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Gold-Catalyzed Dearomative Spirocyclization of N‑Aryl Alkynamides for the Synthesis of Spirolactams
journal contribution
posted on 2018-01-08, 00:00 authored by Taylor
L. Vacala, Paul R. Carlson, Asa Arreola-Hester, Chloé G. Williams, Evana W. Makhoul, Paul A. VadolaA 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.