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1. Recent Advances in Metal‐Catalyzed Functionalization of Indoles

   https://doi.org/10.1002/adsc.202100116  

   Urbina, Kelvin; Tresp, David; Sipps, Karli; Szostak, Michal (April 2021, Advanced Synthesis & Catalysis)

   Abstract Indole is one of the most important heterocycles in organic synthesis, natural products, and drug discovery. Recently, tremendous advances in the selective functionalization of indoles have been reported. Although the most important advances have been powered by transition metal catalysis, exceedingly useful methods in the absence of transition metals have also been reported. In this review, we provide an overview of functionalization reactions of indoles that have been published in the last years with a focus on the most recent advances, aims, and future trends. The review is organized by the positional selectivity and type of methods used for functionalization. In particular, we discuss major advances in transition‐metal‐catalyzed C−H functionalization at the classical C2/C3 positions, transition‐metal‐catalyzed C−H functionalization at the remote C4/C7 positions, transition‐metal‐catalyzed cross‐coupling, and transition‐metal‐free functionalization. magnified image 

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2. Synthesis of Natural Products by C−H Functionalization of Heterocycless

   https://doi.org/10.1002/chem.202104278  

   Zhang, Yang; Szostak, Michal (February 2022, Chemistry – A European Journal)

   Abstract Total synthesis is considered by many as the finest combination of art and science. During the last decades, several concepts were proposed for achieving the perfect vision of total synthesis, such as atom economy, step economy, or redox economy. In this context, C−H functionalization represents the most powerful platform that has emerged in the last years, empowering rapid synthesis of complex natural products and enabling diversification of bioactive scaffolds based on natural product architectures. In this review, we present an overview of the recent strategies towards the total synthesis of heterocyclic natural products enabled by C−H functionalization. Heterocycles represent the most common motifs in drug discovery and marketed drugs. The implementation of C−H functionalization of heterocycles enables novel tactics in the construction of core architectures, but also changes the logic design of retrosynthetic strategies and permits access to natural product scaffolds with novel and enhanced biological activities. 

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3. Recent Strategies in Nickel-Catalyzed C–H Bond Functionalization for Nitrogen-Containing Heterocycles

   https://doi.org/10.3390/catal12101163  

   Yang, Ke; Li, Zhi; Hu, Qingyue; Elsaid, Mazen; Liu, Chong; Chen, Jun; Ge, Haibo (October 2022, Catalysts)

   N-heterocycles are ubiquitous in natural products, pharmaceuticals, organic materials, and numerous functional molecules. Among the current synthetic approaches, transition metal-catalyzed C–H functionalization has gained considerable attention in recent years due to its advantages of simplicity, high atomic economy, and the ready availability of starting materials. In the field of N-heterocycle synthesis via C–H functionalization, nickel has been recognized as one of the most important catalysts. In this review, we will introduce nickel-catalyzed intramolecular and intermolecular pathways for N-heterocycle synthesis from 2008 to 2021. 

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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. 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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