Formal synthesis of P-chiral [16O,17O,18O]phosphoenol pyruvates by means of the α-hydroxyphosphonate-phosphate rearrangement

Transesterification of tris(hexafluoroisopropyl) phosphite with racemic 3-methyl-1-phenyl-butane-1,3-diol gave two isomeric hexafluoroisopropyl-substituted 1,2,3-dioxaphosphinanes. These cyclic phosphites were hydrolyzed rapidly and enantioselectively by water catalyzed by HCl. The respective metalated H-phosphonates were added to ethyl 3-chloropyruvate and underwent a stereospecific α-hydroxyphosphonate-phosphate rearrangement to protected phosphoenol pyruvates. This sequence with oxygen isotope-labeled enantiomers represents an alternative approach to P-chiral [16O,17O,18O]phosphoenol pyruvates.