Gold-Catalyzed Dearomative Spirocyclization of N-Aryl Alkynamides for the Synthesis of Spirolactams.

Abstract

A catalytic redox-neutral method for the synthesis of spirolactams proceeding through the dearomative spirocyclization of N-aryl alkynamides is reported. In contrast to stoichiometric activating agents employed for related transformations, we show that the use of 5 mol % of Au(PPh3)Cl and AgOTf in dichloroethane at 50-80 °C leads to selective spirocyclization, furnishing the products in yields of 35-87%. The substrate scope of the reaction is good, with both electron-donating and electron-withdrawing groups being tolerated around the arene ring, as well as substitution at the amide nitrogen. The identity of the para-alkoxy group on the arene ring is key to achieving selectivity for spirocyclization over alternative mechanistic pathways. While the presence of a para-methoxy group leads to trace amounts of the desired spirolactams, the para-tert-butoxy or para-hydroxy substrate analogues furnish the spirolactams in good yield with high selectivity.