A new and facile preparation of tert-butyl (3R,5S)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate

A facile method for the preparation of tert-butyl (3R,5S)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate is described by a chemoenzymatic approach. In this method, one hydroxyl stereocenter at C5 is obtained with a high ee value (up to 98.0%) via an enzymatic transesterification resolution of l-chloro-3-(4-methylbenzyloxy)-2-propanol. The other hydroxyl stereocenter at C3 was built with 98.0% de, by acid-hydrolysis of a 1,3-diol-acetonide syn/anti-10. It is noteworthy that the reduction of β-hydroxy ketone 8 with sodium borohydride can be carried out smoothly in aqueous isopropyl alcohol with a high diastereomeric ratio syn/anti (dr_s:a) of 4.0:1.