Benzils, asymmetric reduction

More successful asymmetric reductions have been based on amine (particularly alkaloid) complexes of bis(dimethylglyoximato) cobalt(II), also known as cobaloxime(II) and represented Co(dmg)2 (compound VII). Cobaloxime-chiral amine complexes have been used to catalyze the hydrogenation of both olefinic and ketonic substrates (Fig. 24). It has been determined that hydroxyamine modifiers, for example, alkaloids such as quinine, quinidine, and cinchonidine, are most effective. The highest optical purity obtained thus far has been 71%, observed for reduction of benzil in benzene solution at 10° using quinine as the... 

Asymmetric reduction ofbenzil.2 Reduction of benzil with Sml2 in C6H6/THF with quinidine (1) as a proton source yields (R)-benzoin in about 40% ee. Addition of HMPT increases the rate and the enantioselectivity to 56% ee. 

Taking advantage of these findings, a catalytic asymmetric hydrogenation of ketones has been effected [27]. It should be noted in this connection that asymmetric reduction of benzil to benzoin has been found to occur with Z>is(dimethyl-glyoximato)cobalt(II)-quinine system as a catalyst [28]. 

Fig. 4 Asymmetric reduction of benzils with chiral Ru catalyst...

Only a few other cobalt complexes of the type covered in this review (and therefore excluding, for example, the cobalt carbonyls) have been reported to act as catalysts for homogeneous hydrogenation. The complex Co(DMG)2 will catalyze the hydrogenation of benzil (PhCOCOPh) to benzoin (PhCHOHCOPh). When this reaction is carried out in the presence of quinine, the product shows optical activity. The degree of optical purity varies with the nature of the solvent and reaches a maximum of 61.5% in benzene. It was concluded that asymmetric synthesis occurred via the formation of an organocobalt complex in which quinine was coordinated in the trans position (133). Both Co(DMG)2 and cobalamin-cobalt(II) in methanol will catalyze the following reductive methylations ... 

In the reduction of an optically active ketone, the reaction results in the creation of an additional asymmetric center, and two diastereoiso-mers are possible. In many cases it has been found that both isomers are formed, often in comparable amounts. For example, reduction of camphor (XY) gives a mixture of bomeol and isobomeol (XVI).6 Numerous other examples may be noted in the tables at the end of this chapter. However, the reduction of benzil (XVII) or benzoin (XVIII) is reported to give 90% of wieso-hydrobenzoin (XIX). 6... 

Scheme 7.3 Takeuchi s benzil-to-benzoin reductive asymmetric protonation [4].

Diamine 264 is made from the a-diketone benzil by a simple but multiple cyclisation to give the heterocycle 265. Stereoselective dissolving metal reduction gives anti-266 and hence racemic 264 on aminal hydrolysis. Resolution with tartaric acid brings down crystals of the tartrate of one enantiomer. With l-(+)-tartaric acid, the salt with (.S, .S )-264 is less soluble while (R,R)-264 requires treatment with d-(—)-tartaric acid. One important application is the asymmetric Lewis acid46 267. 

Diketones. Chiral 1,2-diols have been extensively utilized as ligands and chiral auxiliaries for asymmetric synthesis. The CBS reduction of 1,2-diketones, such as benzil and heterocyclic derivatives furnishes optically active hydrobenzoins with excellent ee (>99 % ee) and good de (64-86 % de) 63) (Figure 8), whereas the reagent 1 afforded hydrobenzoin in 70 % ee with 34 % de (Cho, B. T., unpublished results). 

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