Cobalt Hydride Oxidase Catalysis Enabled Hydroamination of Unactivated Olefins

Dioxygen is an abundant, selective, and sustainable oxidant that is considered ideal for organic transformations. Oxidative processes using dioxygen as the electron acceptor without oxygen atom incorporation into the substrate are often referred to as oxidase reactions. However, the ground state triplet nature of dioxygen makes such a synthetically valuable pathway incompatible with simple free alkyl radicals, a ubiquitous class of reactive intermediates in the daily synthesis of pharmaceuticals, agrochemicals, and complex natural products. Here we report that a combination of strong cage effect and bimetallic radical-polar crossover successfully addresses this problem, and opens up an oxidase pathway in cobalt hydride catalysis. This leads to a general and chemoselective method that tackles several key challenges in catalytic hydroamination, a fundamental transformation for amine synthesis. Under balloon pressure of dioxygen at ambient temperature, we demonstrate single-step intra- and intermolecular formal addition of a variety of nitrogen nucleophiles, including free amines, sulfonamides, amides, and carbamates, to unactivated alkenes in the presence of a silane, under solvent-free conditions. Important medicinal chemistry building blocks such as a-branched tertiary amines can be easily accessed, which are often difficult targets otherwise due to their steric hindrance and reducing nature. Mechanistic studies including stoichiometric experiments with well-defined organocobalt complexes provide support for the key hypothesis, which points the way to the development of sustainable processes involving other nucleophiles based on the same design elements.