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Radical cascade cyclization of alkenes involving the insertion of sulfur dioxide has proven to be a promising tool to access sulfonylnated heterocycle compounds, whereas cyclization of unactivated alkenes has been much less explored. Here, we developed a three-component cascade of unactive alkenes with sulfur dioxide and aryldiazonium tetrafluoroborates to generate sulfonylated tetrahydropyridines and azepines via the cleavage of alkenyl C-H bonds. Moreover, this protocol exhibited excellent chemical and regioselectivity and compatibility with broad functional groups.
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http://dx.doi.org/10.1021/acs.joc.5c01403 | DOI Listing |
Angew Chem Int Ed Engl
September 2025
State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei, 430079, P.R. China.
Radical-mediated hydroalkylation of alkenes offers a more direct and atom-economical route to α-alkylated carbonyl compounds, enabling the construction of various drug scaffolds, natural products, and functional molecules. However, traditional protocols are generally restricted to active 1,3-dicarbonyl compounds and often require oxidants, large excesses of substrates, and harsh reaction conditions. Herein, we present a photoinduced, general, and practical hydroalkylation of unactivated alkenes with amides.
View Article and Find Full Text PDFJ Org Chem
September 2025
School of Chemistry and Chemical Engineering, Huaibei Normal University, Huaibei, Anhui 235000, P. R. China.
Radical cascade cyclization of alkenes involving the insertion of sulfur dioxide has proven to be a promising tool to access sulfonylnated heterocycle compounds, whereas cyclization of unactivated alkenes has been much less explored. Here, we developed a three-component cascade of unactive alkenes with sulfur dioxide and aryldiazonium tetrafluoroborates to generate sulfonylated tetrahydropyridines and azepines via the cleavage of alkenyl C-H bonds. Moreover, this protocol exhibited excellent chemical and regioselectivity and compatibility with broad functional groups.
View Article and Find Full Text PDFJ Am Chem Soc
August 2025
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, United States.
-vinyl azoles are prevalent moieties in pharmaceuticals, and fluorovinyl groups are widely recognized as carbonyl bioisosteres in drug design. Thus, -fluorovinylated heteroarenes represent highly desirable functional groups in medicinal chemistry. To streamline the development of novel -fluorovinylation and -pentafluoropropenylation reactions, herein we safely handle fluorinated gases, such as vinylidene fluoride (VDF) and hexafluoropropene (HFP), as solid reagents using a metal-organic framework (MOF), Mg(dobdc) (dobdc = 2,5-dioxidobenzene-1,4-dicarboxylate).
View Article and Find Full Text PDFOrg Lett
September 2025
Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, West Bengal, India.
An organophotoredox-catalyzed -Markovnikov addition of the carbamoyl radical generated through the homolytic cleavage of 4-carbamoyl-1,4-dihydropyridine to the challenging unactivated alkene has been developed. Interestingly, the amino acid-derived carbamoyl precursor provided a unique opportunity for -terminus modification of amino acids and peptides. This mild and simple method is suitable for the seamless synthesis and late-stage modification of complex drug molecules and cascade cyclization via radical relay.
View Article and Find Full Text PDFJ Org Chem
September 2025
College of Chemistry and Materials Science, Sichuan Normal University, 5 Jingan Road, Chengdu 610068, People's Republic of China.
A nickel-catalyzed intermolecular hydroamidation of alkenes with dioxazolones has been developed, enabling the efficient synthesis of valuable β- and γ-amino acid derivatives. The presence of a directing group is pivotal to the reaction's success. This methodology is characterized by mild reaction conditions, high regioselectivity, with excellent functional group tolerance, and the elimination of additional ligand requirements.
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