Reduction of unsymmetrical ketones

Asymmetric Reduction of Unsymmetrical Ketones Using Chiral Boron Reagents Review Synthesis 1992, 605. 

Catalytic reduction of unsymmetrical ketones into alcohols by concomitant oxidation of 2-propanol to acetone (Meerwein-Ponndorf-Verley reduction, MPV), with rhodium... 

In particular, reduction of unsymmetric ketones to alcohols has become one of the more useful reactions. To achieve the selective preparation of one enantiomer of the alcohol, chemists first modified the classical reagents with optically active ligands this led to modified hydrides. The second method consisted of reaction of the ketone with a classical reducing agent in the presence of a chiral catalyst. The aim of this chapter is to highlight one of the best practical methods that could be used on an industrial scale the oxazaborolidine catalyzed reduction.1 1 This chapter gives an introductory overview of oxazaborolidine reductions and covers those of proline derivatives in-depth. For the oxazaborolidine derivatives of l-amino-2-indanol for ketone reductions see Chapter 17. 

V K. Singh, Practical and Useful Methods for the Enantioselective Reduction of Unsymmetrical Ketones, Synthesis 1992, 607-617. 

The enantioselective reduction of unsymmetrical ketones to produce optically active secondary alcohols has been one of the most vibrant topics in organic synthesis.8 Perhaps Tatchell et al. were first (in 1964) to employ lithium aluminum hydride to achieve the asymmetric reduction of ketones9 (Scheme 4.IV). When pinacolone and acetophenone were treated with the chiral lithium alkoxyaluminum hydride reagent 3, generated from 1.2 equivalents of 1,2-0-cyclohexylidene-D-glucofuranose and 1 equivalent of LiAlHzt, the alcohol 4 was obtained in 5 and 14% ee, respectively. Tatchell improved the enantios-electivity in the reduction of acetophenone to 70% ee with an ethanol-modified lithium aluminum hydride-sugar complex.10... 

For methods for enantioselective reduction of unsymmetrical ketones see V. K. Singh, Synthesis, 1992, 605. 

Other selected examples are summarized in Table 2. In addition to aldehydes, both cyclic and acyclic ketones can be reduced equally well. sec-Phenethyl alcohol (11, R = Ph) as hydride source works more effectively than t-PrOH. On the basis of this finding, the asymmetric MPV reduction of unsymmetrical ketones with chiral alcohol in the presence of catalyst 10 was examined [30]. Treatment of 2-chloroacetophenone (12) with optically pure (R)-(+)-sec-phenethyl alcohol (1 equiv.) under the influence of catalytic 10 at 0 °C for 10 h afforded (5)-(+)-2-chloro-l-phenylethanol (13) with moderate asymmetric induction (82 %, 54 % enantiomeric excess, ee Sch. 8). Switch-... 

Oxazaborolldines have emerged as important reagents for the enantioselective reduction of a variety of prochiral ketones. CBS reduction (chiral oxazaborolidine-catalyzed reduction)of unsymmetrical ketones with diphenyl oxazaborolidine in the presence of BH3 proceeds catalytically to provide alcohols of predicable absolute stereochemistry in high enantiomeric excess. 

Singh, V. K. Practical and useful methods for the enantioselective reduction of unsymmetrical ketones. Synthesis 1992, 607-617. 

New stereogenic centres from prochiral units in planar molecules Enantiotopic and diastereotopic groups Asymmetric Reduction of Unsymmetrical Ketones Asymmetric boron or aluminium hydrides Asymmetric reduction by boranes Reduction of ketones with Ipc2BCl (DIP-Chloride ) Asymmetric Electrophiles... 

The ordinary yeast used by bakers in their bread making is a valuable organism for the enantioselective reduction of unsymmetrical ketones.2 It is particularly efficient at the reduction of P-keto-esters such as ethyl acetoacetate 1. An Organic Synthesis procedure3 reveals that the true reagent is sucrose, which provides just one H atom, that plenty of yeast is required, and that 3-4 days are needed to make 20-30 g product 2 in only 85% ee. 

Figure 4.1. Reduction of unsymmetrical ketones with yeast.

Chemical Reductions Enantioselective reduction of unsymmetric ketones to optically active alcohols is very important in organic synthesis. In the foreword to this section, we will summarize the best practical and useful methods and reagents. 

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