Organic Chemistry

Section 19.10 Alkylation of the -Carbon: The Michael Reactionb 805

All these reactions take place by the same mechanism: A base removes a proton from
the of the carbon acid, the enolate adds to the of an
carbonyl compound, and the obtains a proton from the solvent.

Notice that if either of the reactants in a Michael reaction has an ester group, the
base used to remove the is the same as the leaving group of the ester. This is
done because the base, in addition to being able to remove an can react as a
nucleophile and attack the carbonyl group of the ester. If the nucleophile is identical to
the OR group of the ester, nucleophilic attack on the carbonyl group will not change
the reactant.

Enamines can be used in place of enolates in Michael reactions. When an enamine
is used as a nucleophile in a Michael reaction, the reaction is called a Stork enamine
reaction.

CH 3 C OCH 3 + CH 3 O−

O

CH 3 OCH 3

OCH 3

C

O−

a-proton,

a-proton

a-carbon

a-carbon b-carbon a,b-unsaturated

O OO

CH 3 CH CHCNH 2 CH 3 CH 2 CCH 2 COCH 3

O

CH 3 CHCH 2 CNH 2

an , -unsaturated a -keto ester

amide

+

CH 3 O−

O O

CH 3 CH 2 CCHCOCH 3

O

CH 3 CH 2 CH CHCOCH 3

O

CH 3 CCH 2 CN

an , -unsaturated a -keto nitrile

ester

+

CH 3 O−

O

CH 3 CH 2 CHCH 2 COCH 3

O

CH 3 CCHC N

Gilbert Storkwas born in Belgium

in 1921. He graduated from the

University of Florida and received a

Ph.D. from the University of

Wisconsin. He was a professor of

chemistry at Harvard University and

has been a professor at Columbia

University since 1953. He is

responsible for the development of

many new synthetic procedures in

addition to the one bearing his name.

addition of the

enolate to the

-carbon

removal of a

proton from

the -carbon

protonation of

the -carbon

O

RCCH 2 CR RCCHCR

O O

−

RCH

RCCHCR

O

CH CR

O

HO

H

O

RCH

RCCHCR

O

CH 2 CR + HO−

O

O − O

HO− RCH CH CR

O

mechanism of the Michael reaction

N

HH

CH 2

HCl, H 2 O

CH CH

O

CH 2 CH

H

H

O

CH

NN

CH 2 CH 2 CH HO−

N

O

O O

CH 2 CH 2 CH

O

−

+

+

+ +

+

mechanism of the Stork enamine reaction