A Radical Addition
Approach to a Heptafluoroisopropyl Substituted Arene, Combined
with a Highly Diastereoselective Annulation Reaction To Synthesize
the Tricyclic Core of BMS-986251
posted on 2021-11-10, 16:05authored byWilliam P. Gallagher, John R. Coombs, Carlos A. Guerrero, Eric M. Simmons, Francisco González-Bobes
We
have devised an asymmetric route to the tricyclic core 10 of BMS-986251. The six-step synthesis utilizes readily
available starting materials, involves the one-step installation of
the perfluoro isopropyl moiety through a radical mechanism, and leverages
a novel diastereoselective annulation to build the pyrrolidine ring.
Overall, 10 was obtained in 49% yield as a single stereoisomer
in 6 steps and 3 isolations using this new route.