Enantioselective Intermolecular Radical C–H Amination

Radical reactions hold a number of
inherent advantages in organic
synthesis that may potentially impact the planning and practice for
construction of organic molecules. However, the control of enantioselectivity
in radical processes remains one of the longstanding challenges. While
significant advances have recently been achieved in intramolecular
radical reactions, the governing of asymmetric induction in intermolecular
radical reactions still poses challenging issues. We herein report
a catalytic approach that is highly effective for controlling enantioselectivity
as well as reactivity of the intermolecular radical C–H amination
of carboxylic acid esters with organic azides via Co­(II)-based metalloradical
catalysis (MRC). The key to the success lies in the catalyst development
to maximize noncovalent attractive interactions through fine-tuning
of the remote substituents of the D2-symmetric
chiral amidoporphyrin ligand. This noncovalent interaction strategy
presents a solution that may be generally applicable in controlling
reactivity and enantioselectivity in intermolecular radical reactions.
The Co­(II)-catalyzed intermolecular C–H amination, which operates
under mild conditions with the C–H substrate as the limiting
reagent, exhibits a broad substrate scope with high chemoselectivity,
providing effective access to valuable chiral amino acid derivatives
with high enantioselectivities. Systematic mechanistic studies shed
light into the working details of the underlying stepwise radical
pathway for the Co­(II)-based C–H amination.