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(Hetero)arenes continue to prove their indispensability in pharmaceuticals, materials science, and synthetic chemistry. As such, the controllable modification of biologically significant (hetero)arenes towards diverse more‐potent complex molecular scaffolds through peripheral and skeletal editing has been considered a challenging goal in synthetic organic chemistry. Despite many excellent reviews on peripheral editing (i. e., C−H functionalization) of (hetero)arenes, their skeletal editings via single atom insertion, deletion, or transmutations have received less attention in the review literature. In this review, we systematically summarize the state‐of‐the‐art skeletal editing reactions of (hetero)arenes using carbenes, with a focus on general mechanistic considerations and their applications in natural product syntheses. The potential opportunities and inherent challenges encountered while developing these strategies are also highlighted. [ABSTRACT FROM AUTHOR]

Catalytic carbene transfer reactions are fundamental transformations in modern organic synthesis, which enable direct access to diverse structurally complex molecules. Despite diazo precursors playing a crucial role in catalytic carbene transfer reactions, most reported methodologies take into account only diazoacetates or related compounds. This is primarily because diazoalkanes, unless they contain a resonance stabilizing group, are more susceptible to violent exothermic decomposition. In this feature article, we present an alternative approach to carbene-transfer reactions based on the formation of highly electrophilic silver carbenes from N-sulfonylhydrazones, where the high electrophilicity of silver carbenes stems from the weak interaction between silver and the carbenic carbon. These precursors are readily accessible, stable, and environmentally sustainable. Using the strategy that employs highly electrophilic silver carbenes, it is possible to develop novel intermolecular transformations involving non-stabilized carbenes, including C(sp3)–H insertion, C(sp3)–C(O) insertion, cycloaddition, and defluorinative functionalization. The silver-catalyzed carbene transfer reactions described here have high efficiency, unusual reactivity, exceptional selectivity, and a reaction pathway that differs from typical transition metal-catalyzed reactions. Our research provided fundamental insight into silver carbene chemistry, and we hope to apply this mode of catalysis to other more general transformations, including asymmetric transformations. [ABSTRACT FROM AUTHOR]

The insertion of carbenes into the α-C–H bonds of ethers represents one of the most powerful approaches to access polysubstituted α-branched ethers. However, intermolecular carbene insertions remain challenging, since current approaches are generally limited to the use of toxic and potentially explosive α-diazocarbonyl compounds. We now report a silver-catalyzed α-C–H benzylation of ethers using bench-stable N-triftosylhydrazones as safe and convenient carbene precursors. This approach is well suited for both inter- and intramolecular insertions to deliver medicinally relevant homobenzylic ethers and 5–8-membered oxacycles in good yields. The synthetic utility of this strategy is demonstrated by its easy scalability, broad scope with valuable functional groups, high regioselectivity, and late-stage functionalization of complex oxygen-containing molecules. The relative reactivities of different types of silver carbenes and C−H bonds were also investigated by experments and DFT calculations. A state-of-the-art tool in synthetic organic chemistry is a rhodium diazocarbene species, which despite its flexibility, is derived from expensive and highly reactive species. Here the authors present a methodology for C–H benzylation of ethers via an analogous silver carbene species, obtained from a more common metal and a more stable starting material. [ABSTRACT FROM AUTHOR]

Sulfinyl radicals – one of the fundamental classes of S-centered radicals – have eluded synthetic application in organic chemistry for over 60 years, despite their potential to assemble valuable sulfoxide compounds. Here we report the successful generation and use of sulfinyl radicals in a dual radical addition/radical coupling with unsaturated hydrocarbons, where readily-accessed sulfinyl sulfones serve as the sulfinyl radical precursor. The strategy provides an entry to a variety of previously inaccessible linear and cyclic disulfurized adducts in a single step, and demonstrates tolerance to an extensive range of hydrocarbons and functional groups. Experimental and theoretical mechanistic investigations suggest that these reactions proceed through sequential sulfonyl and sulfinyl radical addition. Sulfinyl radicals are an underexplored synthon in organic chemistry due to the fact that they reversibly add to pi systems and undergo homodimerization. Here the authors synthesize sulfonyl sulfones, previously thought to be unstable, and demonstrate their broad use as sulfinyl radical precursors in disulfurizations of alkenes and alkynes. [ABSTRACT FROM AUTHOR]

Despite the growing importance of volatile functionalized diazoalkanes in organic synthesis, their safe generation and utilization remain a formidable challenge because of their difficult handling along with storage and security issues. In this study, we developed a bench‐stable difluoroacetaldehyde N‐triftosylhydrazone (DFHZ‐Tfs) as an operationally safe diazo surrogate that can release in situ two low‐molecular‐weight diazoalkanes, diazoacetaldehyde (CHOCHN2) or difluorodiazoethane (CF2HCHN2), in a controlled fashion under specific conditions. DFHZ‐Tfs has been successfully employed in the Fe‐catalyzed cyclopropanation and Doyle–Kirmse reactions, thus highlighting the synthetic utility of DFHZ‐Tfs in the efficient construction of molecule frameworks containing CHO or CF2H groups. Moreover, the reaction mechanism for the generation of CHOCHN2 from CF2HCHN2 was elucidated by density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]