Highly Selective α-Addition and β-Conjugate Addition Products from Peptides Composed of α,β-Unsaturated γ-Amino Acids

β-Addition products are common in conjugate addition reactions consisting of α,β-unsaturated carbonyl compounds. Here, we are reporting an uncommon α-addition product as a major product in the thioacetic acid conjugate addition reaction on a peptide consisting of (E)-α,β-unsaturated γ-amino acids. In addition, we observed highly diastereoselective β-addition products from the thiophenol and thioethanol conjugate addition reaction on peptides. In comparison, (E)-α,β-unsaturated γ-amino amides give both α- and β-addition products with thioacetic acid and only β-addition products in the thiophenol conjugate addition reaction. Further, the conformations of both α-addition and β-addition products were studied in single crystals as well as in solution. The peptide product with α-thioacetate addition (α,γ-disubstituted γ-amino acid) adopted a regular 12-helix conformation, whereas β-addition (β,γ-disubstituted γ-amino acid) products slightly distorted 12-helix conformation. A kink is observed at the site of β-addition in the 12-helix structures of all β-addition products. Overall, the uncommon and stereospecific conjugate addition reactions reported here can be explored to introduce diverse functional groups to the peptide backbone.