Regiocontrol in copper-catalyzed Grignard reactions with allylic substrates

Abstract

The regiochemistry of copper-catalyzed reactions between Grignard reagents and allylic substrates has been studied. A dual regiocontrol was obtained in the Li 2 CuCl 4 -catalyzed Grignard reaction with primary allylic acetates. Reaction conditions that favor formation of an intermediate dialkylcuprate (fast addition of Grignard reagent, low temperature, low concentration of catalyst) gave α-substitution, whereas reaction conditions favoring formation of a monoalkylcopper intermediate (slow addition of Grignard reagent, increased concentration of catalyst) led to a γ-substitution. A remarkable solvent effect was observed for CuCN-catalyzed Grignard coupling with primary allylic acetates. In ether a highly γ-selective reaction took place, but in THF α-substitution predominated. Other allylic substrates such as allylic sulfones and allylic chlorides were also studied. The latter substrates showed a preference for γ-substitution, which is explained by their high reactivity