decarbonylation afford the
corresponding 6-amiophenanthridines 275.4. Various 6-amino-
phenanthridines were obtained in good to excellent yields.
In 2017, Wu et al. reported a dual-catalytic carbonylative
transformation of benzotriazoles 276.1 to afford benzoxazi- to proposed mechanism, oxidative addition of the Pd complex to
nones 276.2 in the presence of PdCl2 and AgOTf catalysts diazonium intermediate 277.7 results in the formation of
(Scheme 276).379 Several benzotriazoles bearing different intermediate 277.8 through nitrogen elimination. Then
electron-donating or -withdrawing groups at the ortho or para insertion of either allene or allenamide 277.2 generates π-allyl
position of the benzotriazole moiety were transformed into complex 277.10, which upon allylic substitution affords the
benzoxazinones in good to excellent yields. Mechanistically, in desired cyclized products with regeneration of the Pd catalyst.
the presence of AgOTf, intermediate 276.3 is formed from the 9.2. Miscellaneous
benzotriazole and undergoes oxidative addition with Pd(0) to In 2015, Shi and co-workers381 demonstrated a ring-opening
give intermediate 276.4. Then CO insertion followed by transformation of N-vinylbenzotriazoles 278.1 using azides as
reductive elimination of the Pd(0) species furnishes the desired radical initiators (Scheme 278). This transformation shows
product 276.2. excellent chemoselectivity depending upon the reagent
Recently, Zhang and co-workers reported the Pd/PC-Phos- combinations, affording quinoxalines 278.2 in the presence of
catalyzed enantioselective denitrogenative transannulation of TMSN3 and nitriles 278.3 in the presence of NaN3. The
benzotriazoles 277.1 with allenes and N-allenamides 277.2 formation of two different products was attributed to the
(Scheme 277).380 Benzotriazoles possessing various functional different basicities of these two azides. According to a plausible
groups such as electron-donating groups (Me, OMe) and mechanism, the formation of quinoxalines could be explained in
halogens (F, Cl, Br) at different positions of the phenyl ring terms of the formation of 278.6 through radical addition to the
afforded the corresponding optically active 3-methyleneindo- azide in the absence of base. However, the mechanism for the
lines in high yields with excellent enantioselectivity. According formation of nitriles was quite unclear. Although radical-
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Scheme 277. Pd/PC-Phos-Catalyzed Enantioselective determining step. Experimental results indicated that the
Synthesis of 3-Methyleneindolines basicity of NaN3 is the main factor for the formation of nitriles.
Experimental data also indicated that 2-triazolyl radical is
reasonably stable. Consequently, path B involving base-
mediated azide denitrogenation followed by radical-promoted
triazole ring opening of 278.11 is more consistent with
experimental data.
Subsequently, Glorius et al. reported three new visible-light-
promoted functionalizations of benzotriazoles 279.1 using the
mechanism-based screening method (Scheme 279).382 This

Scheme 279. Synthesis of Borylated, Alkylated, and Ortho-

Thiolated N-Arylbenzamides

Scheme 278. Denitrogenative Transformation of N-

Vinylbenzotriazoles

method gave facile access to borylated, alkylated, and ortho-

thiolated N-arylbenzamides 279.2−279.4 from the correspond-
ing N-aroylbenzotriazoles 279.1. According to a plausible
mechanism for the alkylation, reductive cleavage of the
benzotriazole ring in 279.1 through a single electron transfer
process in the presence of the Ir photocatalyst generates highly
reactive intermediate 279.5. Nitrogen extrusion followed by
addition to styrene forms stabilized intermediate 279.7, which
furnishes the alkylated product through hydrogen atom transfer
from the radical quencher DIPEA.
Later, Xia and co-workers disclosed a visible-light-induced
denitrogenative phosphorylation of benzotriazoles with phos-
phites in the presence of the photocatalyst [Ir(ppy)2(dtbbpy)]-
(PF6) (Scheme 280).383 This strategy enabled access to diverse
aryl phosphonates in good to excellent yields with high
functional group tolerance. Notably, this reaction worked well
promoted triazole ring opening followed by a 1,5-H shift of on the gram scale also. A plausible mechanism for this
intermediate 278.8 looked very reasonable, path A was unlikely transformation is similar to the one previously reported by
because of the lack of involvement of base in the rate- Glorius et al.382
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Scheme 280. Visible-Light-Induced Denitrogenative Scheme 282. Denitrogenative Suzuki Coupling of

Phosphorylation of Benzotriazoles Benzotriazoles

In 2017, in an attempt to synthesize benzoxazoles through n-

Bu3SnH-promoted transannulation of acylbenzotriazoles 281.1,
the unexpected formation of N-phenylamides 281.2 was
observed by Tiwari and co-workers (Scheme 281).384 Here,

Scheme 281. Synthesis of N-Phenylamides from 10. SUMMARY AND OUTLOOK

Benzotriazoles In summary, the development of novel and elegant synthetic
strategies for the construction of heteroatom-based building
blocks and heterocycles of therapeutic importance is in high
demand in contemporary organic synthesis. This review has
presented a thorough account of denitrogenative functionaliza-
tion of various N-heterocycles that have emerged as efficient
surrogates of diazo compounds. The ring−chain isomerism of
suitably substituted 1,2,3-triazoles and their analogues, includ-
ing thiadiazoles, pyridotriazoles, triazoloindoles, and benzo-
triazoles, to the corresponding diazo compounds facilitates the
generation of a unique class of donor−acceptor metal-
locarbenoids in the presence of various transition metal
catalysts. These in situ-generated metallocarbenoids are
extensively used in the development of diverse selective
transformations, which include transannulations, insertions,
ring opening followed by nitrogen elimination leads to the ylide formation, and rearrangements with a variety of coupling
formation of intermediate 281.5, which undergoes protonation partners such as alkenes, alkynes, nitriles, carbo/heterocycles,
instead of cyclization to afford corresponding amide product X−H/C−X bonds, etc. Although various transition metal
281.2. Various acylbenzotriazoles underwent the transformation catalysts have been examined, rhodium(II) carboxylates have
to furnish a range of amides in high yields. emerged as the most versatile catalysts for ring opening of the N-
Tang and co-workers disclosed a Pd-catalyzed denitrogena- heterocycles and trapping of the resultant diazo compounds.
tive Suzuki coupling and carbonylative Suzuki coupling of Among them, Rh2(Oct)4, Rh2(esp)2, and Rh2(OAc)4 have been
benzotriazoles with arylboronic acids that employs AgBF4 as a found to be best catalysts for most of the transformations
cocatalyst (Scheme 282).385 A diverse range of o-amino- mentioned above. The developed transformations offer access to
substituted biaryl and biaryl ketone derivatives were obtained a wide range of heteroatom-based heterocycles and building
in good to excellent yields. The reaction proceeds through the in blocks in single step that are not available by traditional
situ generation of an o-aminoarenediazonium species. AgBF4 as strategies. Importantly, the use of N-heterocycles as surrogates
an additive plays a crucial role by activating the N1−N2 bond for for diazo compounds features diverse advantages, such as (1) the
ring cleavage through strong coordination with nitrogen. slow release of the diazo compound into the reaction mixture,
To summarize, benzotriazoles are unique in this class because which avoids the requirement of slow addition of traditional
they offer o-aminodiazonium species instead of α-diazoimines, diazo compounds; (2) the ready availability of most of the N-
possibly to gain the aromatic stabilization. Importantly, aryl heterocycles from commercially available starting materials, for
diazonium species have found a special place in organic synthesis instance, the availability of substituted triazoles through CuAAC
as vital synthetic intermediates. Consequently, significant of terminal alkynes and sulfonyl azides; (3) the opportunity to
advancement in denitrogenative transformations of benzotria- tune the reactivity of the metallocarbenoids via appropriate
zoles with different coupling partners in the presence of metal choice of starting materials; and (4) the opportunity to develop
catalysts as well as visible light has been observed in recent times. one-pot reactions through efficient integration of N-heterocycle
Mostly, this strategy facilitates access to various ortho- synthesis and functionalization.
functionalized aniline derivatives and related heterocycles. Despite the exponential growth in denitrogenative trans-
However, its application in the synthesis of natural products formations of various N-heterocycles, there are many questions
and related structural motifs is still in its infancy. that have not yet been answered. For instance, ring-opening
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isomerization of N-heterocycles is highly dominated by the career in the Department of Chemistry at IIT Madras, where currently
electronics of the substituents present. As mentioned earlier, he is a Professor. His research program is focused on the development
mostly rhodium(II) carboxylate catalysts have been found to be of new synthetic strategies employing transition metal catalysis with a
effective for denitrogenative transformations of N-heterocycles. special focus on asymmetric synthesis and their implementation in
These challenges/limitations offer plenty of opportunities to organic synthesis. He is the recipient of the SwarnaJayanti Fellowship of
modern synthetic chemistry for future development through the the Department of Science and Technology (DST), India.
identification of new catalysts and pathways. In addition, the
application of these diazo surrogates in asymmetric trans- ACKNOWLEDGMENTS
formations with proper design of new chiral ligands and metal
catalysts and in the synthesis of complex molecules of diverse We are thankful for the generous financial support from DST-
importance will broaden the scope of denitrogenative Science and Engineering Research Board (DST-SERB), New
functionalization. Considering the recent development of Delhi (Projects SR/S1/OC-48/2012, EMR/2016/003677, and
photocatalysis and electro-organic synthesis, the integration of CRG/2020/004644 and SwarnaJayanti Fellowship SB/SJF/
these approaches with denitrogenative transformations of N- 2020-12/51). M.A. thanks DST for the INSPIRE Fellowship,
heterocycles might bring a new direction to the field. and K.R. thanks IIT Madras for the fellowship.

AUTHOR INFORMATION ABBREVIATIONS

Corresponding Author Ac acetyl
Pazhamalai Anbarasan − Department of Chemistry, Indian acac acetylacetonate
Institute of Technology Madras, Chennai 600 036, India; Ad adamantyl
[Link]/0000-0001-6049-5023; Email: anbarasansp@ Adc 1-adamantanecarboxylate
[Link] AIBN azobis(isobutyronitrile)
Ar aryl
Authors 9-BBN 9-borabicyclo[3.3.1]nonane
Monalisa Akter − Department of Chemistry, Indian Institute of bdpp rac-2,4-bis(diphenylphosphino)pentane
Technology Madras, Chennai 600 036, India Bn benzyl
Kavuri Rupa − Department of Chemistry, Indian Institute of Boc tert-butoxycarbonyl
Technology Madras, Chennai 600 036, India BtH benzotriazole
t
Bu tert-butyl
Complete contact information is available at:
Cbz carboxybenzyl
[Link]
cod cyclooctadiene
CuAAC Cu(I)-catalyzed azide−alkyne cycloaddition
Author Contributions
†
CuTC Cu(I) thiophene-2-carboxylate
M.A. and K.R. contributed equally. Cy cyclohexyl
Notes dba dibenzylideneacetone
The authors declare no competing financial interest. DBU 1,8-diazabicyclo[5.4.0]undec-7-ene
DCB 1,2-dichlorobenzene
Biographies DCM dichloromethane
Monalisa Akter was born in West Bengal, India. She completed her DCE 1,2-dichloroethane
[Link]. in chemistry from Krishnath College (University of Kalyani) in dcypp 1,3-bis(dicyclohexylphosphino)propane
2016 and received her [Link]. (specialization in organic chemistry) from DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
the University of Kalyani, West Bengal in 2018. Currently, she is dF(CF3)ppy 2-(2,4-difluorophenyl)-3-trifluoromethylpyridine
pursuing her Ph.D. as an INSPIRE Fellow at Indian Institute of DFT density functional theory
Technology Madras (IIT Madreas) under the guidance of Prof. DG directing group
Pazhamalai Anbarasan. Her research interests are focused on the DHIQ 4-bromo-1,2-dihydroisoquinoline
development of iron-catalyzed asymmetric organic synthesis. DIBAL-H diisobutylaluminum hydride
DIPEA N,N-diisopropylethylamine
Kavuri Rupa was born in Andhra Pradesh, India. She completed her DMF dimethylformamide
[Link]. at NTR Memorial Degree College (Acharya Nagarjuna DMP Dess−Martin periodinane
University) in 2012 and received her [Link]. (specialization in organic DMS dimethyl sulfide
chemistry) from Dr. B.V. R.I.C.E. College (Andhra University) in 2014. DMSO dimethyl sulfoxide
Currently she is pursuing her Ph.D. under the guidance of Prof. DOSP N-(dodecylbenzenesulfonyl)prolinate
Pazhamalai Anbarasan in the Department of Chemistry at IIT Madras. dpf N,N′-diphenylformamidinate
Her research work focuses on the development of rhodium-catalyzed dppf 1,1′-bis(diphenylphosphino)ferrocene
denitrogenative transformations of N-sulfonyl-1,2,3-triazoles. dtbbpy 4,4′-di-tert-butyl-2,2′-bipyridine
Pazhamalai Anbarasan (b. 1982) obtained his Ph.D. in 2007 from the DTBMP 2,6-di-tert-butyl-4-methylpyridine
Indian Institute of Science (IISc), Bangalore, under the guidance of ECD electronic circular dichroism
Prof. Kavirayani R. Prasad. After spending a year as a research associate EDG electron-donating group
at IISc, he moved to Germany as an Alexander von Humboldt EWG electron-withdrawing group
Foundation Postdoctoral Fellow to join the group of Prof. Matthias ERC electrocyclic ring closure
Beller at the Leibniz Institute for Catalysis (LIKAT). After spending a esp α,α,α′,α′-tetramethyl-1,3-benzenedipropionate
year in the group of Prof. Dean Toste at the University of California, Et ethyl
Berkeley, he returned to India in December 2011 to start his academic FVP flash vacuum pyrolysis
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