Photochemical Strategy Enables the De Novo Synthesis of Saturated Bicyclic Amine Collections

Abstract

Escape-from-Flatland concept have driven chemists pay more attention on the synthesis of C(sp3)-rich small molecules for potential drug candidates. Saturated bicyclic amines are a particularly relevant class of derivatives and their inherent structural rigidity ensures accurate three-dimensional (3D) disposition of exit vectors. Herein, we report the successful realization of a radical-polar crossover bicyclization reaction from easily available cyclopropylamines and substituted alkenes through photoredox catalysis. Notably, this approach introduces an innovative methodology for the de novo synthesis of a diverse collection of 4/5-, 5/5-, 6/5- and 7/5-fused saturated bicyclic amines in a systematic and modular manner that are difficult to achieve in previous methodologies. This work highlights the efficiency and utility of the photoinduced radical-polar crossover bicyclization and the applicability is showcased by excellent functional group tolerance, wide substrate scopes and simple derivatization reactions.