BINAP catalyst

1) Trost s asymmetric nitromethylation was reproduced in the author s laboratory with the cycloheptenyl ester (25°C, 96h, 71% yield, 96% ee), whereas the reaction mixture exploded at 40 °C. 

Some typical examples of PS-PEG resin-supported chiral oxazoline ligands [39], which have aquacatalyhc potential as well as stereoselechve abilihes, are illustrated in Eigure 6.9. 

The rhodium complex 93 coordinated with the chiral phosphoramide hgand 92 was ionically immobihzed on mesoporous aminosilicate AITUD (Eigure 6.10) [40]. AlTUD-93 was used in water, and showed excellent enantiomeric selechvity and activity in asymmetric hydrogenahon. 

(2002) Chemical Reviews, 102, 3385. For a recent review of solid-phase reactions using palladium catalysts, see (a) Uozumi, Y. and Hayashi, T. (2002) Solid-phase palladium catalysis for high-throughput organic synthesis, in Handbook of Combinatorial Chemistry (eds K.C. Nicolaou, R. Hanko and W. Hartwig), Wiley-VCH Verlag GmbH, Weinheim, Chapter 19, pp. 531-584. 

For reviews on aqueous-switching, see (a) Li, C.-J. and Chan, T.-H. (1997) Organic Reactions in Aqueous Media, Wiley-VCH Verlag GmbH, New York. 

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D. 2(S)-(fl-tert-Butoxycarbonyl-a-(R)-hydroxyethyl)-4-(R)-hydroxy-pyrrolidine- 1-carboxylic acid, tert-butyl ester. The identical procedure was followed, in this case using the (,S)-BINAP catalyst (5)-l. Hydrogenation is conducted for 64 hr, and the reaction mixture is then transferred to a 250-mL, round-bottomed flask and concentrated to dryness. The residue is dissolved in 17 mL of methanol and cooled to 15°C. After the slow addition of 7 mL of DI water, the solution is aged for 15 min gradually forming a thin slurry. More DI water (75 mL) is added over 1 hr and the mixture is allowed to stand for an additional 1 hr at 15°C. The resulting crystals (Note 19) are filtered at 15°C, washed with 10 mL of 1 4-MeOH water, and then dried overnight in a vacuum oven (35°C, 686 mm) to yield 7.0 g (70%) of (R)-hydroxy ester 4b (Note 20). 

Reaction Characteristics of Immobilized Ru-BINAP Catalysts in Asymmetric Hydrogenation of Dimethyl itaconate... 

In this work, various Ru-BINAP catalysts immobilized on the phosphotungstic acid(PTA) modified alumina were prepared and the effects of the reaction variables (temperature, H2 pressure, solvent and content of triethylamine) on the catalytic performance of the prepared catalysts were investigated in the asymmetric hydrogenation of dimethyl itaconate (DMIT). 

Fig. 1. shows the P MAS NMR chemical shifts for the immobilized and homogeneous catalyst. The chemical shifts at the -15.2 and -13.7 ppm correspond to PTA while the chemical shifts in the range from 20 and 40 ppm correspond to phosphine oxide. The chemical shifts at the 66 and 118 ppm seems to be those of BINAP ligand, which is confirmed by the spectrum of Ru-BINAP catalyst. This spectrum shows that PTA exist in large amount on the surface of immobilized catalyst and that BINAP ligand is intact after immobilization. 

Reaction experiments were performed at the substrate to catalyst ratios between 250 and 5000 (Table 1). The immobilized catalyst showed a rather constant values of TOP and enantioselectivity in spite of the increase in the S/C ratio, even though these values were slightly lower than those of the homogeneous Ru-BINAP catalyst. After the reaction, the Ru content in the reaction mixture was measured by ICP-AES and was found to be under 2 ppm, the detecting limit of the instrument, indicating the at Ru metal didn t leach significantly during the reaction. These results show that the immobilized Ru-BINAP catalyst had stable activity and enantioselectivity and that the Ru metal complex formed a stable species on the alumina support. 

Effect of reaction conditions on the asymmetric hydrogenation of dimethyl itaconate over immobilized Ru-BINAP catalyst... 

Oxabicyclo [3.2.1]octenes give a poor yield of the ring-opened product in low ee if reacted at room temperature with BU2AIH in the presence of the Ni(COD)2/BINAP catalyst in either toluene or THF solution (Scheme 2-21). However, if the reaction is carried out at 60°C, high yields and enantioselectivities are obtained [78]. Various substitution patterns and protective groups are tolerated (entries 11-15). 

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... 

Enantioselective 1,4-reduction of enones can be done using a copper-BINAP catalyst in conjunction with silicon hydride donors.158 Polymethylhydrosilane (PMHS) is one reductants that is used. 

Krische and coworkers [44] developed a Rh-catalyzed asymmetric domino Michael/aldol reaction for the synthesis of substituted cyclopentanols and cyclohex-anols. In this process, three contiguous stereogenic centers, including a quaternary center, are formed with excellent diastereo- and enantioselectivity. Thus, using an enantiopure Rh-BINAP catalyst system and phenyl boronic acid, substrates 2-108 are converted into the correspondding cyclized products 2-109 in 69-88% yield and with 94 and 95% ee, respectively (Scheme 2.24). 

An efficient dynamic kinetic resolution is observed when an a-bromo- or a-acetylamino-/3-keto phosphate is subjected to the hydrogenation with an Ru-BINAP catalyst under suitable conditions. With RuC12[(A)-BINAP](DMF) (0.18 mM) as the catalyst, a racemic a-bromo-/3-keto phosphonate is hydrogenated at 25 °G under... 

In 2001, Miyaura and Sakuma reported the asymmetric addition of arylboronic acids to a,/3-unsaturated amides in the presence of the Rh(acac)(C2H4)2/(V)-BINAP catalyst (acac = acetylacetonate Scheme 36).112 The... 

Nitroalkenes are good candidates for the rhodium-catalyzed asymmetric 1,4-addition of organoboronic acids. Hayashi et al. reported that the reaction of 1-nitrocyclohexene with phenylboronic acid in the presence of rhodium/ -BINAP catalyst gave 99% ee of 2-phenyl-1-nitrocyclohexane (Scheme 38).117... 

Mikami and Hatano70 demonstrated the efficiency of the dicationic [Pd(MeCN)4](BF4)2/BINAP catalyst system in DMSO with the highly enantioselective synthesis of a variety of quinoline derivatives, including spiro-compound 99 (Equation (63)), resulting from olefin isomerization of the Alder-ene product. 

Asymmetric cyclization was also successful in the rhodium-catalyzed hydrosilylation of silyl ethers 81 derived from allyl alcohols. High enantioselectivity (up to 97% ee) was observed in the reaction of silyl ethers containing a bulky group on the silicon atom in the presence of a rhodium-BINAP catalyst (Scheme 23).78 The cyclization products 82 were readily converted into 1,3-diols 83 by the oxidation. During studies on this asymmetric hydrosilylation, silylrhodation pathway in the catalytic cycle was demonstrated by a deuterium-labeling experiment.79... 

Under a pressure (20 bar) of carbon monoxide, carbonylative silylcarbocyclization of enyne 92 was examined in the presence of a cationic rhodium-BINAP catalyst (Scheme 31).86 Although the enantioselectivity is low, the five-membered carbocycle functionalized with an alkenylsilane moiety and a formyl group was obtained with high selectivity. 

Striking examples of this phenomenon are presented for allyl and homoallyl alcohols in Eqs. (5) to (7). The stereodirection in Eq. (5) is improved by a chiral (+)-binap catalyst and decreased by using the antipodal catalyst [60]. In contrast, in Eq. (6) both antipode catalysts induced almost the same stereodirection, indicating that the effect of catalyst-control is negligible when compared with the directivity exerted by the substrate [59]. In Eq. (7), the sense of asymmetric induction was in-versed by using the antipode catalysts, where the directivity by chiral catalyst overrides the directivity of substrate [52]. In the case of chiral dehydroamino acids, where both double bond and amide coordinate to the metal, the effect of the stereogenic center of the substrate is negligibly small and diastereoface discrimination is unsuccessful with an achiral rhodium catalyst (see Table 21.1, entries 9 and 10) [9]. 

In the hydrogenation of diketones by Ru-binap-type catalysts, the degree of anti-selectivity is different between a-diketones and / -diketones [Eqs (13) and (14)]. A variety of /1-diketones are reduced by Ru-atropisomeric diphosphine catalysts to indicate admirable anti-selectivity, and the enantiopurity of the obtained anti-diol is almost 100% (Table 21.17) [105, 106, 110-112]. In this two-step consecutive hydrogenation of diketones, the overall stereochemical outcome is determined by both the efficiency of the chirality transfer by the catalyst (catalyst-control) and the structure of the initially formed hydroxyketones having a stereogenic center (substrate-control). The hydrogenation of monohydrogenated product ((R)-hydroxy ketone) with the antipode catalyst ((S)-binap catalyst) (mis-... 

With an increase of conversion, the enantiopurity of unreacted (S)-substrate increases and the diastereoselectivity of the product decreases. Using Ru-((S)-binap)(OAc)2, unreacted (S)-substrate was obtained in more than 99% ee and a 49 1 mixture of anti-product (37% ee (2R,iR)) at 76% conversion with a higher kR ks ratio of 16 1 [46]. In the case of a racemic cyclic allyl alcohol 24, high enantiopurity of the unreacted alcohol was obtained using Ru-binap catalyst with a high kR ks ratio of more than 70 1 [Eq. (16)] [46]. In these two cases, the transition state structure is considered to be different since the sense of dia-stereoface selection with the (S)- or the (R)-catalysts is opposite if a similar OH/ C=C bond spatial relationship is assumed. 

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 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]. 

One of the first applications of the then newly developed Ru-binap catalysts for a,/ -unsaturated acids was an alternative process to produce (S)-naproxen. (S)-Naproxen is a large-scale anti-inflammatory drug and is actually produced via the resolution of a racemate. For some time it was considered to be one of the most attractive goals for asymmetric catalysis. Indeed, several catalytic syntheses have been developed for the synthesis of (S)-naproxen intermediates in recent years (for a summary see [14]). The best results for the hydrogenation route were obtained by Takasago [69] (Fig. 37.15), who recently reported that a Ru-H8-binap catalyst achieved even higher activities (TON 5000, TOF 600 h 1 at 15 °C, 50 bar) [16]. 

R)-l,2-Propanediol is an intermediate for (S)-oxafloxazin, a bactericide which until recently was sold as a racemate. The (R)-diol is now produced by Takasago via hydrogenation of hydroxyacetone (see Fig. 37.23) using a Ru-Tol-binap catalyst on a 50 t y 1 scale [92 b[. Recently, it was reported that segphos - a newly developed biaryl diphosphine - shows even better results, achieving >98% ee and TON and TOF of 10000 and 1400 h, respectively [16, 93]. 

Asymmetric hydrogenation of ketones is one of the most efficient methods for making chiral alcohols. Ru-BINAP catalysts are highly effective in the asymmetric hydrogenation of functionalized ketones,54,55 and this may be used in the industrial production of synthetic intermediates for some important antibiotics. The preparation of statine 65 (from 63b R = i-Bu) and its analog is one example (Scheme 6-28).56 Table 6-6 shows the results when asymmetric hydrogenation of 63 catalyzed by RuBr2[(R)-BINAP] yields threo-64 as the major product. 

When the C=N bond is fixed in a ring system in which no (E)/(Z) isomerization can take place, the asymmetric hydrogenation of the C=N bond can be highly enantioselective. Oppolzer et al." found that cyclic sulfonimide was hydrogenated with an Ru(BINAP) catalyst to give a product with essentially quantitative optical yield (Scheme 6-45). 

Figure 8-5. Proposed mechanism for the catalytic arylation of 2,3-dihydrofuran with phenyl triflate in the presence of Pd(OAc)2-(i )-BINAP catalyst.

Cl2Zr(H5C5B-0-)(/i-binap) catalyst for oligomerization of G2H4 in S, H, B, C 105... 

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