posted on 2021-08-02, 11:33authored bySharada
S. Labadie, Karine Thai, Jessica M. Grandner, Yanzhou Liu, Brendan T. Parr
Herein
we present an investigation into the scope and mechanism
for the synthesis of cyclopentyl and heterocyclic fused pyridones
from the corresponding enyne amides. In the presence of a secondary
amine, cyclization proceeds smoothly to form 5,6-bicyclic pyridones
in 12–90% yield. The cyclization fails with enyne amides of
six-membered and larger ring systems. The ring closure reaction is
catalytic in nature with respect to the secondary amine and proceeds
via sequential 1,6-addition of the amine, 6-exo-trig ring closure of the iminium intermediate, and subsequent elimination
of the secondary amine. Computations show reduced conjugation between
the enyne and amide for six-membered and larger systems, thereby providing
an explanation for the inability of such enyne amides to form fused
pyridones.