ISOLATION OF RACEMIC 2,4-PENTANEDIOL AND 2,5-HEXANEDIOL FROM COMMERCIAL MIXTURES OF RACEMIC AND MESO ISOMERS BY WAY OF CYCLIC SULFITES

Enantiomerically pure diols with C-2 symmetry such as 2,3-butanediol, 1,2,4-pentanediol, 2, and 2,5-hexanediol, 3, are useful chiral auxiliaries, but they are expensive because chemists lack good synthetic routes that eliminate both the meso isomer and one enantiomer. Enzymic resolutions efficiently separate the enantiomer, but do not remove the meso isomer. To simplify enzymic resolutions of 2 and 3, we developed simple methods to isolate the racemic isomer from commercial mixtures of racemic and mesoisomers. For 2, the meso isomer selectively reacted with SOCl2 to give a cyclic sulfite that was removed by column chromatography to leave (+/-)-2, 92% de, 1.4 g, 55% yield. For 3, both meso and racemic isomers reacted with SOCl2 to give cyclic sulfites, but the sulfite derived from the meso isomer rearranged to trans-2,5-dimethyltetrahydrofuran under acidic conditions. Hydrolysis of the remaining sulfite gave (+/-)-3, 84% de, 1.1 g. 37% yield. Resolution of (+/-)-2 and (+/-)-3 using lipase from Pseudomonas cepacia yielded (2R,4R)-2-diacetate, 78% ee, >97% de, 40% of theory and (2R,5R)-3-diacetate 94% ee, >97% de, 47% of theory. Previously reported acetylations of 2 and 3 by lipase from Candida antarctica (CAL) or by lipase from Pseudomonas sp. (Amanolipase AK) are more enantioselective and thus, the best route to enantiomerically and diastereomerically pure 2 and 3 is removal of the meso isomer by way of cyclic sulfites followed by resolution with CAL or Amano lipase AK.