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Enantioselective Reduction of Ketones

  1. Shinichi Itsuno

Published Online: 15 APR 2004

DOI: 10.1002/0471264180.or052.02

Organic Reactions

Organic Reactions

How to Cite

Itsuno, S. 2004. Enantioselective Reduction of Ketones. Organic Reactions. 52:2:395–576.

Author Information

  1. Toyohashi University of Technology:Toyohashi, Department of Materials Science, Japan

Publication History

  1. Published Online: 15 APR 2004

Abstract

Enantioselective reduction of prochiral ketones is among the most important methods for preparing enantioenriched secondary alcohols, which are important starting materials for a number of enantiopure compounds, including natural products. Various methods for enantioselective reduction of ketones have been developed for producing enantioenriched alcohols. These methods involve the use of both stoichiometric reagents and catalytic reductions. Metal hydride reagents such as lithium aluminum hydride (LAH) and sodium borohydride (NaBH4) are easily modified by enantiopure compounds. For example, binaphthol-modified aluminum hydride reagent (BINAL-H) is a derivative of LAH in which the enantiopure diol 1,1′-bi-2-naphthol and one other alcohol replace three of the hydrogens. This reagent achieves high selectivity in many ketone reductions. The other impressive area of success is the use of enantiopure alkylboranes. The β hydride of enantiopure alkylboranes is delivered selectively, often exclusively, to one face of the carbonyl group of a ketone.

Despite remarkable success with stoichiometric reagents, their important drawback is that at least one equivalent of reagent is required for reduction of the ketone. Thus catalytic processes are desirable for enantioselective ketone reduction as well as for other asymmetric transformations. Hydrogenation and hydrosilylation of ketones are catalyzed by transition metal catalysts. Enantiopure ligand-transition metal complexes can be used as asymmetric catalysts for these reactions. Recent research makes it possible to achieve high enantioselectivity, not only for the reduction of functionalized ketones in which a transition metal can coordinate to an adjacent functional group, but also for simple ketones such as acetophenone. One of the most remarkable catalytic systems described in recent years is borane reduction in the presence of an oxazaborolidine, which contains adjacent donor (nitrogen) and acceptor (boron) sites. Many biologically active compounds have been synthesized by using oxazaborolidine-catalyzed borane reductions of ketones as the key step. Asymmetric reduction with enzymes is another important method. Some baker's yeast mediated ketone reductions have practical applicability.

This chapter addresses the enantioselective reduction of ketones by various methods including chirally modified hydride reductions, oxazaborolidine catalyzed reductions, Meerwein-Ponndorf-Verley (MPV) reductions, hydrogenations, hydrosilylations, and enzymatic reductions.

Keywords:

  • enantioselective reduction;
  • ketones;
  • chirally modified;
  • lithium aluminum hydride;
  • reagents;
  • scope;
  • limitations;
  • alcohols;
  • diols;
  • amino alcohols;
  • diamines;
  • chirally modified borohydride reagents;
  • quaternary ammonium salts;
  • carboxylic acids;
  • chiral compounds;
  • alkylborohydrides;
  • chiral host compounds;
  • boranes;
  • borohydride reductions;
  • diamine-metal hydride systems;
  • catalytic borane reductions;
  • catalyst;
  • Meerwein-Ponndorf-Verley reductions;
  • transition metal catalyzed reductions;
  • hydrogenation;
  • hydrosilylation;
  • enzymatic reductions;
  • baker's yeast;
  • dihydropyridine reagents;
  • experimental procedures;
  • tabular survey