Gold-Catalyzed Hydroamination of Propargylic Alcohols: Controlling Divergent Catalytic Reaction Pathways To Access 1,3-Amino Alcohols, 3-Hydroxyketones, or 3-Aminoketones

A versatile approach to the valorization of propargylic alcohols is reported, enabling controlled access to three different products from the same starting materials. First, a general method for the hydroamination of propargylic alcohols with anilines is described using gold catalysis to give 3-hydroxyimines with complete regioselectivity. These 3-hydroxyimines can be reduced to give 1,3-amino alcohols with high syn selectivity. Alternatively, by using a catalytic quantity of aniline, 3-hydroxyketones can be obtained in high yield directly from propargylic alcohols. Further manipulation of the reaction conditions enables the selective formation of 3-aminoketones via a rearrangement/hydroamination pathway. The utility of the new chemistry was exemplified by the one-pot synthesis of a selection of N-arylpyrrolidines and N-arylpiperidines. A mechanism for the hydroamination has been proposed on the basis of experimental studies and density functional theory calculations.