Esters asymmetric 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. 

Activated alkene reduction a, -Unsaturated aldehyde, ketone, ester Saturated aldehyde, ketone, ester Asymmetric reduction of C = C bonds Alkene reductase (also known as enoate reductase and ene-reductase)... 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

Dynamic kinetic resolution of racemic ketones proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions. Dynamic kinetic resolution of a-alkyl P-keto ester has been performed through enzymatic reduction. One isomer, out of the four possible products for the unselective reduction (Figure 8.38), can be selectively synthesized using biocatalyst, and by changing the biocatalyst or conditions, all of the isomers can be selectively synthesized [29]. 

The enantioselective hydrogenation of prochiral substances bearing an activated group, such as an ester, an acid or an amide, is often an important step in the industrial synthesis of fine and pharmaceutical products. In addition to the hydrogenation of /5-ketoesters into optically pure products with Raney nickel modified by tartaric acid [117], the asymmetric reduction of a-ketoesters on heterogeneous platinum catalysts modified by cinchona alkaloids (cinchonidine and cinchonine) was reported for the first time by Orito and coworkers [118-121]. Asymmetric catalysis on solid surfaces remains a very important research area for a better mechanistic understanding of the interaction between the substrate, the modifier and the catalyst [122-125], although excellent results in terms of enantiomeric excesses (up to 97%) have been obtained in the reduction of ethyl pyruvate under optimum reaction conditions with these Pt/cinchona systems [126-128],... 

The rhodium-catalyzed enantioselective hydrogenation of enol esters is an alternative to the asymmetric reduction of ketones. Although enol esters are accessible both from ketones and alkynes, the number of studies reporting successful asymmettic hydrogenation has been limited. It appears that, compared... 

This strategy also gives access to a variety of non-natural a-amino acids. Furthermore, rhodium-DuPHOS complexes catalyse the asymmetric reduction of enol esters of the type PhCH = CH — C(OCOCH3) = CH2 to give (R)-2-acetoxy-4-phenylbut-3-ene (94% ee)[64]. 

Asymmetric reduction of ketones. Pioneering work by Ohno et al. (6, 36 7, 15) has established that l-benzyl-l,4-dihydronicotinamide is a useful NADH model for reduction of carbonyl groups, but only low enantioselectivity obtains with chiral derivatives of this NADH model. In contrast, this chiral 1,4-dihydropyridine derivative (1) reduces a-keto esters in the presence of Mg(II) or Zn(II) salts in >90% ee (equation I).1 This high stereoselectivity of 1 results from the beneficial effect... 

Asymmetric reductions. The reagent can effect asymmetric reduction of alkyl aryl ketones and unhindered dialkyl ketones in high optical yield.1 It is the most useful reagent known to date for asymmetric reduction of even hindered a-keto esters to (S)-a-hydroxy esters in >90% ee.2 It is also effective for asymmetric reduction of phosphinyl imines of dialkyl ketones, RlR2C=NP(0)(C6H5)2 (50-84% ee).3... 

Boronic esters have been used in a wide range of transformations. These useful reagents have been transformed into numerous functional groups and are essential reagents for several C-C bond-forming reactions. Transition metal-catalyzed hydroboration of olefins often leads to mixtures of branched and linear products. Several groups have reported asymmetric reductions of vinyl boronic esters [50-52] with chiral rhodium P,P complexes however, the first iridium-catalyzed reduction was reported by Paptchikhine et al (Scheme 10) [53]. 

Production of Chiral 4-Chloro-3-Hydroxybutanoate Ethyl Ester by Microbial Asymmetric Reduction of 4-Chloroacetoacetate... 

Another example showing the utility of 1 is the asymmetric hydrogenation of vinyl esters which usually are used as acyl donors in enzymatic resolution. In this transformation, vinyl esters are converted to ketones which then undergo asymmetric reductive acylation to give chiral esters as described in Scheme 1.13. The overall reaction thus corresponds to the asymmetric hydrogenation of vinyl ester to the corresponding alkyl esters. 

High stereoselectivities (94-100 %) are attained in the reduction of aromatic ketones by use of a new chiral borane complex with (S)-2-amino-3-methyl-l,l-diphenylbutan-l-ol,(S-68) readily prepared in two steps from (S)-valine, in an experimentally convenient procedure961. (S)-Valine methyl ester hydrochloride was converted with excess of phenylmagnesium bromide into (S-68). The same treatment of (R)-valine gave (R-68). In a typical asymmetric reduction the reagent, prepared from (S-68) and borane, and the ketone (69) in tetrahydrofuran were kept at 30 °C for some hours. The corresponding alcohols were obtained in high optical purity. (S-68) could be recovered to more than 80% without racemization 96). 

Chu, Y, Shan, Z., Liu, D. and Sun N. Asymmetric Reduction of Oxime Ethers Promoted by Chiral Spiroborate Esters with an O3BN Framework. J. Org. Chem. 2006, 71, 3998-4001. 

The procedure is very easy to reproduce and the asymmetric reduction may be applied to a wide range of aromatic ketones and keto esters such as ethyl 3-oxopentanoate. 

Asymmetric reduction of a-keto esters The chromium-complexed a-keto ester 1 is reduced to the carbinol by sodium borohydride with surprisingly high... 

Asymmetric reduction of -arylcarbonyl esters.1 Reduction of these esters with lithium borohydride and (R,R )-1 and t-butyl alcohol affords the corresponding 3-hydroxy esters in 80-92% ee (equation I). 

The reagent is also useful for asymmetric reduction of a-keto esters, particularly a-keto /-butyl esters. Thus /-butyl pyruvate is reduced to (S)-/-butyl lactate in 100% ee.1... 

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