Solid-phase synthesis of bicyclic dipeptide mimetics by intramolecular cyclization of alcohols, thiols, amines, and amides with N-acyliminium intermediates

(Chemical Equation Presented) A general strategy for the solid-phase synthesis of structurally diverse bicyclic dipeptide mimetics is presented. Depending on the amino acid side-chain (R¹), peptide-derived N-acyliminium intermediates may undergo nucleophilic attack from either side-chain functional groups (-OH, -NH₂, -SH, and -CONH₂) or the amide backbone (-CONH-) of the peptide, thus affording a range of aza-, thia-, and oxabicycloalkanes in excellent purity and diastereoselectivity.