Reduction diaryl ketone

Reductions. Diaryl ketones are deoxygenated by this reagent system while benzaldehyde and aliphatic ketones are not affeeted. Chalcone undergoes saturation at the double bond only. 

Novel preferential reduction. Diaryl ketones are much more reactive toward Li-N-dihydropyridylaluminum hydride (formula s. 944) than are either dialkyl or arylalkyl ketones. This sequence is in contrast to that found with NaBH4 in isopropanol and appears to be without precedent in nucleophilic addition to carbonyl groups. E. and limitation s. P. T. Lansbury and J. O. Peterson, Am. Soc. 54, 1756 (1962). 

Organotin compounds such as aryl-, alkenyl-, and alkynylstannanes are useful for the ketone synthesis by transmetallation of acylpalladium 529 and reductive elimination of 530 as shown[389-393]. Acetophenone (531) is obtained by the carbonylation of iodobenzene with Me4Sn. Diaryl ketones... 

The course of reduction of unsaturated and aromatic ketones is more complicated. Diaryl ketones, alkylaryl ketones and some aryl alcohols are smoothly reduced to the corresponding hydrocarbons. The recommended way of performing these reductions is to add an equimolar mixture of aluminum chloride and the ketone in ether to an equimolar mixture of aluminum chloride and LiAlH4 in ether. 

Thakar and Subba Rao showed that reductions with diborane give the same result regardless of whether diborane is generated externally or produced internally by the action of NaBH4 and boron trifluoride or aluminum chloride. They found that alicyclic or dialkyl ketones are not reduced beyond the alcohol stage even under drastic conditions however, diaryl ketones are hydrogenolyzed under normal conditions, while aryl ketones or a,i5-unsatu-rated ketones are hydrogenolyzed, in part, under drastic conditions. 

Arylalkyl and diaryl ketones are converted to the corresponding pinacols upon electrochemical reduction in acidic and very alkaline media ... 

The asymmetric formation of industrially useful diaryl methanols can be realized through either the addition of aryl nucleophiles to aromatic aldehydes or the reduction of diaryl ketones. The latter route is frequently the more desirable, as the starting materials are often inexpensive and readily available and nonselective background reactions are not as common. For good enantioselectivity, chemical catalysts of diaryl ketone reductions require large steric or electronic differentiation between the two aryl components of the substrate and, as a result, have substantially limited applicability. In contrast, recent work has shown commercially available ketoreductase enzymes to have excellent results with a much broader range of substrates in reactions that are very easy to operate (Figure 9.6). ... 

Procedure 1 General Procedure for the Ketoreductase Reduction of Diaryl Ketones... 

Figure 9.6 Asymmetric reduction of diaryl ketones with ketoreductases...

Truppo, M. D., Pollard, D. and Devine, P., Enz3Tne-catalyzed enantioselective diaryl ketone reductions. Org. Lett., 2007, 9, 335. 

Two strategies for the synthesis of enantiomerically enriched diaryl methanols 27 are apparent first, asymmetric reductions of the corresponding diaryl ketones 36 [33], and, second, enantioselective aryl transfer reactions to the respective benzaldehyde derivatives 37 (Scheme 2.1.2.5) [34, 35]. 

Reductions.2 In contrast to NaCNBHj, the complex I reduces acid chlorides only to aldehydes under neutral conditions in 50-90% yield. However, under acidic conditions, I reduces carbonyl groups to alcohols (70-80%, yield), although diaryl ketones are reduced in low yields. A useful feature of this reagent is that reduction of ketones is more stereoselective than that with NaCNBH,. Thus reduction of 4-/-butylcyclohexanone gives a 94 6 mixture of irons cis isomeric alcohols if 80% yield. 

Diaryl ketones.2 In the presence of this complex (1 equivalent) S-(2-pyridyl) aryl thioates (1 equivalent), prepared from aryl carboxylic acids, undergo reductive homocoupling to diaryl ketones (equation I). 

Reductions. This combination of NaBH4 -PdCl2 (5 1) reduces diaryl ketones or ben/.ylic alcohols to the hydrocarbon (THF/H,0, 7°) in 70-90% yield. This system (( I I, OH, 20") reduces chloroarencs to arcncs (50 70% yield). The system also reduces 17-keto steroids to 17/1-ols in high yield. 

Catalytic asymmetric synthesis of enantiopure diaryl-methanols and -methylamines (important pharmaceutical intermediates) has been reviewed (76 references), focusing on (i) aryl transfers on to aryl-aldehydes and -imines and (ii) asymmetric reductions of diaryl-ketones and -ketoimines.284... 

The generality of schemes of this type is not clear, but it is an alternative to the e/H transfer sequences for a range of reactions in which oxidant-derived radical anions are found, including the Meerwein-Ponndorf-Verley reduction of diaryl ketones outlined above. 

A very extensive investigation of the reaction of pyridine and lithium aluminum hydride has been made by Lansbury and Peterson.60-82 These authors found that an aged solution of LAH in pyridine possessed unusual and selective reductive properties. Ketones and aldehydes were reduced while carboxylic acids were not, and diaryl ketones were reduced more readily than dialkyl ketones. These distinctive properties were found to result from a dihydropyridine-aluminum complex formed by the reaction of LAH and pyridine. 

The strategy presented above with phenyl cyclohexyl ketone has been established to be general by investigating a number of aryl alkyl ketones and diaryl ketones [281,283]. The best cases of % ee are summarized in Schemes 14 and 15. 2-Ethoxybenzophenone 32 gives intramolecular cyclization product 33 as the only product in solution as well as within NaY. However, in NaY in the presence of chiral amines, intermolecular reduction product 34, in addition to 33, was obtained (Scheme 16). More importantly, with pseudoephedrine and (l/ ,2/ )-... 

Reduction of diaryl ketones. Diaryl ketones or diarylmethanols are reduced to diarylmethanes by NaBH4 in trifluoroacetic acid (equation I.)" ... 

Selective reduction of aldehydes. In the absence of radical initiators, tributyltin hydride does not ordinarily reduce carbonyl groups. However, when slurried in cyclohexane with dried silica gel (activated by heating at 220° under reduced pressure), this hydride reduces aldehydes and ketones to alcohols in high yield. The rate of reduction is aldehydes > dialkyl ketones > aryl alkyl ketones > diaryl ketones. Thus it is possible to reduce aldehydes selectively. The function of Si02 apparently is that of a mild acid catalyst. 

---