Asymmetric Carbonyl Reductions

Asymmetric Carbonyl Reductions. Examples of hydride reagents modified with a chiral auxiliary published during the past year Include 

Boranes complexed with quinine and qulnidine have been used in conjunction with boron trifluoride to produce selectively either enantiomeric benzyl alcohols in the reduction of aryl methyl ketones, with enantiomeric excesses of the products falling in the 

Diisopinocampheylchloroborane has been demonstrated to reduce aromatic prochiral ketones, even those which prove to be less reactive towards Midland s reagent (Vol.2, p.115), in enantiomeric 

Further details have been published on the use of B-(3-pinanyl)- 

9-borabicyclononane in the reduction of prochiral ketones (Vol.2, p.115 Vol.5, p.156). Raney nickel modified with ( ), ( )-tartaric 

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Organocatalytic asymmetric carbonyl reductions have been achieved with boranes in the presence of oxazaborolidine and phosphorus-based catalysts (Section 11.1), with borohydride reagents in the presence of phase-transfer catalysts (Section 11.2), and with hydrosilanes in the presence of chiral nucleophilic activators (Section 11.3). 

Woodward developed an asymmetric carbonyl reduction using catecolborane in the presence of a catalytic amount of a gallium thiobinaphthol (2.5 mol%) and obtained fhe optically active secondary alcohol from propiophenone in 93% ee (Scheme 7.22) [46, 47]. 

Enzymic Asymmetric Carbonyl Reductions. Microbial reduction of ketones continues to result in the highest optical yields of chiral... 

The use of asymmetric carbonyl reductions for the control of the configuration at C-5 and/or C-6 in natural dihydropyrones is scarce (26, 37]. Among the few examples is one enantioselective synthesis of (-)-massoialactone (37aj based on the asymmetric hydrogenation of b-oxoester 97 in the presence of a mthenium-chiral phosphine complex (Scheme 2.19). The resulting fi-hydroxyester 98, obtained in >99% enantiomeric excess, was converted into the corresponding protected aldehyde 99, which... 

Chiral transition-metal complexes have also been featured in the following reports " of asymmetric carbonyl reductions hydrogenation of / -aryl- -ketoesters 0 using H2 and iridium-bearing spiro pyridine-aminophosphine ligand rhodium in a theoretical study of catalysis involving amino acid-derived ligands and in... 

Asymmetric Carbonyl Reduction. The enzyme-like CBS catalysts (e.g. 20) developed by Corey 25) have been applied to the synthesis of arylethanolamines. Recent reports documenting successful enantioselective synthesis of denopamine 18 26) in conjunction with the remarkably high enantioselectivities obtained with these catalysts provided the impetus for our successful approach to R-FNEs. The synthesis began with the production of chloroketones 19b,d from aldehydes 10b,d by a documented procedure (27) (Scheme 2). Reduction of 19b,d with BHa THF in the... 

The development of facial selective addition reactions of cyclohexa-1,4-dienes 7 and 14 has greatly extended the value of the asymmetric Birch reduction-alkylation. For example, amide directed hydrogenation of 15 with the Crabtree catalyst system occurs with outstanding facial selectivity iyw to the amide carbonyl group to give 16 (Scheme 5)."... 

Asymmetric transfer hydrogenation of imines catalyzed by chiral arene-Ru complexes achieves high enantioselectivity (Figure 1.34). Formic acid in aprotic dipolar solvent should be used as a hydride source. The reaction proceeds through the metal-ligand bifunctional mechanism as shown in the carbonyl reduction (Figure 1.24). 

Of the numerous examples of asymmetric reactions catalyzed by Lewis bases, this chapter focuses mainly on the activation of silicon reagents and related processes. Various other types of Lewis basic (nucleophilic) activation, namely the Morita-Baylis-Hillman (MBH) reaction, acyl transfer, nucleophilic carbenes, and carbonyl reduction, are described in the other chapters of this book. 

Fig. 10.23. Asymmetric carbonyl group reduction with the Noyori reagent Note that the chirality of the reducing agent resides in the ligand but that the aluminum atom is not a stereocenter.

Fig. 10.24. Asymmetric carbonyl group reduction with Alpine-Borane (preparation Figure 3.27 for the "parachute-like" notation of the 9-BBN part of this reagent see Figure 3.21). The hydrogen atom that is in the cis-position to the boron atom (which applies to both ft- and /T-H) and that after removal of the reducing agent leaves behind a tri- instead of a disubstituted C=C double bond (which applies to ft-, but not / -H) is transferred as a hydride equivalent. In regard to the reduction product depicted in the top row, the designation S of the configuration relates to the aryl-substituted and R to the Rtert-substituted propargylic alcohol.

Fig. 10.25. Asymmetric carbonyl group reduction with diisopinocampheylchloroborane [Brown s chloroborane, (IPC)2BCL]. Concerning the reduction product depicted in the top row, the designation 5 of the configuration relates to the aryl-substituted and R to the Rttrt-substituted propargylic alcohol.

Fig. 10.26. Catalytic asymmetric carbonyl group reduction according to Corey and Itsuno.

Fig. 8.18. Asymmetric carbonyl group reduction with the Noyori reagent.

A bioreduction system might be applied to many NAD(P)H-dependent enzyme reactions other than carbonyl reduction. Recently, two novel old yellow enzymes (OYEs) catalyzing the asymmetric hydrogenation of C=C bonds were found and applied to a bioreduction system for the production of double chiral compounds. 

Chiral Ligand of L1A1H4 for the Enantioselective Reduction of Alkyl Phenyl Ketones. Optically active alcohols are important synthetic intermediates. There are two major chemical methods for synthesizing optically active alcohols from carbonyl compounds. One is asymmetric (enantioselective) reduction of ketones. The other is asymmetric (enantioselective) alkylation of aldehydes. Extensive attempts have been reported to modify Lithium Aluminum Hydride with chiral ligands in order to achieve enantioselective reduction of ketones. However, most of the chiral ligands used for the modification of LiAlHq are unidentate or bidentate, such as alcohol, phenol, amino alcohol, or amine derivatives. 

This section reviews the literature on asymmetric carbonyl additions and reductions mediated by chiral aluminum Lewis acids. This does not include aldol reactions, cycloaddition reactions, and ene reactions, each of which will be covered in separate sections. The earliest such carbonyl addition reaction to be reported was, along with the Muikaiyama aldol reaction of ketene acetal 7 (Sch. 2), the addition of trimethylsi-lyl cyanide to o-valeraldehyde [6]. The catalyst 13 did not result in asymmetric induction as high in this reaction as it did with the Muikaiyama aldol reaction of ketene acetal 7 with wo-valeraldehyde (Sch. 2). The cyanohydrin 45 was isolated in 65 % yield as a 66 34 mixture of enantiomers only. 

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