Continuous catalytic asymmetric hydrogenation in supercritical CO2

Abstract

Continuous hydrogenation in supercritical fluids has been shown to be a technically viable alternative to traditional batch-wise methodologies. Clearly, the next stage of development of this technology is the application of immobilised enantioselective catalysis in the preparation of optically active products. Enantioselective hydrogenation has been successfully carried out in supercritical carbon dioxide using batchtype reactors but has yet to be efficiently carried out continuously. Here we examine an established method of catalyst immobilisation and demonstrate its suitability for application in continuous reactors using supercritical carbon dioxide as solvent.

Asymmetric Catalytic Synthesis of Organic Compounds using Metal Complexes in Supercritical Fluids

“…In the second and subsequent runs, the conversion remained high (97-98 %) and the ee (87-91 %) was somewhat enhanced compared with the first run An alternative to immobilising the catalyst within an ionic liquid for a continuous flow process using scCO 2 as the mobile phase, which does not appear to have been demonstrated for asymmetric hydrogenation, is to support the catalyst on a solid support. [31] the hydrogenation of dimethyl itaconate has been demonstrated with the transport of substrates and products being effected by flowing scCO 2 (60-120 bar). The best results were obtained at 60 8C (conversion = 66.5 %, ee = 63 %) and continued unchanged for at least 8 h. Neither rhodium nor tungsten (< 1 ppm) was detected in the product recovered by decompression of the scCO 2 , although catalyst leaching (Rh 7 ppm, W 1 ppm) did occur at higher temperatures (100 8C).…”

“…In order to render it soluble in scCO 2 , it has been modified by attaching fluorous ponytails (6, Scheme 3). With C 6 F 13 C 2 H 4 -groups on the phenyl rings of the phosphine moiety, the rhodium catalyst precursor, [RhH(CO) 2 (6)] was sufficiently soluble in scCO 2 for 31 P NMR studies to reveal that it exists exclusively with the P atoms occupying one axial (phosphite P) and one equatorial site (phosphine P), like its unfluorinated analogue. [10] There is no interaction of the hydride with CO 2 .…”

“…The best results were obtained at 60 8C (conversion = 66.5 %, ee = 63 %) and continued unchanged for at least 8 h. Neither rhodium nor tungsten (< 1 ppm) was detected in the product recovered by decompression of the scCO 2 , although catalyst leaching (Rh 7 ppm, W 1 ppm) did occur at higher temperatures (100 8C). [31] More conventional heterogeneous catalysts (cinchonidine-modified Pt on alumina) have been employed for the continuous hydrogenation of ethyl pyruvate using "supercritical" ethane (T c : 328C, P c : 48 bar) as the transport vector. [32] In fact, the system exhibited regions in which it was monophasic and regions where it was biphasic (a liquid phase was present) even well above the critical parameters of pure ethane.…”

Continuous Asymmetric Hydrogenation in Supercritical Carbon Dioxide using an Immobilised Homogeneous Catalyst

“…Previously we have reported the asymmetric hydrogenation of dimethyl itaconate [26] (DMIT), using an established immobilised homogeneous asymmetric catalyst, [27] in continuous flow scCO 2 , Scheme 1. DMIT is often used as a prototypical molecule when evaluating new asymmetric hydrogenation systems.…”

“…DMIT is often used as a prototypical molecule when evaluating new asymmetric hydrogenation systems. [28] In this particular case, [26] we used the catalyst [27] on g-alumina via a phosphotungstic acid linker H 3 O 40 PW 12 . Although respectable conversions (66 %) and ee (63 %) were achieved [26] the true power of this composite catalyst system lies in the fact that it can be used with a wide range of chiral bisphosphine ligands, Scheme 2.…”