A facile preparation of methyl enol ethers from acetals and ketals using trimethylsilyl iodide

Tetrahedron Letters,Vol.23,No.3,pp Printed in Great Brltaln

A FACILE

0040-4039/82/030323-04$03.00/O 01982 Pergamon Press Ltd.

323-326,1982

PREPARATION OF METHYL ENOL ETHERS FROM ACETALS AND KETALS USING TRIMETHYLSILYL IODIDE R D Mdler* and D R McKean IBM Research Laboratory San Jose, Cahforma 95193

Summary

Acetals and ketals are converted

Hnth trlmethylsdyl

Iodide m the presence

m h@ yields to the correspondmg

of hexamethyldlsdazane

Alkyl vmyl ethers are reagents of considerable technique

functionahty

synthetic utlhty ’ Unfortunately,

often hrmt the generahty

of the procedure,

or below

the most useful preparative

particularly

of acid catalysts 2 These when other sensitive

is present

In connection

with another program, we needed a mild, selective procedure

ethers which did not require either elevated temperatures the utlhzatlon

In this regard, tnmethylsdyl

for the preparation

or strong acid catalysis

of the strong afflmty for oxygen of electrophlbc

recent synthetic

&con

denvatlves

iodide 1s such a highly electrophlhc

of methyl vmyl

In this respect, tt seemed that rmght provide the mdd techmque

reagent whch 1s fmdmg considerable

usage 3

Smce we have shown that the treatment stencally

at room temperature

mvolves the pyrolytic cracking of acetals and ketals usually m the presence

vigorous reaction condltlons

needed

methyl vinyl ethers by treatment

hindered

deprotonatlon,4

ammes (e g , 2,6-Q-t-butyl-4-methylpyndme

the apphcatlon

for the formation

of certain oxygenated

of this procedure

functlonahty

wth TMSlI m the presence

and hexamethyldlsdazane

Scheme

of this procedure

(HMDS)) led to rapid

to acetals and ketalss should result m a mdd, selective techmque

of methyl vmyl ethers under neutral or weakly basic conditions

the successful utdlzatlon

of selected

(Scheme

I)

We descnbe

here

for this purpose

I

(RCH2)2C(OMe)2

+ TMSII

base +

+

,OMe RCH =C \cH,R

Exammatton

III

II

I

of Table I shows the scope and utlhty of this process 6 In most cases, the product yields are high

and the isolation procedure

1s simple

are isolated m lugh punty vtiually ketals result m regiolsomers

The reaction progress 1s easdy momtored

uncontammated

by the corresponding

which appear sigmflcantly

eqmhbrated

by NMR or glpc and the products

carbonyl compounds

Consistently

’ Unsymmetrical

when the nuxture of -16a and

acid for 8 days (25”C), the -16b isolated by dlstdlatlon was treated with a catalytic quantity of p-toluenesulfomc ratio of the rasolated enol ethers remained relatively constant (63/37 after eqmbbration versus 67/33 mtially) * 323

324

Table I

startmg

ReactIona

Matenal

Condmons

Products

Mated

CondWzms

Products I831 OMe

OMe OMe

1 0 hr. Cf 153ir250

’

6

C4H9k4H9

05hr Q 1 0 hr 26

OMe

!.?

-to<

C9H19$-CH3

C3H7

[781c

20hr

>=

15 hr. (P

D

2

Ccl,,

fi Me

13 _

-17a

Ph

I

0”

C9H19

L

OMe 2 0 hr 25’

[El1

0

C7H,,CH(OMe),

\

H

al 3 equwalents stereochemistry chemical shifts,

“Relatwe H 0

ITOMe

Ywldr

(281e

,/\/\yPh Ph

I891

HAMDS, 1 2 equwalents

I?!’

(721e 1651

05hr Cf 3 0 hr. 25’

2 0 hr. 0” 2 0 hr. 25’ 15

H OMe

CHC13

CH2C12.

5

1861

H

tsa

OMe

18 I451

30 hr, d 3 0 hr. 25”

-9

OMe

(40)

Me >o

a

1 5 hr. d

-17b

Ph

cc14 CHC13

(601’

47 hr 25’

OMe

OMe OMe

(331

OMe

OMe

CH2C12

CH2C'2

0th

E

OMe

2.

OMe

(67jd

YMe

CHZCIZ K ‘\ C4H9

6

ISa

[851

Me

OMe

OMe

CHCI

-2oa

OMe

143F

m

157F

TMSII

lbsolute Ywlds ‘Smgle 1s0m.x of unknown ?Stereochemlstry tentatwely assigned on the basis of NMR

House, L J Czuba. M Gall and H D Olmstead,

J Org Chem ,g

2324

(1969)

Interestmgly,

the rate of disappearance

was rapld m methylene slower

chlonde

of the startmg matenal was qmte sensitive to the solvent

or chloroform

whde the rate m pentane and carbon tetrachlonde

This solvent effect was explolted m the conversion

disappearance were apparently

unstable m the reactlon media

lower rates but allowed the nolatlon

of the respective

when 2 was treated with TMS&HMDS

chlonde or m chloroform,

The use of carbon tetrachlonde,

but the enol ethers

on the other hand, resulted m

vmyl ethers -18 and 19 m reasonable

m carbon tetrachlonde

was much

In each case, the

of the acetals 8 and 2

of the startmg materml was rapid m either methylene

The reactlon

yields

Interestmgly,

at O’C (3h) and a sample worked up m the usual

fashon,

glpc analysis mdlcated that the major product (unreacted

ketal was present)

Infrared

analysis of the reaction nuxture at thus pomt showed httle aldehyde carbonyl

was capryl aldehyde However, when the

nuxture was allowed to further warm to 25“C for three ad&tional hours and was reanalyzed,

the respective

enol

It IS slgmficant

ethers -16a and -16b were the major products and capryl aldehyde comprised 4%

of the rmxture

that the respective

m the reaction nuxture even

tnmethylsdyl

enol ethers of capryl aldehyde were not detected

though they are produced m good yield when the aldehyde itself was treated mth TMSII-HMDS these observations,

it seems reasonable

to propose that m carbon tetrachlonde

On the basis of

at 0°C an mtermedmte

1s produced

325

which hydrolytlcally ehnunatlon

reverts to the aldehyde upon aqueous work up

IS competltlve

ether should be considered NMR exammatlon triplet (J=5 and E

vinyl ethers are produced

as a possible can&date

were absent

The correspondmg

for the base labde mtermedlate

a-lodooctyl

methyl

In this regard, we note that of a new smgle proton

was stdl m evidence,

but the product enol ethers, -19a of the low field tnplet and to the appearance of

Warmmg to 25’C led to the dsappearance

vmyl ether signals of -19a and -19b at S 6 25 and 5 75

Cyclopropylcarbmyl the correspondmg

ketals (e g , -10) also react rapldly under the reaction condltlons lodo enol ethers

imtlally the enol ether 22 product generated

Contmuous

momtonng

of the reactlon by NMR m&cated that whde -22 was the maJor uutlally, after workup and upon standmg, some of the termmal Isomer -23 was detected 9 The eqmhbratlon

which apparently

by traces of I2 present which IS known to be a very efficient

Me0

catalyst for enol ether eqmhbratlon

ITOMe

c”3

Me

-for Preparation

-23

of Methfi -Enol Ethers

345 mg (2 mmole) of cyclooctanone

dunethyl ketal was dissolved m 4 ml of methylene

coohng to -lO”C, 2 5 mmole (527 ~1) of hexamethyldlsdazane

washed wth cold saturated

sodium bicarbonate

and &ed

from K2C03 using a Kugelrohr apparatus

chlonde under N2

After

and 2 3 mmole (327 11) of TM&I were added

The reaction was stirred 2h at 0°C and allowed to warm to 25’C (2h)

vinyl ether -15

8

ITie

-22

-21

the residue &stied

takes place upon standmg may be caused

OMe

P General Procedure

but wth rmg openmg to yield

In a smular fashion, the ahphatlc ketal -21 rapidly rmg opens to produce

(singlet at 3 866, olefuuc protons)

pentane,

at higher temperatures,

of the crude reactlon nuxture after 2h at -1O’C showed the appearance

Hz) at 15 6 0 9 At ths point, startmg mate&

the charactenstlc

(~90%)

and the respectwe

Altematlvely,

The rmxture was dduted mth 25 ml of

over K2C0,

The pentane was removed and

(85OC, 15 mm) to yield 250 mg (89%)

of the

Glpc analysis (10% SE-30) Indicated that the product was >97% pure

References 1

(a) “The Chemistry

of the Ether Lmkage,”

(b) L S Povarov. Russ Chem Reactions,” Chem -(1963),

Rev , 34, 639 (1965).

New York, New York (1967),

(c) J Colonge and G Descotes,

J Hamer, ed , Acadenuc Press, New York, New York. 238 (1967).

Res , lJ, 27 (1980),

Am Chem ---

S Patal. Ed , Interscience,

Sot ,@,4602

(e) C M Hdl, R Woodbery, (1958),

“l,CCycload&tion

(d) E Wenkert, Act

D E Smunons, M E Hdl, and L Haynes, I_

(f) A J Buch, J M H Graves, and J B Slddall, --J Chem

(g) D J Faulkner and M R Petersen,

Tetrahedron

E,

3243 (1969).

Sot ,4234

(h) T C T Chang,

326

M Rosenblum 2

(a) H Meerwem Theme

Sac ,102, 5930 (1980)

and S B Samuels, ---J Am Chem m Houben-Weyl,

Verlag, Stuttgart,

“Methoden

der OrgamscheChemle," E Mttller, ed , Vol

1965, p 199ff, (b) R A Wohl, Synthesis,

A H Schmidt, Chermker Zeltung, 104, 253 (1980) and references

6/3, Georg

38 (1974)

cited therem

R D Mdler and D R McKean, Synthesis, 730 (1979) Jung and coworkers reagent, 6

have demonstrated

Consistent

spectroscopic

data has been obtained

matenal wth no attempt at optmuzatlon

7

that m the absence of base, TMSlI 1s an effective

M E Jung, W A Andrus, and P L Omstem,

Chromosorb

W)

The apparent

stab&y

Tetrahedron

for all compounds

Reglolsomers

!&,

The yields reported

were separated

of the methyl enol ethers under the stated reaction con&tions

8

and sodmm iodide m acetomtnle,

It IS reported

that the eqmhbrmm

9

Z Kosarych and T Cohen, Tetrahedron

posltlon 1s -60%

The chermcal shft of this signal IS not mconslstent s-lodooctyl

E,

40% m

as determmed

and E E Waah, J Org Chem , 2,

S J Rhoads, J K Chattopadhyay,

is mterestmg.

aldehyde trunethylsdyhodohydrms M E Jung, A B Mossman,

11

The structures

of tnmethylsdyl m

, 3959 (1980)

by mdme eqmhbratlon,

with that expected for the 5 proton of the correspondmg for a number of related

lo

and M A Lyster, J Org Chem ,g,

of 22 and 23 were assured by the displacement

25’C) to produce the correspondmg

m hght of

3352 (1970)

methyl ether and 1s quite smular m position to that recently reported

10

are for isolated

by glpc (10% SE-30 on

the report by Cohen and coworkers that such ethers are rapidly cleaved by a muture chlonde

deketahzatlon

4175 (1977)

thlophenyl

of lo&de usmg hthmm thophenoxlde

methyl enol ether which could be punfled by glpc

smular fashion, the &methyl ketal of y-thlophenyl-2-pentanone same nuxture of enol ethers for spectral and glpc comparison

(Received in USA 5 August 1981)

3698 (1978)

was treated mth TM&I-HMDS

(THF, In a

to yield the