Binaphos ligands, asymmetric hydroformylation

Takaya and co-workers in 1993 were the first to report on asymmetric hydroformylation using phosphite-phosphine ligands [59]. In an attempt to combine the effectiveness of the BINOL chemistry for asymmetric catalysis and the effectiveness of the phosphite moiety for asymmetric hydroformylation, they developed the (.R,S)-BINAPHOS ligand 3, which turned out to be very efficient (Fig. 6). 

Perfluoroalkyl-substituted BINAPHOS ligand 29c was also developed for the asymmetric hydroformylation of vinyl arenes in SCCO2. With this ligand regio-and enantio-selectivity (ee s up to 93.6%) were high without the need for hazardous organic solvents [63,64],... 

The phosphine-phosphite BINAPHOS ligand was first used in the Rh-catalyzed asymmetric hydroformylation of heterocyclic olefins such as 2,5-dihydrofuran, 3-pyrroline derivatives, and 4,7-dihydro-1,3-dioxepin derivatives. It provided the optically active aldehydes as single products with enantioselectivity between 64-76% ee. In the hydroformylation of 2,5-di-... 

Asymmetric rhodium catalysts are discussed in section 8.6. The most interesting ligand discovered for asymmetric hydroformylation is undoubtedly BINAPHOS, introduced by Takaya [18], but certain diphosphites also give high enantioselectivities [19,20],... 

Figure 7 A rhodium complex of chiral phosphine-phosphite ligand (H,S)-BINAPHOS used as a catalyst for asymmetric hydroformylation.

As a unique medium for asymmetric hydroformylation, supercritical carbon dioxide has recently been examined, which can be carried out in an extremely low catalyst concentration. The reactions of styrene (16a) and pentafluorostyrene (16e) catalyzed by Rh-BINAPHOS appear to give mixed results that are highly dependent on the reaction conditions [77,78], Enantioselectivity up to 92-95% ee for 16a or 85 % ee for 16e has been observed [78]. A biphasic reaction system has also been examined for the reaction using Rh(acac)(CO)2 with a sulfonated diphosphine ligand BINAS [79], The reaction proceeds smoothly at 40°C and 100 atm in high conversion with excellent branched aldehyde selectivity (95%), but enantioselectivity is very low (18% ee). The use of these newer reaction conditions is still in the very early stage and further development is expected in the next decade. 

Other approaches that have been suggested include catalytic asymmetric hydroformylation of 2-methoxy-6-vinylnaphthalene (6) using a rhodium catalyst on BINAPHOS ligand followed by oxidation of the resultant aldehyde 7 to yield 5-naproxen (Scheme 6.3).22 However, the tendency of the aldehyde to racemize and the co-generation of the linear aldehyde isomer make the process less attractive. Other modifications related to this process include catalytic asymmetric hydroesterification,23 hydrocarboxylation,24 and hydrocyanation.25... 

ESPHOS (178), a chiral bis(diazaphospholidine) ligand developed by the Wills group, has been found to be active in the asymmetric hydroformylation of vinyl acetate.231 (This ligand system is being commercialized by Stylacats.) Enantioselectivities of 87-89% ee and regioselectivities of 95/5 (b/1) have been obtained at 120 psig pressure of syn gas.232 Unfortunately, the substrate scope is not as broad as BINAPHOS. 

Hydrogenation, by far, has garnished the best results in homogeneous asymmetric catalysis, but efforts continue in the development of asymmetric hydroformylation. Several new ligands (Binaphos, Kelliphite, and ESPHOS) have been designed that have raised the level of enantioselectivities to 90-94% ee and regioselectivities to 88-99% in favor of the branched isomer. 

The asymmetric hydroformylation of alkenes is catalyzed by a number of Rh and Pt complexes with chiral chelating ligands.69 A number of binaphthyl-based chiral phosphites10 and mixed phosphine-phosphite ligand like (22-XXIV) [ // ,S)-BINAPHOS ] have been found particularly effective, e.g., in the asymmetric hydroformylation of styrene in >90% optical yield.71... 

Asymmetric hydroformylation catalyzed by highly cross-linked polystyrene-sup-ported RS-BINAPHOS-Rh(I) complexes (phosphin-phosphite catalysts including dinaphtho-l,3,2-dioxaphosphepine ligands) 03YGK694. 

Takaya and Nozaki invented an unsymmetrical phosphin-phosphite ligand, (R,S)-BINAPHOS, which was used in the Rh(l)-catalyzed asymmetric hydroformylation of a wide range of prochiral olefins, with excellent enantioselectivities [120, 155]. A highly crosslinked PS-supported fR,S)-BINAPHOS(257)-Rh(I) complex was prepared and applied to the same reaction (Scheme 3.83) [156]. Using the polymeric catalyst, the asymmetric hydroformylation of olefins was performed in the absence of organic solvents. The reaction of cis-2-butene, a gaseous substrate, provided (S -methylbutanal with 100% regioselectivity and 82% ee upon treatment with II, and CO in a batchwise reactor equipped with a fixed bed. 

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