General synthesis of polysubstituted thiophenes from diketo sulfides

Tetrahedron Letters,Vol.26,No.l6,pp Printed in Great Britain

GENERAL

SYNTHESIS

OF POLYSUBSTITUTED

Juzo Nakayama,* Department

Haruki

Machida,

of Chemistry,

THIOPHENES

Ryuji

Faculty

Urawa,

0040-4039/85 $3.00 + .oo 81985 Pergamon Press Ltd.

1983-1984,1985

FROM DIKETO and Masamatsu

Saito,

of Science,

Saitama

SULFIDES

Saitama

Hoshino

University

338, Japan

Abstract: Treatment of diketo sulfides with a low-valent titanium reagent at 0 'C _____ (in two cases at room temperature) affords 3,4-dihydroxythiolanesin good yields. The acid-catalyzed (p-toluenesulfonic leads to the corresponding thiophenes Thiophenes, organic

acid) dehydration of in excellent yields.

one of the most fundamental

synthesis'

and their synthetic

monosubstituted

thiophenes

are relatively

polysubstituted

thiophenes

is much more difficult.*

are prepared

from diketo

a low-valent

titanium

we report quenched

sulfides

We reported

reagent

prepared

from titanium(IV)

that this reductive

coupling

reaction,

yields4

and that the acid-catalyzed

yields,

thus

providing

starts from easily

dehydration

an efficient

general compounds. 596

accessible

Table 1 summarizes

the preparation

intermediates

from thiophene,

(1) by an intramolecular

preparation

chloride

coupling

reaction

using

Herein

and zinc powder.3

3,4-dihydroxythiolanes

thiophenes

and

(2) in good

(3) in excellent

of polysubstituted

of polysubstituted

of

out at lower temperatures

of 2 leads to thiophenes

synthesis

in

Although

that 2,5_dihydrothiophenes

reductive

when carried

affords

compounds

to attract much attention.

easily derived

at the early stages of the reaction,

latter

are important

heterocycles,

study continues

the

thiophenes

3 from diketo

which

sulfides

1 by this method. The intramolecular

reductive

coupling

cis-diols

exclusively.7

The cis geometry

chemical

transformations.

For example,

(5j3 with m-CPBA

and then with osmium

lane 1,1-dioxide

(6) in a good yield.

the 3,4-dihydroxythiolane when pure meso-sulfide formed.

tetraoxide

in entry

threo-isomers

(meso

to dehydration

1-4 affords

by spectroscopic

the corresponding methods

and

of 3,4-diphenyl-2,5_dihydrothiophene

gives cis-3,4-dihydroxy-3,4_diphenylthio-

The same compound

was quantitatively

1) by oxidation

to the reduction,

(entries 8-12) diketo sulfides

and subjected

The dehydration

in entries

the oxidation

4 (the product

was subjected

In other cases

reaction

was determined

the sole cis-isomer used are mixtures

and d,l), and hence diols 2 were obtained

derived

with m-CPBA.8

from the

In entry 5,

was selectively

of erythro-

as stereoisomeric

and

mixtures

as they were.

was readily

accomplished

by refluxing

HO

a solution

of 2 in toluene

for

OH

TiCh -Zn

H’ -2H,O

THF

1983

R2

1984

1 h in the

presence

one case).

No products

CsH5

of a catalytic

amount of p-toluenesulfonic

due to pinacol

rearrangement

C6H5

C6H5

HO

OH

m-CPBA

)

acid (BF3*Et20 was used with

were formed.

CsH5

C6H5

OH

HO

C6H5

1. m-CPBA 2.0~04,

NaHS03

4 Table 1

Preparation

entry

of Thiophenes

R1

1

3

4-MeC6H4

H

H

4-MeC6H4

78

95

4

2-naphthyl

H

H

2-naphthyl

71

98

'"3

C"3

'gH5

82

92

93

93

'6"5 '6"5 '6"5

'2"5 H

'6"5

C"3

CH3

'6"5

'"3

CH3

CH3

G"5 CH3

'6"5 CH3

CH3

CH3

CH3

CH3

C"3

C"3

-(CH2)4-

12

CH3

c) The dehydration References

'2"5

CH3

(2)

(%, $ +3_) 98 93

11

a.

2)a) yield 82 84

10

7.

(X, L_

'6"5 4-BrC6H4

9

6.

yield

H

7

5.

R4

_

H

8

4.

H

'6"5 4-BrC6H4

5

3.

R3

H

(1) via Dihydroxythiolanes

2

6

1. 2.

R2

(3) from Diketo Sulfides

73

93

75

89

71

89

71b)

73c)

5ob)

92

73

85

a) Unless otherwise stated, the mixture was stirred at 0 "C l-3 h. . . for _ b) Room temperature for 3 h. was accomplished by using BF3'Et20 in refluxing methylene chloride.

and Notes

A. I. Meyers, "Heterocycles in Organic Synthesis," John Wiley, New York, 1973. (a) D. E. Wolf and K. Folkers, "Organic Reactions," John Wiley, New York, 1951, Vol. 6, p. 410. (b) G. R. Newkome and W. W. Paulder, "ContemporaryHeterocyclic Chemistry," John Wiley, New York, 1982. preceding paper in this J. Nakayama, H. Machida, and M. Hoshino, Tetrahedron z., issue. The following is a typical procedure of the conversion of 1 to 2. To a stirred and cooled (ca. -10 "C) solution of 2.70 g (10 mmol) of diphenacyl sulfide in 80 mL of THF was added 5.0 mL (45 mmol) of titanium(IV) chloride and then 6.0 g (90 mg. atoms) of zinc powder in small portions. The mixture was stirred for 15 min, warmed to 0 "C, and stirred for 1 h at this temperature. The resulting mixture was quenched with 10% aqueous potassium carbonate. Methylene chloride (200 mL) was added to the mixture and the two-phase mixture was filtered through celite. The methylene chloride layer was washed with water, dried, and evaporated. The resulting crude product was purified by silica gel column chromatographyto give 2.23 g (82%) of cis-3,4-dihydroxy-3,4-diphenylthiolane (entry 1). This work was supported in part by the Grant-in-Aid (No. 5940298) from the Ministry of Education, Culture and Science, Japan. Although thiophenes 3 can be prepared from 2,5-dihydrothiophenes(ref. 3) by oxidation with DDQ, the present method is more economical and simple. The reduction of 1,2_diacetylethaneby the low-valent titanium reagent prepared from titanium(IV) chloride and Mg-Hg gives cis-1,2-dihydroxy-1,2-dimethylcyclobutane: E. J. Corey, R. L. Danheiser, and S. Chandrasekaran,J. Org. Chem., 41, 260 (1976). Additional evidence comes from its conversion to meso-2,3_dihydroxy_2,3_diphenylbutane by reduction with Raney nickel (W-2). Preparation of meso-diols by this procedure will be described elsewhere. (Received

in Japan

10 January

1985)