Inverted supercritical carbon dioxide/aqueous biphasic media for rhodium-catalyzed hydrogenation reactions

An inverted supercritical carbon dioxide (scCO(2))/aqueous biphasic system has been used as reaction media for Rh-catalysed hydrogenation of polar substrates. Chiral and achiral CO2-philic catalysts were efficiently immobilised in scCO(2) as the stationary phase, while the polar substrates and products were contained in water as the mobile phase. Notably, product separation and catalyst recycling were conducted without depressurisation of the autoclave. The catalyst phase was reused several times with high conversion and product recovery of more than 85%. Loss of rhodium and phosphorus by leaching were found to be below the detection limit after the first two cycles in the majority of repetitive experiments. The reaction conditions were optimised with a minimum of experiments by using a simplex algorithm in a sequential optimisation. Total turn-over numbers (TTNs) of up to 1600, turnover frequencies (TOFs) of up to 340 h(-1) and ee's up to 99 % were obtained in repetitive batch operations. The scope of the devised catalytic system has been investigated and a semicontinuous reaction setup has been implemented. The chiral ligand (R,S)-3-(HF6)-F-2-BINAPHOS allowed highly enantioselective hydrogenation of itaconic acid and methyl-2-acetamidoacrylate combined with a considerable catalyst stability in these reaction media.