Yvo Crameri

New efficient methods for the synthesis and in-situ preparation of ruthenium(II) complexes of atropisomeric diphosphines and their application in asymmetric catalytic hydrogenations

Abstract A new synthetically useful method for the synthesis of the diphosphine ruthenium dicarboxylato complexes (PP)Ru(O2CR)2 (R = CF3 and CH3) is presented, which uses the easily accessible complex (COD)2Ru2(μ-O2CCF3)4 as starting material. This complex as well as (COD)Ru(η2-O2CCH3)2 and (COD)2Ru2Cl4(NCCH3) have been shown to be suitable precursor complexes for the in-situ preparation of ruthenium(II) dicarboxylato and dichloro complexes of atropisomeric diphosphines, respectively. The high efficacy of the preformed and in-situ generated ruthenium complexes as precatalysts is demonstrated in asymmetric hydrogenations of allylic alcohols, enamides, and a β-keto ester.

Practical synthesis of (S)-2-(4-fluorophenyl)-3-methylbutanoic acid, key building block for the calcium antagonist Mibefradil

Abstract A short, technically feasible route was developed for the synthesis of (S)2-(4-fluorophenyl)-3-methylbutanoic acid (S)- 2 with an overall yield of 80% starting from 4-fluorophenylacetic acid. Asymmetric hydrogenation of the easily accessible unsaturated acid 3 in the presence of ruthenium(II) carboxylato complexes containing chiral atropisomeric diphosphines afforded (S)- 2 in up to 94% ee. The ee of (S)- 2 was upgraded to 98% by crystallization of its sodium salt. The same protocol was also applied to the synthesis of (S)-2-(4-chlorophenyl)-3-methylbutanoic acid.