Enantioselectivity transfer hydrogenation

In addition, the related complexes 13 and 14 act as catalysts in enantioselective transfer hydrogenations (Table 5). The reactivity of acetophenone derivatives... 

Nature uses enantioselective transfer hydrogenation to reduce metabolites, for example pyruvate to give (S)-lactic acid and 2-ketoglutarate to give (S)-2-hydroxy -glutarate. The reaction is reversible and the equilibrium position depends on the concentration of the species. The enzyme catalysts are named dehydrogenases, and they employ a soluble cofactor or hydride acceptor called NAD(P) in its oxi-... 

One of the earliest reports of enantioselective transfer hydrogenation was by Alper et al., who used chiral Schiff bases and a dichlororuthenium(II)benzene complex employing the IPA system [5]. In another report, Lemaire et al. utilized... 

Fig. 35.4 Outline mechanism for the rhodium-catalyzed enantioselective transfer hydrogenation reaction.

Fig. 35.8 Optical activities achieved by enantioselective transfer hydrogenation of alkenes.

Brunner, Leitner and others have reported the enantioselective transfer hydrogenation of alpha-, beta-unsaturated alkenes of the acrylate type [50]. The catalysts are usually rhodium phosphine-based and the reductant is formic acid or salts. The rates of reduction of alkenes using rhodium and iridium diamine complexes is modest [87]. An example of this reaction is shown in Figure 35.8. Williams has shown the transfer hydrogenation of alkenes such as indene and styrene using IPA [88]. 

Numerous enantioselective transfer hydrogenation processes have now been developed and operated at commercial scale to give consistent, high-quality products, economically. These include variously substituted aryl alcohols, styrene oxides and alicyclic and aliphatic amines. Those discussed in the public domain include (S)-3-trifluoromethylphenylethanol [48], (f )-3,5-bistrifluorophenylethanol [64], 3-nitrophenylethanol [92], (S)-4-fluorophenylethanol [lc], (f )-l-tetralol [lc], and (T)-l-methylnaphthylamine [lc]. 

PfefFer, de Vries and coworkers developed the use of ruthenacycles, based on chiral aromatic amines as enantioselective transfer hydrogenation catalysts. These authors were able to develop an automated protocol to produce these catalysts by reacting ligand and metal precursor in the presence of base, KPFS in CH3CN. After removal of the solvent, isopropanol was added followed by the substrate, acetophenone, and KOtBu. In this way, a library of eight chiral... 

Vedejs et al. reported catalyst inhibition during a study on the enantioselective transfer hydrogenation of dihydro-isoquinolines using Noyori s catalyst (Scheme 44.2) [27]. Here, the problem is caused by the bidentate nature of the substrate. Whereas the bromo compound 1 a could be rapidly reduced, the tosylamide-sub-stituted compound lb could not be reduced, and although the problem could be alleviated somewhat by alkylation of the sulfmamide to 1 c, hydrogenation of this was still sluggish. Although the authors propose this to be a case of product... 

Scheme 44.3 Substrate inhibition in enantioselective transfer hydrogenation.

Scheme 64 Enantioselective transfer hydrogenation of a, 3-unsaturated ketones...

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