Synthesis of isoxazolines and isoxazoles from aldoximes by the use of sodium bromite with organotin halide

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

SYNTHESIS

3987-3990,1989 oo40-4039/89 $3.00 + .OO Maxwell Pergamon Macmillan plc

OF ISOXAZlJl.INt:S

ANU ISOXAZOLES

FROM Al.DOXIMES

RY THE USE OF SOUIUM KKOMITE WITH OKGANOTIN HALIDE

Osamu

Moriya,

* Hideki

Nakamura,

and

Department

of

Yokosuka

23,

‘Department

:

Summary tin

The

aldoximrs

via

attention

as

to

This

cetitly,

5. 6’

provide

showed

oxidizing mnre

of

afford

obtained t.he

first. the in

and

amounl,

ines

and

sodium

the on

of

tri

isoxaznltzs

from

for

our

investigations

and

a catalytic

new

hindered by

Ku,SnCl.

treating whereas

reactlvities

have te

as

1.3

1 at

for

the

nitrile

NaBrD2. nitrile

3987

have

in the

on

In

one-pot

oxide temperature

for

and

it

ttlis

The

of

found

that

rc~sul

of

of

aldosimes

has

amount observed

ts

described.

expected

cscess

1 was not

to

compounds.

were

wa,L: conducted,which

wi t.h an

of

the ions

reaction

(2).7’

state

(Hu,SnCt)

report.

transformat

t-v-

seemed

we have chloride

rem

vet-y

title

line.

the

brominca those

shown

of

In

1i nes

effective

a high

use

this

the active

been

trimnmbutyltin

(!I

be

le ic

‘)

I so i soxazu

reagent

oxides

cycloaddition

dehydrogrnation

to

ni tri

heterocycl

dipoles. a

tile related

wt~ich

of

these

the

and

reported

action.

dipotar

room

of

now available

anthraldoximc

stable

the

of

directed

of

a usable

of

of

oxidizing

of

been

progressed

syst.em via

preparations

(NaRrO,),

and

studies

much

reaction

intrrmcdiaies

of

amount

of

oxidizing

&hydrogenaLion

i tes

synthesis

of

isoxazoles

the

properties

the

selectivity

the

utilil.ies

hypohal

ttle

deri-

r~~ceIvln::

cycloadditinn

for

nominated

poIy~functio1)al are

for

dipolar

te

bromi

been

these

int.o

3- di kcloocs.

1,

oxide

bromi

NaBrOa

this

in

nitrile

not

than based

sterically

of

Kanto-

a catalytic

isoxazol

converted

and

[312]

synthetic

procedure

15 X yield

presence

te

hand,

stable

and the

with of

readily

interests

agent,

view

course

isoxazolines

rimizu,

Engineering,

intermedIates

The

of

has

i te,

are

exploited

the

other

hypohal

the

ions

synthetic

’’

formation

On the

a characteristic

At

with

the

hypochlori

of

application

int.o

in

the

combination

of s.

especially

years

a convenient During

to

is

From

purity.

Hashi

.Japan

bromite

prcparat

which

sodium

the

Academy,

of

236,

aminoketones,

class

been

for

to

actions.

an

the

Faculty

sodium

the

ketones,

syn thesj

has

3. ‘)

compounds

the

important

over

Dcfrnsc

Yokohama

usirlg for

isnxazoles,

I product

aldoximes,

reagents.

and

an

studies

Nat ional

cycloaddition.

enamino

olefins

compounds several

system

as

natura

oxide

from

ines

such

IJrata

Chemistry,

Mutuura,

applied

dipolar

Isoxazol vatives

toward

oxidizing is

The

Industrial

University,

chloride

Yoshikiya

’

Japan of

Cakuin

but_yl

Chemistry.

~WYWI~.

’ Toshifumi

been

pt-uduc of in

knuwn t 2 was

NaBrUz the

3988

similar

reaction

readily

with

without

methyl

acrylate

The oxidation by

us to

give

cyclohexene these

in

reaction

this

one-pot

which

the

manner

to

the

give

the

process

was

2 _ was applicability

isoxazolines

(1).

The

in

the

to

give

for

agreement

of

as

the

an

15

the oxidizing

Next, acetaldoxime

with

1-2

the

catalyzed

bond

that

2 reacted 3 in 68 X yield.

acid

has

alkenes

product

with

the

ovet-al

at color

The

for

the

oxidizing

system

in

the

the

to

the

temperature.

of

NaBrO* was chromatography

yield

observed

in

former

process,

in

cyclization

for

and

equivalent).

room

by column

isolated

I yield

intermediate

(0.1

yellow

was purified

presented

styrene

Thus.

Bu,SnCl

dropwise

the

as

By considering

2 was attempted.

h until1

been

such

system.

equivalent),

14 X yield.

Bu$nCl,

reaction.

one-pot

In this

formation

of

and

reacted

efficiently

yields

are

which

have

case,

which

and

products,

but

considered

to

resulted

been

observed

seemed

reaction

to

starting

be

usually

be affected from

was supported

by

the

with

of

nitrile

in high

bond

starting

was also

as cyclohexene only

steric

1,3-dipolar

big

aromatic

that

the

the

group

in

cycloaddition

the

Such the

yield the

of

the

fumarate

also

in step.

The other the

cyclic

dehydrogenation of

the

organotin-

cyclization

in

having

These

decreases

reactions.”

was given

poor

to give

and diethyl

in

cycloaddition hindrance, (1).

to

moderate. effects

and

respectively.

stable

were

bcnz-

and alkynes

osides

yields,

such

the

from

The al kenes

induced

(6)

by a steric

facts

1).

yields

anthraldoxime

to be due to the effects

(Table

alkenes

from

in

the reactions

for

alkynes

triple

the

-3

61

isoxazoles

Disubstituted

cyclic

%

MeQ2CCH=CH2

was applied

(5)

68

-

a carbon-carbon

oxidation. the

assumption

the

catalytic

3 in

alkenes

isoxazolines

indicated

appears

isoxazoline acetic

However,

%

system

various

unsaturated

corresponding

In the

of

isoxazole

14

afforded

the

in Hz0 was added

present

NaHrO2,

results

give

oxide

was demonstrated.

-

terminal

nitrile

presence

scrylate(2

work-up,

isolated

the

present

about

isoxazoline in

to

in

(5 equivalent)

usual

resulting

yields.s”

methyl

was stirred

dipole

the

reaction

NaBrOz

After

CHC13)

high

inactive

one-pot

mixture

disappeared. (SiO,,

by NaBr02 in

anthraialdoxime

dichloromethane.

The

catalyst.

as a dipolarophile

alkenes

virtually

the

results. of

of

a-bromoketones were

solution

organotin

dipole

above

scheme.

product

3

step. 2 to

methyl

This

3989

acrylale

was not affected

further.

the reaction

benzaldoxime this did

so strongly

of the same dipoiarophile

afforded

the cyclic

product

method was that the successive not proceed

cycloaddition as alkoxy

by the steric

in the examples

reactions

and halogen,

often

of z as described

with smaller

aromatic

in moderate yield.

transformations these alkenes,

ether

stage

of such groups

such as

feature The

leaving

+ R2-CH-CH-R3

(5 eq),

d M2C12-H20

or 4

s

R4-C5CH

or

a

Table

1.

Synthesis

of Isoxazolines from

Aldoxime

Alkyne

Alkene

(2) and

Aldoximes Ratio QlAlkene

(4)

Isoxazoles

(5)

Isoxazoline

(5)

(Ala of or

or Isoxazole

RI

R2

R3

Ph

Ph

H

112

91

Ph

Br

l/4

98

H

l/2

72

l/20

23

OBu

R4

+CH2' H

l/2

88

CO2Me

H

l/2

68 50

C02Et

114

CN

H

112

58

Ph

H

l/2

82

l/2

48

CO2Me

H

_----___--------_--Ph

Me

Yield

COMe

CO2Et

Me

Alkyne

_______________-_-________I__________ Ph

112

80

OEt

II3

45

OEt

1/3

72

aAll reactions were carried out at room temperature. b Yields are based on starting aldoxime (4).

group such

under usually

Bu3SnC1 (0.1 eq) R'-CH=N-OH

of

to isoxazole

and B-bromostyrene.

which have a potential

accompany the eliminations

N~-QJ

above and,

aldoxime

The additional

from isoxazoline

using butyl vinyl

involving

effects

(%jb

(5)

3990

employed

basic

conditions.

The related

specie,

sodium

in a similar

manner

aldoximes.

Wi Lh regard

methylsilyl

as

chloride

reactions.

Recently,

or chromic alkenes

have

oxidizing

been

the

Although

catalytic

reactions

using

system

was shown

to possess

leading

to

system

the

cyclizrd

dibutyl those

silyl

tin

compound

CL~chloroketoncs.“’

oxidations

products

from

dichloride

selective

of various

the

and

tri--

nxidative

with

sodium

dichromate

substrates,

in which

!n contrast

with

NaBrO 2 is characterized

such

by a low

bonds. are

the

required

to clarify

selectivity

ines

and

the

I ic catalyst,

organometal

a suitable

of‘ isoxazol

later

oxidations

of N;LBI-OZ for

get

for

employing

unsaturated

NaBrO 2 with

formations

the to

investigations

in the

effective

of’ the

for

to

I ic cnlalysts,

to he also used

instead

unsuccessful

efficiently

-carbon

further

it was

combination

been

converted

to carbon

was applied

the organornetal

found

has

system,

reactivity

to the

anhydride

but

above,

were

chlorite,

for

isoxazoles

actual

oxidizing

tl~e dehydrogenations through

species

9’ the catalytic nitri

oxidizing of aldoximes

le oxide

intermediates.

Heferences

I) For review 2)

For

review

see:

A. P. Kozikowski.

see:

C. Crundmann,

3) C. Grundmann 4)

For

recent

Schffstal

and J.

application

1097:

S.

6) S. Kajigaeshi, references 7) C. Grundmann 9) The organotin and

have

genation

Y. Ueno,

0. S.

to

that

These

bulky

moiety.

in

Japan

.I. Org.

effect.

anthraldoxime.

(Received

N. Nagasaki,

was revealed

no advant.agcous

trbutyltin

2809

(1365). U. Chiacchio.

Tetrahedron.

Y. &no.

and M. Okawara,

Ha, Tetrahedron

catalyst

compared

344.

A. Padwa.

and M. Okawara,

K. Datta.

of aldoximes

factor

see:

410 (19Y4).

D. C. Dean.

Lett.,

1988,

and M. Okawara.

Synthesis,

11169.

1993,

Chem. Lelt.,

198.3. .- _ X15: T. Kar:eyanra, 19x3, 1451.

Chem, Lett., and S. F’uj isakl.

Synthesis,

A. M.

1985.

Y.

674 and

therein.

and S.

I;. Lee and

method

K. Kitamura.

T. Nakagawa, cited

1970. Chem. , 30,

Org.

and K. S. K. Murthy,

Y. Ueno.

A. Katoh.

J.

the

Kawahara,

‘T. Kageyama.

l’obi t.o,

8) J.

of

1, A. Hassner.

5) T. Kageyama,

Synthesis,

M. Uean,

I?,

ACC. Chc:m. Kcs.,

oxidizing

using

sodium

7 April

suggests

1989)

34, _1932,

to accelerate

on the

in our facts

Chem.,

Lett.,

hypobromi that

the

(196Y ).

193. the

cyclization system

2016

decomposition

of sodium

In addition,

step.

was more highly

effrcted

te as displayed

in

activated

oxidizing

the

bromite dehydro-

by a steric

the

reaction

specie

using

may involve

a