Gold-Catalyzed Dearomative Spirocyclization of <i>N</i>‑Aryl Alkynamides for the Synthesis of Spirolactams
2018-01-08T00:00:00Z (GMT) by
A catalytic redox-neutral method for the synthesis of spirolactams proceeding through the dearomative spirocyclization of <i>N</i>-aryl alkynamides is reported. In contrast to stoichiometric activating agents employed for related transformations, we show that the use of 5 mol % of Au(PPh<sub>3</sub>)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 <i>para</i>-alkoxy group on the arene ring is key to achieving selectivity for spirocyclization over alternative mechanistic pathways. While the presence of a <i>para</i>-methoxy group leads to trace amounts of the desired spirolactams, the <i>para</i>-<i>tert</i>-butoxy or <i>para</i>-hydroxy substrate analogues furnish the spirolactams in good yield with high selectivity.