Merging Au(I)-Catalysis and Biocatalysis: Practical and Scalable Synthesis of Chiral Amino Building Blocks from Alkynes

Au(I)-catalyzed hydration of aliphatic terminal alkynes is followed by transaminase-catalyzed reductive amination, leading to enantioenriched chiral amines. The approach features a one-pot reaction with no particular need for a compartmentalization strategy. Final functionalization performed in situ leads to a variety of chiral amines, pyrroles, and 1-pyrrolines obtained in high enantioselectivities. The method demonstrates applicability to the synthesis of bioactive drugs such as clobenzorex (43% yield, 3 steps, 96% ee) and a precursor of lisdexamfetamine (34% yield, 3 steps, dr 98:2).