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

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)13041-13050
Number of pages10
JournalJournal of the American Chemical Society
Volume142
Issue number30
DOIs
StatePublished - Jul 29 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry

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