The Stereochemistry of Substitution at S(VI)

Abstract

Since the re-birth of sulfur-fluoride exchange (SuFEx) chemistry, coined by Sharpless in 2014 as a ‘click’ reaction, the prevalence of sulfur(VI) moieties in medicinal, polymer and materials chemistry has increased significantly. SuFEx and analogous substitution reactions at electrophilic S(VI) reagents are often performed on symmetrical, achiral S(VI) centres. However, when these substitution reactions are applied to chiral S(VI) substrates, often enantioenriched chiral-at-sulfur aza-S(VI) analogues, the stereochemical outcome of the reaction must be considered to obtain the appropriate 3D configuration. In this review, we aim to draw together the stereochemical outcomes and mechanistic understanding of substitution reactions occurring at electrophilic chiral S(VI) reagents to provide support, and potential word of caution, to the growing field. In addition, we review the significant developments in stereocontrolled reactions at S(VI) centres.