Organocatalyzed Enantioselective Michael Addition of 2-Hydroxypyridines and α,β-Unsaturated 1,4-Dicarbonyl Compounds

Yu Chun Wu, Yi Jhong, Hui Jie Lin, Sharada Prasanna Swain, Hui Hsu Gavin Tsai, Duen Ren Hou

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The framework of 2-pyridones is prevalent in biologically and medicinally important molecules. Here we report that chiral N-substituted 2-pyridones were prepared by enantioselective, organocatalytic aza-Michael additions of halogenated 2-hydroxypyridines (pyridin-2(1H)-ones) to α,β-unsaturated-1,4-dketones or 1,4-ketoesters. The reactions were optimized by the choice of solvents and systematic screening of Cinchona alkaloid-based bifunctional catalysts to achieve excellent yields and enantioselectivities (up to 98% yield and >99% ee). Density functional theory calculations provided rationales for the observed enantioselectivity. Formal synthesis of a human rhinovirus protease inhibitor was achieved using the chiral Michael adduct generated by this method. (Figure presented.).

Original languageEnglish
Pages (from-to)4966-4982
Number of pages17
JournalAdvanced Synthesis and Catalysis
Volume361
Issue number21
DOIs
StatePublished - 5 Nov 2019

Keywords

  • 1,4-dicarbonyl
  • 2-pyridone
  • Cinchona alkaloid
  • Michael addition
  • organocatalysis

Fingerprint

Dive into the research topics of 'Organocatalyzed Enantioselective Michael Addition of 2-Hydroxypyridines and α,β-Unsaturated 1,4-Dicarbonyl Compounds'. Together they form a unique fingerprint.

Cite this