Ruthenium-BINAP hydrogenation

Fig. 20. Substituent direction and kinetic resolutions in ruthenium BINAP hydrogenations...

The modified BINAP catalyst 5 has been used for the hydrogenation of a number of analogues of substrate 1 (substrates 32-35, Fig. 30.8 Table 30.6), though again, enantioselectivities were modest [4]. Substrate 31 has also been hydrogenated with a ruthenium-BINAP-hydride cluster with low selectivity (11% ee) [27]. 

There is only one detailed kinetic study of ruthenium enantioselective hydrogenation, in this case involving (BINAP)Ru(OAc)2, and MAC [65]. The extensive study involved reaction kinetics, isotopic analysis of reaction components and products, and in-situ NMR. The derived catalytic cycle is shown in Figure 31.15, differing from the Bergens studies described above in that the intermediates -both observed and assumed - are neutral rather than cationic. Right up to the formation of the alkylruthenium intermediate, the individual steps are revers-... 

Lin et al. [106] studied the hydrogenation of yS-aryl ketoester using a ruthenium BINAP system with different substituents at the 4,4 -position of the BINAP ligand. The best enantioselectivities were achieved with steric demanding and electron-donating 4,4 -substituents. For example, ee-values of 97.2% and 99.5% were obtained for the hydrogenation of ethyl benzoylacetate with R=trimethylsilane (5,... 

BINAP was introduced by Noyori [18], It has been particularly explored for reduction with ruthenium catalysts. While the first generation rhodium catalysts exhibited excellent performance with dehydroamino acids (or esters), the second generation of hydrogenation catalysts, those based on ruthenium /BINAP complexes, are also highly enantioselective for other prochiral alkenes. An impressive list of rather complex organic molecules has been hydrogenated with high e.e. s. 

A further example of ion-exchange of an organometallic complex onto a layered support has been provided by the anion exchange of a sulfonated ruthenium BINAP complex onto the external surface of layered double hydroxides [119]. Although achvihes and enantioselechvities for the hydrogenation of dimethyl itaconate were comparable to the homogeneous catalyst, and catalyst deactivation was not detected, with geraniol as substrate, catalyst deactivation was unavoidable. 

The asymmetric hydrogenation of 2-(6-methoxy-2-naphthyl)acrylic acid using ruthenium-BINAP complexes also yields enantiomerically pure naproxen. 

Diketone 5 is reduced to diol 23 by the method of Noyorv hydrogenation with catalysis by the chiral ruthenium-BINAP complex [(S)-BINAP]RuCE 2-NEt ... 

A remarkable high enantioselectivity was observed in the asymmetric hydrogenation of a cyclic sultam precursor using ruthenium/BINAP (Scheme 63)275. The factors which control this reaction are not fully understood, and it appears to be uniquely suited to... 

From a practical standpoint, it is of interest to devise a one-step synthesis of the catalyst. Since both reactions 2 and 3 are ligand substitution reactions, it is quite conceivable that both steps can be carried out at the same time. When we reacted [Ru(COD)Cl2]n with BINAP and sodium acetate in acetic acid, we indeed obtained Ru(BINAP)(OAc)2 in good yields (70-80%). Interestingly, when the reaction was carried out in the absence of sodium acetate, no Ru(BINAP)(OAe)2 was obtained. The product was a mixture of chloro-ruthenium-BINAP complexes. A 3ip NMR study revealed that the mixture contained a major species (3) (31P [ H] (CDCI3) Pi=70.9 ppm P2=58.3 ppm J = 52.5 Hz) which accounted for more than 50% of the ruthenium-phosphine complexes (Figure 2). These complexes appeared to be different from previously characterized and published Ru(BINAP) species (12,13). More interestingly, these mixed complexes were found to catalyze the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid with excellent rates and enantioselectivities. 

Fig. 6.32. Asymmetric BINAP-ruthenium catalysed hydrogenation of enamide with cis-phenyl...

Rychnovsky and his group have recently developed new synthetic methods that lead to the total syntheses of the polyene macrolides roxaticin [2], roflamycoin [3], and filipin III [4]. The polyol chains of all three natural products were constructed by iterative, stereoselective alkylation of lithiated cyanohydrin acetonides and subsequent reductive decyanation, illustrated here by the synthesis of the polyol framework of filipin III (1) (Scheme I). The bifunctional cyanohydrin acetonide 2, prepared by ruthenium/BINAP catalyzed enantioselective hydrogenation of the corresponding ) -keto ester (BINAP = [ 1,1 -binaphthyl]-2,2 -diylbis(diphenylphosphane)), is deprotonated with LiNEt2 and alkylated with 2-benzyloxy-l-iodoethane. The alkylation product 3 is converted by a Finkelstein reaction into the iodide 4, which is used to alkylate a second... 

Kitamura, M., Tokunaga, M., Pham, T., Lubell, W.D. and Noyori, R., Asymmetric synthesis of a-amino P-hydroxy phosphonic acids via BINAP-ruthenium catalyzed hydrogenation. Tetrahedron Lett., 36, 5769, 1995. 

BINAP complexes of ruthenium are one of the most intriguing catalysts for asymmetric hydrogenation of olefins. Because both R- and 5-forms of BINAP (Figure 10.5) are also commercially available, a series of ruthenium(binap) complexes can be prepared without difficulty [170-172]. For example, Ru(OAc)2(binap) is obtained by the reaction of [RuCLCcod)], with AcONa and BINAP in the presence of Et N [170]. 

Ruthenium(binap) complexes effectively catalyze asymmetric hydrogenation of a-amidocinnamic acids [172], allylic alcohols [173] and acrylic acids with almost quantitative enantiomeric excess [174]. For example, one of the largest-selling anti-inflammatory agents, Naproxen should be supplied as the enantiomerically pure 5-isomer, because the R-isomer is expected to be toxic to the liver. Asymmetric hydrogenation of the precursor by RuCL[(5)- binap] produces 5-Naproxen with 96-98 % ee (eq (47)) [175-176]. 

Furthermore, these ruthenium(binap) complexes are remarkably effective catalysts for the hydrogenation of C=0 bond of 3-ketoesters giving optically active alcohols [175]. 

Taber and co-workers developed a convergent route to ( - )-432 based on the enantioselective hydrogenation of the p-ketoesters 629 and 630 over a ruthenium-BINAP catalyst, which introduced two of the required stereogenic centers with excellent enantioselectivity (ee 98%) (Scheme 83) 485). The products 631 and 632 were transformed into aldehyde 633 and phosphonium salt 634, respectively, after... 

Asymmetric hydrogenation was boosted towards synthetic applications with the preparation of binap 15 by Noyori et al. [55] (Scheme 10). This diphosphine is a good ligand of rhodium, but it was some ruthenium/binap complexes which have found spectacular applications (from 1986 up to now) in asymmetric hydrogenation of many types of unsaturated substrates (C=C or C=0 double bonds). Some examples are listed in Scheme 10. Another important development generated by binap was the isomerization of allylamines into enamines catalyzed by cationic rhodium/binap complexes [57]. This reaction has been applied since 1985 in Japan at the Takasago Company for the synthesis of (-)-menthol (Scheme 10). 

Table 7. 3-Hydroxy Esters by Hydrogenation of 3-Oxo Esters in the Presence of a Ruthenium binap Complex Catalyst ...

A further interesting contrast between rhodium and ruthenium hydrogenation catalysts in kinetic resolution is provided. Most of the published work for the latter relates to ruthenium (BINAP) chemistry but a wider spectrum of allylic alcohols is reduced with satisfactory selectivity the need for an electron-withdrawing group at the a -position is no longer evident. Where a direct comparison can be drawn between rhodium(BINAP) and ruthenium(BlNAP) (Table 6, entry 1), the reduction with a given enantiomer of catalyst gives the opposite enantiomer of a... 

Ruthenium-BINAP complexes have proved to be efficient catalysts for the enantioselective hydrogenation of a,/ -unsaturated carboxylic acids79. Using these catalysts, a variety of a- or /i-disubstitnted substrates have been converted to the corresponding saturated carboxylic acids with good to excellent enantioselectivity and in high yield79. 

---