Asymmetric hydroformylation conditions

Some chiral mono-, acyl- and di-thioureas have been used as ligand for the Rh-catalysed asymmetric hydroformylation of styrene. Although thiourea ligands form inactive systems with [Rh(COD)Cl]2 as the catalyst precursor, in standard conditions (40 °C, 40 bar CO -l- H2 1/1), the cationic Rh complex [Rh(COD)2]Bp4 combined with monothioureas as the ligand showed moderate to good activity (Scheme 29) [114]. 

In 1999, Casado et al. developed heterotetranuclear complexes (TiRh3) depicted in Scheme 10.3 with bridging sullido ligands combined with P-donor ligands. These complexes were further tested as catalysts for the asymmetric hydroformylation reaction of styrene. In this process, [CpTi((/i3-S)3 Rh(tfbb 3] was efficiently active under mild conditions (10 bar, CO/H2 = 1 atm, 353 K). In order to explore the effect of the added phosphorus ligand and the possibilities of this system for the asymmetric hydroformylation of styrene, achiral diphosphines such as dppe (l,2-bis(diphenylphosphine)ethane) and... 

Chiral bis-(binaphthophosphole) (bis(BNP)) ligands have been used in the asymmetric hydroformylation of styrene. In solution, the free diphospholes display fluxional behavior. Consistent with their structure, the reaction of the bis(BNP) compounds with platinum(II) derivatives gives either cis chelate mononuclear complexes or trans phosphorus-bridged polynuclear derivatives. Coordination to platinum enhances the conformational stability of bis(BNP)s and diastereomeric complexes can be detected in solution. In the presence of SnCl2, the platinum complexes give rise to catalysts that exhibit remarkable activity in the hydroformylation of styrene. Under optimum conditions, reaction takes place with high branched selectivity (80-85%) and moderate enantio-selectivity (up to 45% ee). 

A chiral diphosphite based on binaphthol, coordinated with rhodium (I) forming a nine-member ed ring, led to an efficient hydroformylation of vinylarenes, although moderate ees were obtained (up to 46%) at mild pressure and temperature reaction conditions.364 Chiral diphosphites and phosphinite-phosphites derived from spiro[4.4]nonane-l,6-diol were synthesized. Using these catalysts in the asymmetric hydroformylation of styrene, high regioselectivity (97%) and... 

Chiral thioureas have been synthesized and used as ligands for the asymmetric hydroformylation of styrene catalyzed by rhodium(I) complexes. The best results were obtained with /V-phenyl-TV -OS )-(l-phenylethyl)thiourea associated with a cationic rhodium(I) precursor, and asymmetric induction of 40% was then achieved.387,388 Chiral polyether-phosphite ligands derived from (5)-binaphthol were prepared and combined with [Rh(cod)2]BF4. These systems showed high activity, chemo- and regio-selectivity for the catalytic enantioselective hydroformylation of styrene in thermoregulated phase-transfer conditions. Ee values of up to 25% were obtained and recycling was possible without loss of enantioselectivity.389... 

Since the discovery and development of highly efficient Rh catalysts with chiral diphosphites and phosphine-phosphites in the 1990s, the enantioselectivity of asymmetric hydroformylation has reached the equivalent level to that of asymmetric hydrogenation for several substrates. Nevertheless, there still exist substrates that require even further development of more efficient chiral ligands, catalyst systems, and reaction conditions. Diastereoselective hydroformylation is expected to find many applications in the total synthesis of complex natural products as well as the syntheses of biologically active compounds of medicinal and agrochemical interests in the near future. Advances in asymmetric hydrocarboxylation has been much slower than that of asymmetric hydroformylation in spite of its high potential in the syntheses of fine chemicals. 

Thus transition metal complexes capable of effecting cyanation reactions on aromatic nuclei under mild conditions have been discovered Cassar et al. describe such a catalytic system. The past few years have also seen the discovery of asymmetric catalysis. Asymmetric catalysts contain optically active ligands and, like enzymes, can promote catalytic reactions during which substantial levels of optical activity are introduced into the products. This volume contains examples of asymmetric hydrogenation and asymmetric hydroformylation catalysis in the papers, respectively, by Knowles et al. and Pino et al. 

An attempt to use the 3-trifluoro-l jR-camphorate complex (86) as a catalyst for the asymmetric hydroformylation of styrene failed as the ligand dissociated rapidly under the reaction conditions.365... 

The majority of studies of asymmetric hydroformylation with rhodium and platinum complexes have made use of DIOP (49) as a ligand. With either the complex [RhCl(CO)(DIOP)] or [RhCl(C2H4)2]2 plus DIOP, styrene was hydroformylated to 2-phenylpropanal with optical yields of only 16%.366 When a-monodeuterostyrene was used as substrate, with DIOP and complex (34) as catalyst, essentially the same optical yield was obtained.367 The same catalyst with non-deuterated styrene under different conditions gave an optical yield of 25%.368... 

That very high optical yields can be obtained in asymmetric hydroformylation has now been demonstrated. Using [PtCl2(-)-(DIOP)] and SnCl2 in benzene solution, careful choice of the reaction conditions permitted the conversion of styrene to (+)-2-phenylpropanal in an optical yield of 95%.376 With DIOP the best result was 35%. Even slight variation of the reaction conditions caused the optical yield obtained with DIPHOL to fall significantly, indicating clearly that to obtain the best possible results in asymmetric catalysis, all reaction parameters must be optimized. 

One of the difficulties in achieving high enantioselectivity in asymmetric hydroformylation is the propensity of chiral 2-arylpropanal to racemize under the reaction conditions. Accordingly, if the chiral aldehyde can be converted to a less-labile derivative in situ, higher enantioselectivity might be anticipated. In fact, when the asymmetric hydroformylation of styrene and its derivatives catalyzed by PtCl2(BPPM)/SnCl2 was carried out in triethyl orthoformate, the... 

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. 

The greater versatility of rhodium catalysts 21) and the promising results obtained in the first experiments in asymmetric hydroformylation 5,22 24) encouraged research in this field. A great number of substrates have been hydroformylated and a relatively large number of chiral ligands have been used. Furthermore, the influence of the reaction conditions on the optical yield has been investigated for some substrates. 

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... 

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