Ruthenium catalysis asymmetric hydrogenation

The current research areas with ruthenium chemistry include the effective asymmetric hydrogenation of other substrates such as imines and epoxides, the synthesis of more chemoselective and enantioselective catalysts, COz hydrogenation and utilization, new methods for recovering and recycling homogeneous catalysts, new solvent systems, catalysis in two or three phases, and the replace-... 

The first transition metal catalysis using BINAP-ruthenium complex in homogeneous phase for enantioselective hydrogenation of P-ketoesters was developed by Noyori and co-workers [31]. Genet and co-workers described a general synthesis of chiral diphosphine ruthenium(II) catalysts from commercially available (COD)Ru(2-methylallyl)2 [32]. These complexes preformed or prepared in situ have been found to be very efficient homogeneous catalysts for asymmetric hydrogenation of various substrates such as P-ketoesters at atmospheric pressure and at room temperature [33]. 

Ashby, M. T., Halpern, J. Kinetics and mechanism of catalysis of the asymmetric hydrogenation of a,P-unsaturated carboxylic acids by bis(carboxylato) 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl ruthenium(ll), [Rull(BINAP) (02CR)2]. J. Am. Chem. Soc. 1991,113, 589-594. 

The resolution of racemic secondary allyl alcohols can be performed in the presence of certain ruthenium chiral catalysts through enantioselective asymmetric hydrogenation [811, 881], Chiral poisoning also works in such kinetic resolutions. For example, hydrogenation of 2-cyclohexenol under ( )-binap-Ru catalysis in the presence of (II , 25)-ephedrine 1.61 (10 equiv) provides unreacted (J )-2-cydo-hexenol in 95% ee after 60% conversion [857],... 

Pyridines have also been constructed as essential portion of ligands used for transition metal catalysis. Chan and co-workers report the synthesis of dipyridylphosphines as ligands for the Ru-catalyzed asymmetric hydrogenation of p-ketoesters <01SL1050>. Pallet and coworkers report on the synthesis and use of a Ruthenium (R)-QUINAP catalyst for use in enantioselective Diels-Alder reactions <01OM2454>. 

The mechanism of the catalysis (Scheme 20.8) is quite unlike that of the rhodium-DuPhos catalysis of prochiral olefins described above, since the ketone substrate does not bind to the metal (ruthenium) atom. When a substrate binds the metal, as in the rho-dium-DuPhos systems, there are opportnnities for unwanted pathways that terminate the catalysis. On the other hand, a conseqnence of the metal being protected by its ligands in the Noyori-Ikariya catalysis in principle rednces the likelihood of catalyst deactivation and increases the expectation for achieving very high catalyst utilization (substrate/catalyst ratios). Thus, in the asymmetric hydrogenation of acetophenone to (i )-l-phenylethanol, Noyori et al. reported an astounding molar snbstrate/catalyst ratio of 2,400,000 1. ... 

Lime, E. Lundholm, M. D. Forbes, A. Wiest, O. Helquist, R Norrby, P-O. Stereoselectivity in asymmetric catalysis The case of ruthenium-catalyzed ketone hydrogenation. /. Chem. Theory Comput. 2014,10,2427-2435. 

Kejrwords Dynamic kinetic asymmetric transformation (DYKAT) Dynamic kinetic resolution (DKR) Hydrogenation Imine reduction Ketone reduction Mechanism of carbonyl reduction Mechanism of imine reduction Mechanism of dUiydrogen activation Ruthenium catalysis Shvo s catalyst Transfer hydrogenation... 

Chiral amino alcohols are common structures in drug molecules for example, y-secondaiy aminoalcohols are key intermediates in the synthesis of several pharmaceuticals, examples of which are shown in Scheme 14.12. Zhang has shown that Rh-DuanPhos catalysts can be used to synthesise these key intermediates directly via asymmetric hydrogenation of the p-secondary amino ketone. Application to the synthesis of the antidepressant duloxetine is shown in Scheme 14.12. It should be noted that, to date, ruthenium catalysis has not been successfully applied to the reduction of secondary amino substrates a tertiary amino group is required resulting in a less efficient synthesis requiring extra S3mthetic steps. ... 

Another example of the application of DFT-based calculations comes from ruthenium catalyst-based asymmetric hydrogenations of ketones. As shown in Figure 3.5, the rra 5-dihydride complex 339 with chiral BINAP as the ligand is the resting state of the catalyst. Catalysis with 339 is proposed to occur by the transfer of a hydride from the ruthenium and a proton from the amine to the carbonyl group of the substrate, e.g., acetophenone. 

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