Practical, Scalable Merging of Au(I)-Catalysis and Biocatalysis for the Synthesis of Chiral Amino Building-blocks from Alkynes

Au(I)-catalyzed hydration of alkynes is followed with transaminase-catalyzed reductive amination, leading to enantioenriched chiral secondary 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 pyrrolines obtained in high enantioselectivities. The method demonstrated applicability to the synthesis of bioactive drugs such as clobenzorex (44% yield, 3 steps, 96% ee) and a precursor of lidexamfetamine (34% yield, 3 steps dr, 98:2).