Diastereoselective hydrogenation of folic acid esters with the Daniphos ligand

Folic acid dimethylester benzenesulfonate was hydrogenated homogeneously in a rhodium-catalyzed diastereoselective reaction employing a set of the previously published planar-chiral “Daniphos” ligands, which are based on an arene chromium tricarbonyl scaffold. Diastereoselectivities of up to 42% de were achieved, almost matching the benchmark ligand BINAP. An X-ray structure of the most successful ligand P(i-Pr2)/PPh2 is presented and discussed.

Graphical abstractThe “Daniphos” ligand was employed in the hydrogenation of folic acid dimethyl ester benzenesulfonate. Tetrahydrofolic acid dimethylester has been obtained with selectivities of up to 42% de, matching “the state of the art”. An X-ray structure of the most successful ligand is presented and discussed.Figure optionsDownload full-size imageDownload as PowerPoint slide