BINAP ruthenium catalyst

Ruthenium complexes containing this ligand are able to reduce a variety of double bonds with e.e. above 95%. In order to achieve high enantioselectivity, the reactant must show a strong preference for a specific orientation when complexed with the catalyst. This ordinarily requires the presence of a functional group that can coordinate with the metal. The ruthenium-BINAP catalyst has been used successfully with unsaturated amides,23 allylic and homoallylic alcohols,24 and unsaturated carboxylic acids.25... 

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... 

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... 

The achievements of the Noyori group using ruthenium BINAP catalysts are extensive and remarkable. Simple alkenes are reduced whether conjugated or not the very efficient synthesis of the analgesic and anti-inflammatory naproxen 25 from an unsaturated acid 24 resembling 1 is a good example. 

Similar kinetic resolution of Baylis-Hillman adducts may be effected by ruthenium BINAP catalysts, with comparable efficiency. But for some cyclic allylic alcohols, the level of discrimination between the enantiomers is so high that pre-paratively useful routes have been developed to the reactant and both hands of the product in the course of a single set of experiments [70]. In related fashion... 

Scheme 7.9. Catalytic cycle proposed for the asymmetric reduction of functionalized ketones by ruthenium BINAP catalyst (after ref. [76]).

Dendrimeric enlargement was used for restricting a ruthenium-BINAP catalyst in one phase [39]. Reaction was performed in a homogeneous 1 1 mixture of ethanol/hexane. Phase separation followed the addition of water. The Cjq tails render the catalyst insoluble in efhanol/water. The catalyst was re-used twice with a minor decrease in selectivity and activity. 

Further examples also show particularly impressive selectivity. Kiindig has used the cationic iron catalyst (8.83) in the Diels-Alder reaction to give cycloadduct (8.85). The ruthenium (BINAP) catalyst (8.86) effects the Diels-Alder reaction of cyclopentadiene with 2-substituted acrylates with ees up to 99%. Kobayashi has shown that lanthanide and scandium triflate complexes of BINOL with 1,2,6-trimethylpiperidine, formulated as complex (8.87), are effective with oxazohdinone-based substratesand gives good selectivity in the formation of the Diels-Alder product (8.52). 

Huorous compounds are also potentially useful as additives to promote organic reactions in carbon dioxide. For example, a fluorous alcohol RfCH20H assists asymmetric hydrogenations with non-fluorous ruthenium BINAP catalysts, and a fluorous aryl alkyl ether (C8F17C6H4-P-OC12H25) does so in scandium-triflate-catalyzed aldol and Friedel-Crafts reactions. These additives are presumed to act as solubilizers or emulsifiers to promote contact among the various reaction components. Since they are fluorous, they can be readily recovered from the otherwise organic reaction mixtures for reuse. 

We will explore the use of the ruthenium BINAP catalysts in the enantioselective synthesis of chiral drugs in Chapter 14. 

The most recent route to menthol comes from BASF. [130] The main starting material is citral cf. section 3.2.3), which first is hydrogenated to produce a 1 4 mixture of nerol and geraniol. This mixture is then separated by distillation. The enantioselective hydrogenation with a ruthenium-BINAP catalyst and subsequent oxidation leads to (+)-(fl)-citronellal, which may be converted in two stages by known methods into (-)-menthol. 

Takasago Perfumery Ltd. manufactures optically pure (Jl)-muscone from the racemic compound by way of its silyl enol ether which is dehydrosUylated with palladium acetate to the pure (Z)-enone. [202] The enantioselective hydrogenation with ruthenium-BINAP catalysts finally gives the enantiomericaUy pure product. [203]... 

Such dynamic kinetic resolutions can also be conducted on cyclic jS-keto esters. Two examples are shown in Equations 15.59 and 15.60. Such cyclic substrates contain a stereocenter at the carbon between the two carbonyl groups. Again, a dynamic kinetic resolution of these substrates by hydrogenation occurs selectively to form predominantly a single stereoisomer. This reaction occurs to form a 99 1 ratio of diaste-reomers and 93% enantioselectivity of the major diastereomer in the presence of a ruthenium-BINAP catalyst. The positions of the keto and ester functionalities can also be reversed. Reduction of the cyclic p-keto ester in Equation 15.60 generates, in this case, the cis diastereomer with high diastereoselectivity and enantioselectivity. ... 

Ruthenium-BINAP Catalysts. Ruthenium-catalyzed hydrogenations have been directed toward ketone reduction rather than alkene reduction, and... 

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