398
NUCLEOPHILIC REACTIONS INVOLVING ENOLATE ANIONS
Other examples of the Michael reaction are shown
below. Note the relatively mild bases that are
employed in these reactions where the nucleophiles
are 1,3-dicarbonyl compounds.
O
O
C N
acrylonitrile
Et 3 N /
t BuOH
C N
O
O
Ph
Ph
O
CO 2 Et
CO 2 Et
piperidine
MeOH
Ph
O
Ph
CO 2 Et
CO 2 Et
Ph
O
Ph
CO 2 H
acetylacetone
4-acetyl-5-oxohexanonitrile
5-oxo-3,5diphenylpentanoic acid
H
+
heat
(chalcone)
1,3-diphenylpropenone
diethyl malonate
Box 10.19
Michael reaction: the Robinson annulation
A rather nice example of enolate anion chemistry involving the Michael reaction and the aldol reaction is
provided by the Robinson annulation, a ring-forming sequence used in the synthesis of steroidal systems (Latin:
annulus, ring).
In the partial synthesis shown, there are two reagents, the α,β-unsaturated ketone methyl vinyl ketone and the
1,3-diketone 2-methylcyclohexa-1,3-dione.
O
O
O
O
O
O
EtO H
O
O
O
O
O
O
O
O
NaOEt / EtOH
NaOEt / EtOH
O
O
O
testosterone
diketone is more
acidic substrate
Michael
reaction
O
OH
O
O
– H 2 O
Robinson annulation
OH
aldol
reaction
dehydration produces
conjugated system
acidic
protons
O
O
O
acidic
protons
methyl vinyl ketone
2-methylcyclohexa-1,3-dione