Asymmetric Synthesis of a TRPV1 Antagonist via tert-Butanesulfinamide-Directed Reductive Amination with a Chromanone

An expedient asymmetric synthesis of TRPV1 antagonist 1 has been developed and demonstrated on multikilogram scale. The enabling route to 1 is detailed herein and characterized by the following key transformations: an aldol-cyclodehydration sequence to install the chromanone, and an auxiliary-mediated diastereoselective reductive amination.