Alylation of allylic cyclohexenyl esters with trialkylaluminum reagents. A regio and stereochemical study

Tetrahedron Letters,Vol.26,No.4,pp Printed in Great Britain

ALYLATION

OF ALLYLIC

CYCLOHEXENYL

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

519-522,1985

ESTERS

WITH

AND STEREOCHEMICAL

TRIALKYLALUMINUM

REAGENTS.

A REGIO

STUDY

C. Gallina Centro di Studio per la Chimica del Farmaco del C.N.R., Istituto di Chimica Farmaceutica dell'università, P. le A. Moro, I-OO185 Roma (Italy)

Abstract. Regio and stereochemistry of the title reaction appear to be strongly influenced by the nature of both organometallic and allylic reagents. The results are discussed in view of the intervention of ion-pair intermediates.

The alkylation recently

developed

mediates

were

of allyl

acetates

as an exceptionally

recognised

with

mild

to intervene

organoaluminum reagents has been 1 procedure and carbocationic inter-

in the alkylation

of allyl,

benzyl

and

n

cyclopropylmethyl is strongly aluminum

mmole

influenced

reagent

scale by treatement

with

under

nitrogen,

identified

characterized

were

reactions protons

were

leaving

group,

to the Table. with

with

an allylic

cation

of acetates

the mechanism attacked

iBu3Al

_, _, _, 2, 3,4 samples. The cis and

authentic

the extent

by evaluating protons

are reported

of stereoselectivity7

accordance

reagent,

The products

and spectral 1 by H NMR 395 after

to the aromatic

The reaction

on 1 in 6b -

as 98:2 and 19:81 mixtures) were 1 (IR, H NMR, MS) data; cis and trans

by GLC6 while

The results

alkylated

of organoaluminum

catalytic

1-isobutyl-3-phenylcyclohexanes.

relative

When

system,

of the reaction

3b (obtained -2b and -

of -la-ld was obtained

degree

equivalents

attributed

determined

NMR signals.

of the allylic

2 molar

by comparison

by analytical

the corresponding yields

that the outcome

group orientation. 3 4 la-ld -, *, -5a and -5b were -_)

according

isobutylderivatives

configurations

to report

and by the leaving esters

and -7b were

high

by the nature

The cyclohexenyl

hexane,

trans

acetates. c We wish

composition

of a/y-substitution

the abundance

through

careful

into

and

in the

of the vinylic

integration

of their

in the Table.

ti, -Ib and benzoates with

preferente

suggested

on the contrary,

519

&,

-Id with Me3A1

of the trans product,

by Oshima,<

by the nucleophile

is used,

Product

hydrogenation

involving

in

as intermediate

from the less hindered the reaction

shows

becomes

side. stereo-

a

520

H(D) R,AI

Ph

H(D)

Ph&R

+

Ph-b_DfHl

hexane H

H

R2

1

a) R1 = OCOCH

3

2

b(H)

#,R

R2=D

b) R1 =D

R2 = OCOCH

c) I? = OCOPh

R2 =D

d) F? =D

R2 = OCOPh

a) R = CH

3

3 b) R = CH2-CH(CH3)2

\a

R’

l.

‘R2

4

6

a) R1 = OCOCH

3

b: F? =H

specific

reaction

for the Q,

These

ion-pair

for syn-substitution

acetates

findings

3

b) R3 =H

3

for y-substitution of isomeric

preferente

a) R3 = CH

R2 = OCOCH

with preferente

preferente

complex

Ft2=H

L

for the trans _,

R4 = H 4 R = CH

3

and even regiospecific esters

Ib and -Id. Finally, -

5b with Me3Al _

4b and _, -

with

shows

y-substitution. in terms

of regio

and stereochemistry

mechanism

involving tight, asymmetric (2) and loose, 8 in addition to the allylic carbonium intermediates

suggest

a more

symmetric ion (10): -

0

& m

+

X4R3

X-iR, 2

the

only a little

9

8 X = OCOR

0

X-iR,

(2)

521

Table.

Reaction

of allylic

Ester

Reagent

T,"C

t,hr

la G G Gl la la Ic G G lb id G -

iBu3Al iBu Al iBu3Al iBuzA1 Me"A1 Me3Al Me3Al Me3A1 Me3A1 Me3A1 Me3A1 MezA

25 25 25 25 -20 25 -20 25 -20 25 -20 25

15 15 15 15 16 3 16 3 16 3 16 3

4a Fa 4b Z 5a 5a 5b 5b

Me3A1

MegAl Me3A1 Me3Al Me3A1

63 81 3 2

*) c/y ratio for products anti-substitution.

In the absence result

syn,y-substitution carbonium

ion

group:

trhe positive

more

can be delocalized moiety

allylic

7b

4 7 31 31 5 6 22 23

60 48 36 27 46 37 57 28

6 22 23 32 5 19 31 38

30 23 10 ll 43 38 10 ll

of factors

than

nucleophiles,

iBu3Al

is expected

-12 related

should with

60:40 76:24 22:78 29:71 50:50 79:21 79:21 72:28 of

should

probably

attack

that influentes is expected

to the

of the

group

of the benzoates in this case.

promote iBu3Al;

formation iii) Nature

-1 is expected

the outcome

Thus Me3Al ii) Leaving

of the adducts

and its delivery Thus

acetates

of loose

of

to be more

effects.

of a carbocation;

at the carboxylate

to the esters

33:67 32:68 57:43 50:50 52:48 50:50 42:58 38~62

products

and/or

and electronic

the intervention

to be delayed

lb,ld --

*+

for products

with 8 leading

Me3A10COR

steric

group

9O:lO 71:29 54:46 63~37 89:ll 75:25 53:47 61:39

*

site.

reagent:

by the phenyl

in the reaction

cation

92 97 92 95 92 97 87 95

the alkylation

may be considered

induced

47:53 50:50 14:86 8:92 45/55 47:53 35:65 58:42 37:63 26:74 32:68 36:64

63:37 81:19 97:3 98:2 14:86 23:77 14:86 52:48 93:7 9218 91:9 94:6

**) a/y ratio

of the ion-pairs,

by both

charge

than benzoates

carbocations

7a

collapse

iBu3A10COR

promote

rather

6b

i) Organoaluminum

should

allylic

86 77 86 48 93 92 91 94

in hexane

Substitution syn/anti aly

80 74 96 98 18 75 37 74 48 96 52 98

and 9 to the syn,a/y-substitution,

Now a series

than

14 23 14 52 7 8 9 6

of syn-substitution;

reagents

Yield

37 19 97 98

(10) at the less hindered -

the reaction: stabilized

trialkylaluminum

6a ----

of good externa1

from the direct

with

Product composition 3b 2a 3a 2b ----

16 3 16 3 16 3 16 3

-20 25 -20 25 -20 25 -20 25

Me3A1 Me3A1

esters

_,

ion-pairs

of the allylic to be more

-11

to the &, and

system:

stable

the

than 13 -

522

Ph H

H

H H

H

H

.t:-’

H

H H

: +: ...-

H

H

3-

H

H

H

iPr

He H

w

by the esters

strain

are completely

cis and -trans

group

axial

released

to promote

3-

shows

better

a strong

reqlliring minimum intervention

iBu3Al.

the intermediate

isomers

iBu3Al

has been

charge

polarized

of a cyclic

than 4 and 2,

in fact the reaction

of

for the trans product

5,

-12 while

_,

the acetates

are expected process. and _,

iiii) Leaving to generate

In fact

tight

the pseudo-

-5a show more

preferente

for the w,y-substitution.

It is interesting

of positive

of a little

groups

with

of syn,y-substitution

-Id with

carbocation

and torsional

I, rather

for the e,y-substitution;

leaving

-Ib and -Id by reaction

Maximum

preferente

for a m,y-substitution

than their pseudoequatorial

interactions

of the carbocation;

of the common

pseudoaxial suited

í,3-diaxial

for -12. Thus esters

-5b show some preferente

esters

benzoate

only

formation

1 with MegAl

orientation:

ion-pairs

H

H

4 and 2 since both

the intervention

4b and 3, -

+:: ...-

H

13

formed

are expected

H

H

i Pr L2

requiring

H

H

to observe

transfer

transition

synchronous REFERENCES

obtained

for the reaction

that these

to the allylic state which

circumstances,

moiety,

more

of

suggest

closely

the

resembles

process. AND NOTES

1. S. Hashimoto, Y. KItagawa, S. Iemura, H. Yamamoto and H. Nozaki, Tetrahedron m., 1976, 2615. 2. A. Itoh, K. Oshima, S. Sasaki, H. Yamamoto, T. Hiyama and H. Nozaki, Tetrahedron Lett., 1979, 4751. 3. C. Gallina and P. G. Ciattini, J. Am. Chem. Soc., 1979, 101, 1035. 4. C. Gallina, Tetrahedron Lett., 1982, 3093. 5. N. Muller and W. C. Tosch, J. Chem. Phys., 1962, 32, 1167. it is a 6. 300 x .Ol" MBMA (Perkin Elmer) at 130° for products 2a and 3; pleseaure to acknowledge the skilful assistance of pEf. Giovanna Ciranni for these analyses. 2 m x 2 mm i. d. 3% GAJ, on 60-80 mesh Chromosorb G at 180' for products 2b and 3&; 10 m x 2 mm i. d. 15% OV 275 on loo-120 mesh Chromosorb atTIOO for products _, _, 7a and -7b. Nitrogen was used as carrier gas. and stereoselective are used in the sense reported 7. The terms stereospecific of Carbon Compounds, McGraw-Hill, New York, by E. L. Eliel, Stereochemistry 1962, 434-437. The terms regiospecific and regioselective are intended as proposed by H. L. Goering and V. D. Singleton, J. Org. Chem., 1983, 48, 1531. 8. R. A. Sneen, Acc. Chem. Res., 1973, 2, 46 and literature cited therein. (Received

in UK 26 November

1984)