BINAP-Ru chemistry

The above mechanism is novel in that it does not require the interaction of a carbonyl moiety with the metal center. Neither a ketone/Ru complex nor a Ru alkoxide is involved in the mechanism, and the alcohol forms directly from the ketone. This non-classical mechanism also explains the high functional selectivity for the C=0 group. When the chiral molecular surface of the Ru hydride recognizes the difference of ketone enantiofaces, asymmetric hydrogenation is achieved. This is different from the earlier BINAP Ru chemistry where the enantio-face differentiation is made within the chiral metal template with the assistance of heteroatom/metal coordination. Similar heterolyses of H2 ligands have been shown by Morris and others (92) to be the critical step in the mechanism of reaction processes related to the Noyori systems. 

This chemistry is applicable to the hydrogenation of acyclic compounds such as a-acylamino-, a-ammonio-, a-amidomethyl-, and a-chloro-substituted / -keto esters (Fig. 32.26) [14n, 74a, 77-79]. The (R)-BINAP-Ru-catalyzed hydrogenation of the a-acylamino and a-amidomethyl ketones in CH2C12 leads to the 2S,3R (syn) alcohols in up to 98% ee [14n, 74a]. The use of sterically hindered... 

Unlike the Rh-based hydrogenation of a-(acylamino)acrylates, the corresponding Ru chemistry has not been studied extensively. Ru complexes of (S)-BINAP and (S,S)-CHIRAPHOS catalyze the hydrogenation of (Z)-a-(acylamino)cinnamates to give the protected ( -phenylalanine with 92% ee [74] and 97% ee [75], respectively. It is interesting that the Rh and Ru complexes with the same chiral diphosphines exhibit an opposite sense of asymmetric induction (Scheme 1.6) [13,15,56,74,75]. This condition is due primarily to the difference in the mechanisms the Rh-catalyzed hydrogenation proceeds via Rh dihydride species [76], whereas the Ru-catalyzed reaction takes place via Ru monohydride intermediate [77]. The Rh-catalyzed reaction has been studied in more detail by kinetic measurement [78], isotope tracer experiments [79], NMR studies [80], and MO calculations [81]. The stereochemical outcome is understandable by considering the thermodynamic stability and reactivity of the catalyst-enamide complexes. 

The BINAP-Ru catalyzed asymmetric hydrogenation of difunctionalized ketones is applicable to synthesis of several biologically active compounds [lc, 193,195,196]. In Figure 1.12, the stereocenter determined by the BINAP chemistry is labeled by R or S. 

Immobilized catalysts on solid supports inherently have benefits because of their easy separation from the products and the possibility of recycling. They are also expected to be useful for combinatorial chemistry and high-throughput experimentation. The polystyrene-bound BINAP/DPEN-Ru complex (beads) in the presence of (CH3)3COK catalyzes the hydrogenation of l -acetonaphthone with an SCR of 12 300 in a 2-propanol-DMF mixture (1 1, v/v) to afford the chiral alcohol in 97% ee (Fig. 32.35) [113]. This supported complex is separable... 

Very recently, a spectacular improvement in carbonyl reduction chemistry was achieved by Noyori, Ohkuma, and co-workers (Scheme 2-47). They demonstrated that the three-components reduction system, BINAP (15)-Ru(II), 1,2-diamine and KOH is crucial for the chemoselective reduction of ketone carbonyls with H2 in the presence of olefinic units. The extremely efficient reaction conditions [Ru(II) catalyst, 0.5 mol% H2, 1 8 atm 28 "C i-PrOH-toluene] render the reduction quite practical, bringing about almost quantitative yields as well as absolute che-... 

An original approach to the problem has been to support the catalyst, in a polar phase, on an accessible surface. The conspicuous success in this area has come from Davis s work [ 149] the basic principle is shown in Fig. 44. In this, the Ru-BINAP catalyst is adsorbed in a polar solvent phase on a porous glass bead. The substrate (and product) are in a solvent phase which is immiscible with the adsorbed phase, and in the initially described work the reaction was carried out in water, with concomitant reduction in turnover rate compared to the homogeneous variant. Strikingly better results were obtained when the supported phase was ethylene glycol, and here the efficiency rivaled that of the solution chemistry [150]. 

Starting from the readily available parent arenes, ketones 54a,b were prepared by standard Friedel-Crafts chemistry. Environment-friendly electrochemical carboxylation of these gave a-hydroxy acids 55a,b, from which acrylic acids 56a,b were easily obtained. Their reduction, catalyzed by the modified Noyori complex Ru(acac)2/BINAP, afforded in high yields the (. -enantiomers of acids 22 and 57 having 98% and 96% e.e., respectively. Improvements of both processes have been reported [64,65],... 

In comparison to Rh, the chemistry of Ru is more complex, and a broader variety of Ru precursors has actually been used on a regular basis (see Fig. 8). On the other hand, with some notable exceptions, only atropisomeric biaryl diphosphines, all inspired by binap, have led to effective catalysts. Much of this chemistry has been developed by the Noyori group, some of it in collaboration with Takasago [61]. For these Ru diphosphine complexes, the presence or absence of either chloride or bromide ions dominates their catalytic properties. Halides containing Ru complexes... 

Figure 1.23 Transition states leading to R- and S-products optimized under DFT2i8 2iVcoB97X-D33VSDD(Ru)/6-31G (C, H,N, 0,P, K)/SMD(propan-2-olp3 level of theory on the full model of fra s-[RuH2 (S)-BINAP (S, S)-DPEN)] and its K-amidato complexes with acetophenone. The enantioselectivity for each complex is calculated based on difference in electronic energy using absolute rate theory. Some H-atoms are omitted for the ball and stick model. (Reprinted with permission from Dub, P. A. et al, Dalton Trans., 45,6756-6781. Copyright 2016 Royal Society of Chemistry.)...

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