Synthesis of diastereo- and enantiomerically pure anti-3-methyl-1,4-pentanediol via lipase catalysed acylation

Abstract

Racemic trans-4,5-dimethylhydrofuran-2(3H)-one was synthesised from 5-methyl-furan-2(3 H)-one, (α-angelica lactone). The key reaction in the synthesis was the 1,4-conjugate addition of an organocuprate to 5-methylfuran-2(5 H)-one (β-angelica lactone). Different types of organocuprates were tested with the highest anti: syn ratio of 99.4:0.6 being obtained by the use of a Gilman organocuprate reagent. The enantioselective acylation of racemic 3-methyl-pentan-1,4-diol, catalysed by a variety of lipases in organic media, was investigated. The highest enantioselectivity ( E > 400) was obtained when Novozyme 435 was used as the catalyst at a water activity of a w ∼ 0. Thus, both enantiomers, (3 S,4 R)- and (3 R,4 S)-3-methyl-pentan-1,4-diol, were obtained in very high diastereomeric (>99% de) and enantiomeric purities (>99.8% and >97.4% ee, respectively).