Development of atom-economical catalytic asymmetric reactions under proton transfer conditions: Construction of tetrasubstituted stereogenic centers and their application to therapeutics

Naoya Kumagai

Research output: Contribution to journalReview articlepeer-review

18 Citations (Scopus)

Abstract

The development of atom-economical catalytic asymmetric reactions based on two distinct sets of catalyst, a rare earth metal/amide-based ligand catalyst and a soft Lewis acid/hard Brønsted base catalyst, is reviewed. These catalytic systems exhibit high catalytic activity and stereoselectivity by harnessing a cooperative catalysis through hydrogen bond/metal coordination and soft-soft interactions/hard-hard interactions, respectively. The effectiveness of these cooperative catalysts is clearly delineated by the high stereoselectivity in reactions with highly coordinative substrates, and the specific activation of otherwise low-reactive pronucleophiles under proton transfer conditions. The rare earth metal/amide-based ligand catalyst was successfully applied to catalytic asymmetric aminations, nitroaldol (Henry) reactions, Mannich-type reactions, and conjugate addition reactions, generating stereogenic tetrasubstituted centers. Catalytic asymmetric amination and anti-selective catalytic asymmetric nitroaldol reactions were successfully applied to the efficient enantioselective synthesis of therapeutic candidates, such as AS-3201 and the β3-adrenoreceptor agonist, showcasing the practical utility of the present protocols. The soft Lewis acid/hard Brønsted base cooperative catalyst was specifically developed for the chemoselective activation of soft Lewis basic allylic cyanides and thioamides, which are otherwise low-reactive pronucleophiles. The cooperative action of the catalyst allowed for efficient catalytic generation of active carbon nucleophiles in situ, which were integrated into subsequent enantioselective additions to carbonyl-type electrophiles.

Original languageEnglish
Pages (from-to)1-22
Number of pages22
JournalChemical and Pharmaceutical Bulletin
Volume59
Issue number1
DOIs
Publication statusPublished - 2011 Jan
Externally publishedYes

Keywords

  • Asymmetric catalysis
  • Atom economy
  • Proton transfer
  • Rare earth metal
  • Tetrasubstituted stereogenic center

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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