Copper-catalyzed asymmetric synthesis of tertiary α-hydroxy phosphonic acid derivatives with in situ generated nitrosocarbonyl compounds as the oxygen source

Abstract

α-Hydroxy phosphonic acids and their derivatives are highly bioactive structural motifs. It is now reported that these compounds can be accessed through the copper-catalyzed direct α-oxidation of β-ketophosphonates using in situ generated nitrosocarbonyl compounds as an electrophilic oxygen source. These reactions proceeded in high yields (up to 95 %) and enantioselectivities (up to >99 % ee) for both cyclic as well as acyclic substrates. This method was also applied for the synthesis of α,β-dihydroxy phosphonates and β-amino-α-hydroxy phosphonates.

Keywords: asymmetric synthesis; bisoxazoline; copper; oxidation; phosphonic acids.