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1. δ C–H (hetero)arylation via Cu-catalyzed radical relay

   https://doi.org/10.1039/c8sc04366c  

   Zhang, Zuxiao; Stateman, Leah M.; Nagib, David A. (January 2019, Chemical Science)

   null (Ed.)

   A Cu-catalyzed strategy has been developed that harnesses a radical relay mechanism to intercept a distal C-centered radical for C–C bond formation. This approach enables selective δ C–H (hetero)arylation of sulfonamides via intramolecular hydrogen atom transfer (HAT) by an N-centered radical. The radical relay is both initiated and terminated by a Cu catalyst, which enables incorporation of arenes and heteroarenes by cross-coupling with boronic acids. The broad scope and utility of this catalytic method for δ C–H arylation is shown, along with mechanistic probes for selectivity of the HAT mechanism. A catalytic, asymmetric variant is also presented, as well as a method for accessing 1,1-diaryl-pyrrolidines via iterative δ C–H functionalizations. 

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2. β C–H di-halogenation via iterative hydrogen atom transfer

   https://doi.org/10.1039/C8SC01214H  

   Wappes, Ethan A.; Vanitcha, Avassaya; Nagib, David A. (January 2018, Chemical Science)

   A radical relay strategy for mono- and di-halogenation (iodination, bromination, and chlorination) of sp³C–H bonds has been developed. This first example of double, geminal C–H functionalization is enabledviaiterative, hydrogen atom transfer (HAT) byin situgenerated imidate radicals. 

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3. Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of N -alkylbenzamides

   https://doi.org/10.1039/d2sc01962k  

   Rand, Alexander W.; Chen, Mo; Montgomery, John (September 2022, Chemical Science)

   A mechanistic study on the α-arylation of N -alkylbenzamides catalyzed by a dual nickel/photoredox system using aryl bromides is reported herein. This study elucidates the origins of site-selectivity of the transformation, which is controlled by the generation of a hydrogen atom transfer (HAT) agent by a photocatalyst and bromide ions in solution. Tetrabutylammonium bromide was identified as a crucial additive and source of a potent HAT agent, which led to increases in yields and a lowering of the stoichiometries of the aryl bromide coupling partner. NMR titration experiments and Stern–Volmer quenching studies provide evidence for complexation to and oxidation of bromide by the photocatalyst, while elementary steps involving deprotonation of the N -alkylbenzamide or 1,5-HAT were ruled out through mechanistic probes and kinetic isotope effect analysis. This study serves as a valuable tool to better understand the α-arylation of N -alkylbenzamides, and has broader implications in halide-mediated C–H functionalization reactions. 

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4. C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals

   https://doi.org/10.1039/D0SC04881J  

   Sarkar, Sumon; Cheung, Kelvin Pak; Gevorgyan, Vladimir (December 2020, Chemical Science)

   null (Ed.)

   Selective functionalization of ubiquitous unactivated C–H bonds is a continuous quest for synthetic organic chemists. In addition to transition metal catalysis, which typically operates under a two-electron manifold, a recent renaissance in the radical approach relying on the hydrogen atom transfer (HAT) process has led to tremendous growth in the area. Despite several challenges, protocols proceeding via HAT are highly sought after as they allow for relatively easy activation of inert C–H bonds under mild conditions leading to a broader scope and higher functional group tolerance and sometimes complementary reactivity over methods relying on traditional transition metal catalysis. A number of methods operating via heteroatom-based HAT have been extensively reported over the past few years, while methods employing more challenging carbon analogues have been less explored. Recent developments of mild methodologies for generation of various carbon-centered radical species enabled their utilization in the HAT process, which, in turn, led to the development of remote C(sp 3 )–H functionalization reactions of alcohols, amines, amides and related compounds. This review covers mostly recent advances in C–H functionalization reactions involving the HAT step to carbon-centered radicals. 

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5. CdS Quantum Dot Gels as a Direct Hydrogen Atom Transfer Photocatalyst for C−H Activation

   https://doi.org/10.1002/anie.202403186  

   Liu, Daohua; Hazra, Atanu; Liu, Xiaolong; Maity, Rajendra; Tan, Ting; Luo, Long (August 2024, Angewandte Chemie International Edition)

   Abstract Here, we report CdS quantum dot (QD) gels, a three‐dimensional network of interconnected CdS QDs, as a new type of direct hydrogen atom transfer (d‐HAT) photocatalyst for C−H activation. We discovered that the photoexcited CdS QD gel could generate various neutral radicals, including α‐amido, heterocyclic, acyl, and benzylic radicals, from their corresponding stable molecular substrates, including amides, thio/ethers, aldehydes, and benzylic compounds. Its C−H activation ability imparts a broad substrate and reaction scope. The mechanistic study reveals that this reactivity is intrinsic to CdS materials, and the neutral radical generation did not proceed via the conventional sequential electron transfer and proton transfer pathway. Instead, the C−H bonds are activated by the photoexcited CdS QD gel via a d‐HAT mechanism. This d‐HAT mechanism is supported by the linear correlation between the logarithm of the C−H bond activation rate constant and the C−H bond dissociation energy (BDE) with a Brønsted slopeα=0.5. Our findings expand the currently limited direct hydrogen atom transfer photocatalysis toolbox and provide new possibilities for photocatalytic C−H activation. 

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