The continuous flow asymmetric hydrogenation of (hetero)aromatic enamides has been realized using a Rh-Quinaphos catalyst immobilized in a supported ionic liquid phase (SILP) and employing supercritical CO 2 modified with toluene (modCO 2 ) as the mobile phase. This approach allows expansion of the scope of the original SILP/scCO 2 system to nonvolatile substrates with poor solubility in pure CO 2 . The potential of a SILP catalyst in combination with modCO 2 was demonstrated for an industrial case study using the continuous flow hydrogenation for the synthesis of a key intermediate of an active pharmaceutical ingredient (API) from AstraZeneca's portfolio. Toluene was selected as the most promising modifier, and the influence of the ratio of modifier to CO 2 was evaluated in detail. The catalyst support was found to play a major role for maintaining constant performance and the use of hydrophobic fluorous reverse-phase silica (FRP-SiO 2 ) instead of dehydroxylated silica strongly enhanced the long-term stability under continuous flow operation. Virtually a single enantiopure product was obtained over a prolonged time-on-stream of 90 h (quantitative single-pass conversion, ee > 99%) reaching a total turnover number of 10 300 at a space−time yield (STY) of 24 g L −1 h −1 . No metal contamination was detected in the product solutions, indicating effective catalyst retention.

MatPhos, a good mate for hard tasks: The asymmetric hydrogenation of 1-alkyl vinyl esters, thwarted so far by mediocre ee values and low activities, can now be achieved with MatPhos/Rh catalysts with ee values of 96-99% for a variety of substrates at low catalyst loadings (0.1-1 mol %) and under mild conditions (5-20 bar H2, room temperature). After hydrolysis, the corresponding chiral secondary alkyl alcohols can be obtained in high enantiopurities providing a general and practical route to this important product class.

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