Enantioselective Synthesis of syn-α-Aryl-β-hydroxy Weinreb Amides: Catalytic Asymmetric Roskamp Reaction of α-Aryl Diazo Weinreb Amides

A convenient one-pot procedure to synthesize a variety of highly optically active syn-alpha-aryl-beta-hydroxy Weinreb amides using an asymmetric Roskamp/reduction strategy is described. An oxazaborolidinium ion catalyzed asymmetric Roskamp reaction of alpha-aryl diazo Weinreb amides with aldehydes produced alpha-phenyl-beta-keto Weinreb amides, which were in situ reduced with zinc borohydride to give syn-alpha-aryl-beta-hydroxy Weinreb amides in good yields (up to 87%) with high enantioselectivities (up to 99% cc) and syn stereoselectivities (>20:1).