0040-4039/81/292747-04$02.

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01981 Pergamon Press Ltd.

Tetrahedron Letters, Vo1.22, No.??, pp 2747 - 2750, 1981

Printed in Great Britain

HYPERVALENT
A NEW

ROUTE

IODINE

IN ORGANIC

TO a-FUNCTIONALIZED

SYNTHESIS.

CAPHOYYLATE

Robert M. Moriarty* and Henry

Department of Chemistry
[Jniversity of Illinois at Chicago
Chicago, Illinois 60680
Summary
--__

ESTERS.

Hu
Circle

- Aryl

and alkylcarboxylate
esters are converted into the corresponding
or a-alkoxyesters
upon treatment with C6H51(OAc)2
and base in
the appropriate
solvent.

a-hy&-oxy

acids

Recently
as C6HSIzO
This

we xeported

transformation

the iodine
which

undergoes

subsequent

to the ketonic
process

to other

action

of various

either

a-hydroxylation

for this reaction

the use of hypervalent

for the direct

involves

atom of the aryl

nucleophile
synthetic

upon

and C6H51(0Ac)2

addition
iodine

a-hydroxylation

of the enolate

(III) compound

intramolecular
carbony12.
potential

carhoxylate

esters

displacement

It appeared
enolate
with

or a-alkoxylation

Table
alization

acid

in 45% yield.

hydroxyl

groups

the oxidation

by addition

of a

to apply

we now report

C6HsI(OAc)2
may occur.

to

an intermediate

under

conditions

The general

this

the rewhere

expression

C6H51

KOAc

CH3Y
RCHCOOCH3

-I- C6H51

i-

NaOAc

carboxylate

esters.

C6H51 (OAC)~

yields

is not restricted
reacts

of the ketone

of interest

systems.

such

3-,2 .

is the following:

1 presents

carboxylate

compounds

of ketones

anion

to yield

P
RCHCOOH
RCH2COOCH3

iodine

to yield

for various
to arylacetate
the a-hydroxy

The reaction

are not oxidized

of 5B-cholanic

esters
acid

is selective
under

acid-3a-ol

2747

ethyl

in 40% yield

conditions

ester.

a-function-

cyclohexane

and the a-ethoxy

for the enolate

the above
methyl

since

The

since

free

as exemplified.

Isolated

steroidal

in

double
yield

bonds
with

such as C5 6 unsaturated

the phenolic

system

are also

unreactive.

(Table 1, entry

The rather

low

7) may be due to partial

ring

oxidation.

Table

1 - Reaction

of Carboxylate

Csters

with

Phenyliodosodiacetate.

:8
CHC-OR'

::

cyc-OR

A, B, Ca
R'=H

F'=CH9

R'=CHzCH,

b,c
Y

-OH%

1.

CH3

50

131-133O

70

120-121O/lOmm

-OCH2CH,%
b.p.
45 e

2.

CzH5

75

131-133O

75

120-1210/1omm

50

1150/
.2mm

3.

OCH9

CH9

66

100-101~

80

50

4.

Cl

C2H5

60

103-105

80

70

5.

Br

C2Hs

60

117-119

75

60

6.

CH9

CH9

50

88-89O

70

60

7.

OH

CF9

30

149-3.510

40

30

8.

(C6~5)2CHC02CH3

75

148-1500

65

166-167/l~

9.

C.jH11COpCpH5

40

106-107"

65

93-94'/14mXl

m.p.

-OCH3%

b.p.

d
138-139'=/1Omm
d
130-1310/11mm
e

65 150"/
lnun
45

a) Method A - The preferred procedure for obtaining the a-methoxy methyl

ester (R'=CHg, y=OCH,) uses C~H~I(OAC)~:
NaOCH3: ester=l:3:1
in CH3OH. The
reaction
volves

system

tion of H20,

to yield

Method

R'=SH3,

b)

with

Yields

c)

Products
Column

e)

Preparative

temperature

for 3 days.

CH2Cl 2, removal

In Method
of ester

?.'=H, y=OH.

of CH3OH

of solvent
KOH:

Work-up
in vacua,

were

upon

compared

isolated
with

layer

addi-

ester

1:3:1

in CHJOH

C, C6H51(OAc)2

and 3 equivalents

react

in a two phase

system

Using

C~HSOH

in either

consisting

(NaOC2H5)

products.

literature

chromatography.
thin

in-

and distillation

y=0C2H5.

are based

d)

room

E '.nvolves C~H~I(OAC)~:

to one equivalent

R'=CpHS,

at

dil. HC1 at O", removal

y=OCH3.

of C,jH6,&20 to yield
yields

with

extraction

of the product.

of KOH

is stirred

acidification

chromatography.

data where

available.

or R,

2749

We propose

that

is undoubtedly
to yield

the initial

enolate

intermediate

be a good

leaving

of malonate

presumably

because

, direct

('-OH or -OR)

anion

in this

-0P.c , viz. $jPorA---+C.

D while
-

displacement

to yield

tetrahedral

is known

an iodonium

In

ylid

of the yli.P4.

As

does not occur

to add tn the carhonyl

intermediate

to

is favorable3.

displaces

group

C6H51

and

of -OH upon C yiel.ds the acid

F
the a-methoxy ester 2'

attack

the E yields

,o,,OCH3

HOI_

RCH-C

-cm30

OH

dl

Fart

esters

the C6H51(OAc)2

state

at the a-carbon

is considered

RCH-c

IL

OH

HO-

.G

C6H51 tOAd

-OH
e

:
RCH+-OCH3

upon

C-I cleavage

of the anionic

Subsequent

of -OCIS3 upon

attack

by attack

loss of I-IOAcoccurs

of stabilization

the nucleophile

followed

of the various

(III) at the hypervalent

and in the case ofA,

esters,

in the case of ketones

and the alkoxide

formation

Iodine

group

the case

but

anion
&

step in the reaction

RCHi!-OCH,

B
-AcOIn

c H30-

RCH-!
OCH,

CH30-

\-OCH

p\
RCH-C
3

OCH,
.!%.

E_

As would
undergo
mation.

be expected

reaction
Also

because

a mild

based

on this mechanism,

of the necessity

sensitivity

/OCH3

the free acid does

of the initial

to steric

effects

enolate

is indicated

anion

not
for-

by the ohser-

vation

that CH3CTq2rn30H gives poor yields relative to W3cJFT and CH3CHPOH.

._
mentioned reaction compares very well with other procedures
5
which involve a-halogenation
and displ.acement (tiouhle bonds react) , oxygen6
using
ation of anions (a reduction sten is required)
, and a-acetoxylation
7
thallium
(III) acetate (double bonds react) . The ct-hydroxylation of esters
The above

using

molybdenum

results

Acknowledgement
grant

peroxide

comparable

- Genercus

CHF-77-C6F37

and the anion

to those

enabled

obtained

sunport

generated

by LDA in THF-hexane

in the present

by the Vational

us to PO this

research.

study

Science

gives

8,9 .
Foundation

under

2750

REFERENCES
1.

R.M. Moriarty,
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S.C. Gupta,
Sot.,

H.Hu,

1(13, 686

B.R. Berenschot

2.

R.M. .Moriarty, H. Hu and S.C. Gupta,

Tetrahedron

3.

Y. Ogata

1,

and K. Aoki,

D. Chambers,
Perkin
4.

B.G.

I, 822

0. Neilands

7_, 1611

6.

H.H. Wasserman

J. Phem.

Rutledge

Lett.,

(1969);

000

(1981)

R.C.

Cambie,

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J.C.S.

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121,

Sot.,

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C.S. Marvel,

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G.W. Moersch
G.W. Moersch

Pfeffer

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R.A.

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E. Vedejs,

9.

The superiority

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Robey,

Chiang,

K.-T.

1733

1149

(1975);

(1971);

(1971); P.L.

1397
262

and G. McGillivray,

R.L.

D.A. Engler

free hydroxyl
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Creger,

(1970); P.E.
(1970)

Tetrahedron

Lett.,

Liu, B. Favre,

H.T.

and M.E.

J.&n.

A. McKillop

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groups

or ethanol.

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is that under

hydrolysis

displays

in aprotic

10. T. Takaya,
11. K. Narasaka,

A. Enyo

method

are not oxidized.

This may

in the literature

oxidation

system

Chem.,

36,

Ford,

5285

Bozimo,
Chem.

Sot.,

(1976)

8.

ference

Synthesis,

J. Orq.

Lett.

Chem.,

(1967); I?_z_,
1396,

H.W. Altland
Taylor,

Tetrahedron

J. Org.

Zwiesler,
25300

(1970); E.C.

3037

Lipshutz,

Burkett,

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J. Am Chem.

S,

P.S.

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(1971).

C.F. Ward,

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(1980)

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106

J. Org.

Lindsay,

and K.B. White,

(1981).

J. Org.

is also
Indeed,

appear

basic

to aldehydes

condition

completely

188

(3.978)

in the fact

since

that

are carried

the impression

is a good reagent for the

10,ll
. The essential dif-

C~H~I(OAC)~,

different

2,

the reactions

surprising

that CsH51(OAc)2

alcohols

Chem.,

reflected

behavior

C6H51=0

derived

by

from the neutral

solvents.
and F. Imoto,

A. Morikawa,

(1977)

(Received in USA 6 March 1981)

Bull.

K. Saigo

Chem.

Sot. Japan,

and T. Mukaijama,

a.,

5,

1032
50,

(1968)

2773