Nucleophilic Addition to α,β-Unsaturated Carbonyl Compounds

The reactivity pattern of α,β-unsaturated carbonyl compounds involves the basic character of the oxygen atom of the carbonyl group, the relative electrophilicities of the carbonyl carbon and Cβ (C4) of the conjugated system, and the acidic site at Cγ. These chemical properties are analyzed by considering resonance structures (VB theory) and the energies and atomic coefficients in their LUMO orbitals (MO theory). The Michael reaction is introduced, as well as the reactions of α,β-unsaturated carbonyl compounds. Kinetic and thermodynamic control of the regio- and stereoselectivities of these reactions is considered. The racemic and asymmetric versions of the Robinson annulation and the role of imines and enamines in the preparation of enantiomerically enriched α-alkylated carbonyl compounds is discussed. The 1,4-cuprate addition, the Pd(0)-catalyzed nucleophilic addition (Heck–Mizoroki), the Diels–Alder cycloaddition reaction and free-radical-mediated 1,4-additions are discussed both in racemic and asymmetric versions.