1,3-Stereocontrol with phosphine oxides: asymmetric synthesis of all four diastereoisomers of a γ′-benzyloxy β-hydroxy phosphine oxide

Abstract

This paper describes how optically active phosphine oxides with a γ′ stereogenic centre [for example, (R)-1-diphenylphosphinoylheptan-3-yl benzyl ether] can be lithiated and reacted with aldehydes and esters. The reactions exhibit moderate levels of 1,3 asymmetric induction and models are proposed to explain the stereoselectivity observed in terms of the configurational instability and the known structure of lithiated phosphine oxides. We have developed complementary methods for the asymmetric synthesis of all four diastereomeric β-hydroxy phosphine oxides 4-benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)octan-1-ol and our approach constitutes a formal synthesis of all eight possible stereoisomers. A series of similar β-hydroxy phosphine oxides were eliminated to give optically active homoallylic alcohol derivatives.