N-Heterocyclic Carbene Catalyzed [4+3] Annulation of Enals ando-Quinone Methides: Highly Enantioselective Synthesis of Benzo-ε-Lactones

The coenzyme thiamine (vitamin B1), a natural thiazolium salt, is involved in many enzymatic catalyses. Since it has been proposed that the catalytically active species of these reactions is a nucleophilic carbene, many chemists have tried to perform enzyme mimetic asymmetric carbene catalysis. After a long and difficult search, stable carbenes are finally isolated, characterized, and in the chemist's hands. The experiments of decades have finally resulted in successful enantioselective benzoin condensations and enantioselective intramolecular Stetter reactions as important examples of carbene catalyzed asymmetric nucleophilic acylation processes.