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Cross-electrophile coupling reactions have evolved into a major strategy for rapidly assembling important organic molecules 1 . Two readily accessible electrophiles are coupled to form new C-C bonds, providing a key advantage over traditional cross-coupling strategies that require the preformation of reactive organometallic species. Yet, the formation of C(sp 3 )-C(sp 3 ) bonds that form the core of nearly all organic compounds remains highly challenging with current approaches, calling for the design of innovative new strategies. Here we report a distinct, transition-metal-free platform to form such bonds without the need for activating or stabilizing groups on the coupling partners. The reaction is enabled by an unusual single-electron transfer in a frustrated ion pair, and it can couple fragments containing functional groups that would be challenging in related transition-metal-catalysed processes. Moreover, we could further leverage this new mechanistic manifold in the design of other reactions, showing the broad potential of this type of reactivity. We anticipate that our results will provide a framework for further exploration of this reactivity pattern to tackle challenging problems in organic synthesis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We report a photochemical method for the functionalization of pyridines with radicals derived from allylic C-H bonds. Overall, two substrates undergo C-H functionalization to form a new C(sp 2 )-C(sp 3 ) bond. The chemistry harnesses the unique reactivity of pyridinyl radicals, generated upon single-electron reduction of pyridinium ions, which undergo effective coupling with allylic radicals. This novel mechanism enables distinct positional selectivity for pyridine functionalization that diverges from classical Minisci chemistry. Crucial was the identification of a dithiophosphoric acid that masters three catalytic tasks, sequentially acting as a Brønsted acid for pyridine protonation, a single electron transfer (SET) reductant for pyridinium ion reduction, and a hydrogen atom abstractor for the activation of allylic C(sp 3 )-H bonds. The resulting pyridinyl and allylic radicals then couple with high regioselectivity.

We report a radical-based organocatalytic method for the direct benzylation of allylic C-H bonds. The process uses nonfunctionalized allylic substrates and readily available benzyl radical precursors and is driven by visible light. Crucial was the identification of a dithiophosphoric acid that performs two distinct catalytic roles, sequentially acting as a catalytic donor for the formation of photoactive electron donor-acceptor (EDA) complexes and then as a hydrogen atom abstractor. By mastering these orthogonal radical generation paths, the organic catalyst enables the formation of benzylic and allylic radicals, respectively, to then govern their selective coupling. The protocol was also used to design a three-component radical process, which increased the synthetic potential of the chemistry.

Herein, we report a general iminium ion-based catalytic method for the enantioselective conjugate addition of carbon-centered radicals to aliphatic and aromatic enals. The process uses an organic photoredox catalyst, which absorbs blue light to generate radicals from stable precursors, in combination with a chiral amine catalyst, which secures a consistently high level of stereoselectivity. The generality of this catalytic platform is demonstrated by the stereoselective interception of a wide variety of radicals, including non-stabilized primary ones which are generally difficult to engage in asymmetric processes. The system also served to develop organocatalytic cascade reactions that combine an iminium-ion-based radical trap with an enamine-mediated step, affording stereochemically dense chiral products in one-step., (© 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)