Stereoselective Synthesis of Tetrahydropyrans via Tandem and Organocatalytic Oxa-Conjugate Addition Reactions

Abstract

Michael reactions have drawn a great amount of interest from the synthetic community due to their ability to form C–C sigma bonds through the conjugate addition of carbon nucleophiles to many different types of Michael acceptors [1]. However, the analogous conjugate additions of other heteroatom nucleophiles such as amines, thiols, phosphines, and alcohols have not progressed at the same rate [2, 3, 4, 5]. This is especially true for the application of these conjugate addition methodologies in the context of alcohol nucleophiles and α,β-unsaturated carbonyl compounds (oxa-conjugate addition reaction) in order to stereoselectively form tetrahydropyrans. This comparative lack of interest can be mainly attributed to the major disadvantages of the oxa-conjugate addition reaction, including the poor nucleophilicity of oxygen atoms, reversibility of the addition process (retro-oxa-conjugate addition reaction), and the lack of stereoselectivity [1].