Aliphatic Nucleophilic Substitutions: Problematic Electrophiles

Abstract

Nucleophilic substitutions at sp 3-hybridized carbon are among the most useful synthetic transformations, and have been thoroughly investigated [1-3]. The success of these reactions depends mainly on the structures of the nucleophile and electro-phile, their concentration, and on the solvent and reaction temperature chosen. The structure of the electrophile in nucleophilic substitutions is of critical importance, because many unwanted side reactions result from unexpected reactivity of the elec-trophile. In Scheme 4.1 the mechanisms of typical monomolecular (Sn1) and bimolecular (Sn2) nucleophilic substitutions at a neutral electrophile with an anionic nucleo-phile are sketched. Sn1 reactions usually occur when the electrophile is sterically