A simplified catalytic system for direct catalytic asymmetric aldol reaction of thioamides; Application to an enantioselective synthesis of atorvastatin

Yuji Kawato, Mitsutaka Iwata, Ryo Yazaki, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

A new catalytic system was developed for the direct catalytic asymmetric aldol reaction of thioamides. The new lithium-free Cu catalyst (second-generation catalyst) exhibited enhanced catalytic efficiency over the previously developed catalyst comprising [Cu(CH3CN) 4]PF6/Ph-BPE/LiOAr (first-generation catalyst), which required a tedious catalyst preparation process. In the reaction with the second-generation catalyst, the intermediate Cu-aldolate functioned as a Brønsted base to generate thioamide enolate, efficiently driving the catalytic cycle. The present aldol methodology culminated in a concise asymmetric synthesis of atorvastatin (Lipitor®: atorvastatin calcium), a widely prescribed HMG-CoA reductase inhibitor for lowering low-density lipoprotein cholesterol.

Original languageEnglish
Pages (from-to)6539-6546
Number of pages8
JournalTetrahedron
Volume67
Issue number35
DOIs
Publication statusPublished - 2011 Sep 2
Externally publishedYes

Keywords

  • Aldol reaction
  • Asymmetric catalysis
  • Atorvastatin
  • Mesitylcopper
  • Thioamide

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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