Selective Pathways for Carbon-Nitrogen Bond Cleavage

Amines are ubiquitous across natural products, pharmaceuticals, polymers and biomolecules.

The number of commercially available amines, from simple to complex, makes them one of the most accessible native functional groups.

Therefore, they represent an attractive feedstock for the preparation of functionalized molecules through C-N bond activation. Nature long ago developed protocols to promote oxidative deamination reactions.

Inspired by this approach, SCAN (Selective Pathways for CArbon-Nitrogen Bond Cleavage) is designed to open new directions in the field of C-N bond cleavage by unlocking the oxidative deamination pathway.

To achieve this goal, the following specific objectives are proposed: 1) Design of redox-active amines capable of undergoing oxidative C-N cleavage. 2) Development of novel oxidative deaminations using photoredox and metallaphotoredox catalysis.3) Site-selective modifications of peptides through photocatalyzed oxidative deaminations.

The successful implementation will allow the use of one of the most readily available functional groups in a myriad of novel catalytic transformations, including for the first time asymmetric catalysis.

The prevalence of alkyl amines in pharmaceuticals makes SCAN an ideal tool for late stage functionalization and molecular editing of complex molecules.

Moreover, this reactivity could be used to achieve site-selective modifications of NH2 groups in peptides via C-N bond cleavage, which would have a profound impact in the fields of chemistry and chemical biology.

Together, the conceptual novelty, the ability to pursue multiple complementary approaches at once, and the various potential applications will ensure high impact of this project in both the academic and industrial communities.