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C–C Cleavage Approach to C–H Functionalization of Saturated Aza-Cycles

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journal contribution
posted on 13.02.2020, 21:44 authored by Jose B. Roque, Yusuke Kuroda, Justin Jurczyk, Li-Ping Xu, Jin Su Ham, Lucas T. Göttemann, Charis A. Roberts, Donovon Adpressa, Josep Saurí, Leo A. Joyce, Djamaladdin G. Musaev, Charles S. Yeung, Richmond Sarpong
Saturated cyclic amines (aza-cycles) are ubiquitous structural motifs found in pharmaceuticals, agrochemicals, and bioactive natural products. Given their importance, methods that directly functionalize aza-cycles are in high demand. Herein, we disclose a fundamentally different approach to functionalizing cyclic amines which relies on C–C cleavage and attendant cross-coupling. The initial functionalization step is the generation of underexplored N-fused bicyclo α-hydroxy-β-lactams under mild, visible light conditions using a Norrish–Yang process to affect α-functionalization of saturated cyclic amines. This approach is complementary to previous methods for the C–H functionalization of aza-cycles and provides unique access to various cross-coupling adducts. In the course of these studies, we have also uncovered an orthogonal, base-promoted opening of the N-fused bicyclo α-hydroxy-β-lactams. Computational studies have provided insight into the origin of the complementary C–C cleavage processes.