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.