Amines are highly ubiquitous in bioactive natural products, pharmaceuticals, and materials. A close look at the literature data reveals that 82 % of the top 200 small molecule prescription medicines by global sales in 2022 contain at least an amine moiety or a nitrogen-containing heterocycle. Therefore, the development of new catalytic manifolds aimed at promoting de novo C–N bond-forming reactions operating with broad applicability and practicality would be particularly valuable in both pharmaceutical and industrial laboratories.

In line with our ongoing interest in Ni-catalyzed cross-coupling reactions, this doctoral thesis focuses on two main areas: 1) nickel-catalyzed C(sp³)–N bond formation via functionalization of C(sp³)–H linkages or olefins via nitrene transfer, and 2) site-selective, diverse functionalization of C(sp³)–H bonds in aliphatic amines.

The initial study unravels the possibility of conducting a site-selective C(sp³)–H amidation enabled by nickel-nitrenoid catalysis. The approach is characterized by a predictable reactivity by selective C–N bond formation at sp³ sites adjacent to heteroatoms via open-shell species, thereby offering a complementary profile to traditional oxidative-type manner via two-electron transfer processes.

The following chapter focuses on stereodivergent N-glycosylation via nickel catalyzed hydroamidation of glycals. The protocol provides access to either α- or β-N-glycosides through forging C(sp³)–N glycosidic bonds on kinetic or thermodynamic grounds.

On the other hand, we have developed a new platform for enabling remote functionalization of aliphatic amines via a site-selective bromination event at distal C(sp³)–H sites enabled by the intermediacy of ammonium salts in acidic media. The resulting brominated scaffolds serve as a synthetic linchpin that can be easily transformed to a series of carbon–carbon and carbon–heteroatom bonds, thus offering access to advanced sp³ architectures possessing valuable aliphatic amine moieties.

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