A steric isotope effect reconsidered

TetrahedronLetters Wo. 45, pp 4297 - 4300, 1971.

PergamonPress. Printed in Great Britain.

A STERIC ISOTOPE EFFECT RECONSIDERED

A. J. Kresge and V. Nowlan Department

of Chemistry,

University

(Receivedin USA 21 June 1971;

It was recently

reported

bromide

t-BudH-CH=CH2 3 -

K

MgBr

RzCO

t-BuCH-CH=CH2

t kl,

2 -

solution as a rapidly equilibrating is remarkably less crowded

sensitive

(eq l), which exists in

RzSOH

R2CO k3

-1

181, Canada

in this journal that the reaction of

ketones with t-butylallylmagnesium

YgBr t-BuCH=CH-CH2

of Toronto, Toronto

received in UK for publication 8 October 1971)

4 mixture of the isomers 1 and 2_,

to steric effects,

(4) _ to more crowded

and that the proportion

(3) - product

formed,

fact be used as a delicate measure of the effective

[4]/[2], can in bulk of substituent

This criterion was then applied to normal and deuterated

groups.'

acetone, and CH3COCH3 was found to give less of the more hindered product

than CD3COCD3:

therefore

concluded

[4]/[3] - = 3.4 and 3.1 respectively.

It was

that CD3 is less bulky than CH3 and that this

isotope effect is steric in origin.

4297

of

4298

No. 45

Since true steric isotope effects have proved to be both elusive and rare,* this is a significant

result.

It is of some consequence,

that the effect observed here is also consistent

moreover, non-steric

with a

explanation.

The carbonyl puts positive

group is known to be polarized

which

charge on carbon, and, since this carbon atom is trigonal,

the charge can be delocalized adjacent methyl group. this trigonal

in a direction

by hyperconjugative

carbon atom, the delocalization

and this change in hyperconjugation

give rise to secondary

isotope effects.

observed

formation

in hemiacetal

can be expected

from acetone and acetone-d6

phenylhydrazone

have in fact been justified

of ethyl acetate

in just this way;3

that the isotope effects observed

formation from acetophenone

(kH/kD = 0.89) and propiophenone

and kH/kD

and cyclopentanone-d4,

as well as kH/kD = 0.90 found in the saponification

it is also probable

in 2,4-dinitro-

and acetophenone-a,a,a-d3

and propiophenone-a,a-d2

(kH/kD = 0.89)

and the absence of an isotope effect in the case of propiophenone propiophenone-S,S,S-d3

isotope effects can be expected

reaction of acetone with Grignard

reagents.

such as t-butylallylmagnesium

two different

in the

In the case of ambident

bromide,

isotope effects on the

reactions will not in general be of the same magnitude,

and application

of the Hammond postulate5

leads to the prediction

the slower process with the later transition effect.

and

(kH/kD = 1.00) have a similar explanation.4

Similar hyperconjugative

reagents

to

The effects kH/kD = 0.78

= 0.69 for the same reaction of cyclopentanone

and ethyl acetate-ds,

with an

During the course of a reaction which converts

carbon into a saturated

is eliminated,

interaction

that

state will show the stronger

The present reaction gives less 2 than 4, and it also seems

4299

No. 45

likely that the equilibrium

between 1 and 2 lies strongly on the side

since both isotope effects are inverse.

(k~)H/(ks),,

gives

sides by K (K =

[21/[3_1) leads to K(k4/k3)D

= [~l/[~l,

is

equivalent

of course,

is consistent

([41/[~1),

= 3.4

< K(kb/ka)H which,

( [4-l/ [3_1) D < ( [*I/ [?I IH.

with the fact that

These considerations observed

to

<

Rearrangement

(k9/kl)D < (k$/k3)H, and multiplication

this inequality

K(kb/ka)

(k3JH/(k3JD

Thus,

of 1; these factors combine to make k3 c< k4.

([4]/[2]),

of

of both since This,

= 3.1 and

make it unlikely that the isotope effect

in this reaction

is wholly

course, be a steric contribution

steric in origin.

There may, of

to the overall effect, and in this

regard it is of interest to note that steric and hyperconjugative isotope effects might be distinguished Grignard reagent, would be greater would

i-propylallylmagnesium

than kb.6

With such a reagent,

still lead to more reaction of deuterated

substrate than

perhaps

with a less

at the more hindered

( [4_1/[31)H.

reaction,

for which k3

steric isotope effects than undeuterated would remain less

The formation of 3_, however, would now be the faster

with the Hammond

predicted

bromide,

site, and ([41/[31) -D

and, for a hyperconjugative

K(kti/ksjH and

crowded ambident

postulate,

([f11/Igl),

isotope effect operating

(k31H/(k3jD > (k+)H/(k4)D

> ([41/[21)H,

in accord

, or K(k&/kB)D

which is opposite

>

to the result

for a purely steric isotope effect.

References 1)

M. Cherest, H. Felkin, and C. Frajerman, (1971).

Tetrahedron

Letters,

379

4300

2)

NQ. 45

R. E. Weston, Tetrahedron, J. G. Koelling,

and J. G. McDonald,

(1966); G. J. Karabatsos, S. E. Scheppele,

6, 31 (1959); H. C. Brown, M. E. Azzaro, J. Amer. Chem. Sot., 88, 2520

G. C. Sonnischen,

C. G. Papaioannou,

and R. L. Schone, J. Amer. Chem. Sot., 83, 463

(1967); A. J. Kresge and R. J. Preto, J. Amer. Chem. Sot., E,

5510

(1967); J. G. Jewett and R. P. Dunlop, J. Amer. Chem. Sot., 90, 809 (1968).

3)

M. L. Bender and M. S. Feng, J. Amer. Chem. Sot., 82, 6318 J. M. Jones and M. L. Bender, J. Amer. Chem. Sot., g,

4)

V. F. Raen, T. K. Dunham, D. D. Thompson, Chem. Sot., E,

6322

and C. J. Collins,

(1960). J. Amer.

3497 (1963).

5)

G. S. Hammond, J. Amer. Chem. Sot., II, 334 (1955).

6)

In order to show that k3 > kq, K, as well as 14_1/111, be determined.

(1960);

would

have

to