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Oxidative N‐heterocyclic carbene (NHC) organocatalysis, typically leading to the formation of acyl azolium reactive intermediates, constitutes one of the most important activation strategies for the NHC‐catalyzed chemical transformations. Here, we report an unprecedented oxidative radical NHC catalysis by using peroxyester as the external single‐electron oxidant to realize divergent difunctionalization of olefins. The key to success of this chemistry is the catalytic generation of oxygen radicals that could trigger an intermolecular hydrogen atom transfer to activate the inert C−H bonds, thereby enabling the productive radical relay process. With this protocol, commonly used general chemicals could serve as radical precursors to allow efficient synthesis of value‐added products in a straightforward and cost‐effective manner. Preliminary mechanistic investigations, including control experiments and DFT calculations, shed light on the NHC organocatalytic radical reaction mechanism. [ABSTRACT FROM AUTHOR]

The direct functionalization of inert C(sp3)−H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote C(sp3)−H acylation of amides and cascade cyclization through a radical‐mediated 1,5‐hydrogen atom transfer mechanism using N‐heterocyclic carbene as the catalyst. Notably, a diversity of nitrogen‐containing substrates, including simple linear aliphatic carbamates and ortho‐alkyl benzamides, can be successfully applied to this organocatalytic system. With the established protocol, over 120 examples of functionalized δ‐amino ketones and isoquinolinones with diverse substituents were easily synthesized in up to 99 % yield under mild conditions. The robustness and generality of the organocatalytic strategy were further highlighted by the successful acylation of unactivated C(sp3)−H bonds and late‐stage modification of pharmaceutical molecules. Then, the asymmetric control of the radical reaction was attempted and proven feasible by using a newly designed chiral thiazolium catalyst, and moderate enantioselectivity was obtained at the current stage. Preliminary mechanistic investigations including several control reactions, KIE experiments, and computational studies shed light on the organocatalytic radical reaction mechanism. [ABSTRACT FROM AUTHOR]

Titelbild: Remote C(sp3)-H Acylation of Amides and Cascade Cyclization via N-Heterocyclic Carbene Organocatalysis (Angew. Cyclization Reactions, C-H Functionalization, Isoquinolinone, NHC Organocatalysis, Radical Acylation Keywords: Cyclization Reactions; C-H Functionalization; Isoquinolinone; NHC Organocatalysis; Radical Acylation EN Cyclization Reactions C-H Functionalization Isoquinolinone NHC Organocatalysis Radical Acylation 1 1 1 03/30/22 20220404 NES 220404 B Eine organokatalytische b C(sp SP 3 sp )-H-Acylierung von Amiden wurde auf der Grundlage einer 1,5-Wasserstoffatom-Transferstrategie entwickelt. [Extracted from the article]