Organocopper reagents are the most common nucleophiles for the β-addition step. These reagents can be generated catalytically in the presence of Grignard reagents using either copper(I) or copper(II) salts.
Copper reagents can also be used stoichiometrically, and among these, organocuprates are the most common (they are more reactive than the corresponding neutral organocopper(I) compounds). The cuprate counterion may affect the addition and subsequent enolate reaction in subtle ways. Additions involving higher-order cuprates must be quenched with a silyl halide before alkylation.
When unsymmetrical cuprates are employed, the group whose carbon-copper bond contains less s character is almost always transferred to the β-position. A few exceptions exist, however. In the example below, conducting the reaction in THF led to transfer of the vinyl moiety, while other solvents promoted methyl transfer.
Enolates can also be used as nucleophiles for vicinal difunctionalization reactions. To prevent simple Michael addition (which culminates in protonation of the enolate intermediate), trapping by the electrophile must be intramolecular.
Considerations of the electrophile should take into account the nature of the conjugate enolate generated after the first step. Relatively reactive alkylating agents should be used, especially in cases involving the addition of cuprates (enolates resulting from the addition of cuprates are often unreactive). Oxophilic electrophiles should be avoided, if C-alkylation is desired. Electrophiles should also lack hydrogens acidic enough to be deprotonated by an enolate.