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628 Name Reaction

Stork Enamine Synthesis

The Reaction:
R.N.R H &
VH&

1. R-X

2. hydrolysis

Proposed Mechanism:
R

. R

R .a-R
f-

HA X@
R@ R .,

R,

.R

. &

&H

Notes:
M. B. Smith, J. March in March's Advanced Organic Chemistiy, 5" ed., John Wiley and Sons, Inc., New York, 2001, pp. 555,787; T. Laue, A. Plagens, Named Organic Reactions, John Wiley and Sons, Inc., New York, 1998, pp. 250-253 Starting material preparation: - R.N.R

H-YR R *

H,O

The amine used to make enamine is usually pyrrolidine, morpholine, piperidine or diethylamine. Besides alkyl halides, the electrophile can be activated aryl halides, epoxides, anhydrides and Michael additions to activated alkenes.

Examples:

DMSO 94% B. Kist, P. Pojarliev, H.J. Martin, Organic Letters 2001, & 2423

proline (15 mol %) ph&

Name Reaction
stork

629

- &NrJ
H

Pd(OAc)2, PPh,

ennmine synthesis
(

H 5

A~o,),,oA~
Trod 's TMM R e a c h

45%

F. Bouno, A. Tenaglia, Journal o Organic Chemistry 2000, f

3869

Me

CO2Me

N H TsOH, - H2O 67%

3 ' O Z M e

PdC12(MeCN)2 Et,N 37% overall yield for the sequene

Me

hcozMe
m,
Not isolated. Me0

808 Method of: S. Hunig, E. Lucke, W. Brenninger, Organic Syntheses, in: T. Ishikawa, E. Vedo, R. Tani, S. Saito, Journal oforganic Chemistry 2001, &, 186

2. MVK, hydroquinone
3. NaOAc, HOAc

0 J. J. Li, B. K. Trivedi, J. R. Rubin, B. D. Roth, Tetrahedron Letters 1998,=, 61 11

630

Name Reaction

Stork-Wittig Olefination

e
0

The Reaction: 0
H Ph3P-CH21 Base I

Proposed Mechanism:
R Ph,@ Ph-P-f.'

r7
I

Base

Pi

Ph-PT P$ I

@Ph'TPh Ph See: Wttig Reactwa

Ph

Notes:
The Takai Reaction provides the same transformation, but arrives at the E- configuration rather than the Z-.

Examples:

Brc)
0
Ph3P-CHZI I

Et

"'cl

NaHMDS, THF, HMFA*

72%

BrD
Et "'Cl Z:E 9:l

*-CHO

3
I

M. T. Crimmins, M. T. Powell, Journal o the American Chemical Society 2003,125,7592 f

Name Reaction

\ Me,.

$
&.\
OTBS Me

63 1

3 . Ph,P=CHI darion 2.Swem xi l.LiBHdO

I $ \

ph-lti.

Ph-Ii',
62% overall

\
TMSO OTBS

TMSO

K. Lee, J. K. Cha, Journal of rhe American Chemical Society 2001,123.559

Ph3P-CH2I 0 OPMB NaHMDS 80% ?TIPS

I0

*
Me

&i

OPMB
Me

Me

fie

S. S . Harried, C. P. Lee, G. Yang, T. I. H. Lee, D. C. Myles, Journal of Organic Chemistry 2003,68, 6646

J. E. Davies, A. B. Holmes, J. P. Adams, Journal of the American Chemical Society 1999,121,4900

632

Name Reaction

Strecker Amino Acid Synthesis

The Reaction:

Proposed Mechanism:

R'

Notes:
T. Laue, A. Plagens, Named Organic Reactions, John Wiley and Sons, Inc., New York, 1998, pp. 253-254

Examples:

NH chiral catalyst 2 mol %

HCN, MeOH

OMe

97%, 99% ee M. S. Iyer, K. M. Gigstad, N. D. Namdev, M. Lipton, Journal o the American Chemical Sociev f 1996,118,4910

Name Reaction TBSO-(CH&-CHO

633

several steps

q* :
I
he

HCN t chiral Zr catalyst 8 0% 91% ee

O Me

OTBS alOzMe

H. Ishitani, S. Komiyama, Y . Hasegawa, S. Kobayashi, Journal of the American Chemical Society 2000,122,762
An anomolous reduction of a Strecker nitrile:

P. Rajagopalan, B. G. Advani, Tetrahedron Letters 1965,h2197

634

Name Reaction

Strecker Degradation

Proposed Mechanism:
G. P. Rizzi, Journal of Organic Chemisfry 1969,34,2002

proton transfer N

H20
b

imine hydrolysis

dimerizatior

Notes:
The formation of aldehydes (flavorings) in roasting of cocoa beans, for example, is caused by Strecker degradation of amino acids. A. Amoldi, C. Amoldi, 0. Baldi, A. Griffini, Journal OfAgricultural andFood Chemistry 1987, 1035 Other degradation reactions: Bergmann Degradation
1. BnOH

2. Hz , catalyst 3. hydrolysis

1
I

+
R'

J ,
H

C02

benzene + NH3

m 2

Darapsky Degradation (Procedure) 0 1. H?NNH, 2. H ~ N O -

NCYmZ
4.acidic workup

Name Reaction
von Braun (Amide) Degradation /Reaction

63 5

Examples:
This was used as a visual test for amino acids, where alloxane reacted with the amino acid to produce murexide, a colored compound:
NH2

0 0 NH4
NH

oq$o
HN

R ~ c o o H
~

0 H$% HN .;. 1N N
0 0

M. F. Aly, G. M. El-Nagger, T. I. El-Emary, R. Grigg, S.A. M. Metwally, S. Sivagnanam, Tetrahedron 1 9 9 4 , 2 , 8 9 5

MeHNH
+

diglyme

Me

COOH

heat
0

Me

Me Me low yields of isolated products, but rapid loss of the butane dione.

G. P. Rizzi, Journal of Organic Chemistry 1969,34,2002

MeXNH2 +
Me+e Me COOH
0

- MeHo
heat

Me

Me Me GC-MS analysis of head space

C.-K. Shu, Journal ofAgricultura1 andFood Chemistry 1998,46, 1515

M e p C O O H Me

Ninhydrin Steam distillation 61%

~

Me

isolated as 2,4-D derivative

W . S.Fones, Journal of the American Chemical Society 1 9 5 4 , z , 1311

636

Name Reaction

Suzuki Coupling
The Reaction:
N. Miyauri, A. Suzuki, Chemical Reviews 1995, *RO,

2457

R' R" Where X = I 25 Br > OTf >> Cl.

See: A usehl review: S. R. Chemler, D. Trauner, S. J. Danishefsky, Angewandte Chemie International Edition in English 2001,40,4544

Proposed Mechanism:
i;PdcLL H R

reductive elimination R L e R"

R'
cis-trans isomerism

Notes:

General sources of common boron reagents: OR' Hydrolysis R-Li f B@'O), R--B/ OR'

H R -

R-x

">=<

B-oR*

Pd(0) NaORorNaOH.

R'

R"

4- 2L
L-Pd-L [= Pd(O)] k t z t i v e addition L-pd*' R' 'L

;:PdtL OR H H p d - L

+w~
RO-$

*RO,
-OR* R' R" transmetalation

R'

R"

OR*
OR*

OH R- B, OH R

BCl3 + R3SiH

A
Rh H B-C1
ci
R R'OH,

J
HBClz

)=\
H R'O' B-OR'

Name Reaction

637

Examples:
R e L i

96% 98% A.-S. Castanet, F. Colobert, T. Schlama, Organic Letters, 2000, 2,3559.

t-B,+OTf

Me 96% Me dba: dibenzylidene acetone A.F. Littke, C. Dai, G.C. Fu, Journal of the American Chemical Society 2000,127,4020

Ho;Bb r-Bu+P
Pd2(dba)3, P(t-Bu)3. KF, THF, 70 "C
8 8%

HO

Me

YH

a',
CsF
~

M e 0 2 C v B'oH

Pd(Pt-B~3)2 76% M. Rubina, M. Rubin, V. Geforgyan, Journal of the American Chemical Society 2003,125.7198 HO,B/OH

98% SO2Ph OMe Y . Liu, G.W. Gribble, Tetrahedron Letters 2000, 4 , 8717 1

BnO
TBDMSO

1
/
B2H6

Pd(OAc),, P ( ~ - t o l ) ~

TBDMS Pd(dppf)2Clz, Cs2C03 B-(Z2)6)3 OTBDMS

OTBDMS 70% D. Meng, S. J. Danishfesky, Angewandte Chemie, International Edition in English 1999,38, 1485

B(Oi-Pr)s
+

R-B(Oi-Pr),Li

1Pd(Ph3P)d ArBr,DMF

Rr A -

Pd(oAc)z' pcy3 KF, m,rt

Ph0,s

TBDMS T D- + B )@ 0

(cp2)6 OBn

638

Name Reaction

Swern Oxidation
The Reaction:
OdH oxalyl chloride, DMSO CH2C12

8,
0
Me

DMSO - Dimethylsulfoxide

Proposed Mechanism:

c 1
DMSO
oxa l 1 chloride y

cold (bel0w-60"C)~

A sulfurylide b formed with base which then abstracts the aproton, generating the carbonyl and dimethylsuljde.

Notes:
M. B. Smith, J. March in March's Advanced Organic Chemistry, 51hed., John Wiley and Sons, Inc., New York, 2001, p. 1516; T. T. Tidwell, Organic Reactions 39, 3 Triflouroacetic anhydride was used before oxalyl chloride and is also known as the Swern Oxidation. Acetic anhydride can also be used. (Albripht-GoldmanOxidation)

An alternative to the Swern Oxidation:

Me

c 1
N A N CIANACl Et3N

DMSO THF
Me

0)

4 9 Me

N A N CIAiVACl

)-OH Me

Me

Me

Me

Me

Me

)=o

Extremely mild, easy workup.

Me

Name Reaction

639

90% 74% 90% L. DeLuca, G . Giacomelli, A. Porcheddu, Journal oforganic Chemistry 2001, @, 7807

Examples:

+. ;+
Me Me OH

Swern9% 8 Oxidation

Me Me

Jy+p
Me Me
0

X. Fang, U.K. Gandarange, T. Wang, J. D. Sol, D. S. Garvey, Journal oforganic Chemistry 2001,

66,4019

85%
M. K. W. Choi, P. H. Toy, Tetrahedron 2004,

a 2875

Me Me

97%

Cbz

Me

Jujang, D. Ho, Organic Letters 2001, M. F. Semmelhack, Y.

2403

Me(H2C),

= =

CH2OH

-[
Swern

Me(H,C),

CHO

(taken directly into a Win& r e d i m :

T. J. Speed, D. M. Thamattoor, Tetrahedron Letters 2002,43,367

640

Name Reaction

Takai Reaction
The Reaction:
CHI,, CrC12 R

I1
Clcl2 *

R+o H

THF

Proposed Mechanism:
CHI, + CrCl2 Cr"' CHI2]

-[

crIl\cHI] Cr"'

The two Cr-containing intermediates can distribute as shown below:

Notes:
There is also a T a h i Couplingprotocol: MeOzC, LAlH4
51%

Me

P. Breuilles, D. Uquen, Tetrahedron Letters 1998,3,3149 See: Stork- WiniP Olefinution for a related procedure:

Br

(3,
Et

.ICl ,,CHO

I 0Ph3P-CH2I NaN(TMS12, HMPA, THF

12%

Br
Et

M. T. Crimmins, M. T. Powell, Journal of the American Chemical Socieg 2003,125,1592

Name Reaction

641

Examples:

E:Z=81:19 K. Takai, K. Nitta, K. Utimoto, Journal of the American Chemical Sociely 1 9 8 6 , m 7408 I

-P
CrCI,, CHI,
85 %

Me

( C H 2 b v I

""'0 63%CrC12, CHI3 Me" S. Chackalamannil, R. Davies, A. T. McPhail, Organic Letters 2001,3, 1427

Hoi/cHo CrClz

Me

>

HO

J. Cossy, D. Bauer, V. Bellosta, Tetrahedron 2002,58-

5909 I

H OAc

CrC12, CHI, 74%

l&q+
OAc

I. C. Gonzalez, C. J. Forsyth, Journal o the American Chemical Sociew 2000,122.9099 f

M. E. Jung, B. T. Fahr, D. C. D'Amico, Journal o Organic Chemistry 1998,Q, 2982 f

61

CrC12,CH13

TMS

78%

R. Garg, R. S.Coleman, Organic Letters 2001,3,3487

7,
TMS

642

Name Reaction

Tebbe Reagent / Olefination

The Reaction:

Proposed Mechanism:

a . c1

c 1

AlMe,

Q
a hydride abstraction

transmetalation

dTi=CH2 coordination

C1AlMe2

Notes:
See Tebbe Reaeent

Tebbe reactions on beads:

rolR
Tebbe ReactionCHzBr2, Zn TiCl,, THF
L
1

A. G. M. Barrett, P. A. Procopiou, U. Voigtmann, Organic Letters 2001, The Oshima modification provides another entry into methylenation:

s, 3165

BrZn

ZnBr

For details of competitive regiochemical analysis with a number of reagents, see: Me

___Lc

O -M H e C T. Okazoe, J.-I. Hibino, K. Takai, H. Nozakil, Tetrahedron Letters 1985,

5581

Name Reaction

643

Examples:

d
w s

Tebbe Reaeettt

G4-S 0 Me

M. E. Jung,J. Pontillo, Tetrahedron 2003,59,2729

CP

K. C. Nicolaou, M. H. D. Postema, C. F. Claibome, Journal ofthe American Chemical Society 1996,

1 8 1565 1,

Me

Me

M. Cortts, J. A. Valderrama, M. Cuellar, V. Armstrong, M. Preite, Journal of Natural Products 2001, 348

Me Me 6799 N. A. Petasis, M. A. Patane, Tetrahedron Letters 1990,

644

Name Reaction

Thiele-Winter Reaction (Acetoxylation) (Thiele Reaction)

The Reaction:
0
OAc

OAc

Proposed Mechanism:
acetic anhydride

__t

Me
0 0 0 0 0

K Me
keto-enol tautomerism
OAc

OH
0 0 OAc OAc OAc

Me
OAc OAc

Notes:
Ortho-quinones will give the same product.
0

Name Reaction

645

Examples:

80%
Ac~O CF3-SOzF
It

OAc

88%

"-o-"'
OAc
A 62% c 2
c~ A@ cJ O

D. Villemin, N. Bar, M. Hammadi, Tetrahedron Letters 1 9 9 7 , B , 4777

Lj #
a

CH2

EtO

OAc

EtO calixerane

calixerane

P. A. Reddy, C. D. Gutsche, Journal of Organic Chemistry 1 9 9 3 , s , 3245

96%

W. M. Mclamore, Journal of the American Chemical Society 1951,73,2225

S . Spyroudis, N. Xanthopoulou, Journal o Organic Chemistry 2002,B, f 4612

646

Name Reaction

Thorpe Reaction (If interrnolcular, known as the Thorpe-Ziegler Reaction.)

The Reaction:

Proposed Mechanism:

proton transfer 2. A
NH2

Hydrolysis (if desired)

I iydrolysis and decarboxylstion (if dcsi red)

Notes:
M. B. Smith, J. March in March s Advanced Organic Chemistry, 5thed., John Wiley and Sons, Inc., New York, 2001, pp. 1219, 1238; for Thorpe-Ziegler, p. 1239. The Thorpe reaction is often better than the Diekmann Cvclization for ring sizes > 7. What of the reaction of an ester and a nitrile? Dieckmann Nitrile and Ester

2 RCOOR'

Thorpe

0
2 R-CN

NaH

15%

NC
0 H. Plienenger, W. Muller, Chemische Berichte 1960,93,2029 (AN 1961:13347)

Examples:

0 Me

0 Me Me 68% A. Toro, P. Nowak, P. Deslongchamps, Journal o the American Chemical Society 2000,122,4526 f
Me

46)

1. t-BuOO, 1-BuOH

2. AcOH, H3P04

Name Reaction

647

L. Lu, R. K. Shoemaker, D. M. S . Wheeler, Tetrahedron Letters 1989,

B h z c :
CN
91%

Me-N
I

Me

xgH2
a, 6993
CN CN N H 2 CN

A. Hashimoto, A. K. Przybyl, J. T. M. Linders, S. Kodato, X.Tian, J. R. Deschamps, C. George, J. L. Flippen-Anderson, A. E. Jacobson, K. C. Rice ,Journal of Organic Chemistry 2 0 0 4 , B , 5322

Me

Sz K: s
No yield given

Me S w

Me

Me

G. Seitz, H. Monnighoff, Tetrahedron Letters 1971,l2,4889

J. J. Bloomfield, P. V. Fennessey, Tetrahedron Letters 1964, 5 2273

N. E. Kayaleh, R. C. Gupta, F. Johnson, Journal oforganic Chemistry 2000, & 4515

648

Name Reaction

Tiffeneau-Demjanov Rearrangement
The Reaction:
0

Proposed Mechanism:
NaN02, HX

Notes:
M. B. Smith, J. March in March's Advanced Organic Chemixtv, 51h ed., John Wiley and Sons, Inc., New York, 200 1, p. 1399
Possible sources of starting material: Me ;NO2

RARH C S N
w

LiCHBr2 Li,
~

OH

OH

N( & , ;

3 (:&NH2
Li @CH~B~ Li ,

Takuchi Modification

0' "

BuLi_

a-elimination

Name Reaction

649

Examples:

E@ HO *

Takuchi Modificatwn

62%
0

0
0

Z. Wang, D. Yang, A. K. Mohanakrishnan, E. Hamel, M. Cushman, Journal of Medicinal Chemistry 2000, 2419

HzNH2C

NaN02b HOAc CHZNH,

%
0

54%

S. Kim, R. Bishop, D. C. Craig, I. G. Dance, M. L. Scudder, Journal of Organic Chemictry 2 0 0 2 , a 3221

0

NaN02
____c

NOH H

NaNO, H2S04
100%

83%

4
0

+
(2: 1)

4
0

+
(12:l)

D. Fattori, S. Henry, P. Vogel, Tetrahedron 1993,

1649

No yield given

( 9:l)

J. T. Lumb, G. H. Whitham, Tetrahedron 1965, & 499

R. B. Woodward, J. Gostel, I. Ernest, R. J. Friary, G. Nestler, H. Raman, R. Sitrin, C. Suter, J. K. Whitesell, Journal of the American Chemical Society 1973, M 6853

650

Name Reaction

Tischenko Reaction
The Reaction:
AI(OEt),
___)

Proposed Mechanism:

Notes:
An AldoCTischenko reaction is sometimes observed as a byproduct of Aldol condensation:
0

OH W E t

7 6% P. M. Bodnar, J. T. Shaw, K. A. Woerpel, Journal of Organic Chemisty 1997,62,5674

Name Reaction

65 1

Examples:

ncHo
Me0

Si(W3

+
72%

Et3SiH, KOz
18-Crown-6

Me0

Me0

28%

OMe

F. LeBideau, T. Coradin, D. Gourier, J. Henique, E. Samuel, Tetrahedron Letters 2 0 0 0 , s 5215

T. Sek, H. Tachikawa, T. Tamada, H. Hattori, Journal o Catalysis 2003,217, 117 f

DCH0
88% H
Me 0 Me 4

Cp2NdCH(TMS)2

S.-Y.Onozawa, T. Sakakura, M. Tanaka, M. Shiro, Tetrahedron 1996,

4291

This reaction will take place slowly by storing an aqueous solution of the aldehyde at 60 "C.

H2 0 94% 2219

G. K. Finch, Journal o Organic Chemistry 1960, f

652

Name Reaction

Trosts TMM (trimethylenemethane) Cycloaddition

The Reaction:
TMS&OAc
+

rEWG
v

Pdo L EWG

Proposed Mechanism:
TMSJCOAC w E EWG can stabilize the anion and allow for bond rotation.
G

pdo EWG

\i

4
Notes:

EWG

An analysis of the use of orbital theory to rationalize product formation from the diradical Th4M analog formed by nitrogen extrusion:

+s-(y& 3
P
L UMO

-6

LUMO

R. K. Siemionke, J. A. Berson, Journal o the American Chemical Society 1980,102,3870 f

Name Reaction

653

Examples:
0

60%

J. Cossy, D. Belotti, J. P. Pete, Tetrahedron 1990,46, 1859

CaMe 'CQMe Pd(PPh,),, DPPE, THF MeO,C 50%

%02Me

25:l /@am: toluene cis 1.3 / 1 trans: cis THF

B. M. Trost, D. M. T. Chan, Journal of the American Chemical Sociely 1983,105,23 15

.liCO2Me

Pd(OAc)2, P(i-Pr)3, toluene 50% "'C02Me

A. Heumann, S. Kadly, A. Tenagli, Tetrahedron 1994,5& 539

L. A. Paquette, D. R. Sauer, D. G. Cleary, M. A. Kinsella, C. M. Blackwell, L. G. Anderson,Journal of the American Chemical Sociev 1992,114,7375

654

Name Reaction

Tscherniac-Einhorn Reaction
The Reaction:
0

0
0

@NJoH /
0

3@ :0

Proposed Mechanism:

4 total resonance structures

H. E. Zaugg, R. W. DeNet, J. E. Fraser, A. M. Kotre, Journal of Organic Chemistry 1969,34,14

Notes:
Sometimes the reaction can continue with hydrolysis of the phthalimide group:

@ :
0

hydrolysis
+

Ar
H2NA

Name Reaction

655

Examples:

P. S. Anderson, M. E. Christy, C. D. Colton, W. Halczenko, G. S. Ponticello, K. L. Shepard, Journal of Organic Chemistry 1979,43 15 19

F. Hess. E. Cullen, K. Grozinger, TefrahedronLeffers1971,Q, 2591

F. K. Hess, P. B. Stewart, Journal ofMedicina1 Chemisfry 1975,B, 320

656

Name Reaction

Tsuji-Trost Reaction
The Reaction:

X = leaving group
J. Tsuji, H. Takahashi, M. Morikawa, TetrahedronLetfers 1965,6,4387 B. M. Trost, T. J. Fullerton, Journal o the American Chemical Society 1973, f

s, 292

ProDosed Mechanism:

Notes:
major product Nu when: R ' = H Nu R' = SiR3

L'O'L

ph

L = ligand

V. Branchadell, M. Moreno-Manas, R. Pleixats, S. Thorimbert, C. Commandeur, C. Boglio, M. Malacria, Journal of Organometallic Chemistry 2003,687,337

Examples:

1. NaH, THF, DMSO 2. Pd,(dba),, (i-PrO)3P,CHCI,

3.

OCOzEt

Me
55 - 67%

J. H. Hong, M. J. Shim, B. 0. Ro, 0. H. KO, Journal o Organic Chernisty 2002,67,6837 f

Name Reaction
A water-mediated, transition metal free reaction:

657

MeOzcXH MeOzC H

,K2a3
D

HZO, DMF

71%
Me C. Chevrin, J. Le Bras, F. Henin, J. Muzart, Tetrahedron Letters 2003,
8099

Pd(OAch, dppe AcO COzMe

*
AcO

J=T
COzMe SiEt, Me

sat3

64%

0 MeOzC

SiEt, OAc Pd(OAch, dppe COZMe M $e -' 30%

~

MeOzC

V. Branchadell, M. Moreno-Manas, R. Pleixats, S . Thorimbert, C. Commandeur, C. Boglio, M. Malacria, Journal of Organometallic Chemistv 2003,687,331

Catalytic allylation of aldehydes: PPh, (20 mol%) Pd(OAc)z (10 mol%),

D

EtjN, LiCl, Et3B, THF 92% M. Kimura, Y . Horino, R. Mukai, S. Tanaka, Y . Tamaru, Journal of the American Chemical Society
2001,123,10401

658

Name Reaction

Ueno-Stork Cyclization
The Reaction:

Proposed Mechanism:

0'" - aoroEt "ToEt

Examples:
Bu3SnH D

G. Stork, R. Mook, Jr., S. A. Biller, S. D. Rychnovsky, Journal of the American Chemical Society 1983,105,3741

OH

koEt

1.NBS OEt

2. AIBN,HSn(n-Bu)r

Br

Br

AIBN
50 - 55%

Name Reaction

659

t-BuO k 0 t - h

-G-t-BuO
-0

4
Me O

7
9 8%

Bu3SnH

F. Villar, 0. Equey, P. Renaud, Organic Letters 2000,2, 1061

EtopBr
b 0 t - B ~
98% NIS
t

EtO

9- M e O b

F.Villar, 0. Equey, P.Renaud, Organic Letters 2000,2, 1061

44Y O

1 : 1 mixture

F. Villar, P. Renaud, Tetrahedron Letters 1998,

a 8655

660

Name Reaction

Ugi Reaction
The Reaction:

Prooosed Mechanism:

Notes:
This reaction is similar to the Passerini reaction. It is characterized by the four components going into the reaction mix:

MeO

Me

71%

OMe
P. Cristau, J.-P. Vors, J. Zhu, Organic Letters 2001,3, 4079

Name Reaction

66 1

Examples:
A chemical library developed
R'

R'CHO, R"NH2 O N EC: * R R C. Hulme, J. Pen& S.-Y. Tang,C.J. Bums, I. Morize, R. Labaudiniere, Journal oforganic Chemistry 1998,63- 8021

&Nv,
t-Bu i-PrCHO, MeOH t-BuNC 0 96% A. Basso, L. Banfi, R. Riva, G. Guanti, Tetrahedron Letters 2004,45, 587

NIC:

CO2H

6
H

3:l CHCI,:TFE__

P. Cristau, J.-P. Vors, J. Zhu, Tetrahedron 2003,

G. Dyker, K. Breitenstein, G. Henkel, Tetrahedron: Asymmetry 2002, & 1929

H?N

38%

OHC

= 2,2,2-trifhi0r0etha1101

a 7859

Me

662

Name Reaction

Ullmann Coupling Reaction

The Reaction:
2 Ar-I
cu A

heat

Ar-Ar

CuI2

Proposed Mechanism:
Ar-I +

cu

Ar-Ar

cu

Ar-cu-I

cu-I

Ar-cu

Ar-I
oxidative addition

I
I

A Ar.cu 'r

reductive elimination

oxidative addition

Notes:
M. B. Smith, J. March in March's Advanced Organic Chemistry, 5" ed., John Wiley and Sons, Inc., New York, 2001, p. 870. Problem with mixed coupling:
Ar-I
+

A?-I

cu
A

Ar -Ar
Ar-Ar'

+ +

+ cuI2

Ar'-AlJ

Examples:
1. Cu, A

2. KCN, NH3 90% G. Wad, I. Horvath, Journal ofOrganic Chemistry 2002,

a 6550

OMe

51%

OMe

OMe

C. W. Lai, C. K. Lam, H. K. Lee, T. C. W. Mak, H. N. C. Wong, Organic Lefters 2003,5,823

Name Reaction

663

Me 87%

95%

J.-H. Y.-X. Xie, D.-L. Yin, Journal of Organic Chemistry 2 0 0 3 , a , 9867 Li,

OMe OMe OMe

\t-Bu
A. I. Meyers, J. J. Willemsen, Tetrahedron Letters 1996,37, 791

664

Name Reaction

Ullmann Ether Synthesis

The Reaction:
AIOH, base

Ar'-x

Cu(I) salts, A b

/ Ar' ,

X includes halides, -NOz, -NR;, -OR, or -OH

ProDosed Mechanism:
Ar-0-H +base reductive elimination
I

cu-0-Ar

addition

M!x

Notes:
Ulfmunn-Vpereactions can replace Ar-0 with Nu-H.
The copper-catalyzed addition of amines and amides (GoldbergReaction) are placed in this section:

Ulimann Reaction (Jourdan-UUmann Synthesis)

COOH

There is also the related Jourdan Synthesis: COOH

COOH

02N

Examples:
c u l , cs2co3
NMP, microwave

t-Bu

90%

t-Bu

Y.-J. Wu, H. He, Tetrahedron Letters 2003,%, 3445

Name Reaction

665

D. Ma, Q. Cai, Organic Letters 2003,2, 3799

CHO H *N \Ac

A. V. R. Rao, J. K. Chakraborty, K. L. Reddy, A. S . Rao, Tetrahedron Letters 1992, Me

I

M. Wolter, G . Nordmann, G. E. Job, S . L. Buchwald, Organic Letters 2002,4 973

OBr '
Br
+

J. H. M. Lange, L. J. F. Hofmeyer, F. A. S . Hout, S . J. M. Osnabrug, P. C. Verveer, C. G. Kruse, R. W. Feenstra, Tetrahedron Letters 2002,43- 1101

'Qb
/ \
F Me

J. A. Ragen, B. P. Jones, M. J. Castaldi, P. D. Hill, T. W. Makowski, Organic Syntheses, -418

\ n

HO

/o

CUI, cs,co, N,N-dimethylglycineb

95%

1.NaH

2.61% CuBr

+oq
CHO 0 MeOzC

'1

eN

~ A C

a 4799

8 1%

'

cu,r~KzC%
microwave 76%

aNo
Me

&N,,ph 0

CuI, K2CO3 rmcrowave

66%

CuC1, NaOMe MeOH,DMF

5 8%

F Me

666

Name Reaction

Upjohn Dihydroxylation Protocol

The Reaction:
oSO4, NMO

HO OH
+

t-BuOH, H 2 0

V. VanRheenen, R. C. Kelly, D. Y. Cha, Tetrahedron Letters 1976,

n 1973

Proposed Mechanism:
Me
I

\=/

N-Methyl morpholine

N-Methyl morpholine N-oxide

Notes:
A procedure for the catalytic use of OsOa:
O S O (cat.), NMO ~

HO OH

t-BuOH, H2O

V. VanRheenen, R. C. Kelly, D. Y. Cha, Tetrahedron Letters 1976,

1973

Name Reaction

667

Examples:
Modification making H202 the terminal oxidant. general scheme: example substrates below. cat. 0 ~ 0 4cat. NMM, , cat. flavin, cat. TEAA H202, solvent

95%
TEAA = Et4N+AcO-= tetraethylammonium acetate

91%

91%

95%

S. Y. Jonsson, K. Farnegirdh, J.-E. Backvall Journal ofthe American Chemical Society 2001,123,

1365

DMAP-0~04 [BmimIPFs

Modification using
\

[BrnimlPFs = 1-butyl-3-methylimidazolium hexafluorophosphate

Q. Yao Organic Letters 2002,$, 2197

recyclable - reuseable

OsO,, NMO,

quinuclidine 16%
0 ~ 0 4 TMEDA, ,

68 : 32

CH2C12 82%

99 : 1 PMB =p-methoxybenzyl

T. J. Donohoe, J. W. Fisher, P. J. Edwards Organic Letters 2004,6,465

668

Name Reaction

Vilsmeier-Haack Reaction
The Reaction:
Ar-H

DMF

Proposed Mechanism:

Notes:
A substituted phenyl group is shown for illustration. Heterocycles are also common substrates. The reaction is more efficient when the aromatic ring has electron-donating groups as the Gsubstituent in the scheme above.
Vifsmeierchemistry can also be carried out on alkenes.

Name Reaction

669

Examples:
0

POC13

aYCHO
Ph NAO Ph

Cl

S. Hesse, G. Kirsch, Tetrahedron Letters 2002,& 1213

H.N.Bz L C O Z M e Ph

VilsmeierReagent

6H

>9 5%

P>

COzMe

P. G. M. Wutz, J. M. Northuis, T. A. Kwan, Journal o Organic Chemistry 2000,@, 9223 f

TES

n: POBr3 DMF 64%

H Brh

R. A. Aungst, Jr., C. Chan, R. L. Funk, Organic Letters 2001,3,2611

80%
D. L. Comins, A. L. Williams, Organic Letters 2001,3,3217

670

Name Reaction

Vinylcyclopropane-Cyclopentene Rearrangement
The Reaction:

Proposed Mechanism:

LA stereocenter can J r invert going backwards.

I
I
1
I

Examples:

0
N

Li +

D-CEN

- &or
N

(cat .)t A

68%

unstable

R. V. Stevens, M. C. Ellis, M. P. Wentland, Journal o the American Chemical Society 1968,9J, f 5576

H. W. Pinnick, Y.-H. Chang, Tetrahedron Letters 1 9 7 9 , a , 837

Name Reaction

%
H' H H' Me e M '

671

- Q _ $+&
97%
0

B. M. Trost, J. R. Paraquette, Journal of Organic Chemistry 1994,59,7568

o-dichlorobenzene

100%

J. L. Wood, A. B. Smith, 1 1 Journal of the American Chemical Society 1992,114, 1, 10075

M% e% ' Heat to 550C

Me

75%
OTBS OEt

T. Hudlicky, A. Fleming, L. Radesca, Journal of the American Chemical Society 1989,111,6691 SMe O H SMe

Me

65%
J. Satyanarayana, M. V. B. Rao, H. Ila, H. Junjappa, Tetrahedron Letters 1996,37,3565

TBDMSO
80%

TBDMSO

E. J. Corey, A. G. Myers, Journal o the American Chemical Society 1985,107,5574 f

672

Name Reaction

von Braun Reaction

Notes:
Cyanogen bromide has been classified as a "counter-attack" reagent. See: J. R. Hwu, B. A. Gilbert, Tetrahedron 1989, 1233 After attack at the cyan0 group, the released bromide counter-attacks at the least hindered position.

Examples:

CN-BI CHCl3 Me
90%

CN Me0

MeO

H. Rapoport, C. H. Lovell, H. R. Reist, M. E. Warren,Jr., Journal of the American Chemical Sociev 1967, 1942

COOMe

COOMe

79%

W. Verboom, G. W. Visser, D. N. Reinhoudt, Tetrahedron 1 9 8 2 , 3 , 183 1

Name Reaction

613

CHC13 CNBr

Me0 OH

12%

Me0

OH
6309

S. %Lee,Y. J. Lin, M. Z. Chen, Y. C. Wu, C. H. Chen, Tetrahedron Letters 1992,33-

Y. Nakahara, T. Niwaguchi, H. Ishii, Tetrahedron 1977,

1591

CNBr benzene
46%

H. Niwa, M. Toda, S. Ishimaru, Y. Hirata, S . Yamamura, Tetrahedron 1974,

This work w s a kinetic study showing the reaction is extremely fast. a

a 3031

&NB.+ I CHC13
Me No yield given G. Fodor, S. Abidi, Tetrahedron Letters 1 9 7 1 , u 1369

CN

674
28

Name Reaction

von Richter Reaction

The Reaction:

EtOH, heat KCN

NO2

'+OH

+ N2

M. Rosenblum, Journal of the American Chemical Society 1960,82,3796

Name Reaction

675

Examples:
Note solvent change:

KCN

c1pNaN
+

DMSO
40%

clyNo
CN

CN

H NH2

CN

G. T. Rogers, T. L. V. Ulbricht, Tetrahedron Letters 1968,2, 1029

This substrate was subjected to the reaction conditions to test the validity of it being a proposed intermediate.

q
0

'CN,

aq EtOH

NHZ

20%

-0
C02H

K. M. Ibne-Rasa, E.Koubak, Journal of Organic Chemistry 1963,28,3240

EtOH, H20 NO2 Br

7%

Br

J. F. Bunnett, M. Rauhut, M. D. Knutson, G. E. Bussell, Journal of the American Chemical Society 1954,76,5755

616

Name Reaction

Wacker Oxidation Reaction

The Reaction:
WO), H,O H H Pd(O), H20 H Me

HxH H
0

Proposed Mechanism:
+HC1 C ! " &d H @ P- 2 ,O -e 'G Pd(0)

'u
c'cl
C1-PdTC1,

+C

R HO & >

Pd CzH2

c .pd,cl 1
\ '

Y R
'C1

See 0. Hamed, C. Thompson, P.M. Henry, Journal ofOrganzc Chemisfry 1997,62,7082 for useful mechanistic discussion.

Notes:
Attack of water is always at the more substituted carbon of the alkene. Given competition between a terminal alkene and a more substituted one, preference will be for the terminal bond.
CatalyticAsymmetrie Wucker-Type Cyclizntion

Y.Uozumi, K. Kato, T. Hayashi, Journal of the American Chemical Society 1997,119,5063

Name Reaction

611

Examples:

62% J.-H. Ahn, D. C. Sherrington, Macromolecules 1996,

R R

4164

aldehydes only

Wacker oXidari*on
19%

MeMq
CHO HO M e L y i O Me
0

T.-L. Ho, M. H.Chang, C. Chen, Tetrahedron Letters 2003,44,6955

? & e M HO
0

+ ,

DMF, HzO PdCl2

81%

Y. Kobayashi, Y.-G. Wang, Tetrahedron Letters 2002,%, 4381

Me

Me
02,

Me Cu(OAc)2,10% PdC12 AcNMe2,HzO

Me

Me
Me Me

Me Me

84 - 88%

A. B. Smith, 111, Y. Cho, G. K. Friestad, Tetrahedron Letters 1998,3J, 8765 S.

678

Name Reaction

Wagner-Meerwein Rearrangement
See: L. Birladeanu, "The Story of the Wagner-Meewein Rearrangement", Journal of Chemical Education 2000,n, 858

The Reaction:
R
R"

OH

R'

R"

Proposed Mechanism:
R R! H R r = , H@ R R"'

R"

OH

R ' H 7 R" @HZ

- HzO

R R"

R"'

A 1,2-shift is called a Whimore Shifr.

R'

R"

R"

Notes:
M. B. Smith, J. March in March 's Advanced Organic Chemistry, 5* ed., John Wiley and Sons, Inc., New York, 2001, p. 1393
The rearrangement of camphene hydrochloride is called the Nametkin Rearrangement

Me

The "classical" - "non-classical" carbocation controversy concerned the Wugner-Meenvein rearrangement of norbornyl systems: CLASSICAL*

h &
CLASSICAL

L+-

&L

undergoes solvolysis reaction significantly faster than the endo isomer:

L

The reaction is also regulated by stereoelectronic factors:

HO'

p-Amyrin

4
\

Me

Me Me

enol of Freidelin

E. J. Corey, J. J. Ursprung, Journal ofthe American Chemical Society 1 9 5 6 ,z , 5041

@ &

&I

&

/J &

Me Me

Me

Name Reaction

679

Examples: Demjanov (Demyanov) Rearrangement The Reaction:

Examples:
.Me
BF,.OEt2 benzene Me0 90% J. R. Bull, K. Bischofberger, R. I. Thomson, J. L. M. Dillen, P. H. Van Rooyen, Journal of the Chemical Society, Perkin Transactions I 1992,2545 Me0 A detailed biosynthetic pathway analysis:

f OPP
Cyclase

$ $
\

Me

he Me T. Eguchi, Y.Dekishima, Y . Hamano, T. Dairi, H. Seto, K. Kakinuma, Journal of Organic Chemistry 2003,6& 5433

OM?

HCO2H
____)

Me

80%

S. Baeurle, T. Blume, A. Mengel, C. Parchmann, W. Skuballa, S. Baesler, M. Schaefer, D. Suelzle, H.-P. Wrona-Metzinger, Angewandte Chemie, International Edition in English 2003,42, 3961

680

Name Reaction

Watanabe-Conlon Transvinylation
The Reaction:
Et

-o*
HgiZ

Proposed Mechanism:
Hg(0Ac)z

Hg(OAc) + AcO

0
0

@Hg(OAc)

+ Et*o/\\

+ D

0-h
0

Et-O

Hg-OAc

(-yh
0 Hg-OAc

Notes:
This reaction generally uses about 10% molar equivalent of Hg(0Ach. This reaction is generally part of a sequence followed by Ciaisen rearranEement to generate a remote functional group (aldehyde).

0
OH

1. Et *o2. Heat

This approach was developed by Burgstahler for:

&(yJ-q

@O

CHO

f A. W. Burgstahler, I. C. Nordin, Journal o the American Chemical Society 1959,

a 3151

Name Reaction

681

Examples:

6
TBDMS~
&ie

EtO\// Hg+* 72%

*
CHO

f D. L. J. Clive, H. W. Manning, Journal o the Chemical Society, Chemical Communications. 1993, 666

E t d O d Hg(OAc12 60% Hg+2 OH 79%

& e
%O

HO

V. Godebout, S. Leconte, F. Levasseur, L. Duhamel, Tetrahedron Letters 1 9 9 6 , z 7255

EtC02C EtCOzC

EtJkH

D. H. Williams, D. J. Faulkner, Tetrahedron 1996,=, 4245

MEM

EtOd HgfZ 43%

MEM OHC +Me

F &Me OH

F
11327

S. T. Patel, J. M. Percy, S. D. Wilkes, Tetrahedron 1995,5-l,

682

Name Reaction

Weiss Reaction
The Reaction:
R R' O

xo+pCQR"

o (= =$ o

R'

co2 R"

R's= H, alkyl, aryl or could be a cyclobutane ring or larger

Proposed Mechanism:

MeOzC transfer
___I)

Me02C Ho

C02Me H

-H,O Me02C

Me02C

CO2Me

Ho ,H20
MeOzC C02Me MQC CO2Me saponification

Notes:
A number of examples are reported in: U. Weiss, J. M. Edwards, Tetrahedron Letters 1968, 9, 4885

Name Reaction

683

Examples:

>70%

G. Kubiak, X. Fu, K. Bupta, J. M. Cook, Tetrahedron Letters 1 9 9 0 , 2 4 2 8 5

0

1.

Meo2C

&C02Me,

pH 5.6

2. 10% HC1, HOAc

85%

(dashed bonds meant to idicate a mixture of isomers) L. A. Paquette, M. A. Kesselmayer, G. E. Underiner, S.D. House, R. D. Rogers, K. Meerholz, J. Heinze, Journal of the American Chemical Society 1992,l&2652 0 Me0,C &C02Me K2C03,MeOH

48 - 50%
A. K. Gupta, J. M. Cook, U. Weiss, Tetrahedron Letters 1988, 29,2535

1. NaOH

58 - 63%

2 . H , A 88-90% COOCH, S. H. Bertz, J. M. Cook, A. Gawish, U. Weiss, Organic Synthesis

w,SO

684

Name Reaction

Wharton Olefination

Examples:
0.

m>
COzMeO

HzN-NHz

HOAc, MeOH
5 0%

P. A. Zoretic, R. J. Chambers, G. D. Marbury, A. A. Riebiro, Journal of Organic Chemistv 1985,

50,2981

Name Reaction

685

OQy
0

:.::icH20-

pd
L m s
bBr%OH

Lms

G. Kim, M. Y . Chu-Moyer, S.J. Danishefsky, G. K. Schulte, Journal of the American Chemical Society 1993,115,30

Br%

b '
Me

H2N-M12 95%

Me 0

E:Z=l:l

T. Sugahara, H.Fukuda, Y .Iwabuchi, Journal of Organic Chemisoy 2004,

a 1744

NH2-?W,*H,O, MeOH

%H 'O

iie

o
0

Me

AcOH 86%

F. J. Moreno-Dorado, F. M. Guerra, F. J. Aladro, J. M. Bustamante, 2.D. Jorge, G. M. Massanet, Journal of Natural Products 2000, 934

HZN-NHZ, HzO

Me 52%

Me

L. Castedo, J. L. Mascarnenas. M. Mourino, Tetrahedron Letters 1987, 32099

686

Name Reaction

Wichterle Reaction
The Reaction:

:GH
+o

'.y
1.Base

Me Cl 1,3dichloro-cis-2-butene 3. "H20-equivalent"

Proposed Mechanism:

Notes:
This is a modification of the Robinson annufation in which 1,3-dichloro-cis-2-butene used in is place of methyl vinyl ketone.
O A number of "H' H " equivalents are used: Oxvmercuration conditions or formic acid and protic acid, followed by hydrolysis of the formate ester are two common approaches.

A variation of this approach:

aor
Ph3P, Et3N benzene
92 %
~

COOEt

COOEt

M. P. VanBrunt, R. 0. Ambenge, S. W. Weinreb, Journal o Organic Chemistry 2003,6& 3323 f

Name Reaction

687

Examples:
Or-BU

1 r i

-'' NU.

HCOOH HC104 37%

hie G.Stork, E. W. Logusch, Journalof the American ChemicalSociety, 1980,102, 1219

a #ICHzC1
Me
l

Me

1. NaH, DMSO

Me

Me

Me

Me

2. Me

C1

L. A. Paquette, D. T. Belmont, Y.-L. Hsu, Journal of Organic Chemistry 1985,%, 4667

Fujimoto-Belleau Reaction
The Reaction:

a&oqo
R-MBx*

Mechanistic Example: Me

M. Haase-Held, M. Hatzis, J. Mann, Journal ofthe Chemical Society Perkin Transactions 1 1993, 2907

688

Name Reaction

Widman-Stoermer Synthesis

eR
The Reaction:
Ar

Ar

NaN02,HC1

NH2

Proposed Mechanism:

Notes:
See the Borsche Cinnoline Svnthesis and the von Richter CinnolineSvnthesis for other preparations of cinnolines.

Name Reaction

689

Examples:

vclvcl
L

95%

J. W. Barton, N. D. Pearson, Journal o the Chemical Socie& Perkin Transactions I , 1987, 1541 f

HCLN*Ozc 90%

NH2

N-N

MedN.Me

Me8 'Me

B. S. Ross, R. A. Wiley, Journal of Medicinal Chemistry 1985,28, 870 Me

Et

Me

M. H. Palmer, P. S. McIntyre, Tetrahedron 1971,=, 2913

690

Name Reaction

Willgerodt-Kindler Reaction
The Reaction:
Ar

.Me + (CH2)n

m2

s8

1
Arp(CH2),, NR2

hydrolysis

Ar/iCH2 &OH

HZS

HNR2

Proposed Mechanism:

jA, ,
S

H20*

hydrolysis

Notes:
M. B. Smith, J. March in March's Advanced Organic Chemistry, 5'h ed., John Wiley and Sons, Inc., New York, 2001, p. 1567; T. Laue, A. Plagens, Named Organic Reactions, John Wiley and Sons, Inc., New York, 1998, pp. 267-269. The original Willgerodt Reaction conditions required high temperature and pressure, with use of ammonium polysulfide (NH.&S, and HzO to give either an amide or the ammonium salt of the corresponding acid. Kindler's modification, shown above, eliminated these problems and substituted SSand a dry amine, most commonly morpholine. The reaction will introduce the acid at the terminal carbon, no matter where the carbonyl position is occupied in the starting material:

L. Cavalieri, D. B. Pattison, M. Carmack, Journal o the American ChemicalSociety 1945,67, 1783 f

Name Reaction

69 1

Examples:

1. Sg, morpholine

2. NaOH
57%

I. W. Davies, J.-F. Marcoux, E. G. Corky, J. Journet, D.-W Cai, M Palucki, J. Su, R. D. Larsen, K. Rossen, P. J. Pye, L. DeMichele, P. Dormer, P. J. Reider, Journal of Organic Chemistry 2000,65,
8415

Me

1.

sg,

morpholine, Ph-SO3H

2. Br-CH2-C02H 3. H2S 24%

G. Levesque, P. Arsene, V. Fanneau-Bellenger, T.-N. Pham, Biornacrornolecules 2000,1,387

S ; m81%p h ~ ~ _ or

G&Me

S;molph~J~e 55 - 74%

mNJ rnNd
-I
G

G = C1, Me, NH,, OMe M. Mooshabadi, K. Aghapoor, H. R. Darabi, M. M. Mujtahedi, Tetrahedron Letters 1999, Q 7549

H
S,, morpholine
60%

T. Bacchetti, A. Alemagna, B. Daniel, Tetrahedron Letters 1965, fj, 2001

692

Name Reaction

Williamson Ether Synthesis

The Reaction:
R,O,H L = laving ~

1. base 2. R-L

R.OcR

O U P -X, =

-OTS,-OMS, 0 - S Q R

Proposed Mechanism:

Most Williumson Ether Syntheses proceed by an S Nmechanism. Stereochemical inversions can be ~ expected, where appropriate, as a result.

Notes:
Secondary R groups usually give low yields. Tertiary R groups are typically not successful due to elimination: H V

Examples:

o,cH2Br
HO H O OZN

NaH DMF 62%

PhHZC-0 0-CHzPh

S. Hecht, J. M. Frechet, Journal of the American Chemical Society 1999,121,4084

HOm

M. Attolini, T. Boxus, S. Biltresse, J. Marchand-Brynaert, Tetrahedron Letters 2002,

H O -

E. E. Dueno, F. Chu, S.-I. Kim, J. W. Jung, Tetrahedron Letters 1999,

COzt-Bu

MeI, K2C03
t

CH3CN F0 3 100%

+
Me0
0

75:25

Me0

Me0
0

1187

CsOH,rBqNI, 4A MS, DMF Be M 92%

rO
a1843

Name Reaction Phr. Pe O h 'M OH

693

1. NaH, 15eown-5, TH$ 2.

OTs

f'.?
71%

OTs

H. C. Aspinall, N. Greeves, W.-M. Lee, E. G. McIver, P. M. Smith, Tetrahedron Letters 1 9 9 7 , 3 , 4679 This work discusses the question of substitution vs. elimination, and has useful commentary from a synthetic point of view.

(Wang resin)

A. Weissberg, A. Dahan, M. Portnoy, Journal of Combinatorid Chemistry 2001,3,154

694

Name Reaction

Wittig Indole Synthesis

The Reaction:

ci
N H R

Ph

W R
Ph Ph Ph

Proposed Mechanism:
Ph

base

&?@
H
0 PhR

y\ Ph Ph

II

Examples:

K. Miyashita, K. Kondoh, K. Tsuchiya, H. Miyabe, T. Imanishi, Journal ofthe Chemical Society: Perkin Transactions I 1996, 1261

Name Reaction

695

CN - qcoo q
t-BuOK COOEt

64%

Me

Me

B. Danieli, G . Lesma, G . Palmisano, D. Passarella, A. Silvani, Tetrahedron 1 9 9 4 , 2 , 6 9 4 1 Ph

t-BuOK H
Me

96%

Me

M. Le Core, Y. Le Stane, A. Hercouet, H. Le Brown, Tetrahedron 1985,a, 5313

696

Name Reaction

Wittig Reaction (Wittig Olefination Reaction)

The Reaction:
Ph\ PhyP Ph
+

R R ' t X

1. base
I""#; '

s ph,q\ph
Ph

H
R"

KR"'

R"

Proposed Mechanism:

-x o
phosphonium salt

trip henylphosphine

phosphorous ylide or phosphorane

betaine

oxaphosphetane

Notes:

Phosphorous and oxygen form very strong bonds, driving the manner of oxaphosphetane decomposition.

Ph\ PhyP=O Ph

R"

triphen ylphosphine oxide

Other phosphines may be used for this reaction, but the choice should not contain a protons that could be abstracted as is the proton on the halide coupling partner, as a mixture of desired and undesired ylides would be formed. Usually, one uses a strong base such as BuLi, NaNHz / N H 3 , NaH or NaOR. Preferred anti attack ofylide, minimizing steric interactions. Bond rotation follows to As a result, this reaction often gives the cis / Z - alkene. form the betaine.

00

Name Reaction

697

If the halide contains an electron withdrawing group, the negative charge in the ylide is delocalized, decreasing its nucleophilicity and reactivity. Aldehydes may still react, but ketones most likely will not. Ph Ph Ph I ,Ph

OG

Bestman's Protocol: The intermediate ylide can be cleaved by ozone. By careful addition one can

carry out a unique Winig reaction: PPhp=(

-%

Ph3P0 + 0

Examples:
0

Me,&$ Me0

'

H2C

S.P. Chavan, R. K. Kharul, R. R. Kale, D. A. Khobragade, Tetrahedron 2003, a 2737

go:\ +
Ph*y'Ph Ph OAC

65%

OAc MeOzC

MeOzC

R. K. Boeckman, Jr., T. R. Aless, Journal of the American Chemical Society 1982,104,3216

15 - 25%

->rN /
0

Reaction with polymersupported PhP3 ratha than Bu3P gave:

A

43%

B. J. Neubert, B. B. Snider, Organic Letters 2003,2,765

698

Name Reaction

[1,2]-Wittig Rearrangement
The Reaction:
H

R'

R = H, Alkl, Aryl, Alkenyl, Alkynyl, -COOR, -COOM R' = Alkyl, Ally, Benzyl, Aryl

Proposed Mechanism:
solvent cage

1 0-H

oO,io

/?.H0

R'
RAOdH

1,2 sigmatropic rearrangement

Notes:
The oxygen can be replaced by nitrogen and then the reaction is known as /I,Z]-Aza-Winig
Rearrangement:

R'
I

Examples:
TIPS

n-BuLi, TMEDA

Me
78%

Me

P.Wipf, T. H. Graham, Journnl of Organic Chernisfry 2003,@, 8798

Name Reaction

699

87%

Mi

R. E. Maleczka, Jr., F. Geng, Journal ofthe American Chemical Society 1998,120. 8551

MM e 0 e

m s 71% n-BuLi

MeO+TMs M e 0 Me0

K. Tomooka, H. Yamamoto, T. Nakai, Journal of the American Chemical Society 1996,118. 33 17 ' 3 C x o B n

Phy 0 Me

65%

Phy Me

(4:6)

A. Garbi, L Allah, F. Chorki, M. Ourevitch, B. Crousse, D. Bonnet-Delpon, T. Nakai, J.-P. Begue, Organic Letters 2001,2,2529

Via dehydration of major product: OH Me

0 5

Me0
L. Lemiegre, T. Regnier, J.-C. Combret, J. Maddaluno, Tetrahedron Letters 2003, 44, 373

LiEs-

F3cflBn

F3cqr
Bn

Ph

Y Me

700

Name Reaction

[2,3] -Wittig Rearrangement

ProDosed Mechanism:

R'z:
Examples:
Y. J. Li, P.-T. C.-M. Yang, Y.-K. Chang, Y.-C. Weng, Y.-H. TefruhedronLeffers2004,45, Lee, Liu, 1865

Name Reaction

701

OTBDPS 72%
A. S. Balnaves, G. McGowan, P. D. P.Shapland, E. J. Thomas, Tetrahedron Leffers2 0 0 3 , s 2713

Me BU'Q&H2 BuLi

Me

Bu * e C H 2

'

"7''snBu3 Et
Me Bu+CH2
O

OYLi Et

76%

Et

BuLi 2 8% snBu3

Bu

2
I
HO

7' '
Et

AEt

+fl
Bu
Et

(24:76)

K. Tomooka, T. Igarashi, N. Kishi, T.Nakai, TefruhedronLefters 1999,40,6257

6 6
. \OH
___t

Me

t-BuLi THF 79%

Me CH2

M. Tsubuki, K. Takahashi, T. Honda, Journal of Organic Chemistry 2003,&f

10183

702

Name Reaction

Wolff Rearrangement
The Reaction:

Proposed Mechanism:
0

avoiding the carbene intermediate.

Notes:
M. B. Smith, J. March in March's Advanced Organic Chemistry, 5Ih ed., John Wiley and Sons, Inc., New York, 2001, p. 1405 Smith's Vinylogous Wolff Rearrangement:

c42

Me

Me

&Jcm2

cc;+ ;a2
5 6%
Me
C02Me

A. B. Smith, 111, B. H. Toder, S. J. Branca, Journal of the American Chemical Society 1985,106, 1995

Name Reaction

conditions
___L_

MeOH

AgzO,
CuSO4,A

hv Smith, et. al. (continued)

56 1 4 2 0 :85 92: 8

microwave

o/-yHz
92%

S. G. Sudrik, S. P. Chavan, K. R. S. Chandrakumar, S. Pal, S. K. Date, S. P. Chavan, H. R. Sonawane, Journal of Organic Chemistiy 2002,67, 1574

1. NaH, H-C0,Et
2. T s , N ~
b

AOM

MeOzC

3. hv OMe
48%

D. P. Walker, P. A. Grieco, Journal o the American Chemical Society 1999,121, 9891 f

hv H .N, Me Boc MeOH

48%

Me%OMe H

.N.

Boc

H. Yang, K. Foster, C. R. J. Stephenson, W. Brown, E. Roberts, Organic Letters ZOOO,z, 2177

Cu(acac)2 MeOH, A

5 0%
0

Me

B. Saha, G. Bhattacharjee, U. R.Ghatak, Tetrahedron Letters 1986,27,3913

( . y MeC O z M e L Me

dMe
703 COzMe

704

Name Reaction

Wolff-Kishner Reduction
The Reaction:
R

iw

H2N-NH2 * H2O

KOH, A

R'

Proposed Mechanism:

M. B. Smith, J. March in March's Advanced Organic Chemistv, 5* ed., John Wiley and Sons, Inc., New York, 2001, p. 1548

Notes:
See cutecholborune for a mild and selective alternative to the Wolff-Kishner reduction.
TS-NH-NH~

g N * N H T s

Enone systems can undergo rearrangement

0
The commonly used approach (above) is better recognized as the Huung-Minlon modification.

Under WolffKishnerconditions. a Drimarv mine can be converted to an alcohol:

<

/O/CH2iw2
,.
hydrazine, KOH
54%

Me0

diethylene glycol, 21 0C

Me0
8

S.M. A. Rahman, H.Ohno, N. Maezaki, C. Iwata, T. Tanaka, Organic Letters 2000,z 2893

Name Reaction

705

Examples:

Wolf-Kishner 79% for the two steps

Me' 8 Hlrt

bH

M. Harmata, P. Rashatasakhon, Organic Letters 2001,2,2533

&
Me Me
H

Wolf-Kishner *

8
Me H

81%

Me

H. Nagata, N. Miyazawa, K. Ogasawara, Organic Letters 2001,3, 1737

J. P. Marino, M. B. Rubio, G. Cao, A. de Dios, Journal of the American Chemical Society 2002,124,

13398

Me

w
Me

1. WolfiKishner

Me Me
f

2. Followed by esterification of the hydrolyzed ester with CH2N2

25%

' e C 0 O M e Me

n
Me

Raney Ni 90%

A. Srikrishna, K. Anebouselvy, Journal of Organic Chemistiy 2001,&, 7102

706

Name Reaction

Woodward Modification of the Prevost Reaction

The Reaction:
silver acetate

acetic acid, H 2 0

HO cis

OH

Proposed Mechanism:

less-hindered face

H
proton transfer

H4$-H

Notes:
The Prevost Reaction:

12

' K0 oAg0 R
Contrast this reaction with oso4 hh040 or Steric "bulk"

tram diol

This Woodward-Prevost reaction provides cis diols at the more hindered face. This is due to the first step, the addition of iodine from the less-hindered face.

oso4
7

Woodward-Prevost

HO

OH

Name Reaction

Examples:

&)
H -

less-hindered face

D. Jasserand, J. P. Girard, J. C. Rossi, R. Granger Tetrahedron Letters 1976,11, 1581

;* OHHH water during reaction

707

1. NBA, AgOAc

2. HOAC,HzO 3. LAH

HO

Hofi
H

85%

S. H a m , L. Hennig. M, Findeisen, D. Muller, P. Weizel, Tetrahedron 2000, 5 6 , 1345

Examples are available to show that show the necessary acetate participation does not always take place:

Me
M. A. Brimble, M. R. Naim, Journal of Organic Chemistry 1996,6l, 4801

708

Name Reaction

Wurtz (Coupling) Reaction and Related Reactions

In the Wurtz Reaction, both halides are alkyl. For the Wurtz-FittigReaction, there is one alkyl and one aryl group, while in the Fittig Reaction, both coupling partners are aryl halides.

Wurtz (Coupling) Reaction: 2 Na 2 R-X R-R + 2NaX Fittig Reaction

2Ar-x

Wurtz-Fittig Reaction
Ar-X

2 Na
k-k

+ 2NaX

R-X

2 Na

Ar-R

2NaX

Proposed Mechanism:
Much is not known about the details of the reaction. It could be a simple S Nor S N ~ : ~ 2 Na Na-X + R0 Na 0 R-X

or a radical pathway could be followed: 2 Na R-X + R-X 2NaX + R

solvent cage

I.

R-R

Notes:
M. B. Smith, J. March in March's Advanced Organic Chemistry, 5 ed., John Wiley and Sons, Inc., ' New York, 2001, p. 1452; T. Laue, A. Piagens, Named Organic Reactions, John Wiley and Sons, Inc., New York, 1998, p. 282
See: T. D. Lash, D. Berry, Journal o Chemical Education 1985,Q, 85 f

Examples:
Me
Me

J. W. Morzycki, S. Kalinowski, Z. Lotowski, J. Rabiczko, Tetrahedron 1997,2, 10579

Name Reaction B r o C l dioxane

709

0
m,133
Pr

78 - 94% G . M. Lamprnan, J. C. Aumiller, Organic Syntheses

TMSCl

+
PI
Pr

Na wire EQ 63% Na wire

____)

Pr

TMSCl + Hex

EQ

64%

Hex

P. F. Hudrlik, A. K. Kulkami, S.Jain, A. M. Hudrlik, Tetrahedron 1983,3,877

+ CD~I
Me Me

Na cyclohexane
rn

40%

Me

Me

T. L. Kwa, C. Boelhouwer, Tetrahedron 1969,

me F
c 1
60%

5711

f-Bu-C1

Na (molten)

3 5%
C. C. Chappelow, Jr., R. L. Elliott, J. T. Goodwin, Jr., Journal o Organic Chemistq 1962,z,1409 f

PhiC1

*
27%

Phf

Ph

c 1
Ph Ph

Ph

H. Nozaki, T. Shirafuji, Y . Yarnamoto, Tetrahedron 1969,25,3461 Mn, CuClz

81%

J. Ma, T.-H. Chan, Tetrahedron Letters 1998,2,2499

710

Name Reaction

Yamaguchi Esterification / Reagent

The Reaction:
2,4,6-trichlorobenzoyl chloride

OH

Et3N,DMAP,R'OH

Proposed Mechanism:

DMAP = N,N-Dimethylaminopyridine

Me

he 4 resonance structures

Me

- DMAF'
___c

;.Me Me
I

Name Reaction

71 1

Examples:

NEt, DMAP, toluene

Repeated isomerizations provide 75% of one isomer. R. Nakamura, K. Tanino, M. Miyashita, Organic Letters 2003, 5 , 3 5 8 3 OH

Me

Me

M. Berger, J. Mulzer, Journal of the American Chemical Society 1999,121, 8393

OTBS

P.A. Wender, J. L. Baryza, C. E. Bennett, F. C. Bi, S.E. Brenner, M. 0. Clarke, J. C. Horan, C. Kan, E. LacBte, B. Lippa, P. G. Nell, T. M. Turner, Journal of the American Chemical Society 2001, 1 4 13684 2,

712

Name Reaction

Yamamoto Esterification
The Reaction:
O. A R Sc(OT03, MeCN

ProDosed Mechanism:

Notes:
Sc(0Tf)l is commercially available. This reaction provides good yields and is able to esterify relatively hindered alcohols:

91%

Me
Ph catalyst Ph

Me

MI

DMAP, Et3N SC(OT03

15%

> 95%

K. Ishihara, M. Kubota, H. Kurihara, H. Yamamoto, Journal oforganic Chemistry 1996, Alcohols react preferentially over phenols; an observation not common to other methods.

a 4560

The reaction is readily extended to lactone synthesis:

n
&2 Q

r Y 7
COOH

OZN Sc(OTf),

HO

MeCN THF
9 2%

K. Ishihara, M. Kubota, H. Kurihara, H. Yamamoto, Journal oforgunic Chemistry 1996,

CYh
0

a 4560

Name Reaction

713

Examples:
Yamamoto has examined a number of catalyst systems for the reaction. A simple process using HfCI, in a soxhlet extractor has shown usehl characteristics: P- O H hC O

HE4 Ph-CH20H

THF
97%

K. Ishihara, S. Ohara, H. Yamamoto, Science 2000,290, 1140