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The direct functionalization of inert C(sp3)‐H bonds to form carbon‐carbon and carbon‐heteroatom bonds offers vast potential for chemical synthesis and therefore receives increasing attention. At present, most successes come from strategies using metal catalysts/reagents or photo/electrochemical processes. The use of organocatalysis for this purpose remains scarce, especially when dealing with challenging C−H bonds such as those from simple alkanes. Here we disclose the first organocatalytic direct functionalization/acylation of inert C(sp3)‐H bonds of completely unfunctionalized alkanes. Our approach involves N‐heterocyclic carbene catalyst‐mediated carbonyl radical intermediate generation and coupling with simple alkanes (through the corresponding alkyl radical intermediates generated via a hydrogen atom transfer process). Unreactive C−H bonds are widely present in fossil fuel feedstocks, commercially important organic polymers, and complex molecules such as natural products. Our present study shall inspire a new avenue for quick functionalization of these molecules under the light‐ and metal‐free catalytic conditions. [ABSTRACT FROM AUTHOR]

The development of catalyst‐controlled methods for direct functionalization of two distinct C−H bonds represents an appealing approach for C−C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp3)−H bonds employing readily available aldehyde as "acyl source" involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp3)−H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho‐cyanoiodobenzene is essential in the oxidative radical N‐heterocyclic carbene catalysis to give a ketyl radical and C(sp3) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C−C formations in high efficiency under a metal‐ and light‐free catalytic conditions. Moreover, the prepared products show promising anti‐bacterial activities that shall encourage further investigations on novel agrochemical development. [ABSTRACT FROM AUTHOR]

Developing methods to directly transform C(sp3) −H bonds is crucial in synthetic chemistry due to their prevalence in various organic compounds. While conventional protocols have largely relied on transition metal catalysis, recent advancements in organocatalysis, particularly with radical NHC catalysis have sparked interest in the direct functionalization of “inert” C(sp3) −H bonds for cross C−C coupling with carbonyl moieties. This strategy involves selective cleavage of C(sp3) −H bonds to generate key carbon radicals, often achieved via hydrogen atom transfer (HAT) processes. By leveraging the bond dissociation energy (BDE) and polarity effects, HAT enables the rapid functionalization of diverse C(sp3)−H substrates, such as ethers, amines, and alkanes. This mini‐review summarizes the progress in carbene organocatalytic functionalization of inert C(sp3)−H bonds enabled by HAT processes, categorizing them into two sections: 1) C−H functionalization involving acyl azolium intermediates; and 2) functionalization of C−H bonds via reductive Breslow intermediates. [ABSTRACT FROM AUTHOR]