C-H/C-C Functionalization Approach to N-Fused Heterocycles from Saturated Azacycles.

Jin Su Ham, Bohyun Park, Mina Son, Jose B Roque, Justin Jurczyk, Charles S Yeung, Mu-Hyun Baik, Richmond Sarpong

Journal of the American Chemical Society 2020 Jul 29

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Herein we report the synthesis of substituted indolizidines and related N-fused bicycles from simple saturated cyclic amines through sequential C-H and C-C bond functionalizations. Inspired by the Norrish-Yang Type II reaction, C-H functionalization of azacycles is achieved by forming α-hydroxy-β-lactams from precursor α-ketoamide derivatives under mild, visible light conditions. Selective cleavage of the distal C(sp2)-C(sp3) bond in α-hydroxy-β-lactams using a Rh-complex leads to α-acyl intermediates which undergo sequential Rh-catalyzed decarbonylation, 1,4-addition to an electrophile, and aldol cyclization, to afford N-fused bicycles including indolizidines. Computational studies provide mechanistic insight into the observed positional selectivity of C-C cleavage, which depends strongly on the groups bound to Rh trans to the phosphine ligand.

Citation

Jin Su Ham, Bohyun Park, Mina Son, Jose B Roque, Justin Jurczyk, Charles S Yeung, Mu-Hyun Baik, Richmond Sarpong. C-H/C-C Functionalization Approach to N-Fused Heterocycles from Saturated Azacycles. Journal of the American Chemical Society. 2020 Jul 29;142(30):13041-13050