Rh BINAPHOS

Isobutylphenyl)propanal with 92% ee is obtained from p-isobutylstyr-ene using the Rh-BINAPHOS catalyst, which is the precursor of anti-inflammatory drug (5)-ibuprofen. " In a similar manner, the precursor of (5)-naproxen is obtained... 

Asymmetric Hydroformylation of Other Olefins In contrast to vinylarenes, the asymmetric hydroformylation of aliphatic alkenes, especially 1-aIkenes, is still very challenging, although the Rh-BINAPHOS (5a) catalyst has made significant improvement in enantioselectivity as compared to that achieved by previous catalysts. Representative results are summarized in Scheme 4.5. The reaction of... 

Takasago group and Nozaki reported the synthesis of the 1-methylcarbapenem intermediate 78 by hydroformylation of the 4-vinyl / -lactam, (3BINAPHOS system followed by oxidation (Scheme 8, Table 13, entry Slightly better selectivities are... 

V)-2-(4-Isobutylphenyl)propanal (17b) with 92% ee is obtained from p-isobutylstyrene (16b) by using the Rh-BINAPHOS catalyst, which is the precursor of antiinflammatory drug (S)-ibuprofen (entry 15) [19,64,65]. In a similar manner, the precursor of (S)-naproxen is obtained with 85% ee and excellent regioselectivity in the reaction of 16c catalyzed by Rh-(diphosphite 9) complex (entry 16) [25], Pentafluorostyrene (16e) is converted to the corresponding branched aldehyde 17e by the catalysis of the Rh-BINASPHOS complex with... 

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. 

Reaction of cinnamyl alcohol (36) catalyzed by Rh-BINAPHOS gives the product as lactol 37 (1 1 mixture of diastereomers at the anomeric carbon) with high enantioselectivity (88% ee) [94] (Scheme 7.7). The enantiopurity of lactol 37 is determined by oxidizing the lactol to the corresponding lactone 38. In the same manner, homoallyl alcohol (39) is converted to the corresponding a-methyl-y-butyrolactone (42) with 73% ee via lactol 40 [94] (Scheme 7.7). However, the regioselectivity of the reaction is not favorable to the formation of 40, forming achiral 6-lactol 41 as the major product. 

Rh-BINAPHOS catalyst system mechanisms, 11, 444 Asymmetric hydrogenation in C-H bond formation... 

The production of 10-methylcarbapenem (184), which has antibacterial activities and enhanced chemical and metabolic stability, has been reported by asymmetric hydroformylation of 4-vinyl-0-lactams 185 catalyzed by Rh-BINAPHOS complexes (Scheme 12.75). Under optimized conditions, the observed regioselectivity was 55/45 (b/1), enantioselectivity was 93/7 (1860 18600 at 95% conversion, and S/C = 1000.233... 

Figure 29 In situ P H HPNMR spectra (phosphine region) of the co-polymerisation of CO with styrene catalysed by Rh-BINAPHOS (a) in a zirconiaNMR tube, recorded at 202.5 MHz (b) in a bubble column reactor, recorded at 81.0 MHz. Note only the alkyl intermediate 2 is observed in the unmixed HPNMR tube due to inefficient mass transfer of CO into solution. In the bubble column, delivery of CO to the catalyst is efficient, and so the acyl intermediate 1 is also observed ...

Table 7.18 Sequential asymmetric hydroformylation of alkenes catalyzed by crosslinked polystyrene-supported Rh-BINAPHOS 60 in pulsed flowing SCCO2.

Solinas M, Gladiali S, Marchetti M (2005) Hydroformylation of aryloxy ethylenes by Rh/BINAPHOS complex - catalyst deactivation path and application to the asymmetric synthesis of 2-aryloxypropanoic acids. J Mol Catal A 226 141-147... 

The models which explain the enantiofacial selection in the Rh-BINAPHOS systems assume that the aUcene insertion in the Rh-H bond is irreversible. The old model proposed by Consiglio and Pino [46] has been used by Takaya [ 14]. The model involves partitioning the space around the metal center into four quadrants and for each of these the steric encumbrance is estimated. This simple model differentiates between the enantiofaces of the alkene and it has often been successfully applied. For RhH(CO)2(R,S-BINAPHOS) the aldehyde enantiomer expected from this model was indeed obtained [15]. 

In a rare study on the stability of chiral ligands employed in AHF, Solinas and Gladiah [34] found a dramatic decrease in enantioselectivity accompanied by an increase of the Hb ratio during the hydroformylation of styrene with a Rh(BINAPHOS) catalyst (Figure 2.44). They explained this effect by the reaction of the chiral ligand with the formed aldehyde, but unfortunately no detailed information about the degradation products was given. 

Similar to the reaction with 2,3-dihydrofurans as a substrate, related 2,3-pyrrohns may also isomerize under hydroformylation conditions into the corresponding 2,5-isomers (Scheme 4.28). The latter, in turn, are transformed into pyrrolidin-3-carbaldehyde [44]. An example of the a-regioselective reaction was given by the Nozaki group in the framework of an asymmetric hydroformylation [21a]. The A-Boc protected substrate was reacted with syngas in the presence of a chiral Rh(BINAPHOS) catalyst to give the desired carbaldehyde with a moderate a/p-ratio. 

P-Halogen Substituted Olefins Hydroformylation of 3,3,3-trifluoropropene with Rh(BINAPHOS) gives the corresponding branched aldehyde in excellent regio-and enantioselectivity (Scheme 4.86) [36]. The comparison of results obtained with the enantiomeric ligand gives an illustrative impression of the high reproducibility of the transformation. 

Rhodium-Catalyzed Asymmetric Hydroformylation 77 Table 3.5 Several substrates efficiently hydroformylated using Rh-BINAPHOS system. 

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