Design and Synthesis of Chiral Diene Ligands for Rh I ‐Catalyzed Enantioselective Arylation of N ‐DPP‐protected Aldimines: Synthesis of the Antifungal Agent Bifonazole

Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the Rh I ‐catalyzed enantioselective addition reaction of arylboronic acids to N ‐diphenylphosphinyl ( N ‐DPP)‐protected aldimines. Unlike the analogous Rh I ‐catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N ‐DPP‐aldimines and arylboronic acids, producing the desired optically active N ‐DPP‐protected amines with yields between 31–99 % and with ee values up to 91–99 %. The synthetic utility of the method was demonstrated by the conversion of N ‐DPP‐protected amine 3 ae into the antifungal agent, bifonazole ( 13 ).