Asymmetric Synthesis of 1,1‐Diarylalkyl Units by a Copper Hydride Catalyzed Reduction: Differentiation Between Two Similar Aryl Substituents

An efficient method for the preparation of enantiomerically enriched 1,1‐diarylalkyl units has been developed. The use of copper hydride complexed by the (R)‐1‐[(S)‐2‐diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine (Josiphos) ligand effects a highly enantioselective conjugate reduction of β,β‐diaryl‐substituted α,β‐unsaturated nitriles with aryl groups of similar steric demand and no secondary coordination site. A range of substrates with meta and para substituents on the aryl group were reduced with good to excellent enantioselectivities (up to 97 % enantiomeric excess (ee)) and this methodology was applied to the formal synthesis of indatraline.