Organic Chemistry

Section 19.9 Alkylation and Acylation of the -Carbon via an Enamine Intermediatea 803

This means that electrophiles can be added to the of an aldehyde or a ketone by
first converting the carbonyl compound to an enamine (by treating the carbonyl
compound with a secondary amine), adding the electrophile, and then hydrolyzing the
imine back to the ketone.

Because the alkylation step is an reaction, only primary alkyl halides or methyl
halides should be used (Section 10.2).
One advantage to using an enamine intermediate to alkylate an aldehyde or a ketone
is that only the monoalkylated product is formed.

In contrast, when a carbonyl compound is alkylated directly, dialkylated and O-alkylated
products can also be formed.

In addition to being able to be alkylated, aldehydes and ketones can also be acylated
via an enamine intermediate.

Notice that the of an aldehyde or a ketone can be made to react with an
electrophileeither by first treating the carbonyl compound with LDA or by converting
the carbonyl compound to an enamine.

LDA −

O O O

E+

E

a-carbon

O N

+

N

N

H

+ O

−

O

CCH 3

Cl

N

+ O

CCH 3

O

CCH 3

Cl−

CH 3 CCl

O

HCl H 2 O

+

N

+

HH

catalytic

H+

OO

1. LDA


2. CH 3 Br

O

H 3 C

+++

O

CH 3

CH 3

CH 3 CH 3

OCH 3

OO

1. secondary amine
   catalytic H+


2. CH 3 Br


3. HCl, H 2 O

CH 3

SN 2

a-carbon

3-D Molecule:

Pyrrolidine enamine of

cyclohexanone

+ +

N

H

N+

N

an enamine

N+

CH 3 Br

O O

HCl

H 2 O

CH 3 CH 3

HH

catalytic

H+