01/12/2023, 21:21 Epoxide synthesis by epoxidation

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Synthesis of epoxides

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Name Reactions

Jacobsen-Katsuki Epoxidation

Prilezhaev Reaction

Sharpless Epoxidation

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01/12/2023, 21:21 Epoxide synthesis by epoxidation

Shi Epoxidation

Recent Literature

2,2,2-trifluoroacetophenone is an efficient organocatalyst for a cheap, mild, fast, and environm

epoxidation of alkenes. Various olefins, mono-, di-, and trisubstituted, are epoxidized chemos
to quantitative yields utilizing low catalyst loadings and H2O2 as a green oxidant.
D. Limniois, C. G. Kokotos, J. Org. Chem., 2014, 79, 4270-4276.

Trifluoroacetone catalyzes a mild and operationally simple epoxidation of various alkens in go

hydrogen peroxide as primary oxidant at high pH. The use of H2O2 as oxidant significantly red
amount of solvent and salts introduced.
L. Shu, Y. Shi, J. Org. Chem., 2000, 65, 8807-8810.

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01/12/2023, 21:21 Epoxide synthesis by epoxidation

An effective epoxidation of lipophilic alkenes using hydrogen peroxide was accomplished with
sulfate/bicarbonate catalytic system in an ionic liquid at room temperature.
K.-H. Tong, K.-Y. Wong, T. H. Chan, Org. Lett., 2003, 5, 3423-3425.

Methyltrioxorhenium (MTO) catalyzes an epoxidation of alkenes with 30% aqueous hydrogen

addition of 1-10 mol % of 3-cyanopyridine increases the system's efficiency resulting in high is
the corresponding epoxides. Alkenes yielding epoxides more sensitive to nucleophilic ring ope
mixture of 3-cyanopyridine and pyridine.
H. Adolfsson, C. Copéret, J. P. Chiang, A. K. Yudin, J. Org. Chem., 2000, 65, 8651-8658.

Organometallic rhenium species (e.g., CH3ReO3) can be replaced by less expensive inorgan
oxides (e.g., Re2O7, ReO3(OH), and ReO3) using bis(trimethylsilyl) peroxide (BTSP) as oxida
aqueous H2O2. Using a catalytic amount of a proton source, controlled release of hydrogen p
preserve sensitive peroxorhenium species and enables catalytic turnover to take place.
A. K. Yudin, J. P. Chiang, H. Adolfsson, C. Copéret, J. Org. Chem., 2000, 65, 4713-4718.

In MTO-catalyzed epoxidation, aqueous hydrogen peroxide is typically added dropwise to a d

solution of the olefin, pyrazole as accelerant, and MTO. The use of sodium percarbonate (SP
release of hydrogen peroxide, that can be accelerated using trifluoroacetic acid.
A. R. Vaino, J. Org. Chem., 2000, 65, 4210-4212.

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01/12/2023, 21:21 Epoxide synthesis by epoxidation

The complex [MnII(R,R-mcp)(CF3SO3)2] is a very efficient and practical catalyst for the epoxi
scope of olefins including terminal, tertiary, cis and trans internal, enones, and methacrylates
acid as the terminal oxidant.
A. Murphy, G. Dubois, T. D. P. Stack, J. Am. Chem. Soc., 2003, 125, 5250-5251.

A bench-stable, solid triazine-based oxidizing reagent, 2-hydroperoxy-4,6-diphenyl-1,3,5-triaz

be synthesized from inexpensive starting materials. This reagents has been used for epoxida
possessing acid-sensitive functionalities in good to excellent yields. The accompanying nonac
coproduct can be easily removed by filtration.
K. Yamada, Y. Igarashi, T. Betuyaku, M. Kitamura, K. Hirata, K. Hioki, M. Kunishima, Org. Lett
2015-2019.

An in situ generated catalyst system based on Mn(CF3SO3)2, picolinic acid, and peracetic ac
broad scope of olefins to epoxides at 0 °C in <5 min. The reaction offers remarkable oxidant e
R. A. Moretti, J. Du Bois, T. D. P. Stack, Org. Lett., 2016, 18, 2528-2531.

Bubbling SO2F2 gas into a solution of olefin, 30% aqueous hydrogen peroxide, and 2 M aque
carbonate in 1,4-dioxane at room temperature for 1 h provides the corresponding epoxides in
excellent yields. This inexpensive, mild, and highly efficient epoxidizing system is suitable to a
olefinic substrates including electron-rich and electron-deficient ones.
C. Ai, F. Zhu, Y. Wang, Z. Yan, S. Lin, J. Org. Chem., 2019, 84, 11928-11934.

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01/12/2023, 21:21 Epoxide synthesis by epoxidation

An efficient epoxidation of a broad range of olefins using hydrogen peroxide as the oxidant ha
accomplished in the presence of acetic acid and a manganese catalyst that exhibits an uncom
chemoselectivity.
I. Garcia-Bosch, X. Ribas, M. Costas, Adv. Synth. Catal., 2008, 351, 348-352.

A manganese catalyst containing a tetradentate ligand derived from triazacyclononane exhibi

activity in epoxidation reactions using peracetic acid as oxidant. The system exhibits broad su
and is remarkably selective toward aliphatic cis-olefins. Mechanistic studies point toward an e
oxidant delivering the oxygen atom in a concerted step.
I. Garcia-Bosch, A. Company, X. Fontrodona, X. Ribas, M. Costas, Org. Lett., 2008, 10, 2095

A non-heme iron complex catalyzes highly enantioselective epoxidation of olefins with H2O2 i
of catalytic amounts of carboxylic acid additives. Ligand and carboxylic acid synergistically co
promoting efficient O-O cleavage and creating highly chemo- and enantioselective epoxidizing
provide a broad range of epoxides in synthetically valuable yields and short reaction times.
O. Cussó, I. Garcia-Bosch, X. Ribas, J. Lloret-Fillol, M. Costas, J. Am. Chem. Soc., 2013, 135

An epoxidation of alkenes using hydrogen peroxide as the terminal oxidant is promoted by ca

(1.0-0.1 mol %) of manganese(2+) salts, and must be performed using at least catalytic amou
bicarbonate buffer. Various aryl-substituted, cyclic, and trialkyl-substituted alkenes were epox
these conditions using 10 equiv of hydrogen peroxide, but monoalkyl-alkenes were not. Addit
sodium acetate and salicylic acid enhanced the rate of the desired epoxidation reaction by 2-3
mechanisms for the reaction are discussed.
B. S. Lane, M. Vogt, V. J. DeRosa, K. Burgess, J. Am. Chem. Soc., 2002, 124, 11946-11954.

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Enantioselective epoxidations of alkenes were achieved using a Shi-type carbohydrate-derive

Oxone. The chiral platform provided by the catalyst tolerates a wide range of substituents pro
yields and enantioselectivities. However, styrene derivatives were only converted with poor se
N. Nieto, I. J. Munslow, H. Fernández-Pérez, A. Vidal-Ferran, Synlett, 2008, 2856-2858.

Aryl benzyl selenoxides are efficient catalysts for the epoxidation of various olefinic substrates
Baeyer-Villiger oxidation of aldehydes and ketones with hydrogen peroxide.
M. A. Goodman, M. R. Detty, Synlett, 2006, 1100-1104.

A tungsten-bishydroxamic acid complex promotes a simple, efficient, and environmentally frie

epoxidation of allylic, and homoallylic alcohols at room temperature using aqueous hydrogen
oxidant.
C. Wang, H. Yamamoto, J. Am. Chem. Soc., 2014, 136, 1222-1225.

A new catalytic system for the asymmetric epoxidation of allylic alcohols has been developed
enantioselectivity for Z olefins, catalyst loading of less than 1 mol%, reaction temperatures of
temperature over a shorter time, use of aqueous tert-butyl hydroperoxide (TBHP) instead of a
as an achiral oxidant, and simple workup procedures for small expoxy alcohols.
W. Zhang, A. Basak, Y. Kosugi, Y. Hoshino, H. Yamamoto, Angew. Chem. Int. Ed., 2005, 44, 4

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01/12/2023, 21:21 Epoxide synthesis by epoxidation

Chiral amino acid-based hydroxamic acids can be effective asymmetric catalysts for the epox
alcohols, especially disubstituted allylic alcohols. The mild reaction conditions, e.g., reasonab
low degree of catalyst loading, and halogen-free solvent, extend the scope of this process.
Y. Hoshino, H. Yamamoto, J. Am. Chem. Soc., 2000, 122, 10452-10453.

Homoallylic alcohols were efficiently epoxidized to the corresponding 3,4-epoxy alcohols in ex

the presence of methyltrioxorhenium (MTO) as catalyst, aqueous hydrogen peroxide as the te
and 3-methylpyrazole as an additive. Organic solvent-free conditions accelerate the reaction.
S. Yamazaki, J. Org. Chem., 2012, 77, 9884-9888.

Chiral bishydroxamic acid ligands provided good yields and high enantioselectivities in the va
catalyzed asymmetric epoxidation of homoallylic alcohols.
W. Zhang, H. Yamamoto, J. Am. Chem. Soc., 2007, 129, 286-287.

Use of a solvent with greater density than the fluorous phase is an alternative to the U-tube m
vanishing reactions in cases where both reactants are less dense than the fluorous phase.
N. K. Jana, J. G. Verkade, Org. Lett., 2003, 5, 3787-3790.

N. K. Jana, J. G. Verkade, Org. Lett., 2003, 5, 3787-3790.

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01/12/2023, 21:21 Epoxide synthesis by epoxidation

A highly chemo- and enantioselective epoxidation of conjugated cis-enynes using readily ava
derived ketones as catalysts and Oxone as oxidant forms cis-propargyl epoxides in high ee's.
between the alkyne substrate and the oxazolidinone moiety of the ketone catalyst are importa
stereodifferentiation.
C. P. Burke, Y. Shi, J. Org. Chem., 2007, 72, 4093-4097.

Highly enantio- and diastereoselective one-pot procedures for the synthesis of epoxy alcohols
asymmetric addition of an alkylzinc reagent to an enal or asymmetric vinylation of an aldehyd
reagents. Exposure of the reaction mixtures to dioxygen and addition of catalytic titanium tetra
yields epoxy alcohols with good to excellent yields.
A. E. Lurain, A. Maestri, A. R. Kelli, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2004, 126, 1

A. E. Lurain, A. Maestri, A. R. Kelli, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2004, 126, 1

A series of 20 chiral epoxides were obtained with excellent yields and enantioselectivities with
times using hybrid amide-based Cinchona alkaloids as catalysts at very low loading. Moreove
solution can be reused 10times, without further catalyst addition to the reaction mixture.
M. Majdecki, A. Tyszka-Gumkowska, J. Jurczak, Org. Lett., 2020, 22, 8687-8691.

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A simple and efficient enantioselective epoxidation of α,β-unsaturated ketones is catalyzed by

metal amides in the presence of phenoxy-functionalized chiral prolinols at room temperature u
butylhydroperoxide (TBHP) as the oxidant. The combination of an Yb-based amide and a chir
provided chiral epoxides in excellent yields and enantiomeric excess of up to 99%.
C. Zeng, D. Yuan, B. Zhao, Y. Yao, Org. Lett., 2015, 17, 2242-2245.

An aerobic photoepoxidation of α,β-unsaturated ketones is driven by visible light in the presen

tetramethylguanidine (TMG), tetraphenylporphine (H2TPP), and molecular oxygen under mild
provide α,β-epoxy ketones in good yields in 96 h. The reaction time can be shortened to 5 h u
synthesis.
Y. Wu, G. Zhou, Q. Meng, X. Tang, G. Liu, H. Yin, J. Zhao, F. Yang, Z. Yu, Y. Luo, J. Org. Che
13051-13062.

A chiral N,N'-dioxide/ScIII complex catalyzes an enantioselective epoxidation of α-substituted

the presence of H2O2 as the oxidant to provide key epoxide intermediates for the synthesis o
antifungal agents. The reaction proceeded efficiently in high yields and with good enantiosele
Q. He, D. Zhang, F. Zhang, X. Liu, X. Feng, Org. Lett., 2021, 23, 6795-6800.

Using cinchona alkaloid-derived primary amines as catalysts and aqueous hydrogen peroxide
highly enantioselective Weitz-Scheffer-type epoxidation and hydroperoxidation reactions of α,
carbonyl compounds take place. Acyclic enones, cyclic enones, and α-branched enals can be
Intermediates have been characterized by MS and NMR. DFT calculations explain the activat
O. Lifchits, M. Mahlau, C. M. Reisinger, A. Lee, C. Farès, I. Polyak, G. Gopakumar, W. Thiel,
Chem. Soc., 2013, 135, 6677-6693.
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Using cinchona alkaloid-derived primary amines as catalysts and aqueous hydrogen peroxide
highly enantioselective Weitz-Scheffer-type epoxidation and hydroperoxidation reactions of α,
carbonyl compounds take place. Acyclic enones, cyclic enones, and α-branched enals can be
Intermediates have been characterized by MS and NMR. DFT calculations explain the activat
O. Lifchits, M. Mahlau, C. M. Reisinger, A. Lee, C. Farès, I. Polyak, G. Gopakumar, W. Thiel,
Chem. Soc., 2013, 135, 6677-6693.

Heterobimetallic complexes stabilized by chiral phenoxy-functionalized prolinolate are highly a

catalyzing the epoxidation of α,β-unsaturated ketones, while the enantioselectivity varies acco
ionic radii of the rare earth center. A series of chalcone derivatives were converted to chiral ep
ee at 0°C using TBHP as the oxidant.
Q. Qian, Y. Tan, B. Zhao, T. Feng, Q. Shen, Y. Yao, Org. Lett., 2014, 16, 4516-4519.

Visible-light-driven hydroacylations and epoxyacylations in water using methylene blue as pho

and persulfate as oxidant deliver ketones and epoxyketones from a range of aromatic and alip
as well as conjugated and nonconjugated olefins as abundant and inexpensive chemical feed
G. F. P. de Souza, J. A. Bonacin, A. G. Salles, Jr., J. Org. Chem., 2018, 83, 8331-8340.

Under the synergistic actions of photocatalyst Ru(bpy)3Cl2, tert-butyl hydroperoxide, cesium c

visible light irradiation, a range of styrenes and benzaldehydes smoothly form α,β-epoxy keto
light-enabled photocatalytic generation of acyl radicals as key intermediates.
J. Li, D. Z. Wang, Org. Lett., 2015, 17, 5260-5263.

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Chiral primary amine salts catalyze highly enantioselective epoxidations of cyclic enones with
peroxide.
X. Wang, C. M. Reisinger, B. List, J. Am. Chem. Soc., 2008, 130, 6070-6071.

An asymmetric 1,2-addition of alkyl groups to conjugated cyclic enones gave allylic alcohols w
quaternary centers. The resultant allylic alcohols are converted into epoxy alcohols with exce
diastereoselectivities. A semipinacol rearrangement provided α,α-dialkyl-β-hydroxy ketones w
chiral quaternary centers.
S.-J. Jeon, P. J. Walsh, J. Am. Chem. Soc., 2003, 125, 9544-9545.

The catalytic asymmetric addition of alkyl groups to ketones under highly concentrated and so
conditions permits reduction in catalyst loading by a factor of 2- to 40-fold compared with stan
conditions employing toluene and hexanes. Using cyclic conjugated enones, solvent-free asy
followed by a diastereoselective epoxidation using 5.5 M decane solution of tert-butyl hydrope
generated epoxy alcohols.
S.-J. Jeon, H. Li, P. J. Walsh, J. Am. Chem. Soc., 2005, 127, 16416-16425.

A chiral bisaryl-silyl-protected pyrrolidine acts as a very selective epoxidation organocatalyst u

oxidation agents. The scope of the reaction is demonstrated by the formation of optically activ
aldehydes in high yields and enantioselectivities. The asymmetric epoxidation reactions proce
environmental friendly reaction conditions in, for example, water mixtures of alcohols.
M. Marigo, J. Franzen, T. B. Poulsen, W. Zhuang, K. A. Jorgensen, J. Am. Chem. Soc., 2005,

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A catalytic asymmetric epoxidation reaction of various α,β-unsaturated esters via a conjugate

oxidant using an yttirium-chiral biphenyldiol catalyst yielded the corresponding α,β-epoxy este
yield and 99% ee.
H. Kakei, R. Tsuji, T. Ohshima, M. Shibasaki, J. Am. Chem. Soc., 2005, 127, 8962-8963.

Promising, dual-functioning chiral catalysts for the highly enantioselective epoxidation of α,β-u
ketones gave epoxy chalcones in excelllent yield and high enantioselectivity using 13% NaOC
agent in toluene under mild phase-transfer conditions.
T. Ooi, D. Ohara, M. Tamura, K. Maruoka, J. Am. Chem. Soc., 2004, 126, 6844-6845.

A highly enantioselective catalytic epoxidation of α,β-unsaturated diaryl enones was achieved

chemical yield by using aqueous hydrogen peroxide in the presence of a guanidine-urea bifun
organocatalyst. The catalyst performs cooperatively by interaction of the guanidine group with
peroxide and the urea group with the enone or vice versa.
S. Tanaka, K. Nagasawa Synlett, 2009, 667-670.

The epoxidation of trans-chalcones proceeds under mild conditions at room temperature in al

afford the corresponding epoxides in excellent yields using trans-3,5-dihydroperoxy-3,5-dimet
dioxolane as an efficient oxygen source.
D. Azarifar, K. Khosravi, Synlett, 2010, 2755-2758.

A new and efficient chiral catalyst system, lanthanum-chiral BINOL-tris(4-fluorophenyl)phosph

cumene hydroperoxide, was developed for the epoxidation of α,β-unsaturated ketones, thus p
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corresponding epoxy ketones with excellent enantioselectivities (up to >99% ee) in good to ex
room temperature.
R. Kino, K. Daikai, T. Kawanami, H. Furuno, J. Inanaga, Org. Biomol. Chem., 2004, 2, 1822-1

1-Trifluoroboratoalkenes are oxidized by dioxirane, providing air-stable, crystalline oxiranyltrifl

without cleavage of the carbon-boron bond. The first Suzuki-Miyaura coupling of an epoxytrifl
been accomplished.
G. A. Molander, M. Ribagorda, J. Am. Chem. Soc., 2003, 125, 11148-11149.

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