Ketones ruthenium-catalyzed enantioselective

Recently, the first report was made on the ruthenium-catalyzed enantioselective hydrogenation of aryl-methyl ketones using monodentate phosphonites (Scheme 28.18). In particular, ligand 15f induced excellent ee-values. One very early report on rhodium-catalyzed hydrogenation of ketones using the monophosphine bmpp 1 f met with a low e.e. [95]. 

IN SITU FORMATION OF LIGAND AND CATALYST APPLICATION IN RUTHENIUM-CATALYZED ENANTIOSELECTIVE REDUCTION OF KETONES... 

C3-TunePhos (1,13-bis(diphcnylphosphino)-7,8-dihydro-6//-dibenzo f,h] [l,5]dioxonin) ruthenium catalyzes the hydrogenation of a-phthalimido ketones with enantioselectivities of >94%,651 leading to a highly enantioselective route to /3-aminoethanols. 

Far more ruthenium-complex-catalyzed enantioselective hydrogenation has been directed towards ketone reduction rather than alkene reduction. Recent studies carried out on the mechanism of C=C hydrogenation has been rather limited. 

The asymmetric hydrogenation of enol esters is an alternative to asymmetric ketone hydrogenation. The precursors can be prepared from the ketones but also via ruthenium-catalyzed addition of the carboxylic acids to the 2-postion of terminal alkynes. This latter method allows the study of the effect of the carboxylate on the enantioselectivity of the asymmetric hydrogenation. A remarkable study by Reetz and colleagues established that it is possible to hydrogenate enolate... 

Ruthenium-catalyzed asymmetric reductions of aromatic ketones 180 can be performed under microwave irradiation. Moberg [98] described this reaction using a monomode microwave reactor and ruthenium complexes 182 with enan-tiomerically pure chiral diamines 181 (Scheme 5.51). The reaction is very fast and efficient even sterically hindered tert-butylphenylketone, which is normally quite umeactive, was reduced in almost quantitative yield in 3 minutes. The enantio-selectivity was, however, lower than that obtained under standard conditions similarly to that described by Larhed [77] in the enantioselective Heck reaction between cydopentene 115 and phenyl triflate 116 (Scheme 5.33). 

Additional catalyst development identified the positive effect of 1,2-diamines as additives in the (BlNAP)Ru(OAc)2-catalyzed enantioselective hydrogenations of ketones [24], This discovery ultimately led to the synthesis of a class of (diphosphine) Ru(diamine)X2 (X = H, halide) compounds [25] (Figure 4.1) which have emerged as some of the most active and selective hydrogenation catalysts ever reported [26]. Mechanistic studies by Noyori [14] and Morris [27] have established bifunctional hydrogen transfer to substrate from the cis Ru-H and N-H motifs and identified the importance of ruthenium hydridoamido complexes for the heterolytic splitting of H2. This paradigm allows prediction of the absolute stereochemistry of the chiral alcohols produced from these reachons. 

Having demonstrated the potential of artificial metalloenzymes for the reduction of V-protected dehydroaminoacids, we turned our attention towards organometallic-catalyzed reactions where the enantiodiscrimination step occurs without coordination of one of the reactants to the metal centre. We anticipated that incorporation of the metal complex within a protein enviromnent may steer the enantioselection without requiring transient coordination to the metal. In this context, we selected the palladium-catalyzed asymmetric allylic alkylation, the ruthenium-catalyzed transfer hydrogenation as well as the vanadyl-catalyzed sulfoxidation reaction. Indeed, these reactions are believed to proceed without prior coordination of the soft nucleophile, the prochiral ketone or the prochiral sulfide respectively. Figure 13.5. 

Bai W-J, Xie J-H, Li Y-L, Liu S, Zhou Q-L. Enantioselective synthesis of chiral (3-aryloxy alcohols by ruthenium-catalyzed ketone hydrogenation via dynamic kinetic resolution (DKR). Adv. Synth. Catal 2010 352(l) 81-84. 

The use of chiral ruthenium catalysts can hydrogenate ketones asymmetrically in water. The introduction of surfactants into a water-soluble Ru(II)-catalyzed asymmetric transfer hydrogenation of ketones led to an increase of the catalytic activity and reusability compared to the catalytic systems without surfactants.8 Water-soluble chiral ruthenium complexes with a (i-cyclodextrin unit can catalyze the reduction of aliphatic ketones with high enantiomeric excess and in good-to-excellent yields in the presence of sodium formate (Eq. 8.3).9 The high level of enantioselectivity observed was attributed to the preorganization of the substrates in the hydrophobic cavity of (t-cyclodextrin. 

PhanePhos-ruthenium-diamine complexes catalyze the asymmetric hydrogenation of a wide range of aromatic, heteroaromatic, and cx,P-unsaturated ketones with high activity and excellent enantioselectivity (Burk, 2000). 

The Michael addition of malonates to cyclic enones, catalyzed by chiral Ru( 6-arcnc)(p-lolucncsulfonyl-1,2-diaminc), has been performed to afford the adduct with excellent enantiomeric excess [91,92]. A related catalyst was designed to perform sequentially the Michael addition to cyclic enone and the enantioselective hydrogenation of the ketone. Thus, the chiral ruthenium catalyst B containing trans hydride and borohydride ligands was able to enan-tioselectively (96% ee) promote the Michael addition of malonate to cyclo-hexenone. Further in situ catalytic hydrogenation (400 psi H2) was performed and led to excellent diastereoselectivity trans/cis 30/1 [93] (Scheme 43). 

---