Phosphonate analogs of N-benzoyl-and N-Boc-3-phenylisoserine, the taxol C-13 side chain

Article abstract of DOI:10.1016/S0040-4020(98)00435-9

Diastereoselectivity of the addition of diethyl phosphite to N-Boc-phenylglycinal reached 50% when NEt₃ or KF were used as catalysts but employing lithium diethyl phosphonate lower d.e. was obtained. Separation of the required syn diethyl 2-[(tert- butoxycarbonyl)amino]-1-hydroxy-2-phenylethylphosphonate (8a) from the antiisomer 8b was best achieved as O-benzoate 10a or O- trimethylsilyl 9a derivatives. Diethyl 2-(benzoylamino)-1-hydroxy- 2-phenylethylphosphonate (12a) was efficiently prepared (HCl- AcOEt) from 10a in a one-step procedure. The absolute configuration at C-1 in 8a and 8b was established from ¹H and ¹³C NMR spectral data of their N,O-isopropylidene derivatives. Acyclic phosphonates from the a series (8, 10, 12) adopt antiperiplanar conformations.