Stereocontrolled route to some optically active β-hydroxy phosphine oxides using the stereoselective addition of metallated phosphine oxides to proline-derived keto aminals

Abstract

An asymmetric Horner–Wittig addition reaction with a chiral auxiliary attached to the electrophile is described. The key step is the addition of metallated phosphine oxides to Mukaiyama's proline-derived keto aminals (for which improved syntheses are described) and a detailed study of the factors affecting the stereoselectivity of these reactions is presented. In particular, by suitable choice of metallation conditions, complementary stereoselectivities are observed: reactions in THF with no additives are syn selective (Felkin non-chelation control) whereas reactions in toluene with added lithium bromide are anti selective (Cram chelation control).