Supercritical catalytic asymmetric hydrogenations

The effects of added C02 on mass transfer properties and solubility were assessed in some detail for the catalytic asymmetric hydrogenation of 2-(6 -meth-oxy-2 -naphthyl) acrylic acid to (Sj-naproxen using Ru-(S)-BINAP-type catalysts in methanolic solution. The catalytic studies showed that a higher reaction rate was observed under a total C02/H2 pressure of ca. 100 bar (pH2 = 50bar) than under a pressure of 50 bar H2 alone. Upon further increase of the C02 pressure, the catalyst could be precipitated and solvent and product were removed, at least partly by supercritical extraction. Unfortunately, attempts to re-use the catalyst were hampered by its deactivation during the recycling process [11]. 

Catalytic asymmetric hydrogenations have also been performed in supercritical carbon dioxide [79-81]. For example, a-enamides were hydrogenated in high enantioselectivities comparable to those observed in conventional solvents, using a cationic rhodium complex of the EtDuPHOS ligand (Fig. 7.24) [79]. More recently, catalytic asymmetric hydrogenations have been performed in scC02 with... 

Recent work by several research groups has shown that supercritical fluids can be superior to other solvents for several chemical processes. For example, DeSimone has demonstrated the ability of supercritical CO2 to replace Freons in the free radical polymerization of fluorinatkl acrylate monomers. 34) Noyori has shown that significant rate enhancements can be achieved in supercritical carbon dioxide relative to other solvents for the homogeneous catalytic hydrogenation of carbon dioxide to either formic acid or its derivatives in the presence of triethylamine or triethylamine/methanol respectively, (equation 1). (55-57) As discussed below, we have recently demonstrated that improved enantioselectivities can be achieved in supercritical carbon dioxide for the catalytic asymmetric hydrogenation of several enamides. 5 8)... 

Supercritical carbon dioxide represents an inexpensive, environmentally benign alternative to conventional solvents for chemical synthesis. In this chapter, we delineate the range of reactions for which supercritical CO2 represents a potentially viable replacement solvent based on solubility considerations and describe the reactors and associated equipment used to explore catalytic and other synthetic reactions in this medium. Three examples of homogeneous catalytic reactions in supercritical CC are presented the copolymerization of CO2 with epoxides, ruthenium>mediated phase transfer oxidation of olefins in a supercritical COa/aqueous system, and the catalyic asymmetric hydrogenation of enamides. The first two classes of reactions proceed in supercritical CO2, but no improvement in reactivity over conventional solvents was observed. Hythogenation reactions, however, exhibit enantioselectivities superior to conventional solvents for several substrates. 

Burk MJ, Feng S, Gross MF et al (1995) Asymmetric catalytic hydrogenation reactions in supercritical carbon dioxide. J Am Chem Soc 117(31) 8277-8278... 

Jessop and co-workers have pointed out that homogeneous catalysis in supercritical fluids can offer high rates, improved selectivity, and elimination of mass-transfer problems.169 They have used a ruthenium phosphine catalyst to reduce supercritical carbon dioxide to formic acid using hydrogen.170 The reaction might be used to recycle waste carbon dioxide from combustion. It also avoids the use of poisonous carbon monoxide to make formic acid and its derivatives. There is no need for the usual solvent for such a reaction, because the excess carbon dioxide is the solvent. If the reaction is run in the presence of dimethy-lamine, dimethylformamide is obtained with 100% selectivity at 92-94% conversion.171 In this example, the ruthenium phosphine catalyst was supported on silica. Asymmetric catalytic hydrogenation of dehydroaminoacid derivatives (8.16) can be performed in carbon dioxide using ruthenium chiral phosphine catalysts.172... 

Table 5.15. Supercritical fluids (SCF s) most suitable for asymmetric catalytic hydrogenation.

In addition, as discussed above, oxidation reactions and reactions which use CO2 as a reagent as well as a solvent are worth investigating. Examples of both are discussed below. Finally, electrophilic processes may be advantageously transferred to supercritical CO2, as demonstrated by the improved isomerization of C4-C12 paraffins catalyzed by aluminum bromide. 2,44) Below, we describe three catalytic reactions which appear promising by these criteria asymmetric catalytic hydrogenation of enamides, ruthenium-catalyzed two-phase oxidation of cyclohexene, and the catalytic copolymerization of CO2 with epoxides. 

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