Reduction of ketone

Reduction of Ketones.—Gas-chromatographic analysis has permitted accurate determination of ratios of epimeric alcohols obtained from a range of steroid ketones by use of various common reducing agents. Some of the results (see Table 2 for a representative selection of data) differ appreciably from those in 

The Henbest reagent (a phosphito-iridium complex of uncertain structure ) is highly efficient for reducing either 5a- or 5 -3-oxosteroids to give the corresponding axial alcohols. Oxo-functions at the C-2,6,7,11,12,17, and 20 positions are completely unreactive, although reduction of pregnane-3,20-diones is complicated by equilibration at C-17 (17a 17 ).  

An extensive study of the reduction of pregnan-20-ones with alkali-metal-alcohol systems has revealed marked dependence of product ratios on the particular metal and alcohol used. Optimum yields ca. 73%) of the 20a-ol result 

Nambara, T. Kudo, H. Hosoda, K. Motojima, and S. Goya, Chem. and Pharm. Bull. (Japan), 1969, 17, 1366. 

Reductions of a)S-unsaturated oxo-compounds with sodium borohydride may be complicated by saturation of the ethylenic bond, and by base-catalysed conjugate addition of alkoxide to give a 1,3-diol monoether. The factors controlling these reactions have been studied for a variety of aliphatic compounds, and the findings may prove useful in steroid chemistry.  

The asymmetric hydrogenation of dimethyl itaconate catalyzed by Ru-complexes of 21 and 23 in MeOH as a solvent was reported by Stuart and coworkers [48]. As 

Products obtained by reduction of ketones and keto esters. 

Synthesis of (a) an intermediate for arachidonic acid metabolites by reduction of ketones by enzymes from Thermoanaerobacter sp. and Lactobacillus brevis (b) an intermediates for NK-1 receptor antagonists by Lactobacillus kefir and antagonists currentiy under clinical evaluation by Rhodococcus erythropolls (c) intermediates for antibacteriai quinoione by Phaeocrepsis sp. JCM 1880 (d) modioiide A using PIchIa mlnuta iAM 12215 and Yamadazyma farinose NBRC 10896  

The immense number of reductions performed on ketones dictates subdivision of this topic into reductions of aliphatic, alicyclic, aromatic and unsaturated ketones. However, since differences in behavior toward reduction are very small between aliphatic and alicyclic ketones the section on reductions of alicyclic ketones includes only specific examples due to stereochemistry of the ring systems. 

The selective organosilane reduction of ketone functions can be effected in the presence of a number of other functional groups including epoxides,320,366 ketals,86,367 thioketals,368 other ketones,369,370 /1-lactams,371 alkynes,372 esters,79,80,83,84,87,320,373,374 a-bromides,76,80,83 amides80,83,84,86,276,320,375 

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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 ... 

Comprehensive Organic Synthesis 1991, vol 8, 307. - reduction of ketones to saturated hydrocarbons... 

Low-valent nitrogen and phosphorus compounds are used to remove hetero atoms from organic compounds. Important examples are the Wolff-Kishner type reduction of ketones to hydrocarbons (R.L. Augustine, 1968 D. Todd, 1948 R.O. Hutchins, 1973B) and Barton s olefin synthesis (p. 35) both using hydrazine derivatives. 

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). 

A noteworthy development is the use of KH for complexing alkylboranes and alkoxyboranes to form various boron hydrides used as reducing agents in the pharmaceutical industry. Potassium tri-j -butylborohydride [54575-50-7] KB(CH(CH2)C2H )2H, and potassium trisiamylborohydride [67966-25-0] KB(CH(CH2)CH(CH2)2)3H, are usefiil for the stereoselective reduction of ketones (66) and for the conjugate reduction and alkylation of a,P-unsaturated ketones (67). 

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)... 

LiBH4 reductions are usually done in tetrahydrofuran. They are also done in ethanol at —10°, ether, pyridine and diglyme. In dry pyridine the reduction of ketones goes very slowly and sometimes c)ttly takes place on aqueous work-up. " The best solvents for LitOC(CH3)3]3AlH are diglyme and tetrahydrofuran, " Reductions of unhindered ketones take... 

The reduction is general for a variety of substituted benzophenones Such substituents as CH3 OH, OCH3, F, Br. N(CH3)2, NO2. COOH, COOCH3, NHCOC Hreaction conditions and do not alter the course of the reduction Diarylmethanols are reduced to diarylmethanes under the same conditions and probably are the intermediates in the reduction of ketones [26] Triethylsilane also can be used as a reducing agent in trifluoroacetic acid medium [27J This reagent is used for the reduction of benzoic acid and some other carboxylic acids under mild condiUons (equation 14) Some acids (phthalic, sue cinic, and 4-nitrobenzoic) are not reduced under these conditions [27]... 

Recent advances in the asymmetric catalytic reduction of ketones using chiral oxazaborolidines as ligands 98MI64. 

Another important synthetic method for the reduction of ketones and aldehydes to the corresponding methylene compounds is the Woljf-Kishner reduction. This reaction is carried out under basic conditions, and therefore can be applied for the reduction of acid-sensitive substrates it can thus be regarded as a complementary method. The experimental procedure for the Clemmensen reduction is simpler however for starting materials of high molecular weight the Wolff-Kishner reduction is more successful. 

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. ... 

The lithium aluminum hydride-aluminum chloride reduction of ketones is closely related mechanistically to the Meerwein-Ponndorf-Verley reduction in that the initially formed alkoxide complex is allowed to equilibrate between isomers in the... 

So far only two groups have reported details of the use of ionic liquids with wholecell systems (Entries 3 and 4) [31, 32]. In both cases, [BMIM][PF(3] was used in a two-phase system as substrate reservoir and/or for in situ removal of the product formed, thereby increasing the catalyst productivity. Scheme 8.3-1 shows the reduction of ketones with bakers yeast in the [BMIM][PF(3]/water system. 

Scheme 5. Corey s diastereoselective catalytic reduction of ketone 21.

With this single example we have in tact described two uses of enzymes in alicyclic chemistry, the reduction of ketone groups and the resolution of racemic mixtures. 

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

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