Multiple Component Reactions: An Efficient Nickel-Catalyzed Reformatsky-Type Reaction and Its Application in the Parallel Synthesis of β-Amino Carbonyl Libraries

Multiple-component condensations (MCC) where three or more reactants combine to afford a new core structure possessing the molecular features of its composite building blocks is a powerful method for the preparation of molecular diversity. We have developed an efficient, nickel-catalyzed, Reformatsky-type three-component condensation (3CC) reaction that affords β-amino carbonyl compounds. The scope of the reaction is demonstrated both in the gram and microscale settings; 15 β-amino esters, amides, and a ketone were prepared efficiently at the mmol scale, and a library of 64 β-amino carbonyl compounds was generated at the μmol scale.