Unlocking new photoinduced carbamoylation to expand the synthetic toolbox for peptidomimetics preparation

Peptidomimetics are widely investigated as valuable tools in drug discovery and medicinal chemistry, and their synthesis typically relies on classical amide-bond formation using non-natural amino acids. Here, we report an innovative photochemical carbamoylation of imines and oximes that directly enables CC bond formation within peptide or amino-acid frameworks, providing straightforward access to peptides and peptidomimetics. In the presented reaction, formamides serve as carbamoyl radical precursors and the facile preparation of N-formyl amino acids and N-formyl-peptide sequences makes this strategy particularly versatile for the in situ introduction of non-natural structural motifs. The reaction displays diastereoselectivity with sulfonyl imines, while oximes give access to more demanding architectures, including sequences featuring α,α-disubstituted amino acids, as well as analogues of bioactive macrocycles. Overall, this methodology expands the synthetic toolbox for peptidomimetics, allowing efficient construction of both linear and cyclic structures that are otherwise challenging to prepare.