Unprecedented base effect on the synthesis of chiral phosphinate esters: A new route to P-chiral phosphine oxides of high enantiomeric purity

Abstract

The stereochemical outcome of the reaction of chiral secondary alcohols with a phosphinyl chloride was found to be highly dependent on the achiral base used. Thus, the reaction of the readily available sugar derived carbinols, 1 and 2, with methylphenylphosphinyl chloride in the presence of triethylamine yields stereoselectively the corresponding Snp-phosphinates 3S p and 5S p in 94 and 92% diastereomeric excess (de). Simply changing the base from triethylamine to pyridine affords Rp-phosphinates 4R p and 6R p epimers to 3S p and 5S p at the phosphinyl phosphorus in 50 and 40% de respectively. These phosphinate esters were found to be good P-chiral transferring intermediates, they react with Grignard reagents under very mild conditions to give the corresponding phosphine oxides. Both enantiomers Sp- and Rp- o-anisylmethylphenylphosphine oxide (PAMPO) as well Sp- and Rp- methylphenylpropyl phosphine oxide were obained enantiomerically pure in high yields