The Nickel/Copper-Catalyzed Direct Alkylation of Heterocyclic C-H Bonds

摘要

Aromatic heterocycles are an important class of molecules which have been widely used as synthetic building blocks, bio-active molecules, pharmaceuticals, and organic materials. There are now many methods available for the preparation of aromatic heterocycles that are substituted with aryl, alkenyl, alkynyl, and even activated alkyl groups, the most recent method involves C-H functionalization. However, the synthesis of heterocyclic compounds substituted by non-activated alkyl groups containing P-hydrogen atom remains challenging. Traditional methods such as Friedel-Crafts and radical alkylation reactions pose severe limitations on the electronic properties of the heterocycles, and are often incompatible with sulfur containing heterocycles. Additionally, the Friedel-Crafts alkylation requires strong acids, and suffers from side reactions such as multiple alkylation and isomerization. Likewise, the method of deprotonation by strong bases, for example nBuLi, and subsequent electrophilic trapping requires cryogenic conditions, active electrophiles, the protection of acidic and/or electrophilic groups, and special bases.