Catalytic Reductive Functionalization of Tertiary Amides using Vaska's Complex: Synthesis of Complex Tertiary Amine Building Blocks and Natural Products

Daniel Matheau-Raven, Pablo Gabriel, Jamie A. Leitch, Yaseen A. Almehmadi, Ken Yamazaki, Darren J. Dixon

Research output: Contribution to journalReview articlepeer-review

44 Citations (Scopus)

Abstract

The tertiary amide is a ubiquitous functional group and plays an irreplaceable role in medicinal chemistry. Its robust nature has meant-in the past-that selective manipulation of this motif remained elusive. The reductive activation through hydrosilylation of tertiary amides-using Vaska's complex (IrCl(CO)(PPh3)2)-has emerged as a powerful strategy for the chemoselective transformation of amides into reactive enamines and iminium ions. Furthermore, these synthetically valuable species can be accessed in the presence of traditionally more reactive functional groups. This approach to amide reductive activation via hydrosilylation has been exploited in a range of downstream C-C bond forming processes and has seen significant applications in total synthesis, enabling streamlined routes for the synthesis of complex natural product architectures. This perspective covers the development of this synthetic strategy, from initial hydrosilylation studies to its flourishing use in the reductive functionalization of amide-containing molecules, both simple and complex.

Original languageEnglish
Pages (from-to)8880-8897
Number of pages18
JournalACS Catalysis
Volume10
Issue number15
DOIs
Publication statusPublished - Aug 7 2020
Externally publishedYes

Keywords

  • amine
  • hydrosilylation
  • iridium catalysis
  • lactam
  • reductive functionalization
  • tertiary amide

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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