Synthesis and enzymatic resolution of methyl ferrocenylpentanoate using Thermomyces lanuginosus lipase for construction of ferrocene alkyl thiols

Abstract

Racemic methyl 3-methyl-5-ferrocenylpentanoate was synthesized by the acylation of ferrocene with 3-methylglutaric anhydride under Friedel-Crafts conditions followed by the Clemmensen reduction of the obtained (±)-3-methyl-4-ferrocenylbutanoic acid and subsequent esterification. The kinetic resolution of the obtained compound in phosphate buffer, pH 7.0 using Thermomyces lanuginosus lipase was studied. After two consecutive steps of hydrolysis the unaltered methyl (+)-3-methyl-5-ferrocenylpentanoate with enantiomeric excess (ee) up to 87% was isolated. The other enantiomer, methyl (–)-3-methyl-5-ferrocenylpentanoate with ee 73%, was synthesized by the esterification of (–)-3-methyl-5-ferrocenylpentanoic acid formed in the hydrolysis reaction. The enan­tiomeric purity of the obtained esters was determined by NMR using a chiral shift reagent. These enantiomerically enriched compounds could be used as starting materials in the synthesis of chiral (S)- and (R)-ferrocene electroactive substrates containing ter­minal mercapto functions.