Asymmetric reduction of carbonyl compounds

Asymmetric reduction of carbonyl compounds can usually be achieved either through direct catalytic hydrogenation or by metal hydride reduction. It should be mentioned here that reduction of carbonyl compounds by catalytic hydrogenation may not be chemoselective. Other co-existing functional groups such as the C=C bond may also undergo hydrogenation. 

Boranes have opened the door to asymmetric reduction of carbonyl compounds. The first attempt at modifying borane with a chiral ligand was reported by Fiaud and Kagan,75 who used amphetamine borane and desoxyephedrine borane to reduce acetophenone. The ee of the 1-phenyl ethanol obtained was quite low (<5%). A more successful borane-derived reagent, oxazaborolidine, was introduced by Hirao et al.76 in 1981 and was further improved by Itsuno and Corey.77 Today, this system can provide high stereoselectivity in the asymmetric reduction of carbonyl compounds, including alkyl ketones. 

Native ADH catalyzes the asymmetric reduction of carbonyl compounds to the corresponding R-configured alcohols using NADPHh-H as cofactor (Scheme 3.2.2). 

The field of organoboron chemistry pioneered by Brown [40] also provides a wealth of excellent transformations. Consider the asymmetric reduction of carbonyl compounds by Alpine-Borane [41]. Alpine-Borane is prepared by the following sequence ... 

Chiral (l-hydroxy esters are versatile synthons in organic synthesis, specifically in the preparation of natural products [62-64], The asymmetric reduction of carbonyl compounds using Baker s yeast has been demonstrated and reviewed... 

Kataoka, M., Nomura, Y., Shimizu, S., and Yamada, H. 1992a. Enzymes involved in the NADPH regeneration system coupled with asymmetric reduction of carbonyl compounds in microorganisms. Biosci. Biotech. Biochem., 56,820-821. 

In contrast to the asymmetric reduction of carbonyl compounds where fairly high e.e. had been realized, the asymmetric addition of organometallic reagents to aldehydes in a chiral solvent, or by using chiral ligands such as (—)-spartein and (—)-N-methylephedrine to afford optically active alcohols had met with only... 

Although highly eflfective asymmetric reduction of carbonyl compounds has been extensively investigated, enantioselective reduetion of imine derivatives to amines has been less studied, mainly in homogeneous supported catalysis [66],... 

Scheme 5. Mechanism of the asymmetric reduction of carbonyl compounds (e. g. 25) with borane and chiral oxazaborolidine catalysts (e. g. 26).

The asymmetric reduction of carbonyl compounds using boranes has been further developed, principally by Brown s research group. (3-Pinanyl)-9-borabicyclo[3.3.1]nonane, Alpine borane, reduces... 

Table 17. Asymmetric reduction of carbonyl compounds by HMH under the catalysis of Grignard reagent or potassium tert-butoxide.

Asymmetric reduction of carbonyl compounds and production of isotopically labelled species has been achieved. A system based on deuterated formate and formate dehydrogenase provides the best system for the introduction of deuterium through nicotinamide-cofactor catalysed process (Table 2). 

In the last three decades, the asymmetric reductions of carbonyl compounds have been actively investigated by organic chemists [6]. 

Other microorganisms have also been used for the asymmetric reduction of carbonyl compounds. Simple ahphatic ketones as well as aromatic ketones can be reduced with very high enantioselectivity by using biocatalysts. For example, aliphatic ketones such as... 

Kohra S, Hayashida H, Tominaga Y, Hosomi A. Pentaco-ordinate organosilicon compounds in synthesis asymmetric reduction of carbonyl compounds with hydrosilanes catalyzed by chiral bases. Tetrahedron Lett. 1988 29 89-92. 

Chiral (3-hydroxy esters are versatile synthons in organic synthesis specifically in the preparation of natural products [68-70]. The asymmetrical reduction of carbonyl compounds using baker s yeast has been demonstrated and reviewed [5,71,72]. In the stereoselective reduction of P-keto ester of 4-chloro- and 4-bromo-3-oxobutanoic acid, specifically 4-chloro-3-oxobutanoic acid methyl ester, Sih and Chen [73] demonstrated that the stereoselectivity of yeast-catalyzed reductions may be altered by manipulating the size of ester group using y-chloroacetoacetate as substrate. They also indicated that the e.e. of the alcohol produced depended on the concentration of the substrate used. Nakamura et al. [74] demonstrated the reduction of p-keto ester with baker s yeast and controlled... 

The asymmetrical reduction of carbonyl compounds by BY constitutes one of the most widely applicable reactions. Thus, ketones with varying aUcyl/aryl substituents are reduced by yeasts [32-35] and the secondary alcohols obtained were mainly of (S) configuration. Sterically hindered ketones are not reduced at all. From these findings a hydrogen transfer... 

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