An efficient synthesis of Gly-Gly-type (E)-methylalkene and (Z)-chloroalkene dipeptide isosteres is realized by organocuprate-mediated single electron transfer reduction.

Described here is the synthetic, spectroscopic, crystallographic, and computational analysis of a series of peptidomimetics containing l-Xaa-d-Yaa-type (Z)-chloroalkene dipeptide isosteres (CADIs) that were measured in an investigation of the β-turn mimicry of this peptide bond surrogate. We found that the 1,3-allylic strain across the chloroalkene moiety engenders the hyperconjugative interactions between the chloroalkene moiety and the C–H bonding or antibonding orbitals of the C–H bonds in allylic positions. These effects contribute significantly to the stabilization of β-turn structures.