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

ABSTRACT: 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 ?-hydroxy-?-lactams from precursor ?-ketoamide derivatives under mild, visible light conditions. Selective cleavage of the distal C(sp²)-C(sp³) bond in ?-hydroxy-?-lactams using a Rh-complex leads to ?-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.

SUBMITTER: Ham JS

PROVIDER: S-EPMC7773224 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Ham Jin Su JS Park Bohyun B Son Mina M Roque Jose B JB Jurczyk Justin J Yeung Charles S CS Baik Mu-Hyun MH Sarpong Richmond R

Journal of the American Chemical Society 20200719 30

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(sp<sup>2</sup>)-C(sp<sup>3</sup>) bond in α-hydroxy-β-lactams using a Rh-complex l ...[more]

PMID: 32627545

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