Asymmetric reduction of aldehydes and ketones

There are several ways for achieving asymmetric reduction of aldehydes and ketones. For example, a chiral catalyst or chiral reagent can be used for the enantioselective reduction. 

Metal alkoxides have promising role in catalytic reactions. In this chapter, we briefly review the history, chciracteristics, cuid synthesis routes of metal alkoxide and then discuss some catalytic processes that are performed with them. These processes include polymerization of different olefin oxides and cyclic esters asymmetric reduction of aldehydes and ketones oxidation of sulfides and olefins and a variety of other asymmetric reactions. The rest of the chapter discusses the characteristics of these catalytic systems from different points of view. 

Chiral reductions are now quite common with these reagents when used either in stoichiometric amounts [CT4, MT6, SCI] or in catalytic amounts in the presence of BH3 THF, catecholborane [G6, GB6, QWl, SK5], or BH3 Me2S as achiral reducing co-reagent [DS6, JM3, N5, S5, SCI, SM6, TA3, TBl, YL4]. The asymmetric reduction of aldehydes, various ketones, a-enones, and a-ynones usually take place with an excellent enantiomeric excess [BB13, CL2, CL6, CR2, CT4, DS5, DK2, GB6, MT6, NNl, PL2, S4, SM6, WM2] (Figure 3.24). The reduction of ketones is carried out between -20°C and r.t., while that of aldehydes requires - 126°C for a good asymmetric induction. 

The catalytic reduction of aldehydes and ketones when carried out via hydrosilylation, gave high optical yield (60%) (Dumont et aL, 1973). The mechanism of this reduction is thought to involve the intermediate formation of an asymmetric siloxane. 

A review describing the major advances in the field of asymmetric reduction of achiral ketones using borohydrides, exemplified by oxazaborolidines and /9-chlorodiisopino- camphenylborane, has appeared. Use of sodium borohydride in combination with chiral Lewis acids has been discussed.298 The usefulness of sodium triacetoxyboro-hydride in the reductive amination of aldehydes and ketones has been reviewed. The wide scope of the reagent, its diverse and numerous applications, and high tolerance for many functional groups have been discussed.299 The preparation, properties, and synthetic application of lithium aminoborohydrides (LABs) have been reviewed. 

Procter reported a solid-phase variant of Fukuzawa s asymmetric y-butyr-olactone synthesis (see Chapter 5, Section 5.2) that involves the intermolecular reductive coupling of aldehydes and ketones with a,p-unsaturated esters, immobilised using an ephedrine chiral resin 12.44 For example, treatment of acrylate 13 and crotonate 14 with cyclohexanecarboxaldehyde, employing Sml2 in THF, with tert-butanol as a proton source, gave lactones 15 and 16, respectively, in moderate yield and good to high enantiomeric excess (Scheme 7.11).44 The ephedrine resin 12 can be conveniently recovered and recycled.45... 

Alnminium alkoxides have long been used as catalysts for the reduction of aldehydes or ketones by secondary alcohols and recently lanthanide alkoxides were reported to act similarly in addition to catalysing the epoxidation of allylic alcohols with tert-butyl hydroperoxide. Aluminium alkoxides have also been used to catalyse the conversion of aldehydes to alkylesters (Tischtchenko reaction). A review gives a fascinating account of the use of heterometal alkoxides in asymmetric catalysis. 

Hantsch esters, such as (89), having monosaccharide substituents, have been synthesised from sugar aldehydes as chiral NADH models, and used in the asymmetric reduction of several prochiral ketones with ee s up to 79% being attained. ... 

Reduction of carbonyl groups Terpene and aromatic aldehydes (lOOppm) were reduced by microalgae. In a series of chlorinated benzaldehyde, m - or p-chlorobenzaldehyde reacted faster than the o-derivative. Due to toxicity, the substrate concentrations are difficult to increase. Asymmetric reductions of ketones by microalgae were reported. Thus, aliphatic " and aromatic " ketones were reduced. 

Asymmetric reduction of ketones or aldehydes to chiral alcohols has received considerable attention. Methods to accomplish this include catalytic asymmetric hydrogenation, hydrosilylation, enzymatic reduction, reductions with biomimetic model systems, and chirally modified metal hydride and alkyl metal reagents. This chapter will be concerned with chiral aluminum-containing reducing re-... 

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