Development of Atom-Economical Catalytic Asymmetric Reactions under Proton Transfer Conditions: Construction of Tetrasubstituted Stereogenic Centers and Their Application to Therapeutics

• Kumagai Naoya

  The University of Tokyo

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.

Journal

• Chemical and Pharmaceutical Bulletin

  Chemical and Pharmaceutical Bulletin 59 (1), 1-22, 2011

  The Pharmaceutical Society of Japan

Keywords

• rare earth metal
• asymmetric catalysis
• atom economy
• proton transfer
• tetrasubstituted stereogenic center

Details

• CRID: 1390282679150547584
• NII Article ID: 130000405482
• NII Book ID: AA00602100
• DOI: 10.1248/cpb.59.1
• ISSN: 13475223
• ISSN: 00092363
• NDL BIB ID: 10926734
• Web Site: http://id.ndl.go.jp/bib/10926734
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10926734
• Web Site: https://www.jstage.jst.go.jp/article/cpb/59/1/59_1_1/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2011287545
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed