Selective Access to<i>E</i>- and<i>Z</i>-ΔIle-Containing Peptides via a Stereospecific E2 Dehydration and an O → N Acyl Transfer

Abstract

A concise synthesis of peptides that contain E- or Z-dehydroisoleucine (ΔIle) residues is reported. The key reaction is an unusual anti dehydration of β-tert-hydroxy amino acid derivatives that is mediated by the Martin sulfurane. A subsequent tandem Staudinger reduction-O → N acyl transfer process forges an amide bond to the ΔIle residue with minimal E/Z alkene isomerization. Density functional calculations attribute the stereospecific dehydration to a highly asynchronous E2 anti process.