C-H bond functionalization generates molecular complexity in single-step transformation. However, the activation of C-H bonds requires expensive metals or stoichiometric amounts of oxidizing/reducing species. In many cases, they often require pre-functionalization of starting molecules. Such pre-activating measures cause waste generation and their separation from the final product is also troublesome. In such a scenario, reactions activating elements generating from renewable energy resources such as electricity and light would be more efficient, green, and cost-effective. Further, incorporation of growing flow technology in chemical transformation processes will accelerate the safer accesses of valuable products. Arenes & heteroarenes are ubiquitous in pharmaceuticals, natural products, medicinal compounds, and other biologically important molecules. Herein, we discussed enabling tools and technologies used for the recent C-H bonds functionalization of arenes and heteroarenes.
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http://dx.doi.org/10.1002/tcr.202300119 | DOI Listing |
Chem Commun (Camb)
January 2025
College of Materials, Chemistry & Chemical Engineering, Chengdu University of Technology, Chengdu 610059, China.
Due to the special structure and physicochemical properties of sulfoximines, research on sulfoximines has achieved great progress in recent decades, especially in chemical and medicinal fields. This review highlights recent advancements in the N-functionalization of NH-sulfoximines, focusing on classical cross-coupling reactions with electrophilic agents and oxidative coupling reactions with extensive organic compounds, including specific (hetero)arenes, alkenes (1,4-naphthoquinones), alkanes (cyclohexanes), nucleophiles (thiols, disulfides, sulfinates, diarylphosphine oxides), organyl boronic acids, and arylhydrazines. Transition metal-catalyzed, metal-free, electrochemical and radical oxidative coupling reactions are discussed.
View Article and Find Full Text PDFNat Commun
December 2024
National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, P.R. China.
Skeleton editing for heteroarenes, especially pyrazoles, is challenging and remains scarce because these non-strained aromatics exhibit inert reactivities, making them relatively inactive for performing a dearomatization/cleavage sequence. Here, we disclose a cycloaddition-induced scaffold hopping of 5-hydroxypyrazoles to access the pyrazolopyridopyridazin-6-one skeleton through a single-operation protocol. By converting a five-membered aza-arene into a five-unit spine of a 6/6 fused-bicyclic, this work unlocks a ring-opening reactivity of the pyrazole core that involves a formal C = N bond cleavage while retaining the highly reactive N-N bond in the resulting product.
View Article and Find Full Text PDFACS Catal
December 2024
Organic Chemistry Department and Center for Innovation in Advanced Chemistry (ORFEO-CINQA), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain.
Herein, we demonstrate the ability of isonitriles to be used as alkyl radical precursors in a photoredox-catalyzed transformation involving selective C-N cleavage and Csp-Csp bond formation. This protocol allows for the preparation of functionalized heteroarenes from readily available isonitriles through a decyanation process. The reaction is general for primary, secondary, and tertiary substrates, including amino acid derivatives and druglike molecules.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Institute for Organic Chemistry, University of Regensburg, 93053 Regensburg, Germany.
Diarylmethanes play, in part, a pivotal role in the design of highly potent, chiral, nonracemic drugs whose bioactivity is typically affected by the substitution pattern of their arene units. In this context, certain arenes such as -substituted benzenes or unsubstituted heteroarenes cause particular synthetic challenges, since such isosteric residues at the central methane carbon atom are typically indistinguishable for a chiral catalyst. Hence, the stereoselective incorporation of isosteric (hetero)arenes into chiral methane scaffolds requires the use of stoichiometrically differentiated building blocks, which is typically realized through preceding redox-modifying operations such as metalation or halogenation and thus associated with disadvantageous step- and redox-economic traits.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH, 43210, United States.
We report copper(II) and copper(III) trifluoromethyl complexes supported by a pyridinedicarboxamide ligand (L) as a platform for investigating the role of electron transfer in C(sp)-H trifluoromethylation. While the copper(II) trifluoromethyl complex is unreactive towards (hetero)arenes, the formal copper(III) trifluoromethyl complex performs C(sp)-H trifluoromethylation of a wide range of (hetero)arenes. Mechanistic studies using the copper(III) trifluoromethyl complex suggest that the mechanism of arene trifluoromethylation is substrate-dependent.
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