Organic Chemistry

Alternatively, the of an aldehyde or a ketone can be made to react with a

nucleophileby first brominating the of the carbonyl compound.

PROBLEM 15

Describe how the following compounds could be prepared using an enamine intermediate:

a. b.

19.10 Alkylation of the -Carbon:

The Michael Reaction

In Section 18.13, you saw that nucleophiles react with aldehydes and

ketones, forming either direct addition products or conjugate addition products; in

Section 18.14, you saw that nucleophiles react with carboxylic acid

derivatives, forming either nucleophilic acyl substitution products or conjugate addi-

tion products.

When the nucleophile is an enolate, the addition reaction has a special name—it is

called a Michael reaction. The enolates that work best in Michael reactions are those

that are flanked by two electron-withdrawing groups: enolates of

esters, and nitriles. Because these enolates are relatively

weak bases, addition occurs at the of aldehydes and ke-

tones. The enolates also add to the of esters and amides be-

cause of the low reactivity of the carbonyl group. Notice that Michael reactions form

1,5-dicarbonyl compounds—if one carbonyl carbon is given the 1-position, the other

carbonyl carbon is at the 5-position.

b-carbon a,b-unsaturated

b-carbon a,b-unsaturated

b-diesters,b-keto b-keto

b-diketones,

O

RCH CHCR

1. Nu

O

RCH CHCR +

direct addition conjugate addition

OH

Nu Nu

RCHCH 2 CR

2. H 3 O+

−

a,b-unsaturated

a,b-unsaturated

B

O O

CCH 2 CH 3

O

CH 2 CH 2 CH 3

Br 2

H 3 O+

O O O

Br −Nu Nu

a-position

a-carbon

OOO

CH 2 CHCH CH 3 CCH 2 CCH 3

O

CH 2 CH 2 CH

an , -unsaturated a -diketone

aldehyde

+

HO−

OO

CH 3 CCHCCH 3

OOO

CH 3 CH CHCCH 3 CH 3 CH 2 OCCH 2 COCH 2 CH 3

O

CH 3 CHCH 2 CCH 3

an , -unsaturated a -diester

ketone

+

CH 3 CH 2 O−

O

CH(COCH 2 CH 3 ) 2

804 CHAPTER 19 Carbonyl Compounds III

Michael reactions form 1,5-dicarbonyl
compounds.

Arthur Michael (1853–1942)was
born in Buffalo, New York. He studied
at the University of Heidelberg, the
University of Berlin, and L’École de
Médicine in Paris. He was a
professor of chemistry at Tufts and
Harvard Universities, retiring
from Harvard when he was 83.