Synthetic Applications of Enamines (p.960).

Recall that the

reaction of a ketone with a 2° amines gives an enamine
(Ch. 17.11)
O N N
H+ - H+
+
N -H2O
H
ketone
Iminium ion Enamine
or aldehyde 2° amine
w/ !-protons

Enamines are reactive equivalents of enols and enolates and

can undergo α-substituion reaction with electrophiles

N N

H H
O O

Reaction of enamine with α,β-unsaturated ketones (Michael

reaction).
O O
N O
+
CH3 then H2O

H2O

N O

N O

CH3

N O N O

H OH

Enamines react on the less hindered side of unsymmetrical ketones

O
O O O
N CH3
H3C H3C
+ H3C
then H2O
N
H

1
Type II Aldolase uses enamine chemistry

CH2OPO32- CH2OPO32-
H CHO
O Lys N aldolase + CH2OH
aldolase H OH H
HO H HO H
Lys N
H OH H O H CH2OPO32-
HO H HO2C Asp
H OH H OH O2C Asp D-glyceraldehyde-
3-phosphate
CH2OPO32- CH2OPO3 2-

D-fructose-
1,6-bisphosphate

CH2OH CH2OH
H
O H2O Lys N
Lys NH2
CH2OH HO H
H
Dihydroxyacetone