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1. Catalytic β C–H amination via an imidate radical relay

   https://doi.org/10.1039/c8sc05685d  

   Stateman, Leah M.; Wappes, Ethan A.; Nakafuku, Kohki M.; Edwards, Kara M.; Nagib, David A. (February 2019, Chemical Science)

   null (Ed.)

   The first catalytic strategy to harness imidate radicals for C–H functionalization has been developed. This iodine-catalyzed approach enables β C–H amination of alcohols by an imidate-mediated radical relay. In contrast to our first-generation, (super)stoichiometric protocol, this catalytic method enables faster and more efficient reactivity. Furthermore, lower oxidant concentration affords broader functional group tolerance, including alkenes, alkynes, alcohols, carbonyls, and heteroarenes. Mechanistic experiments interrogating the electronic nature of the key 1,5 H-atom transfer event are included, as well as probes for chemo-, regio-, and stereo-selectivity. 

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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. Copper Catalyzed Benzylic sp ³ C-H Alkenylation

   https://doi.org/10.1039/D4SC03430A  

   Chen, Ting-An; Staples, Richard J; Warren, Timothy H (September 2024, Chemical Science)

   The prenyl group is present in numerous biologically active small molecule drugs and natural products. We introduce benzylic C-H alkenylation of substrates Ar-CH3 with alkenylboronic esters (CH2)3O2B-CH=CMe2 as a pathway to form prenyl functionalized arenes Ar-CH2CH=CMe2. Mechanistic studies of this radical relay catalytic protocol reveal diverse reactivity pathways exhibited by the copper(II) vinyl intermediate [CuII]-CH=CMe2 that involve radical capture, bimolecular C-C bond formation, and hydrogen atom transfer (HAT). 

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4. Remote C–H Functionalization via Selective Hydrogen Atom Transfer

   https://doi.org/10.1055/s-0036-1591930  

   Stateman, Leah; Nakafuku, Kohki; Nagib, David (April 2018, Synthesis)

   The selective functionalization of remote C–H bonds via intramolecular hydrogen atom transfer (HAT) is transformative for organic synthesis. This radical-mediated strategy provides access to novel reactivity that is complementary to closed-shell pathways. As modern methods for mild generation of radicals are continually developed, inherent selectivity paradigms of HAT mechanisms offer unparalleled opportunities for developing new strategies for C–H functionalization. This review outlines the history, recent advances, and mechanistic underpinnings of intramolecular HAT as a guide to addressing ongoing challenges in this arena. 1 Introduction 2 Nitrogen-Centered Radicals 2.1 sp3 N-Radical Initiation 2.2 sp2 N-Radical Initiation 3 Oxygen-Centered Radicals 3.1 Carbonyl Diradical Initiation 3.2 Alkoxy Radical Initiation 3.3 Non-alkoxy Radical Initiation 4 Carbon-Centered Radicals 4.1 sp2 C-Radical Initiation 4.2 sp3 C-Radical Initiation 5 Conclusion 

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5. A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor

   https://doi.org/10.1038/s41467-021-27165-z  

   Leibler, Isabelle Nathalie-Marie; Tekle-Smith, Makeda A.; Doyle, Abigail G. (November 2021, Nature Communications)

   Abstract Photoredox catalysis has provided many approaches to C(sp³)–H functionalization that enable selective oxidation and C(sp³)–C bond formation via the intermediacy of a carbon-centered radical. While highly enabling, functionalization of the carbon-centered radical is largely mediated by electrophilic reagents. Notably, nucleophilic reagents represent an abundant and practical reagent class, motivating the interest in developing a general C(sp³)–H functionalization strategy with nucleophiles. Here we describe a strategy that transforms C(sp³)–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. The resulting carbocation is functionalized by a variety of nucleophiles—including halides, water, alcohols, thiols, an electron-rich arene, and an azide—to effect diverse bond formations. Mechanistic studies indicate that HAT is mediated by methyl radical—a previously unexplored HAT agent with differing polarity to many of those used in photoredox catalysis—enabling new site-selectivity for late-stage C(sp³)–H functionalization. 

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