Lipase mediated resolution of 1,3-butanediol derivatives: chiral building blocks for pheromone enantiosynthesis. Part 3

Abstract

( R,S)-1,3-Butanediol 5 was kinetically resolved by enzymatic acetylation with vinyl acetate under the presence of Chirazyme™ L-2, c–f, yielding ( S)-1- O-acetyl-1,3-hydroxybutane 6 and ( R)-1,3-di- O-acetyl-1,3-butanediol 7 with enantiomeric excesses of 91% ( E=67.3). Compounds 6 and 7 were easily transformed into the corresponding ( S)-3- O-(2-methoxyethoxymethyl)-3-hydroxybutanal 10 and ( R)-3-benzyloxybutanal 19, through a protection–deprotection and functional group interchange methodology. Subsequent reaction of 10 and 19 with 3-(methoxycarbonylpropionylmethylene)triphenylphosphorane afforded methyl ( E, S)-8- O-(2-methoxyethoxymethyl)-4-oxo-5-nonenoate 12 and ( E, R)-8-benzyloxy-4-oxo-5-nonenoate 20. The alkenes 19 and 20 were then catalytically hydrogenated to the corresponding saturated esters 13 and 21. Treatment of 13 and 21 with 1,2-ethanedithiol/F 3B·OEt 2 afforded dithioketals 14 and 22, which were respectively reduced to ( S)-1,8-dihydroxy-4-nonanone ethylidenedithioketal 15 and ( R)-8- O-benzyl-1,8-dihydroxy-4-nonanone ethylidenedithioketal 23. Finally, deprotection of 15 by catalytic hydrogenation under acidic conditions gave the expected (5 S,7 S)-(−)-7-methyl-1,6-dioxaspiro[4.5]decane 1. The (5 R,7 R)-(+)- 1 enantiomer was analogously prepared from 23. Both compounds were formed by this procedure with an e.e. of 91%.