Photo-Induced Aliphatic C–H Amination Mediated by Hydrogen Atom Transfer of an Alkoxycarbonyloxyl Radical and Its Utilization for Diastereoselective Modification of Proline Residues in Peptides

A metal- and additive-free photosensitized C(sp³)-H amination reaction has been achieved capitalizing on newly developed oxime carbonates as the iminylation reagents. Photoinduced energy transfer catalysis enables the homolysis of nitrile-containing oxime carbonates, which afford not only reactive alkoxycarbonyloxyl radical species capable of cleaving strong C-H bonds via hydrogen atom transfer (HAT) but also suitable persistent iminyl radicals. The C-N bonds can eventually be constructed via cross-coupling of an iminyl radical and a carbon radical formed upon HAT, or a radical chain propagation with nitrile-containing oxime carbonates. The nitrile-bearing amination moiety is readily converted to fragments such as amide, α-nitrile amine, primary amine, and pyrrole. A wide range of functional groups can be compatible in this transformation that is feasible for late-stage amination of bioactive compounds. Various aliphatic amines participated in this reaction as limiting reagents, selectively forging C-N bonds at α-C(sp³)-H sites. By employing proline-containing C-H substrates, the protocol is amenable to precise manipulation of peptide skeletons through a diastereoselective process.