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. However, the selective catalytic cleavage of C-N bonds in amines is a difficult challenge, mainly due to the high bond dissociation
energy of the carbon-nitrogen bond compared to other carbon-heteroatom bonds, and the ability of the amido leaving group to serve as a strong ligand promoting catalyst deactivation pathways.
SCAN (Selective Pathways for CArbon-Nitrogen Bond Cleavage) is designed to open new directions in the field of C-N bond cleavage by unlocking novel and general deamination pathways. To achieve this goal, the following specific objectives are proposed:
1) Design of novel amine derivatives capable of undergoing homolytic C-N cleavage.
2) Development of novel deamination protocols using photoredox and metallaphotoredox catalysis.
3) Site-selective modifications of peptides through photocatalyzed deaminative transformations.
The successful implementation will allow the use of one of the most readily available functional groups in a myriad of novel catalytic transformations. The prevalence of alkyl amines in pharmaceuticals makes SCAN an ideal tool for late-stage functionalization and molecular editing of drug analogs, providing a tool to accelerate the drug discovery process. 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.
