Deoxy-Arylation of Amides via a Tandem Hydrosilylation/Radical- Radical Coupling Sequence.

Abstract

Vaska's complex is a prominent catalyst for the hydrosilylation of amides. The O-silyl hemiaminal intermediate formed in these processes has been demonstrated as an electrophile for nucleophilic additions. More recently, these intermediates have been shown to be suitable for single electron reduction to generate α-amino radicals. Leveraging the ability to generate α-amino radicals from these hemiaminals, we describe a two-step, one-pot, deoxy-arylation of amides utilizing iridium-catalyzed hydrosilylation and photoredox catalysis. This transformation can be tailored toward the late-stage functionalization of biologically relevant molecules, with drug discovery applications as shown in the streamlined synthesis of an NPY Y2 inhibitor.