Peptidomimetic Synthesis by Way of Diastereoselective Iodoacetoxylation and Transannular Amidation of 7–9-Membered Lactams

Azacyclo- and azabicycloalkanone peptidomimetics were synthesized regio- and diastereoselectively by iodoacetoxylation and transannular amidation reactions on unsaturated lactam precursors contingent on ring size, olefin position, solvent, and hypervalent iodine­(III) reagent. 4-Iodopyrrolizidinone 1, 7-iodoindolizidinone 2, and 4-iodo-5-acetoxylactams (e.g., 6 and 7) were made stereospecifically from 7–9-membered olefins 16, iodine, and hypervalent iodine­(III) in acetonitrile or toluene, respectively. X-ray crystallography demonstrated potential for mimicry of natural peptide turn side chain and backbone conformations.