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 journalArticle

49 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 - Sep 2 2011
Externally publishedYes

Fingerprint

Thioamides
Catalysts
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lithium
LDL Cholesterol
Atorvastatin Calcium
3-hydroxybutanal

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

A simplified catalytic system for direct catalytic asymmetric aldol reaction of thioamides; Application to an enantioselective synthesis of atorvastatin. / Kawato, Yuji; Iwata, Mitsutaka; Yazaki, Ryo; Kumagai, Naoya; Shibasaki, Masakatsu.

In: Tetrahedron, Vol. 67, No. 35, 02.09.2011, p. 6539-6546.

Research output: Contribution to journalArticle

Kawato, Yuji ; Iwata, Mitsutaka ; Yazaki, Ryo ; Kumagai, Naoya ; Shibasaki, Masakatsu. / A simplified catalytic system for direct catalytic asymmetric aldol reaction of thioamides; Application to an enantioselective synthesis of atorvastatin. In: Tetrahedron. 2011 ; Vol. 67, No. 35. pp. 6539-6546.
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