3 years ago

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

Gold-Catalyzed Dearomative
Spirocyclization of N-Aryl Alkynamides for
the Synthesis of Spirolactams
Evana W. Makhoul, Asa Arreola-Hester, Chloé G. Williams, Taylor L. Vacala, Paul A. Vadola, Paul R. Carlson
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.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b03125

DOI: 10.1021/acs.joc.7b03125

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