Direct catalytic asymmetric Michael reaction of hydroxyketones: Asymmetric Zn catalysis with a Et2Zn/ linked-BINOL complex

Shinji Harada, Naoya Kumagai, Tomofumi Kinoshita, Shigeki Matsunaga, Masakatsu Shibasaki

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115 Citations (Scopus)

Abstract

Full details of our direct Michael addition of unmodified ketones using new asymmetric zinc catalysis are described. Et2Zn/(S,S)-linked-BINOL complexes were successfully applied to direct 1,4-addition reactions of hydroxyketones. The first generation Et2Zn/(S,S)-linked-BINOL 1 = 2/1 system was effective for 1,4-addition of 2-hydroxy-2′-methoxyacetophenone (3). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et2Zn, we found that a 1,4-addition reaction of β-unsubstituted enone proceeded smoothly at 4 °C to afford products in high yield (up to 90%) and enantiomeric excess (up to 95%). In the case of β-substituted enones, however, the first generation Et2Zn/(S,S)-linked-BINOL 1 = 2/1 system was not at all effective. The second generation Et2Zn/(S,S)-linked-BINOL 1 = 4/1 with MS 3A system was developed and was effective for various β-substituted enones to afford products in good dr, yield (up to 99%), and high enantiomeric excess (up to 99% ee). With the Et2Zn/1 = 4/1 systems, catalyst loading for β-unsubstituted enone was reduced to as little as 0.01 mol % (substrate/chiral ligand = 10 000). The new system was also effective for 1,4-addition reactions of 2-hydroxy-2′-methoxypropiophenone (9) to afford chiral tert-alcohol in high enantiomeric excess (up to 96% ee). Mechanistic investigations as well as transformations of the Michael adducts into synthetically versatile intermediates are also described.

Original languageEnglish
Pages (from-to)2582-2590
Number of pages9
JournalJournal of the American Chemical Society
Volume125
Issue number9
DOIs
Publication statusPublished - 2003 Mar 5
Externally publishedYes

ASJC Scopus subject areas

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

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