Reduction of Aromatic Ketones

Like aliphatic ketones, armnatic and aromatic aliphatic ketones are reduced to alcohols very easily. Since the secondary alcoholic group adjacent to the benzene ring is easily hydrogenolyzed, special precautions must be taken to prevent the reduction of the keto group to the methylene group, especially in catalytic hydrogenations. 

An interesting example of hydrogenation with hydrogen in the absence of transition metal catalyst is reduction of benzophenone to benzhydrol with hydrogen in /er/-butyl alcohol containing potassium /er/-butoxide at 150-210° and 96-135 atm. Although the yields range from 47 to 98% the method is not practical because of its drastic conditions, and because of a cornucopia of more suitable reductions. 

Catalytic hydrogenation of aromatic ketones was successful over a wide range of catalysts under mild conditions (25°, 1 atm). Of the noble metal family some metals more than others tend to hydrogenolyze the alcohol formed, and/or saturate the ring. Evaluation of some metal catalyst is based on hydrogenation of acetophenone as a representative [35,814]. 

In contrast to hydrogenation over noble metals hydrogenation of acetophenone over different nickel catalysts and over copper chromite results in the formation of 1-phenylethanol without hydrogenolysis [43,45,49,50]. 

Surprisingly good results in the reduction of aromatic ketones were obtained in treating the ketones with a 50% nickel-aluminum alloy in 10-16% aqueous sodium hydroxide at temperatures of 20-90° (yields 65-90%) [769, 827]. 

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Unsaturated hydrocarbons are present in nearly all products of the Clemmensen reduction of aromatic ketones and must be removed, if the hydrocarbon is requiral pure, by the above process. Secondary alcohols, often produced m small amount are not appreciably steam-volatile. 

This procedure illustrates a general method for preparing aromatic hydrocarbons by the tandem alkylation-reduction of aromatic ketones and aldehydes.2 Additional examples are given in Table I. 

Formate is one of the most representative hydrogen sources for the biocatalytic reduction because CO2 formed by the oxidation of formate is released easily from the reaction system [4]. For example, for the reduction of aromatic ketones by the... 

Resting cell of G. candidum, as well as dried cell, has been shown to be an effective catalyst for the asymmetric reduction. Both enantiomers of secondary alcohols were prepared by reduction of the corresponding ketones with a single microbe [23]. Reduction of aromatic ketones with G. candidum IFO 5 767 afforded the corresponding (S)-alcohols in an excellent enantioselectivity when amberlite XAD-7, a hydro-phobic polymer, was added to the reaction system, and the reduction with the same microbe afforded (R)-alcohols, also in an excellent enantioselectivity, when the reaction was conducted under aerobic conditions (Figure 8.31). 

Reduction of aromatic ketones by 45 normally gives satisfactory results. Scheme 6-24 and Table 6-4 show the results of some such reactions. 

TABLE 6-4. Enantioselective Reduction of Aromatic Ketones with BINAL-H (R"0=C2H50) ... 

Table 11.2 Reduction of aromatic ketones using oxazaphosphinamide catalyst1131 (results according to the literature).

Scheme 31 Influence of sonication on the selectivity in the cathodic reduction of aromatic ketones diol 10-23% (without sonication), 36-42% (with sonication).

As shown in Figure 1.26, a chiral Sm(III) complex catalyzes asymmetric reduction of aromatic ketones in 2-propanol with high enantioselectivity. Unlike other late-transition-metal catalysis, the hydrogen at C2 of 2-propanol directly migrates onto the carbonyl carbon of substrate via a six-membered transition state 26A, as seen in the Meerwein-Ponndorf-Verley reduction. ... 

A chiral p-keto iminato Co complex in the presence of tetrahydrofuryl alcohol (THFA) and ethanol (or methanol) results in high enantioselectivity in reduction of aromatic ketones using NaBH4 as a hydride source (Figure 1.29). The in situ generated NaBH2(OR)(OC2H5) (ROH = THFA) reduces the Co complex to form a true catalytic CoH species. 

Reduction of aromatic ketones to hydrocarbons occurs very easily as the carbonyl group is directly attached to an aromatic ring. In these cases reduction produces benzylic-type alcohols which are readily hydrogenolyzed to hydrocarbons. This happens during catalytic hydrogenations as well as in chemical reductions. 

However, most frequently used methods for reduction of aromatic ketones to hydrocarbons are, as in the case of other ketones, Clemmensen reduction [160, 161, 758, 843, 844] Procedure 31, p. 213), Wolff-Kizhner reduction [280,281,282, 759, 774,845] Procedure 45, p. 216), or reduction of p-toluene-sulfonylhydrazones of the ketones with lithium aluminum hydride [811, 812] or with borane and benzoic acid [786]. 

Attempts to achieve optical induction during the reduction of aromatic ketones to the secondary alcohol by immobilising a single layer of chiral catalyst on a solid electrode surface have been much less successful. The preparation of such coatings... 

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). 

Degni, S., Wilen, C.-E. and Rosling, A. Highly Catalytic Enantioselective Reduction of Aromatic Ketones using Chiral Polymer-supported Corey, Bakshi, and Shibata Catalysts. Tetrahedron Asymmetry 2004, 15, 1495-1499. 

Pinacol reduction.1 In a strongly basic medium (pH 11-12), TiCl3 effects pinacol reduction of aromatic ketones, ArCOCH3 or C6H5COR, previously effected with a Ti(II) species (7, 373-374). Both the dl- and meso-pinacols are formed with marked preference for the former isomer. 

A combination of chiral cobalt-catalyst and sodium borohydride was successfully applied to the asymmetric reduction of aromatic ketones. A chiral cobalt complex 164 (5 mol%), prepared from the corresponding salen-type chiral bisketoaldimine and cobalt(II) chloride, catalyzed the reduction of dimethylchromanone 165 in the presence of sodium borohydride (1.5 equiv to ketone) in chloroform, including a small amount of ethanol at -20°C for 120 h to give alcohol 166 92% ee (S ) in 94% yield (Scheme 2.18) [94], Addition of tetrahydrofurfuryl alcohol (THFFA) to the reaction system or the use of pre-modified borohydride, NaBH2(THFFA)2, improved the catalyst activity, that is, using this protocol, the reactions of ketone 165 and... 

A new, metal-free protocol involving (heteroaryl)oxazoline catalysts for the enantioselective reduction of aromatic ketones (up to 94% ee) and ketimines (up to 87% ee) with trichlorosilane has been developed. The reaction is characterized by an unusual, long-ranging chiral induction.The enantiodifferentiation is presumed to be aided by aromatic interactions between the catalyst and the substrate.360 Asymmetric reduction of A-arylketimines with trichlorosilane is catalysed by A-methyl-L-amino acid-derived Lewis-basic organocatalysts with high enantioselectivity (up to 92% ee) 61... 

A new chiral acyloxyborohydride has been prepared by combining sodium borohy-dride with a tartaric acid-based reagent. This reagent effects the reduction of aromatic ketones to provide the product alcohols in ees of 93-98%. Several aliphatic ketones were also reduced with moderate to excellent enantioselectivity. A mechanism has been provided with supporting calculations for the proposed active species and tran- sition state.262... 

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