Cooperative activation of alkyne and thioamide functionalities; Direct catalytic asymmetric conjugate addition of terminal alkynes to α,β-unsaturated thioamides

Ryo Yazaki, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

A detailed study of the direct catalytic asymmetric conjugate addition of terminal alkynes to α,β-unsaturated thioamides is described. A soft Lewis acid/hard Brønsted base cooperative catalyst, comprising [Cu(CH3CN)4]PF6, bisphosphine ligand, and Li(OC6H4-p-OMe) simultaneously activated both substrates to compensate for the low reactivity of copper alkynylide. A series of control experiments revealed that the intermediate copper-thioamide enolate functioned as a Brønsted base to generate copper alkynylide from the terminal alkyne, thus driving the catalytic cycle through an efficient proton transfer between substrates. These findings led to the identification of a more convenient catalyst using potassium hexamethyldisilazane (KHMDS) as the Brønsted base, which was particularly effective for the reaction of silylacetylenes. Divergent transformation of the thioamide functionality and a concise enantioselective synthesis of a GPR40 receptor agonist AMG-837 highlighted the synthetic utility of the present catalysis.

Original languageEnglish
Pages (from-to)1778-1790
Number of pages13
JournalChemistry - An Asian Journal
Volume6
Issue number7
DOIs
Publication statusPublished - Jul 4 2011
Externally publishedYes

Fingerprint

Thioamides
Alkynes
Copper
Chemical activation
Lewis Acids
Catalysts
Proton transfer
Substrates
Catalysis
Protons
Potassium
Ligands
Experiments

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry
  • Organic Chemistry

Cite this

Cooperative activation of alkyne and thioamide functionalities; Direct catalytic asymmetric conjugate addition of terminal alkynes to α,β-unsaturated thioamides. / Yazaki, Ryo; Kumagai, Naoya; Shibasaki, Masakatsu.

In: Chemistry - An Asian Journal, Vol. 6, No. 7, 04.07.2011, p. 1778-1790.

Research output: Contribution to journalArticle

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