Page 211 - Advanced Organic Chemistry Part B - Reactions & Synthesis

2.6. Conjugate Addition by Carbon Nucleophiles 183

SECTION 2.6
The previous sections dealt with reactions in which the new carbon-carbon bond
Conjugate Addition by
is formed by addition of the nucleophile to a carbonyl group. Another important
Carbon Nucleophiles
method for alkylation of carbon nucleophiles involves addition to an electrophilic
multiple bond. The electrophilic reaction partner is typically an , -unsaturated ketone,
aldehyde, or ester, but other electron-withdrawing substituents such as nitro, cyano,
or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack.
The reaction is called conjugate addition or the Michael reaction.

O – O R 3
R 2 + EWG EWG
R 1 R 3 R 1
R 2

More generally, many combinations of EWG substituents can serve as the anion-
stabilizing and alkene-activating groups. Conjugate addition has the potential to form
a bond to one group and to the other to form a , -disubstituted system.
R
EWG EWG′
EWG EWG′ – + R EWG EWG′
or R + –
R R
R R R R
The scope of the conjugate addition reaction can be further expanded by use of Lewis
acids in conjunction with enolate equivalents, especially silyl enol ethers and silyl
ketene acetals. The adduct is stabilized by a new bond to the Lewis acid and products
are formed from the adduct.
LA
LA 3 O
O R 3 O O R
+
R′ SiO O
3
R 2 + 4 R 1 R 4 R 1 R 4
R 1 R 3 R R 2 R 2
Other kinds of nucleophiles such as amines, alkoxides, and sulfide anions also react
with electrophilic alkenes, but we focus on the carbon-carbon bond forming reactions.

2.6.1. Conjugate Addition of Enolates
Conjugate addition of enolates under some circumstances can be carried out with
a catalytic amount of base. All the steps are reversible.
O O –
RCCHR + B – RC CR + BH
2
2
O – O R EWG
EWG
RC CR + CC RC C C C –
2
R
O R EWG O R EWG
–
RC C C C – + BH RC C C C H + B
R R