Iminium-Radical Catalyzed Functionalization of Unactivated, Aliphatic C–H Bonds

Abstract

The direct and selective functionalization of aliphatic C(sp3)–H bonds holds great strategic and economic promise by circumventing prefunctionalized molecules, allowing modifications at sites unattainable by traditional methods. With respect to hydrogen atom transfer, most of these protocols employ the hydrogen abstracting species in stoichiometric fashion. Through the advent in photoredox catalysis, radical cations found application as catalytic hydrogen abstracting species in non-chain processes, allowing to vary selectivities based on the properties of the in situ generated radical cation. The existing protocols rely almost exclusively on the usage of aliphatic, bridgehead aminium radicals, with quinuclidine being the most prominent example. These systems resist primary reaction pathways of radical cation, e.g., fragmentation and deprotonation, rendering hydrogen atom transfer feasible. However, these systems lack structural diversity and the possibility of tuning important structural and electronical properties making them unsuitable to address more complex selectivity issues. The presented work deals with the search for alternative radical cationic hydrogen atom transfer agents that also resist primary reaction pathways of radical cations and readily participate in C(sp3)–H abstractions of unactivated, aliphatic hydrocarbons. Thereby, the radical cation is generated from a p- rather than an n-donor system by single electron oxidation by an excited state photoredox catalyst. We identified N-pyridylidenesulfonamides as reactive hydrogen atom transfer agents in combination with acridinium-based photoredox catalysts. The developed systems were tested mostly, but not exclusively, for the azidation of aliphatic hydrocarbons using cyclohexane as test system and their radical reactivity and stability was probed experimentally and computationally. During this research we have identified several side reaction pathways with the protocol being ultimately limited in its applicability by chlorine background catalysis in chlorinated solvents and competing rate kinetics for cage escape and back electron transfer between the acridinium photocatalyst, the in situ generated radical cation, and the azide trapping agent. Still, the presented results give a first impression of the modularity of the system and the possibilities to tune the system to address more complex selectivity issues.