Alcohols reduction of ketones

Although metal-alcohol reductions of ketones suffer from possible epimerization of the product alcohol as well as isomerization of the substrate ketone (see Section 1.4.3.1.1), it was found possible to employ the latter type of epimerization to advantage in the preparation of an alcohol used as a chiral director in asymmetric synthesis.In this preparation an 85 15 mixture of ketones (23) and (24 equation 11) was reduced with Na-isopropyl alcohol in toluene to afford alcohol (25) as the only isolated product in good yield. 

Reduction of aldehydes to alcohols Reduction of ketones to alcohols... 

Reduction of ketones either with sodium and absolute alcohol, example ... 

Reduction of ketones, with zinc powder and alcoholic sodium hydroxide leads to secondary alcohols, for example ... 

Carbonyl deductions. The classical Wolff-Kishner reduction of ketones (qv) and aldehydes (qv) involves the intermediate formation of a hydrazone, which is then decomposed at high temperatures under basic conditions to give the methylene group, although sometimes alcohols may form (40). 

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method for the production of chiral alcohols. HLAD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates (Table 11). It efficiendy reduces all simple four- to nine-membered cycHc ketones and also symmetrical and racemic cis- and trans-decalindiones (167). Asymmetric reduction of aUphatic acycHc ketones (C-4—C-10) (103,104) can be efficiendy achieved by alcohol dehydrogenase isolated from Thermoanaerohium hrockii (TBADH) (168). The enzyme is remarkably stable at temperatures up to 85°C and exhibits high tolerance toward organic solvents. Alcohol dehydrogenases from horse Hver and T. hrockii... 

Stereoselective reduction of ketones to alcohols by means of boiohydncle reagents (U S-BU3BH or t-BuCIBR (or lormation ol chiral alcohols)... 

The reduction of ketones to secondary alcohols and of aldehydes to primary alcohols using aluminum alkoxides is called the Meerw>ein-Ponndorf-Verley reduction. The reverse reaction also is of synthetic value, and is called the Oppenauer oxidation. ... 

Figure 8.2 Reduction of ketone with alcohol dehydrogenase from Thermoanaerobacter brockii using glucose-6-sulfate as a hydrogen source [3],...

Figure 8.6 Reduction of ketone with ruthenium complex and alcohol dehydrogenase using molecular hydrogen as a hydrogen source [5c],...

Figure 8.30 Reduction of ketones by the dried cell of C. candidum, NAD(P), and secondary alcohol [14],...

SECTION 42A REDUCTION OF KETONES TO ALCOHOLS ASYMMETRIC REDUCTION... 

The tvans alcohol (47) might be made by reduction of ketone (48). Oxidation of (45) would give (48), but an alternative is to add an activating group and disconnect as a 1,3-dicarbonyl compound - standard strategy ior a symmetrical ketone. 

The reduction of ketones, aldehydes, and olefins has been extensively explored using chemical and biological methods. As the latter method, reduction by heterotrophic microbes has been widely used for the synthesis of chiral alcohols. On the contrary, the use of autotrophic photosynthetic organisms such as plant cell and algae is relatively rare and has not been explored because the method for cultivation is different from that of heterotrophic microbes. Therefore, the investigation using photosynthetic organisms may lead to novel biotransformations. 

Table 9 Result of one-pot preparation method of optically active sec-alcohols (65a,b, 65e-i) by a combination of reduction of ketone and enantiomeric resolution in a water susupension medium... 

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

Manufacture of ruthenium precatalysts for asymmetric hydrogenation. The technology in-licensed from the JST for the asymmetric reduction of ketones originally employed BINAP as the diphosphine and an expensive diamine, DAIPEN." Owing to the presence of several patents surrounding ruthenium complexes of BINAP and Xylyl-BINAP, [HexaPHEMP-RuCl2-diamine] and [PhanePHOS-RuCl2-diamine] were introduced as alternative catalyst systems in which a cheaper diamine is used. Compared to the BINAP-based systems both of these can offer superior performance in terms of activity and selectivity and have been used in commercial manufacture of chiral alcohols on multi-100 Kg scales. 

Reduction of Ketones and Enones. Although the method has been supplanted for synthetic purposes by hydride donors, the reduction of ketones to alcohols in ammonia or alcohols provides mechanistic insight into dissolving-metal reductions. The outcome of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl radical formed by a single-electron transfer. The radical intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.209 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. Net reduction can also occur by a disproportionation process. As is discussed in Section 5.6.3, dimerization can become the dominant process under conditions in which protonation does not occur rapidly. 

Eliel, E. L., and M. N. Rerick Reduction with Metal Hydrides, VIII. Reduction of Ketones and Epimerization of Alcohols with Lithium-Aluminium Hydride — Aluminium Chloride. J. Amer. chem. Soc. 82, 1367 (1960). 

The reduction of ketones to alcohols by sodium in alcohol probably involves a very similar mechanism, but there appear to be some differences between... 

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