Radical-Polar Crossover Bicyclization Enables a Modular Synthesis of Saturated Bicyclic Amines

自由基极性交叉双环化反应实现了饱和双环胺的模块化合成

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Abstract

The rapid assembly of diverse cyclic amines from simple precursors is now considered as an ideal platform with respect to efficiency and sustainability. To date, numerous synthetic methods have been successfully developed however, most of them are limited to a narrow subset of cyclic amines, with variations in ring size often requiring different substrates and distinct synthetic strategies. Furthermore, the "escape-from-Flatland" concept has led chemists to focus on the synthesis of C(sp(3))-rich small molecules for potential drug candidates. Herein, the successful realization of a radical-polar crossover bicyclization reaction is reported from easily available cyclopropylamines and substituted alkenes through photoredox catalysis. This approach introduces an innovative methodology for the de novo synthesis of a diverse collection of 4/5-, 5/5-, 6/5-,7/5-, and 5/6-fused saturated bicyclic amines in a systematic and modular manner with excellent diastereoselectivity. This work highlights the efficiency and utility of the photoinduced radical-polar crossover bicyclization, the applicability of which is showcased by excellent functional group tolerance, wide substrate scopes, and simple derivatization reactions.

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