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628 Name Reaction

Stork Enamine Synthesis

The Reaction:
R.N.R
H
& 1. R-X
VH&

2. hydrolysis

Proposed Mechanism:

R .R R .a-R
f- HA- X@
R@
., R
&H
R, .R .&

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 * E l l + 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:
n

6 ph& (15 mol %)

proline
DMSO
94%
B. Kist, P. Pojarliev, H.J. Martin, Organic Letters 2001, & 2423
F N 0 2
Name Reaction 629

stork - &NrJ Pd(OAc)2, PPh, c

( H5 0
ennmine synthesis
-
H
A~o,),,oA~
0

Trod 's TMM R e a c h

D C H i 45%

F. Bouno, A. Tenaglia, Journal of Organic Chemistry 2000, 3869

#
Me CO2Me
- N
H
TsOH, - H2O
3 ' O Z M e PdC12(MeCN)2
Et,N
67% 37% overall yield
for the sequene

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

2. MVK, hydroquinone
Not isolated.
3. NaOAc, HOAc
Me0

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

630 Name Reaction

Stork-Wittig Olefination

e
The Reaction:
0
H Ph3P-CH21 I
Base
0

Proposed Mechanism:
R
r7
Ph,@ Base
Ph-P-f.' Ph-PT
Pi I P$ I @-
Ph'T- Ph
Ph
See: Wttig Reactwa
R

Ph

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

Examples:

Brc)
Et "'cl
0
Ph3P-CHZI I
0
NaHMDS, THF, HMFA* BrD
Et "'Cl

*-CHO 72%

Z:E
3 I
9:l

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

 $
Name Reaction 63 1

\ Me,. 32.Swem
l.LiBHdO
. Ph,P=CHI
xidarion I $ \

ph-lti. &.\ Ph-Ii', \

62% overall TMSO
TMSO
OTBS OTBS

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

0
Ph3P-CH2I I0
*
NaHMDS
OPMB
Me Me &i 80%

?TIPS

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' 0

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 of the American Chemical Sociev
1996,118,4910
Name Reaction 633

TBSO-(CH&-CHO +
q:*
I
he
HCN
chiral Zr catalyst
8 0%
t
P O

Me
H

--
91% ee

OTBS
several steps 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:

F

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 O
H20
imine hydrolysis
b

I 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, a

1035

Other degradation reactions:

Bergmann Degradation

H
0
1. BnOH
2. Hz , catalyst
3. hydrolysis
w R 1 m2
+
R'
0
J
,
H
+ C02 + benzene + NH3

Darapsky Degradation (Procedure)

0 1. H?NNH,
2. H ~ N O-
NCYmZ I
4.acidic workup R
Name Reaction 63 5

von Braun (Amide) Degradation /Reaction

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 NH40

oq$o HN R ~ c o o H ~ 0 HN
H1
N$N%.;. NH

0 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
heat
Me COOH Me H
0
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
+
COOH
Me+e

0
- MeHo
heat
Me H
+
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 Ninhydrin
Steam distillation
Me Me
61%
~

Y
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, 2457
*RO,

R-x +
R'
">=<
R"
B-oR*

Where X = I 25 Br > OTf >> Cl.

Pd(0)
NaORorNaOH.
R' R"

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

R' R"
;:PdtL OR
cis-trans
isomerism
H
H p d - L
R' R"
+w~ OR*
*RO,
-OR*

RO-$ R' R"

OR* transmetalation

Notes:
General sources of common boron reagents:

R-Li f B@'O), a
R--B/
OR'

OR'
-
Hydrolysis
R- B,
OH

OH

BCl3 + R3SiH
A
J R
H
R-
HBClz
* Rh
H B-C1
R'OH,
H
)=\
B-OR'
ci R'O'
Name Reaction 637

Examples:

R e L i -
B(Oi-Pr)s
R-B(Oi-Pr),Li
@
8
1- Pd(Ph3P)d
ArBr,DMF
RA
-r

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

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

t-B,+OTf

dba: dibenzylidene acetone

+

r-Bu+P
Me
Pd(oAc)z' pcy3
KF, m,rt
96%

A.F. Littke, C. Dai, G.C. Fu, Journal of the American Chemical Society 2000,127,4020
Me

Me
M e 0 2 C v B'oH
YH a',
Pd(Pt-B~3)2
76%
CsF ~

M. Rubina, M. Rubin, V. Geforgyan, Journal of the American Chemical Society 2003,125.7198

HO,B/OH

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

TBDMSO
SO2Ph OMe

BnO - 1
98%
Y . Liu, G.W. Gribble, Tetrahedron Letters 2000, 41, 8717

B2H6
/

TBDMS
Ph0,s

(cp2)6
TBDMS
Pd(dppf)2Clz,
B-(Z2)6)3Cs2C03 TBD)-@+ 0 OBn
OTBDMS OTBDMS
70%
D. Meng, S. J. Danishfesky, Angewandte Chemie, International Edition in English 1999,38, 1485
638 Name Reaction

Swern Oxidation
The Reaction:
OdH oxalyl chloride, DMSO
CH2C12 * R 8,
DMSO - Dimethylsulfoxide

Proposed Mechanism:
cold 0
(bel0w-60"C)~
c1
Me
DMSO
oxa ly 1 chloride

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

c1 0)
4
9Me Me

N A N

CIANACl
-
DMSO

THF
N A N

CIAiVACl
- Me)-OH
Me
Me Me

Me

- Et3N Me

Me
)=o Extremely mild, easy workup.
Name Reaction 639

90% 74% 90%

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

+;.+
Examples:
Me Me
Swern
8 9%
Oxidation

Me Me OH
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

- 97% Cbz
Me Me Me

M. F. Semmelhack, Y.Jujang, D. Ho, Organic Letters 2001, 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
R+o H THF

CHI, + CrCl2 -[
Proposed Mechanism:
Cr"' CHI2] Clcl2 * [ 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
H Me
51%

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 I

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

Name Reaction 641

Examples:

H
-P
CrCI,, CHI,
85 %
Me ( C H 2 b v I

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

""'0
Me"63%-
CrC12, CHI3

S. Chackalamannil, R. Davies, A. T. McPhail, Organic Letters 2001,3, 1427

Me
Hoi/cHo
CrClz > HO

J. Cossy, D. Bauer, V. Bellosta, Tetrahedron 2002,58- 5909

H
CrC12, CHI,
74%
P H l&q+
OAc OAc
I. C. Gonzalez, C. J. Forsyth, Journal of the American Chemical Sociew 2000,122.9099

61
M. E. Jung, B. T. Fahr, D. C. D'Amico, Journal of Organic Chemistry 1998,Q, 2982

TMS
CrC12,CH13

78%
R. Garg, R. S.Coleman, Organic Letters 2001,3,3487
~

I 7, TMS
 642 Name Reaction

Tebbe Reagent / Olefination

The Reaction:

a‘ .’ c1
c1
-
Proposed Mechanism:
AlMe,

transmetalation
Q
dTi=CH2
a hydride abstraction
-
C1AlMe2

coordination

Notes:
See Tebbe Reaeent

Tebbe reactions on beads:

rolR Tebbe Reaction- 0

A. G. M. Barrett, P. A. Procopiou, U. Voigtmann, Organic Letters 2001, s, 3165

The Oshima modification provides another entry into methylenation:

CHzBr2, Zn
r BrZn ~ ~

V
ZnBr 1
*
TiCl,, THF

L 1
For details of competitive regiochemical analysis with a number of reagents, see:

Me
___Lc

O
H
C- M
e

T. Okazoe, J.-I. Hibino, K. Takai, H. Nozakil, Tetrahedron Letters 1985, 5581

Name Reaction 643

Examples:

w
d 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,

118,1565

Me Me

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

2001, a 348

Me
4 Me
4
N. A. Petasis, M. A. Patane, Tetrahedron Letters 1990, 6799
644 Name Reaction

Thiele-Winter Reaction (Acetoxylation) (Thiele Reaction)

The Reaction:
0 OAc

0 OAc

Proposed Mechanism:
acetic anhydride

__t

Me
0 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% I
0 OAc
Ac~O

0
CF3-SOzF

It
88% "-o-"' OAc

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

L#j EtO
calixerane
a 2
A 62%
c 2 c~
AcO@J
~
OAc
~
EtO
calixerane
CH2

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 of Organic Chemistry 2002,B,4612

646 Name Reaction

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

The Reaction:

Proposed Mechanism:

proton
transfer
2. A
NH2
Hydrolysis I iydrolysis and decarboxylstion
(if desired) (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 Thorpe

0
2 RCOOR' n
NaH
0
2 R-CN

15%
NC
0
H. Plienenger, W. Muller, Chemische Berichte 1960,93,2029 (AN 1961:13347)

Examples:

46)
0 Me Me
1. t-BuOO, 1-BuOH
2. AcOH, H3P04

68%
0
Me Me
A. Toro, P. Nowak, P. Deslongchamps, Journal of the American Chemical Society 2000,122,4526
Name Reaction 647

91% Me-N
Me
I
xgH2
L. Lu, R. K. Shoemaker, D. M. S . Wheeler, Tetrahedron Letters 1989,

CN
B h z c :

CN
a,6993

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

SKz:s
Me Me

Me
w
CN

N H 2

Me No yield given

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

CN

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

0
RARH C S N
w
- N
&,;(
OH

3 (:&NH2
OH

Takuchi Modification
Li Li ,

0"' LiCHBr2 ~ @CH~B~ BuLi_ a-elimination m

Li,
Name Reaction 649

0
Examples:

EHO
*@ Takuchi Modificatwn
c 0

62%
0

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

2000, 2419

HzNH2C NaN02b
HOAc
%
CHZNH, 54% 0

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

3221

4 NOH H 2
NaN02
____c

83%
4 0
+
(2:1)

- NaNO,
H2S04
4 0
+
(12:l)
100%

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), 0
___)

Proposed Mechanism:

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

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:
Si(W3

Me0
ncHo Et3SiH, KOz
18-Crown-6
Me0 72%
+

Me0 OMe
28%

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 of Catalysis 2003,217, 117

DCH0 Cp2NdCH(TMS)2

88%

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.

H Me 0 Me 4 - H2 0

94%

G. K.Finch, Journal of Organic Chemistry 1960, 2219

652 Name Reaction

Trost’s TMM (trimethylenemethane) Cycloaddition

The Reaction:

TMS&OAc + rEWG Pdo

L
EWG

Proposed Mechanism:
TMSJCOAC

w
E‘

EWG can stabilize

the anion and allow
G

EWG
v
pdo \i
for bond rotation.

EWG
4
Notes:
An analysis of the use of orbital theory to rationalize product formation from the diradical Th4M
analog formed by nitrogen extrusion:

+s-(y3& -6
P L UMO LUMO

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

Name Reaction 653

Examples:
0

60%

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

CaMe

'CQMe
Pd(PPh,),, DPPE, THF

50%
~

MeO,C
b
25:l /@am:
%02Me
cis toluene
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

"'C02Me
50%

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:

@: hydrolysis Ar
+ H2NA

0 0
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 of the American Chemical Society 1973, s,292
ProDosed Mechanism:

Notes:

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

ph L = ligand
L'O'L

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 of Organic Chernisty 2002,67,6837

Name Reaction 657

A water-mediated, transition metal free reaction:

MeOzcXH
MeOzC H ,K2a3
D
HZO, DMF

71%
Me

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

sat3

J=T
Pd(OAch, dppe
*
AcO AcO
COzMe
COzMe
64%

SiEt, SiEt,

0
A OAc
Pd(OAch, dppe
COZMe
~

MeOzC Me
MeOzC
M
$-'e
30%

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%), O H C C p h
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:

R 2 OH + koEt
1.NBS
2. AIBN,HSn(n-Bu)r OEt

Proposed Mechanism:

0'""ToEt- aoroEt
Examples:

+ Bu3SnH D O E t
AIBN
Br Br
50 - 55%

G. Stork, R. Mook, Jr., S. A. Biller, S. D. Rychnovsky, Journal of the American Chemical Society
1983,105,3741
Name Reaction 659

k 0 t - h

-G--
t-BuO
4Me
O O O
Bu3SnH
7
9 8%
t-BuO

-0

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

EtopBr b 0 t - B ~
t
EtO

NIS
98% O b M e
9-

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

44YO
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

6
3:l CHCI,:TFE__
+
~

+ T O H

NIC: CO2H H?N 38%

OHC

= 2,2,2-trifhi0r0etha1101

Me
P. Cristau, J.-P. Vors, J. Zhu, Tetrahedron 2003, a 7859

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

662 Name Reaction

Ullmann Coupling Reaction

The Reaction:
2 Ar-I -cu
A
Ar-Ar + CuI2

Proposed Mechanism:

Ar-I + cu -heat

oxidative
Ar-cu-I
cu
u
cu-I

Ar-cu - Ar-I

oxidative
I
I
Ar.cu 'Ar

addition addition

- reductive
elimination
Ar-Ar

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'
+
Ar'-AlJ
+ cuI2

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 95%
87%

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

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
H

There is also the related Jourdan Synthesis:

COOH COOH

02N

Examples:

c u l , cs2co3
NMP, microwave
t-Bu t-Bu
90%

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

Name Reaction 665

I \n I + HO /o CUI, cs,co,

N,N-dimethylglycineb
95%

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

CHO

H *N \Ac
1.NaH

CuBr
2.61% +oq
CHO
0 MeOzC

H
'1
eN ~ A C

A. V. R. Rao, J. K. Chakraborty, K. L. Reddy, A. S . Rao, Tetrahedron Letters 1992, a 4799

Me
I

8 1%

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

OBr
' +

'
cu,r~KzC%
microwave
76%
aNo
Br 0
&N,,ph
- CuI, K2CO3
rmcrowave
66%

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
CuC1, NaOMe
MeOH,DMF
5 8%
Me

F Me

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

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

95% 91% 91% 95%

TEAA = Et4N+AcO-=
tetraethylammonium acetate

S. Y.Jonsson, K. Farnegirdh, J.-E. Backvall Journal ofthe American Chemical Society 2001,123,
1365

DMAP-0~04 Modification using

\

[BmimIPFs

[BrnimlPFs =
hexafluorophosphate
1-butyl-3-methylimidazolium I recyclable - reuseable I
Q. Yao Organic Letters 2002,$, 2197

OsO,, NMO,
68 : 32
quinuclidine
16%
0 ~ 0 4 TMEDA,
,
99 : 1
CH2C12
82% 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 H
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 G-
substituent in the scheme above.

Vifsmeierchemistry can also be carried out on alkenes.

Name Reaction 669

Examples:
0 Cl
POC13

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

H.N.Bz Ph
VilsmeierReagent
L C O Z M e NAO
Ph
6H >9 5%
Ph
P> COzMe

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

TES
‘0
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:

L A stereocenter can
r invert going backwards.
J
I
I 1 I

Examples:

0 N
Li + D-CEN - &or” N
I
N
A
(cat .)t

Y 68%
unstable

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

5576

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

%
Name Reaction 671

- Q _ $+&
H' 97%
0

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

o-dichlorobenzene

100%
H'
H
MeM
'e

J. L. Wood, A. B. Smith, 111, Journal of the American Chemical Society 1992,114,10075

Me%%
' 0 S

Heat to 550°C
* Me 0
- /
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 TBDMSO
80%

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

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
MeO Me0

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 M I F M e

/ /
Me0
Me0 12%
OH OH

S. %Lee,Y. J. Lin, M. Z. Chen, Y. C. Wu, C. H. Chen, Tetrahedron Letters 1992,33- 6309

Y. Nakahara, T. Niwaguchi, H. Ishii, Tetrahedron 1977, 1591

- CNBr
benzene

46%

H. Niwa, M. Toda, S. Ishimaru, Y. Hirata, S . Yamamura, Tetrahedron 1974, a 3031

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

& NI B . +
CHC13
Me CN
No yield given

G. Fodor, S. Abidi, Tetrahedron Letters 1 9 7 1 , u 1369

674 Name Reaction
28
von Richter Reaction
The Reaction:

EtOH,
KCNheat ~ '+OH + N2
NO2

0 0

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

Name Reaction 675

Examples:

c1pNaN
Note solvent change:

+ C l e O H

- H CN

clyNo
KCN CN
C l 0 N 0 2 + +
DMSO

40% + C l P W
H CN
0 NH2

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
NHZ
'CN, aq EtOH

20% -0 C02H

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

EtOH, H20
NO2
7%
Br 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 H Me

R -
HxH H
Pd(O), H20

Proposed Mechanism:
0 +HC1

"@&Pd,-OH2
C! Pd(0) 'u c'cl
C1-PdTC1,
+C P

I
-'Ge
f Y R
c1.pd,cl
R&HO
> Pd CzH2 \' '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, 4164

R R

aldehydes only

Wacker oXidari*on

19% * MeMq CHO

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

? ? & e M +
-, DMF,
PdCl2
HzO HO
M e L y i O

HO
81% Me
0
0

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

Me Me Me Me
02, Cu(OAc)2,10% PdC12
AcNMe2,HzO Me
Me Me 84 - 88% Me Me

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

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" OH
R
R ' H 7
R" @HZ
R"'
-- HzO R

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

R' 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:

&I
CLASSICAL* & = /&J @
&

h&CLASSICAL

L+-
undergoes solvolysis reaction significantly faster than the endo isomer:
&L
L
The reaction is also regulated by stereoelectronic factors:
Me Me

p-Amyrin
-
HO'
4
\
Me Me
Me Me

enol of Freidelin
E. J. Corey, J. J. Ursprung, Journal ofthe American Chemical Society 1 9 5 6 ,z , 5041
Name Reaction 679

Examples:
Demjanov (Demyanov) Rearrangement
The Reaction:

Examples:

.Me
BF,.OEt2
benzene
Me0 90% Me0
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

A detailed biosynthetic pathway analysis:

f OPP

Cyclase

Me H

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

Me

HCO2H
____)
A
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-
* O o F
D O H HgiZ

Proposed Mechanism:
0 0
Hg(0Ac)z = Hg(OAc) + AcO

0 Et-O

@Hg(OAc) + Et*o/\\ + D O H 2 0-h 0 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 *o-

2. Heat
,

This approach was developed by Burgstahler for:

@O

&(yJ-q CHO

A. W. Burgstahler, I. C. Nordin, Journal of the American Chemical Society 1959, a 3151

Name Reaction 681

Examples:

TBDMS~
6 Et’O\//

Hg+*
72%
*
CHO

D. L. J. Clive, H. W. Manning, Journal of the Chemical Society, Chemical Communications. 1993,

666

&ie -E t d O d &
e

HO Hg(OAc12 %O
60%

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

EtC02C EtCOzC
EtJkH
*
Hg+2
OH 79%

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

MEM - Et’Od

HgfZ
MEM

OHC +Me
F&Me OH 43%
F
S. T. Patel, J. M. Percy, S. D. Wilkes, Tetrahedron 1995,5-l, 11327
682 Name Reaction

Weiss Reaction
The Reaction:

xo+p-
CQR"
R O
R' o=($=o R'
co2R"
R's= H, alkyl, aryl or could be a cyclobutane ring or larger

Proposed Mechanism:

MeOzC
transfer
___I)

-H,O
C02Me
Me02C Ho H Me02C

Me02C R 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:

H >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%
0
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> 0. COzMeO

B
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

Lms
:.::icH20- pd
L m s
G. Kim, M. Y . Chu-Moyer, S.J. Danishefsky, G. K. Schulte, Journal of the American Chemical
Society 1993,115,30

Br% b' H2N-M12

95% bBr%OH

Me Me E:Z=l:l
0

T. Sugahara, H.Fukuda, Y .Iwabuchi, Journal of Organic Chemisoy 2004, a 1744

NH2-?W,*H,O, MeOH

%
'OH iie o Me
AcOH
86%
- H O q :

0 0
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

Me
HZN-NHZ, HzO

52%
Mec
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
+
5 u o

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-buteneis used in
place of methyl vinyl ketone.

A number of "H'O H " equivalents are used: Oxvmercuration conditions or formic acid and protic
acid, followed by hydrolysis of the formate ester are two common approaches.

aor
A variation of this approach:

COOEt
Ph3P, Et3N
benzene
~

COOEt
0

92 %

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

Name Reaction 687

Examples:
Or-BU

I I I
1 r i
-'' NU. c -
HCOOH
HC104
37%

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

a #ICHzC1
Me Me
l
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

a&oqo
The Reaction:

R-MBx*
R
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

NH2
NaN02,HC1
Ar

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 of the Chemical Socie& Perkin Transactions I , 1987, 1541

HCLN*Ozc

NH2 90% 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
1 .Me +
(CH2)n
-
m2
A
9 s8
Arp(CH2),,
1 NR2 -
hydrolysis
Ar/iCH2 &OH
+ HZS +
0

HNR2
Proposed Mechanism:

jA, , H20*

S hydrolysis 0

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 of the American ChemicalSociety 1945,67, 1783

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

P
d M e S ; m81%
orph~~_ mNJ
G&Me

G = C1, Me, NH,, OMe

55 - 74%
S;molph~J~e rnNd
G
-I

M. Mooshabadi, K. Aghapoor, H. R. Darabi, M. M. Mujtahedi, Tetrahedron Letters 1999, Q 7549

O H 0 s
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 - 1. base
2. R’-L
R.OcR‘

L = laving ~ = -X,
O U P -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
-
-
‘OH
NaH
L
DMF
62%
PhHZC-0
-
0-CHzPh

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

OZN COzt-Bu MeI, K2C03

t
CH3CN
HOm y C F0 3 100%

+
Me0 Me0 Me0
75:25
0 0

M. Attolini, T. Boxus, S. Biltresse, J. Marchand-Brynaert, Tetrahedron Letters 2002, 1187

HO- CsOH,Br-Me
BqNI,
92%
4A MS, DMF rO
E. E. Dueno, F. Chu, S.-I. Kim, J. W. Jung, Tetrahedron Letters 1999, a1843
Name Reaction 693

Phr. OH 1. NaH, 15eown-5, TH$

P
O
h'Me 2. f'.?
OTs OTs
*
71%

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:
Ph

ci N
H
R
W R
Proposed Mechanism:
Ph Ph

&?@
Ph Ph
\
base

0
II
PhR y\ Ph
Ph

Examples:

K. Miyashita, K. Kondoh, K. Tsuchiya, H. Miyabe, T. Imanishi, Journal ofthe Chemical Society:

Perkin Transactions I 1996, 1261
Name Reaction 695

q - qcoo
CN H
Me
COOEt
t-BuOK

64%
Me

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

Ph

t-BuOK

Me Me
H 96% H

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 +
R
R ' t X
1. base
I""#; ' +
s
ph,q\ph
Ph H R R" Ph
R"
KR"'
Proposed Mechanism:
- xo

trip henylphosphine phosphonium salt

phosphorous ylide betaine oxaphosphetane

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

- Ph\
PhyP=O
Ph
+
R R"
triphen ylphosphine
oxide

Notes:
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, Bond rotation follows to As a result, this reaction often
minimizing steric interactions. form the betaine. gives the cis / Z - alkene.

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 I ,Ph
Ph

0 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
+

MeOzC
OAC 65%
MeOzC
OAc

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

15 - 25%
->r- 0
N /
Reaction with polymer-
supported 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

R
1 - /?.H0
oO,io
0-H 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:
H R'

I
H

Examples:
TIPS

n-BuLi, TMEDA

Me Me
A 78% H

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 O ~ o ~ m s
n-BuLi
71% ~ MeO+TMs
Me0 Me0

' 3 C x o B n F3cflBn + F3cqr

K. Tomooka, H. Yamamoto, T. Nakai, Journal of the American Chemical Society 1996,118. 33 17

LiEs- Bn

Phy
Me
0 65% Phy
Me
0
(4:6)
Ph Y
Me

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 05
Me0

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

[2,3]-Wittig Rearrangement

ProDosed Mechanism:

R'z:
Examples:

Y. J. Li, P.-T.Lee, C.-M. Yang, Y.-K. Chang, Y.-C. Weng, Y.-H.

Liu, TefruhedronLeffers2004,45,
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 Me

BU'Q&H2 BuLi '

Bu * e C H 2

"7'Et'snBu3 O YEt L i
76% Et

Me
BuLi Bu 2
Bu+CH2

O 7''
Et
snBu3
2 8%
HO AEt
I
+fl
(24:76)
Bu
Et

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

6 6 Me
___t

t-BuLi
THF
79%
. \OH
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.

H

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 c;ca;2+

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
( . y Me
L C OMe
zMe + dMe COzMe
703

AgzO, 56 1 4 2
CuSO4,A 0 :85
hv 92: 8

Smith, et. al. (continued)

microwave

o/-yHz
92%

S. G. Sudrik, S. P. Chavan, K. R. S. Chandrakumar, S. Pal, S. K. Date, S. P. Chavan, H. R.

AOM
Sonawane, Journal of Organic Chemistiy 2002,67, 1574

1. NaH, H-C0,Et
2. T s , N ~
b MeOzC
3. hv
OMe 48%

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

- hv
MeOH
Me%OMe

.N, Me .N. 0
H Boc H Boc
48%

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

Cu(acac)2
MeOH, A
5 0%
Me
0

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

704 Name Reaction

Wolff-Kishner Reduction
The Reaction:

Riw H2N-NH2 * H2O

KOH, A * R
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.

/O/CH2iw2 ,.
Under WolffKishnerconditions. a Drimarv mine can be converted to an alcohol:
hydrazine, KOH
<

diethylene glycol, 21 0°C

Me0 Me0
54%
8

S.M. A. Rahman, H.Ohno, N. Maezaki, C. Iwata, T. Tanaka, Organic Letters 2000,z 2893
Name Reaction 705

Examples:

Wolf-Kishner 8
Me'Hlrt M e
79% for the
two steps

bH

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

0&
Me Me
Wolf-Kishner *

81%
8
Me Me

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

H H
J. P. Marino, M. B. Rubio, G. Cao, A. de Dios, Journal of the American Chemical Society 2002,124,
13398

w
Me Me
1. WolfiKishner

n
25%

/
-
2. Followed by esterification of
the hydrolyzed ester with CH2N2

Raney Ni
Me Me

' e C 0 O M e 90%

F
Me Me

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 OH
cis
Proposed Mechanism:

less-hindered face

H H
proton
transfer

H4$-H

Notes:
The Prevost Reaction:

12

'R K0 oAg0 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.

Contrast this reaction with oso4or hh040

Steric "bulk"

oso4 Woodward-Prevost
7 *
HO OH
 ;*
Name Reaction 707

Examples:

&) -
H = OHHH

less-hindered face
1. NBA, AgOAc
2. HOAC,HzO
3. LAH

85%
* Hofi
HO H

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

water during reaction

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.

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

2Ar-x -
Fittig Reaction
2 Na
k-k + 2NaX

Ar-X + -
Wurtz-Fittig Reaction
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 ~ :
R-X 2 Na Na-X + R0 Na 0

R-X + R-X -
or a radical pathway could be followed:
2 Na
2NaX + R
[ I.
solvent cage
- 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 of Chemical Education 1985,Q, 85

Examples:
Me
Me

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

Name Reaction 709

B r o C l dioxane 0
78 - 94%

G . M. Lamprnan, J. C. Aumiller, Organic Syntheses m,133

TMSCl +
PI Pr
- Na wire

EQ Pr Pr
63%
Na wire
TMSCl + ____)

Hex EQ Hex
64%

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

Na
+ CD~I rn
cyclohexane
Me Me Me Me
40%

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

+ f-Bu-C1 -
5711

Na (molten)

3 5%

C. C. Chappelow, Jr., R. L. Elliott, J. T. Goodwin, Jr., Journal of Organic Chemistq 1962,z,1409

PhiC1
c1
*60%
Phf

c1
Ph

Ph Ph Ph
27%

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

I
Me

he Me
4 resonance structures

- DMAF'
___c
0
;.Me
I
Me
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
Y
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,
124,13684
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 y“
Ph Ph
catalyst

Me MI

DMAP, Et3N ‘ 15%

SC(OT03 > 95%
K. Ishihara, M. Kubota, H. Kurihara, H. Yamamoto, Journal oforganic Chemistry 1996, a 4560
Alcohols react preferentially over phenols; an observation not common to other methods.

The reaction is readily extended to lactone synthesis:

n

&Q2

r Y 7 CYh
OZN Sc(OTf),
COOH HO MeCN THF
9 2% - 0
K. Ishihara, M. Kubota, H. Kurihara, H. Yamamoto, Journal oforgunic Chemistry 1996, 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:

HE4
Ph-COOH + Ph-CH20H
THF
97%

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