The reactions and syntheses with organometallic compounds IV. The new synthesis of oxindole derivatives by utilization of organonickel complex

TetrahedronLettersNo. 21. pp 1807 - 1810, 1976. PergamonPress. Printed in

THE REACTIONS THE NEW

AND

SYNTHESIS

SYNTHESES

WITH

OF OXINDOLE

ORGANOMETALLIC

DERIVATIVES

ORGANONICKEL

Greet

COMPOUNDS

BY UTILIZATION

Britain.

IV. OF

COMPLEX

Miwako Mori and Yoshio Ban Faculty

of Pharmaceutical

Sciences, Hokkaido University, Sapporo, 060 Japan

(Receivedin Japan 6 Larch 1976; receivedin UK for publication12 April 1976) In the preceding communication,

1) we described a new synthesis of indole

derivatives from 2-chloro-=N-alkyl-N-allylaniline by using tetrakis(triphenylphosphine)nickel[Ni(PPh3)41. It

was expected that this method could be extended to a new synthesis of

oxindole derivatives when 2-chloro-N-alkyl-N-acrylanilides starting materials. Ni(PPh3)4

are chlosen as the

Thus, 2-chloro-N-methyl-N-acrylanilide(4) -

which was prepared in situ from Ni(acac)2 and AlEt

was mixed with in the presence

of PPh3 in toluene, and the mixture was heated at 50-60' for several hours to give 1,3-dimethyloxindole(5)

in 43.5% yield with N-methylquinolone(g)(7.3%),

but 1-methyl-3-methylene-oxindole(1)

was never detected.

Similarly, the

compound(?), which was easily prepared from 2-chloro-N-methylaniline anhydride, was converted to N-methyl-2-hydroxyindolyl yield(70.5%).

product

acetate(g) in a high

In the case of 2-chloro-N-methyl-N_cinnamanilide(l0), -

reaction was relatively complicated.

and maleic

l-Methyl-3-benzyloxindole(u)

the was a main

(57.4%) when toluene was used as a solvent, and the two stereoisomeric

compounds(l1 - and G)2)

were obtained as minor products.

When DME' was used as

a solvent in place of toluene, the unsaturated compounds(l1 12) became - and the main products as are shown in Table 1.

These compounds(l1 12) were - and -

easily reduced with NaBH4 in EtOH to give 13.

1807

No.

1808

Me

4

W”’ Me

9

mNcph

70.5 %

d:

Ni(PPh3)4,a”

Me

Me

Me

10

11

wph Me

13

12 ,

I

NaBH4- Et0 H Table

1 Solvent

Total Y&d

DMF

86.6 84.0

To luene

f--J;rC” I4

aiH2+

%

11 55.0

Yield

of

%

10.9 %

N;;pFh3)4T

20.7 5 7.4

2.3

24.3

f-‘J-J-CN

CH2Ph

CYPh

1. DCC 2. PhCH2 Br- NaH I c:OH

Is

36.4

11*3

13

12

%

%

3/ J?2

21

No.

21

Moreover,

the compound with

2-chloroaniline and benzyl

bromide,

-15 in 36.4% synthesis

for the

benzene

ring,

alkaloids.

because

alkaloids, compound

3)

acid,

followed

by benzylation

halide.

be a very

success

according

(16) was warmed -

with

Ni(PPh3j4

in DMF

the

,

a1

may

be due

the reaction.

reaction

mixture

but even

with

of that

It

why

ze

the reduced

to the result Therefore,

under

this pure

the

Thus

for 5 hours

the to provide

~~h3~~o~OMe

0

tie

17

with

10% HCl

to give

was

the

reduced

it free

removed product

stable

60.8

as a reducing from

agent the

from A1Et2(acac), products since

as a hydride,

were

hydrogen

and

it was

(19). -

==RJztTjgy R I

11 bi30+

still

C-3

N iCI(PPh3)2 h*+

%

and 17) were

separated

the reduced

relatively

be easily

acted

carefully

to make

Ni(PPh3)4,

that 18 was not

(2, 2, 12, E

that A1Et2(acac)

of argon

crystalline

(lfl) could

products

Ni(PPh3)4

stream

may be assumed

compound

decomposed

on the

of the natural

to this method. at 50-60"

advan-

for the position

l_s One of the reason

obtained.

for the

of 6-methoxy-

synthesis

noMe

Me0

2,

during

to afford

substituents

is destined

NaH

yield.

MeOk..!h&lMeOH-c,%S04

generated,

with

intermediate

the preparation

for the

of

is particularly

with

of cyclization

necessary

same manner

useful

method

Therefore,

was

in the

derivatives

with

17 in 60.8% -

by condensation

The present

attempted

was

prepared

Ni(PPh3)4

of oxindole

which

was

might

the direction

aromatic

derivatives,

with

compound

synthesis

of the original oxindole

reacted

This

of indole

tageous

@-cyanoacrylic

was

yield.

(141, which

+ HNi Cl(PPh312

lRl0

No.

These easily

results

synthesized

Acknowledgement:

exhibit according

This

Research

(Nos. 001503

Culture,

Japan,

are gratefully technical

M. Mori

2.

The

to this method.

Further

research and

was

047007)

and by a Research acknowledged.

and Y. Ban,

structures

basis

supported

from Grant

derivatives

could

studies

in progress.

by Grants-in-Aid

the Ministry

We express

901

Tetrahedron

of the

of Antey's

Y. Ban, 5023

oxindole

from

for Scientific

of Education,

the Mitsubishi

thanks

are

be

Science

Foundation,

to Mr. N. Sasaki

and

which

for his

and Notes:

1.

3.

the various

cooperation.

References

22,

that

21

isomeric

report.

Letters,

the preceding

communication.

compounds(lland 12) were deduced on the and F. C. Tahk, Tetrahedron,

R. L. Antrey

(1967). T. Ohnuma,

(1972).

M. Nagai,

Y. Sendo

and T. Oishi,

Tetrahedron

Letters,