Hydrogenation, catalytic, alkene enantioselectivity

In hydrogenation, early transition-metal catalysts are mainly based on metallocene complexes, and particularly the Group IV metallocenes. Nonetheless, Group III, lanthanide and even actinide complexes as well as later metals (Groups V-VII) have also been used. The active species can be stabilized by other bulky ligands such as those derived from 2,6-disubstituted phenols (aryl-oxy) or silica (siloxy) (vide infra). Moreover, the catalytic activity of these systems is not limited to the hydrogenation of alkenes, but can be used for the hydrogenation of aromatics, alkynes and imines. These systems have also been developed very successfully into their enantioselective versions. 

As recently recognized by the Nobel Chemistry award committee, the conceptualization, development, and commercial application of enantioselective, homogeneous hydrogenation of alkenes represents a landmark achievement in modem chemistry. Further elaboration of asymmetric hydrogenation catalysts by Noyori, Burk, and others has created a robust and technologically important set of catalytic asymmetric synthetic techniques. As frequently occurs in science, these new technologies have spawned new areas of fundamental research. Soon after the development of... 

Only one paper has reported on catalytic asymmetric hydrogenation. In this study by Corma et al., the neutral dimeric duphos-gold(I)complex 332 was used to catalyze the asymmetric hydrogenation of alkenes and imines. The use of the gold complex increased the enantioselectivity achieved with other platinum or iridium catalysts and activity was very high in the reaction tested [195] (Figure 8.5). 

Ligand-metal bifunctional catalysis provides an efficient method for the hydrogenation of various unsaturated organic compounds. Shvo-type [83-85] Ru-H/OH and Noyori-type [3-7] Ru-H/NH catalysts have demonstrated bifimctionality with excellent chemo- and enantioselectivities in transfer hydrogenations and hydrogenations of alkenes, aldehydes, ketones, and imines. Based on the isoelectronic analogy of H-Ru-CO and H-Re-NO units, it was anticipated that rhenium nitrosyl-based bifunctional complexes could exhibit catalytic activities comparable to the ruthenium carbonyl ones (Scheme 29) [86]. 

The synthesis of cationic rhodium complexes constitutes another important contribution of the late 1960s. The preparation of cationic complexes of formula [Rh(diene)(PR3)2]+ was reported by several laboratories in the period 1968-1970 [17, 18]. Osborn and coworkers made the important discovery that these complexes, when treated with molecular hydrogen, yield [RhH2(PR3)2(S)2]+ (S = sol-vent). These rhodium(III) complexes function as homogeneous hydrogenation catalysts under mild conditions for the reduction of alkenes, dienes, alkynes, and ketones [17, 19]. Related complexes with chiral diphosphines have been very important in modern enantioselective catalytic hydrogenations (see Section 1.1.6). 

The TEAF system can be used to reduce ketones, certain alkenes and imines. With regard to the latter substrate, during our studies it was realized that 5 2 TEAF in some solvents was sufficiently acidic to protonate the imine (p K, ca. 6 in water). Iminium salts are much more reactive than imines due to inductive effects (cf. the Stacker reaction), and it was thus considered likely that an iminium salt was being reduced to an ammonium salt [54]. This explains why imines are not reduced in the IPA system which is neutral, and not acidic. When an iminium salt was pre-prepared by mixing equal amounts of an imine and acid, and used in the IPA system, the iminium was reduced, albeit with lower rate and moderate enantioselectivity. Quaternary iminium salts were also reduced to tertiary amines. Nevertheless, as other kinetic studies have indicated a pre-equilibrium with imine, it is possible that the proton formally sits on the catalyst and the iminium is formed during the catalytic cycle. It is, of course, possible that the mechanism of imine transfer hydrogenation is different to that of ketone reduction, and a metal-coordinated imine may be involved [55]. 

Tetrasubstituted alkenes are among the most challenging substrates for catalytic hydrogenation reactions. Towards this end, Buchwald and co-workers recently reported efficient and highly enantioselective Zr-catalyzed hydrogenations of a range of styrenyl tetrasubstituted alkenes (Scheme 6.41) [123]. Precedents based on efficient polymerization reactions promoted by cationic zirconocenes led these workers to consider similar catalyst species, derived from dimethylzirconocene 107, for this purpose. 

Related catalytic enantioselective processes Although great progress has been achieved in the area of metal-catalyzed hydrogenation reactions [124], examples of catalytic asymmetric hydrogenations of tetrasubstituted alkenes are rare. One other example, reported by Pfaltz and co-workers, is depicted in Eq. 6.26 (81 % ee, absolute stereochemistry of the product not determined) [125],... 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

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