Highly Efficient Asymmetric Hydrogenation of 2-Methylenesuccinamic Acid Using a Rh-DuPHOS Catalyst

An extremely efficient route to highly enantiomerically enriched 2-methylsuccinamic acid via asymmetric hydrogenation has been developed. By using [( S,S )-Et-DuPHOS Rh COD]BF 4 as the precatalyst under a set of broadly optimised process parameters, ( R )-2-methylsuccinamic acid was obtained in 96% ee at a substrate-to-catalyst ratio (S/C) of 100000 (average turnover frequency ∼13000 h - 1 ). The exclusion of chloride-containing contaminants in the substrate was found to be crucial in obtaining exceptionally low catalyst loadings. This material could be upgraded with a single-crystal digestion to yield ( R )-2-methylsuccinamic acid in >99.5% ee containing less than 1 ppm rhodium.