ASYMMETRIC CATALYSIS .67. DIASTEREOSELECTIVE HYDROGENATION OF FOLIC-ACID WITH OPTICALLY-ACTIVE RHODIUM(I)-DIPHOSPHANE COMPLEXES

With immobilized rhodium(I)-diphosphane catalysts supported on silica gel, the C = N bonds of the pyrazine ring of folic acid (1) are reduced with hydrogen in aqueous solution to give 5,6,7,8-tetrahydrofolic acid. A mixture of the two diastereomers 2a and 3a is obtained with (6S)- and (6R)-configuration, respectively, at the newly formed asymmetric center in the pterine system and (S)-configuration in the L-glutamic acid moiety. The unstable hydrogenation products are derivatized with (-)-menthyl chloroformate. An improved HPLC procedure for the analysis of the products has been developed. By using optically active chelate phosphanes as cocatalysts together with [Rh(cod)Cl]2, a diastereomeric excess of up to 24% of the natural isomer 2a with (6S,S)-configuration is attained in the heterogeneous hydrogenation of folic acid.