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

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

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2929-2941
Number of pages13
JournalACS Catalysis
Volume10
Issue number5
DOIs
StatePublished - Mar 6 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Catalysis

Keywords

  • C-C cleavage
  • Norrish-Yang
  • cross-coupling
  • cyclic amines
  • palladium
  • strain release

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