Cyclization of Imides to 2-Azabicycles via Aminoketyl Radicals by Using Samarium(II) Iodide-Water: Reaction Development, Synthetic Scope, and Mechanistic Studies.

The first highly selective method for direct addition of aminoketyl radicals [R-C*(O-)NR1R2], generated from five- or six-membered cyclic imides, to nonactivated π-systems by using the SmI2-H2O reagent is reported. The transformation is operationally simple, scalable, and provides access to valuable angular 2-azabicycles containing three contiguous stereocenters with excellent diastereoselectivity (>95:5 dr). The protocol accommodates a wide range of π-acceptors that can be modulated by the alcohol additive used. Notably, the transformation provides the first general method for generation of aminoketyl radicals by a direct electron capture to amide bonds, thus opening new vistas for applications of these underutilized intermediates in a diverse array of open-shell reaction pathways. Systematic studies on the effects of additives, the scope and limitations of the reaction, and the reaction mechanism are reported. [ABSTRACT FROM AUTHOR]