α-Amino bicycloalkylation through organophotoredox catalysis
Jeremy Nugent, Adrián López‐Francés, Alistair J. Sterling, Min Yi Tay, Nils Frank, James J. Mousseau, Fernanda Duarte, Edward A. Anderson
Abstract
α-amino/amido bicycloalkanes) is highly desirable for drug discovery applications, but their synthesis is challenging. Here we report an approach to α-amino BCPs and BCHeps through the visible-light enabled addition of α-amino radicals to the interbridgehead C-C bonds of [1.1.1] and [3.1.1]propellane respectively. The reaction proceeds under exceptionally mild conditions and displays broad substrate scope, providing access to an array of medicinally-relevant BCP and BCHep products. Experimental and computational mechanistic studies provide evidence for a radical chain pathway which depends critically on the stability of the α-amino radical, as well as effective catalyst turnover.