Formal Alkyne Aza-Prins Cyclization: Gold(I)-Catalyzed Cycloisomerization of Mixed N,O-Acetals Generated from Homopropargylic Amines to Highly Substituted Piperidines

A new gold (I)-catalyzed cycloisomerization to access highly substituted piperidines has been developed. By combining a conceptually new way of generating iminium ions using cationic gold(I) complexes and an efficient cyclization reaction that can minimize a potentially competing aza-Cope rearrangement, the proposed reaction successfully circumvents a long-standing problem in the classical aza-Prins reaction. Synthetic utility of the catalytic reaction was demonstrated by a synthesis of optically active 2-alkyl-pipendin-4-one.