Ruthenium BINAP complexes

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. 

Thus, a synthetic cycle for the formation of enantiomerically pure propargylic alkylated compounds from an achiral propargylic alcohol has been accomplished by starting from the ruthenium-BINAP complex 66 (Scheme 12). This stepwise reaction provides the first synthetic approach to highly enantioselective propargylic substitution reactions. 

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 ... 

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. 

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]. 

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 ...

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. 

Ruthenium/BINAP complexes have been successfully used in the asymmetric reduction of acrylic acids. This methodology has been used to prepare the antiinflammatory drug (S)-Naproxen (2.78) by reduction of the acrylic acid (2.77). Ruthenium/PQ-Phos species catalyse the same transformation with comparable ee. ... 

Shao, L., T. Seki, H. Kawano, and M. Saburi Asymmetric Hydrogenation of Methyl 3,5-Dioxohexanoate Catalysed by Ruthenium-binap Complex A Short Step Asymmetric Synthesis of Dihydro-6-methyl-2H-pyran-2-one. Tetrahedron Letters, 32, 7699 (1991). 

Ketones bearing polar groups one to three carbons away can also be reduced with very high enantioselectivity to the secondary alcohol with ruthenium-BINAP complexes. 

The mechanism of the hydrogenation of a,j -unsaturated carboxylic acids by chiral ruthenium BINAP complexes has been investigated (Scheme 5). The rate-limiting step in methanol at near-ambient temperature is the activation of H2 to give a anionic hydrido complex. The reaction is sensitive to strong acids one equivalent CF3SO3H per Ru prevents catalysis, while base has no effect. Over 90% enantiomeric excess (ee) was achieved. ... 

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