Synthesis and reactions of 5-(tributylstannyl)isoxazoles

0040-4039/89 $3.00 + .OO 4249-4250,1989 Maxwell Pergamon Macmillan plc

Tetrahedron Letters,Vo1.30,No.32,pp Printed in Great Britain

SYNTHESIS

AND REACTIONS

OF

5-(TRIBUTYLSTANNYL)ISOXAZOLES

Yoshinori Kondo, Daishi Uchiyama, Takao Sakamoto, and Hiroshi Yamanaka* Pharmaceutical Institute, Tohoku University Aobayama, Aoba-ku, Sendai 980, Japan 3-Substituted 5-(tributylstannyl)isoxazoles were synthesized Abstractin good yields by the 1,3-dipolar cycloaddition reaction of ethynyltributylstannane with nitrile oxides generated -in situ. 3-Methyl-5-(tributvlstannvl)isoxazole was easilv converted to the correspondins 5-benzoyl-- and S-arylisoxazoles by the palladium-catalyzed reaction. It is well known that isoxazole derivatives are versatile synthons in organic syntheses, because of their masked 1,3-dicarbonyl character.

In

spite of development of the methods for the synthesis of isoxazole derivatives,

the

preparation

accomplished.

For

of

5-metalated

example,

the

isoxazoles

has

not

yet been

3,4-disubstituted isoxazoles with butyllithium resulted in the ring cleavage 1 .

R3BuLi_ THF _

lithiation

R4C3COLi

+

of

R3CN

-6O'C In the present

Scheme 1 communication, we report

tuted 5-(tributylstannyl)isoxazoles ethynyltributylstannane

(1)

with nitrile oxides.

reactions of the stannylisoxazoles When

oxide

stannyl)isoxazole

(1) generated

(2aJ2

(3a)

was

of 3-substiof

We also describe some

thus obtained.

ethynyltributylstannane

acetonitrile

the synthesis

by the 1,3-dipolar cycloaddition

obtained

was in -in

treated situ,

in

benzene

with

3-methyl-5-(tributyl-

nearly

quantitative

yield.

Similarly, 3-phenyl-5-(tributylstannyl)isoxazole

(3b) was synthesized by 2. Ethyl 5-(tributylstannyl)isoxazole-3-carboxylate (3~) was' obtained in excellent yield by the reaction of 1 with ethoxycarbonylnitrile oxide (2~)3 prepared -in situ in ether. R Bu3SnCZCH + RCEN+O the

reaction

of

1 with

benzonitrile

1

oxide

(2b)

2a-c 3a-c

a: R=Me When catalytic

3a

was amount

heated of

b: R=Ph

c: R=COOEt

with

Scheme 2 benzoyl chloride

in

the

presence

dichlorobis(triphenylphosphine)palladium

reflux in anhydrous dioxane for 3 h, 5-benzoyl-3-methylisoxazole 4249

of

a

under (41, mp

4250

Table I. 3-Substituted 5-(Tributylstannyl)isoxazoles Product

&

0.6-1.8(27H,m),2.33(3H,s),6.22(lH,s) 0.6-1.8(27H,m),6.70(lH,s),7.2-7.6(3H,m) 7.8-8.0(2H,m) 0.7-1.9(30H,m),4.47(2H,q,J=7.OHs),6.82(lH,s)

97 100

Me Ph

3a 3b

lH-NMR(CDCl3,'TMS) 6

Yield(%)

R

(3a-c)

COOEt 85 3c All products were obtained as viscous Oil. 67-69"C,

was

obtained

At room temperature,

3a

reacted

to give 5-iodo-3-methylisoxazole

(51, mp

in 80 % yield.

with iodine in tetrahydrofuran 78-79-C, in 57 % yield. inspect In order to

the

possibility

the

on

5-isoxazolyl moiety as a masked 1,3-dicarbonyl

introduction

of

side-chain into aromatic

rings,

the palladium-catalyzed cross-coupling of 3a with bromobenzene, iodobenzene, 2-bromopyridine, and 3-bromopyridine was carried out, and the satisfactory results were obtained. Me

PhCOCl

t

Pd(PPh3)2C12 dioxane Me

;

4 Me

I2 THF

/ I 5

ArX Pd(PPh3j2c12

Ar=Ph Ar=2-pyridyl Ar=3-pyridyl

*

THF or dioxane

6a-c

Scheme

Table II. Palladium-catalyzed Product

Iodobenzene Bromobenzene

6a

6b

2-Bromopyridine

6c

3-Bromopyridine

REFERENCES 1. u.

Cross-coupling of Aryl Halides with 3a

Solvent

Aryl halide

3

7 5.5 6 25 14.5 6 15 4

THF THF dioxane dioxane THF dioxane THF dioxane

mp("C) or

Yield (%I

Reaction time (h)

bp ("C)/mmHg 65-68

82 18 59 72 17 64 15 60

55-57 62-63

AND NOTES

Schijllkopf

and

I.

Hoppe,

Angew.

Chem.,

Int.

Ed.

Engl.,

14,

(1975).

2.

T. Mukaiyama

and T. Hosono,

3. A; R. Kozikowski (Received

in Japan

J. Am. Chem.

and M. Adamczyk, 8 May

1989)

J. Org.

Sot.,

82,

Chem.,

5339

48,

366

(1960). (1983).

765