Direct catalytic enantio- and diastereoselective aldol reaction of thioamides

Mitsutaka Iwata, Ryo Yazaki, I. Hon Chen, Devarajulu Sureshkumar, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH 3CN) 4]PF 6/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Brønsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides. Strict control of the amount of the hard Lewis base was essential to drive the catalytic cycle efficiently with a minimized retro-aldol pathway, affording syn-aldol products with high stereoselectivity. Divergent transformation of the thioamide functionality is an obvious merit of the present aldol methodology, allowing for a facile transformation of the aldol product into the corresponding aldehyde, ketone, amide, amine, and ketoester. An aldehyde derived from the direct aldol reaction was subjected to a second direct aldol reaction, which proceeded in a catalyst-controlled manner to provide 1,3-diols with high stereoselectivity.(Figure Presented)

Original languageEnglish
Pages (from-to)5554-5560
Number of pages7
JournalJournal of the American Chemical Society
Volume133
Issue number14
DOIs
Publication statusPublished - Apr 13 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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