General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides and Lactams

Ken Yamazaki, Pablo Gabriel, Graziano Di Carmine, Julia Pedroni, Mirxan Farizyan, Trevor A. Hamlin, Darren J. Dixon

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

An iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3 + 2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using 1 mol% Vaska's complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent regio- and diastereoselective, inter- and intramolecular dipolar cycloaddition reactions with variously substituted electron-deficient alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures, which ultimately control the unusual selectivities observed in certain cases.

Original languageEnglish
Pages (from-to)7489-7497
Number of pages9
JournalACS Catalysis
Volume11
Issue number12
DOIs
Publication statusPublished - Jun 18 2021
Externally publishedYes

Keywords

  • amide reduction
  • azomethine ylide
  • density functional calculations
  • polycyclic amine
  • pyrrolidines
  • Vaska's complex
  • [3 + 2] cycloaddition

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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