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

GRAPHICAL ABSTRACT

ABSTRACT

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.

KEYWORDS:

• α-Hydroxyphosphonate-phosphate rearrangement
• cyclic H-phosphonate
• tris(hexafluoroisopropyl) phosphite
• phosphoenol pyruvate
• hydrolysis

Acknowledgements

The authors thank V. Philippitsch for performing the α-phosphonate-phosphate rearrangement with DBU as base, S. Felsinger for recording NMR spectra, E. Macoratti for the preparative HPLC separation, and J. Theiner for combustion analyses.

Additional information

Funding

Austrian Science Fund (P19869-N19).