Synthesis of aryl methylthio ethers employing α-oxoketene dithioacetals

Tetrahedron Printed in

Letters,Vol.26,No.l,pp Great Britain

39

0040-4039/85 $3.00 + .OO 01985 Pergamon Press Ltd.

- 42,1985

SYNTHESIS OF ARYL METHYLTHIO ETHERS EMPLOYING a-OXOKETENE DITHIOACETALS

and Yawares

R. Karl Dieter*

Department

of Chemistry,

Jenkitkasemwong

Boston University,

Lin

Boston, Massachusetts

02215

Reaction of a-oxoketene dithioacetals with methallyl magnesium chloride followed by Abstract: The methylthio substituent acid treatment affords simple and annulated aryl methylthio ethers. can be easily removed with Raney Ni, undergo a Ni catalyzed substitution reaction with Grignard reagents, or serve as a directing and protecting group in Friedel-Crafts acylation reactions.

We have, over the past few years, satile substrates

for the sequential

via a cascade of 1,2 and/or ing a 1,3-carbonyl discovered

transposition

an annulated

HBF4,

aryl methylthio

In recent years,

pattern

severa1

have been developed

methylthio

aromatic

benzenoid

aromatic

a-oxoketene magnesium

compounds

and cyclization

as an alternative

annulation

bond forming

employing

of methallyl

bonds

In the course of develop-

dithioacetals chloride

it was

to &, followed

led not to a rearranged a,B-unsaturated thiol ester, but to 3b . This transformation provides a direct synthetic

annulation

ether in which

carbon-carbon

reactions. 2,3

addition

are ver-

of new carbon-carbon

with complete

control of the

(eq. 1).

require protecting/deprotecting reported

sequence addition

construction

dithioacetalsl

ether

route to simple and annulated alkyl substitution

that a-oxoketene

regioselective

1,4-nucleophilic

that 1,2-nucleophilic

by treatment with aqueous

demonstrated

to aromatic

sequences. procedure

reactions

method,

vinylogous

alkylthio

to substituted strategies5 although

silyl esters

substituent

and serve as a protecting

39

4

substitution

The present

employing

the easily removed

approaches

aromatic

which

compounds

generally

similar to a recently 4d , affords an aryl

can be utilized

and/or a directing

in additional 6

substituent

.

40

Table

1.

Synthesis

of Aryl Methylthio

Alcohol a ( % Yield)

Substrate

Entry

Ethers

and an Aromatic

Cyclizationb conditions

Hydrocarbon.

Product(s) ( % Yield)a

R

?Y SCH,

1 Q

92c

R = SCH

A

43

2 R=CH3 ,-!,

87

B

64

C

22

D

28

SCH,

5

89

D

6

85'

A

55

B

62

7

15

CH3 SCH,

SCH,

# 8

D

5 R=H % 6 R=CH Q,

80

F

60'

E

37

11

B

47

12

D

52

C

29

9

3

7

10

12

‘I>

13 ayields

are based upon products

ether) unless otherwise B = HgC12,

60 - 7OoC, CH3CN,

D = BF3*Et20, lh.

noted.

CH3N02,

purified by column chromatography (silical gel, petroleum b Procedure. A = THF, H20 (4:1), 10% (v/v) HBF4 (1 part).

Ih.

OoC, lh.

'Basad upon crude product

C = BF3*Et20, E = HgC12,

CS2, OoC (1.5h) to room temperature

60 - 70°C, aq CH3CN.

and determined

by NMR.

F = A1C13,

CH3N02,

(1.5h). OoC,

41

The synthesis dithioacetals points

of aryl methylthio

,J,,2-x and vinylogous

are noteworthy.

excellent

yields

First,

(entries

dithioacetal

acidic conditions

quantities

of the rearranged

substrates

anhydrous

(entries

annulation

presumably

decrease

Severa1

to moderate

yields Second,

upon the acid/solvent

couple

yield

of aromatic

dithioacetals

thiol esters

1.

1 and 2 afford

(entries 7,8,9,12).

product

$ and 1 afforded

(entries

1,6,10).

or A1C13/CH3N%

even

significant

For the latter

proved more effective

the greater

cyclohexadiene

substituent

[80 %, [ca], -195'

facility

desulfurization

in low yields sulfides

(eq. 2).

Consequently, was converted G

The alkylthio

and @[94%,

complicated

reductive

dithioacetal

cleavage

of

of ll-menthone

(entry 5) which

[al, -71'

from

sulfide.

afforded

(c 0.2, hexane)]

a

upon Raney

group can also be removed after serving as a protecting

for the Friedel-Crafts

is, however,

the ketene

to the thioether

in an

elimination

intermediate

effected

(entries

dithioacetals

via methanethiol

than from the corresponding

ether 2 with W-2 Raney Ni cleanly

of trans-(-)/&-(+)-calamenenes8

substituent

for aromatization

dithioacetal

(c 2.6, hexane)]

Ni (W-2) desulfurization. and directing

hydrocarbon

with an earlier unsuccessful attempt to use vinyl 4d . The higher yields obtained with a-oxoketene

of aryl methylthio

the methylthio

to the aromatic

process

reflects

an intermediate

mixture7

an excellent

BF3.Et20/CH3N02,

'$ could only be converted

3-4) which was consistent

Treatment

is dependent

a-oxoketene

a,8-unsaturated

HgC12/CH3CN,

t-1

dithioacetals

7-9,11-12).

Vinyl sulfide

aromatic

product

k afforded

whereas

ethers which substrates

from a-oxoketene

are listed in Table

ring a-oxoketene

ring and acyclic

the yield of aromatic

a-Oxoketene

employed.

under aqueous

hydrocarbon

thiol ester x, respectively,

the six membered

1,5) of aryl methylthio

(43-62%) for the five membered for each substrate

ethers and an aromatic

acylation

by reduction

reaction

(eq. 4).

of the carbonyl

Here Raney Ni

and the yield of ketones

W-2 Raney Ni, EtOH, rt, 1 h

75%R=H

eq. 2

R

MeMgBr

66 %

eq. 3

R = CH3

t reflux, PhH,

CH3COC1,

A1C13,

2 h

rt, 1 h

n=l n=2

eq. 4

SCH, 10

n = 1

(86 X)

g

n = 2

(90 W)

ti

an=l Zn=2 S

LI

42

&$ a-b and alcohols of 8

with

a

a-b is dependent

of &,& (0.28 mmol,

afforded Finally,

reaction

of thioether

[1,2-bis(diphenylphosphino)ethane] in 66% yield sulfides

(eq. 3).

a-oxoketene

ethers

processes

involving

Acknowledgements:

substituted

of the cyclization products

iCH2C12, rt, 7 h) problem.

in the presente the aromatic

of dichloro

hydrocarbon

to the use of substituted aromatic

vinyl

hydrocarbons.

to acknowledge

step and a vinyl group may not cyclize.

can be exploited

direct or electrophilic

We are pleased

Science Foundation

an alternative

reduction

(59%) and

can be converted to simple and annulated aryl 3b The substitution and nucleophilicity of the participating

of the aromatic

either

bromide

ab

dithioacetals

in good yields.

substituent

provides

oxidation

reflux affords

of 0.31 mm01

(65%) while

to the over reduction

magnesium

under

of regiospecifically

olefin will limit the generality methylthio

2 with methyl

Treatment

a good yield of ketone

chlorochromate

a solution

nickel(II)'

This reaction

for the synthesis

In summary, methylthio

Pyridinium

&$a in 83% yield providing

structure.

$$,a (13%) and Ra

2.0 g Raney Ni, EtOH, 1 day) afforded

only a trace of the alcohol ,j&b (4%). of Ga

upon the substrate

1.0 g of Raney Ni (EtOH, rt, 0.5 h) yielded

aromatic

support

in carbon-carbon

substitution

bond

The

forming

reactions.

of this investigation

by the National

(Grant CHE-8219093).

Referentes 1.

For the synthesis 5033 (1981).

2.

(a) R.K. Dieter, J.R. Fispaugh, (b) R.K. Dieter and L.A. Silks, J. Org. Chem., 5, J.W. Dieter, J.C.S. Chem. Commun., 1378 (1983).

of a-oxoketene

dithioacetals

see:

R.K. Dieter,

2786 (1983).

3. Org. Chem., 0,

5031-

> 23, 3751 (1982). (c) R.K. Dieter and

3.

(a) R.K. Dieter and Y. Jenkitkasemwong, Tetrahedron Lett., _, 3747 (1982). Y. Jenkitkasemwong Lin, and J.W. Dieter, J. Org. Chem., 0, 3183 (1984).

4.

(a) M.A. Tius, A. Thurkauf, and J.W. Truesdell, Tetrahedron Lett., _, 2823 (1982). (b) K. Takaki, M. Okada, M. Yamada, and K. Negoro, J.C.S. Chem. Commun., 1183 (1980). (c) T.H. Chan, and P. Brownbridge, 3. Am. Chem. Soc., 102, 3534 (1980). (d) M.A. Tius, (e) S. Danishefsky, T. Harayama, and R.K. and S. Ali, J. Org. Chem., 5, 3163 (1982). Singh, J. Am. Chem. Soc., 101, 7008 (1979).

5.

M. Tashiro,

6.

M.R. Euerby and R.D. Waigh,

7.

The synthetic mixture of -_ trans:cis diastereomers was calculated to be 91:Y or 82:18 using a measured or caIcuIated value of -820 or -96O, respectively, for the optical rotation of The relative peak heights of the isopropyl doublets in the NMR trans-(-)-calamenene. 0.74, 1.01) indicate an 82:18-86:14 ratio of trans: spectrum (z: 0.66, 0.84. *: K.D. Croft, E.L. Ghisalberti, For optical rotations and NMR data see: cis diastereomers. C.H. Hocart, P.R. Jefferies, C.L. Raston, and A.H. White, J.C.S. Perkin Trans. 1, 1267 (1978).

8.

(a) M. Artico, G. De Martino, and V. Nacci, For previous syntheses of the calemenenes see: (b) S.V. Bhatwadekar, K.G. Gore, K.K. Chakravarti, and S.K. Chem. and Ind., 1601 (1968). (c) referente 4d. Paknikar, Indian J. Chem., 0, 1111 (1972).

9.

(a) K. Tamao, K. Sumitani, Y. Kiso, M. Zembaynski, A. Fujioka, S. K;~:"H: A. Minato, and M. Kumada, Bull. Chem. Soc. Jpn., 0, 1958 (1976). H. Sugimura, and H. Okamura, Chem. Lett., 1447 (1979). (Received

Synthesis,

in

USA

13

(b) R.K. Dieter,

921 (1979). J.C.S. Chem. Commun.,

Auqust

1984)

127 (1984).

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