Ketones to secondary alcohols

It will also reduce acid chlorides, acid anhydrides and aldehydes to primary alcohols, ketones to secondary alcohols, and amides to the corresponding amines R-CONHi -> R CHiNH. Nitro-hydrocarbons if aromatic are... 

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. ... 

Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. 

Oxazaborolidine catalysts behave like an enzyme in the sense of binding with both ketone and borane, bringing them close enough to undergo reaction and releasing the product after the reaction. Thus these compounds are referred to as chemzymes by Corey.78 The oxazaborolidines listed in Figure 6-6 are representative catalysts for the asymmetric reduction of ketones to secondary alcohols. 

Trifluoroacetic acid is the best solvent for several platinum-catalysed hydrogenation processes. For example the rate of reduction of ketones to secondary alcohols is about three times faster than in acetic acid. The ketones are taken in concentrated solutions to keep the reactions faster. 

Reduction reactions mediated by microorganisms may include the reduction of nitro bonds, sulfoxide reduction, and reductive dehalogenation. Reduction of the nitro group to amine involves the intermediate formation of nitrase and hydroxy amino groups. Selected reductive reactions may involve the saturation of double bonds, reduction of aldehydes to alcohols or ketones to secondary alcohols, or of certain metals. The main reductive processes in the subsurface environment have been discussed earlier in this chapter. 

Somewhat less frequent than the reductions of aliphatic ketones to secondary alcohols and to hydrocarbons are one-electron reductions to pinacols. These are accomplished by metals such as sodium, but better still by magnesium or aluminum. Acetone gave 43-50% yield of pinacol on refluxing with magnesium amalgam in benzene [140], and 45% and 51% yields on refluxing in methylene chloride or tetrahydrofuran, respectively [825. ... 

Strong reducing agents like sodium borohydride and lithium aluminum hydride are capable of reducing aldehydes to primary alcohols and ketones to secondary alcohols. The general reaction is the reverse of the reactions used to form aldehydes and ketones by the oxidation of primary and secondary alcohols, respectively (to review, see the earlier section Oxidation reactions ). However, the mechanisms for reduction are different. 

The reduction of ketones to secondary alcohols is a reaction of general interest in organic chemistry and, therefore, different methods have been described to achieve this transformation. In this context, we have recently developed a novel procedure... 

At the outset, an a-dimethylation leads to compound 17. Reduction of the ketone to secondary alcohol 18 and acetylation of the latter provides ester 19 The ester group functions under acidic conditions as a leaving group, and it is replaced by a hydride anion with formation of compound 20. The last step is a Birch reduction These five steps were accomplished with an overall yield of 85%. 

The periodinane (10) may also be prepared from o-iodobenzoic acid by oxidation with potassium bromate and then treatment with acetic anhydride18 (see Expt 6.36 for detailed formulation). It should be noted that the organic derivatives of pentacoordinate iodine(v) are termed periodinanes.18b This compound (the systematic name is l,l,l-triacetoxy-2,l-benzoxiodol-3(3//)-one) has found use as an oxidant of primary alcohols to aldehydes and alicyclic ketones to secondary alcohols it is claimed to have advantages over the chromium-based oxidation reagents. 

This ligand, in combination with a rhodium complex prepared in situ from Rh(NBD)2+C104 (NBD = norbomadiene), can be used for an enantioselective hydrogenation of prochiral ketones to secondary alcohols (equation IV).5... 

Usually, a stoichiometric amount of metal hydride, such as a selectride reagent, is required for diastereoselective reduction of aliphatic ketones to secondary alcohols. Now the same purpose can be achieved by the Ru-catalysed diastereoselective... 

Table 9.4 Chemoselective hydrogenation of unsaturated ketones to secondary alcohols.

Sodium borohydride (NaBH4) reduces aldehydes to primary alcohols, and ketones to secondary alcohols. The reactions take place in a wide variety of solvents, including alcohols, ethers, and water. The yields are generally excellent. 

Lithium aluminum hydride (LiAlH4, abbreviated LAH) is a much stronger reagent than sodium borohydride. It easily reduces ketones and aldehydes and also the less-reactive carbonyl groups those in acids, esters, and other acid derivatives (see Chapter 21). LAH reduces ketones to secondary alcohols, and it reduces aldehydes, acids, and esters to primary alcohols. The lithium salt of the alkoxide ion is initially formed, then the (cautious ) addition of dilute acid protonates the alkoxide. For example, LAH reduces both functional groups of the keto ester in the previous example. 

Enantioselective Reduction ofa,P-Ynones. Oxazaborolidine ligands 1 are among the most effective catalysts for the enantioselective reduction of ketones to secondary alcohols. Substitution of the methyl or butyl group on boron by a trimethylsilylmethyl group led to a much improved catalyst for the catecholborane mediated reduction of a, 3-ynones. For example, the enantioselectiv-ities for the reduction of an a, 3-ynone was improved from 60% to 98.5% when the nature of the R group was modified (eq 1). ... 

All five Group I metals (Li, Na, K, Rb and Cs) and three Group II metals (Ca, Sr, Ba) have been used in NH3 to effect the reduction of ketones to secondary alcohols. " In addition, it has been reported that Yb-NH3 reduction of a,p-unsaturated ketones affords the saturated alcohol as the major product, which presumably arises via reduction of the intermediate saturated ketone.Reduction of (+)-camphor with Yb-NH3 both in the absence and presence of NH4CI affords the same 86 14 ratio of bomeol (2) to iso-bomeol (3). In the presence of NH4CI, the ketone is completely consumed and dimeric reduction products are not observed. Excess Yb-THF-HMPA effects bimolecular reduction of aromatic ketones, but aliphatic ketones are apparently inert to Yb-THF. - ... 

Conversely, as previously stated, the aldehydes on reduction yield the primary alcohols and in the case of benzaldehyde, which is a commonly occurring substance in oil of bitter almonds, this method is used in the preparation of the alcohol. In the case of the secondary alcohols oxidation to ketones is not easily accomplished but the reverse reaction, the reduction of the ketones to secondary alcohols does take place with ease. 

Some biotransformations introduce an asymmetric center into a drug and these often proceed stereospeci-fically. The most common examples are hydroxylation of a secondary carbon and the reduction of ketones to secondary alcohols. Ibuprofen undergoes both co and co-l oxidation of the isobutyl side chain, and formation of the resulting carboxylic acid metabolite introduces a second asymmetric center into the molecule. Both ibuprofen enantiomers have been shown to undergo stereospecific oxidation to give a metabolite with the same configuration at the new asymmetric center. 

Aldehydes can be reduced tojjrimary alcohols, and ketones to secondary alcohols, either by catalytic hydrogenatloiToTB jse of chemical reducing agents Ke lithium aluminum hydride, LiAlH4. Such reduction is useful for the preparation of certain alcohols that are less available than the corresponding carbonyl cc mpounds, in particular carbonyl compounds that can be obtained by the aldol condensation (Sec. 21.7). For example ... 

Cp2TiCl2 is reduced by Zn to generate the Ti(m) compound Cp2TiCl, used as electron-transfer catalyst for the synthesis of cyclopropanes and cyclobutanes with epoxides as radical precursors.1160 This system is suited for the reduction of ketones to secondary alcohols.1161... 

K Nakagawa, K Minami. Reduction of organic compounds with thiourea dioxide. I. Reduction of ketones to secondary alcohols. Tetrahedron Lett 5 343-346, 1972. 

Hydromagnesiation is not limited to carbon-carbon multiple bonds as discussed above, but also occurs with carbon-heteroatom unsaturated bonds as shown in Scheme 3.15. The hydromagnesiation of a earbon-oxygen double bond can be seen in reduction of ketones to secondary alcohols 111)41, esters to primary alcohols 11051. and carboxylic acids to aldehydes 1106] with i-BuMgBr in the presence of a catalytic amount... 

S,S-dioxide. Reducing agent for dye. Used in organic synthesis to reduce ketones to secondary alcohols. Solid mp = 126 (dec) soluble in H2O (3.0 g/100 mi). Allchem Ind. Cia-Shen Degussa AG Rhone-Poulenc UK. 

Alkaline reducing agents are usually recommended for reduction of ketones to secondary alcohols since pinacones are formed preferentially in an acid medium. Sodium in alcohol or in moist ether or benzene, sodium amalgam, and zinc dust in sodium hydroxide solution, etc., are often used for this purpose. 2-Heptanol, for example, is formed in good yield on addition of sodium to an aqueous-alcoholic solution of methyl w-pentyl ketone.306 Reduction is also often carried out by adding sodium to an aqueous-ethereal suspension but by this method the double bond of unsaturated ketones is also partially reduced. 

Meerwein-Ponndorf-Verley reduction of ketones to secondary alcohols proceeds analogously to that of aldehydes, although usually more slowly. The method cannot, however, be used for ketones such as j8-keto esters or / -diketones that have a strong tendency to enolize, since they form aluminum enolates which are not reduced such compounds are preferably reduced by sodium borohydride, by potassium borohydride, or catalytically. 

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