Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/linked-BINOL complex: Synthesis of either anti- or syn-β-amino alcohols

Shigeki Matsunaga, Takamasa Yoshida, Hiroyuki Morimoto, Naoya Kumagai, Masakatsu Shibasaki

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Abstract

Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-β-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-β-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-β-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.

Original languageEnglish
Pages (from-to)8777-8785
Number of pages9
JournalJournal of the American Chemical Society
Volume126
Issue number28
DOIs
Publication statusPublished - Jul 21 2004
Externally publishedYes

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Amino alcohols
Amino Alcohols
Imines
Catalysts
Catalysis
Zinc
Nitrogen
naphthol BINOL

All Science Journal Classification (ASJC) codes

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

Cite this

Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/linked-BINOL complex : Synthesis of either anti- or syn-β-amino alcohols. / Matsunaga, Shigeki; Yoshida, Takamasa; Morimoto, Hiroyuki; Kumagai, Naoya; Shibasaki, Masakatsu.

In: Journal of the American Chemical Society, Vol. 126, No. 28, 21.07.2004, p. 8777-8785.

Research output: Contribution to journalArticle

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abstract = "Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-β-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-β-amino alcohols in anti/syn = up to >98/2, up to >99{\%} yield, and up to >99.5{\%} ee, while Boc-imine 4 gave syn-β-amino alcohols in anti/syn = up to 5/95, up to >99{\%} yield, and up to >99.5{\%} ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol {\%} (TON = up to 4920) for the anti-selective reaction and 0.05 mol {\%} (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.",
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AU - Shibasaki, Masakatsu

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