Ruthenium diphosphine catalysts

The DuPHOS/potassium tert-butoxide system was also used to hydrogenate these substrates, in addition to substrates 19 and 22 (Fig. 30.6 Table 30.4) [6], Under normal conditions, ruthenium-diphosphine catalysts are known to be unreactive with styrenes however, in the presence of potassium tert-butoxide, the substrates 15-22 were hydrogenated with high conversion. 

A range of other terminal alkenes has been hydrogenated with ruthenium-diphosphine catalysts. The first set of substrates (Fig. 30.7 Table 30.5) was hydrogenated with Ru-BINAP in dichloromethane (DCM) at 30°C. Products of double bond migration were also detected [5]. 

Madec, J., Pfister, X., Phansavath, P, Ratovelomanana-Vidal, V, and GeneL J.P, Asymmetric hydrogenation reactions using a practical in situ generation of chiral ruthenium-diphosphine catalysts from anhydrous RuClj, Tetrahedron, 57, 2563, 2001. 

For enantioselective transfer hydrogenations using formic acid/triethylamine and ruthenium diphosphine catalysts see J. M. Brown, H. 

Kinetic resolution results of ketone and imine derivatives are indicated in Table 21.19. In the kinetic resolution of cyclic ketones or keto esters, ruthenium atrop-isomeric diphosphine catalysts 25 induced high enantiomer-discriminating ability, and high enantiopurity is realized at near 50% conversion [116, 117]. In the case of a bicyclic keto ester, the presence of hydrogen chloride in methanol served to raise the enantiomer-discriminating ability of the Ru-binap catalyst (entry 1) [116]. 

The bis-indole diphosphine delivers the best ee and as the heterocyclic units are also electron rich aromatics this also gives the added advantage of the highest activity of the catalyst system. This overcomes one drawback often encountered, that high hydrogen pressures are frequently needed for ruthenium-based catalysts. 

The reductions of /i,<5-dikcU)cslcrs 51 with ruthenium/BINAP catalysts result in formation of the /raw.v-diols 52 in high selectivity and e.e. Experiments have revealed that it is likely that the reduction takes place via the coordination of both ketones to the metal—the selectivity matches that obtained in the reduction of /1-diketones222. Biaryl diphosphines closely related in structure to BINAP have also given excellent results223. Other excellent... 

Preparation of the JST class (see Section 12.3.4) of the ruthenium-diphosphine-diamine complex, [(PhanePhos)Ru(diamine)Cl2], produced highly active and enantioselective catalysts in the reduction of aryl methyl ketones (128, R = Me), as well as a,P-unsaturated ketones.162-163 Higher... 

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]. 

Genet, J.P, Pinel, C., Ratovelomanana-Vidala, V., MaUarL S., Pfister, X., Cano De Andrade, M.C., and Laffitte, J.A., Novel, general synthesis of the chiral catalysts diphosphine-ruthenium (II) diallyl complexes and a new practical in situ preparation of chiral ruthenium (II) catalysts. Tetrahedron Asymmetry, 5, 665, 1994. 

Asymmetric hydrogenation was catalyzed by ruthenium clusters containing atropoisomeric diphosphines. Catalyst precursors were Ru4(/t-H)4(CO)]o (S)-(-)-BINAP (BINAP = 2,2 -bis(diphenylphosphino)-l,l -binaphthyl) and Ru4(/t-H)4(CO)io (S)-(-)-MOBIPH (MOBIPH = 2,2 -bis(diphenylphosphino)-6,6 -dimethoxy-l,l -diphenyl). Substrates included prochiral alkenes such as tiglic acid, (Z)- and ( )-2-methylbutendioic acids, ( )-2-methylbute-noic acid, and acetophenone. Optical purities up to 38% were obtained, but most results were low ee s. 

When the cobalt catalyst was combined with a diphosphine-modified ruthenium hydrogenation catalyst at 103 bar total syngas pressure, a tandem reaction could be realized that gave directly 1,4-PDO in 71% yield (Scheme 6.107) [19]. ... 

In 2000, these authors also developed a very efficient diphosphine-bithiophene ligand, tetraMe-BITIOP, which is depicted in Scheme 8.29. The ruthenium complex of this electron-rich diphosphine was used as the catalyst in asymmetric hydrogenation reactions of prostereogenic carbonyl functions of a-... 

Manufacture of ruthenium precatalysts for asymmetric hydrogenation. The technology in-licensed from the JST for the asymmetric reduction of ketones originally employed BINAP as the diphosphine and an expensive diamine, DAIPEN." Owing to the presence of several patents surrounding ruthenium complexes of BINAP and Xylyl-BINAP, [HexaPHEMP-RuCl2-diamine] and [PhanePHOS-RuCl2-diamine] were introduced as alternative catalyst systems in which a cheaper diamine is used. Compared to the BINAP-based systems both of these can offer superior performance in terms of activity and selectivity and have been used in commercial manufacture of chiral alcohols on multi-100 Kg scales. 

The sense of diastereoselectivity in the dynamic kinetic resolution of 2-substi-tuted / -keto esters depends on the structure of the keto ester. The ruthenium catalyst with atropisomeric diphosphine ligands (binap, MeO-biphep, synphos, etc.) induced syn-products in high diastereomeric and enantiomeric selectivity in the dynamic kinetic resolution of / -keto esters with an a-amido or carbamate moiety (Table 21.21) [119-121, 123, 125-127]. In contrast to the above examples of a-amido-/ -keto esters, the TsOH or HC1 salt of /l-keto esters with an a-amino unit were hydrogenated with excellent cwti-selectivity using ruthenium-atropiso-... 

In summary, the asymmetric hydrogenation of olefins or functionalized ketones catalysed by chiral transition metal complexes is one of the most practical methods for preparing optically active organic compounds. Ruthenium and rhodium-diphosphine complexes, using molecular hydrogen or hydrogen transfer, are the most common catalysts in this area. The hydrogenation of simple ketones has proved to be difficult with metallic catalysts. However,... 

Maraval et al 39) synthesized core- and periphery-functionalized ruthenium and palladium dendritic diphosphines (Fig. 12) that were applied in three reactions (Stille coupling, Knoevenagel condensation, and diastereoselective Michael addition). The catalyst was recovered by using the precipitation strategy. 

In a related report, ruthenium-catalyzed enantioselective hydrogenation of 3-keto esters was utilized to prepare the crucial alcohol intermediate 36 (Scheme 14.16). The required (3-keto ester 49 was readily prepared from commercial thiophene carboxylic acid 40. Hydrogenation of 49 then led to the desired (S)-alcohol 50 in quantitative yield and 90% enantiomeric excess, catalyzed by a chiral diphosphine-ruthenium complex generated in situ. Catalyst-substrate ratios used were as low as 1/20,000, rendering this approach amenable to industrial application. Alcohol 50 was then converted to known intermediate 36 in three steps and 60% overall yield. 

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