Catalytic, asymmetric synthesis of phosphonic γ-(hydroxyalkyl)butenolides with contiguous quaternary and tertiary stereogenic centers

Abstract

A procedure that enables high yielding access to phosphonic γ-(hydroxyalkyl)butenolides with excellent regio-, diastereo- and enantiocontrol is reported. The simultaneous construction of up to two adjacent quaternary stereogenic centers by a catalytic asymmetric vinylogous Mukaiyama aldol reaction unites biologically and medicinally relevant entities, namely α-hydroxy phosphonates and γ-(hydroxyalkyl)butenolides. This is achieved by utilizing a readily available chiral copper-sulfoximine catalyst showing a broad functional group tolerance for both the electrophilic and nucleophilic reactants. A discussion about potential factors affecting the observed level of enantioselectivity, which stems from the enantiopure sulfoximine ligand, is also included.

Keywords: aldol reaction; asymmetric catalysis; butenolides; sulfoximines; α-hydroxy phosphonates.