Synthesis of chiral (alpha,alpha-difluoroalkyl)phosphonate analogues of (lyso)phosphatidic acid via hydrolytic kinetic resolution

The hydrolytic kinetic resolution of 1,1-difluoro-3,4-epoxy-butylphosphonate using a chiral salen-Co complex was employed as a key step to obtain enantiomeric diols in 99% ee as key intermediates. The enantiomerically homogeneous (alpha,alpha-difluoroalkyl)phosphonates were obtained after selective esterification and deprotection of the corresponding phosphonates. These compounds are novel phosphatase-resistant analogues of lysophosphatidic acid and phosphatidic acid. [reaction: see text]