Enantiomer-differentiating hydrogenation of methyl 3-cyclopropyl-2-methyl-3-oxopropanoate over tartaric acid-modified nickel: Performance of heterogeneous catalyst in dynamic kinetic resolution

A racemic mixture of methyl 3-cyclopropyl-2-methyl-3-oxopropanoate was hydrogenated over the tartaric acid-modified Raney nickel. Discrimination of the 2-methyl group during the reaction was high enough to perform the enantiomer differentiation, (2S)/(2R)-product = 16, and to cause an efficient dynamic kinetic resolution that resulted in one stereoisomer up to 93% of all the hydrogenation products. The diastereomer ratio was syn:anti = 97:3, and ee values of the respective diastereomers were 93% and 41%. However, the low reactivity of the substrate caused deactivation of the catalyst during the reaction and needed us to tune the reaction conditions to achieve both the high stereoselectivity and the high conversion. By introducing a small-scale reactor, 96% conversion was achieved with slight decrease in the enantiomer selectivity (=12).

Graphical abstractA racemic mixture of methyl 3-cyclopropyl-2-methyl-3-oxopropanoate was hydrogenated over the tartaric acid-modified Raney nickel. Discrimination of the 2-methyl group during the reaction was high enough to perform the enantiomer differentiation, (2S)/(2R) = 16, and to cause an efficient dynamic kinetic resolution that resulted in one stereoisomer up to 93% of all the four hydrogenation products. Figure optionsDownload full-size imageDownload as PowerPoint slide