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

A concise synthesis of peptides that contain E- or Z-dehydroisoleucine (Delta Ile) residues is reported. The key reaction is an unusual anti dehydration of beta-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 Delta Ile residue with minimal E/Z allcene isomerization. Density functional calculations attribute the stereospecific dehydration to a highly asynchronous E2 anti process.