Regioselective difunctionalization of arenes remains a long-standing challenge in organic chemistry. We report a novel and general Fe/Ti synergistic methodology for regioselective synthesis of various polysubstituted arenes through either E/E' or Nu/E difunctionalizations of arenes. Preliminary results showed that an unprecedented 1,2-Fe/Ti heterobimetallic arylene intermediate bearing two distinct C-M bonds is essential to the regioselective difunctionalization.
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http://dx.doi.org/10.1021/jacs.2c13207 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.
The azidofunctionalization of alkenes under mild conditions using commercially available starting materials and easily accessible reagents is reported based on a radical-polar crossover strategy. A broad range of alkenes, including vinyl arenes, enamides, enol ethers, vinyl sulfides, and dehydroamino esters, were regioselectively functionalized with an azide and nucleophiles such as azoles, carboxylic acids, alcohols, phosphoric acids, oximes, and phenols. The method led to a more efficient synthesis of 1,2-azidofunctionalized pharmaceutical intermediates when compared to previous approaches, resulting in both reduction of step count and increase in overall yield.
View Article and Find Full Text PDFOrg Lett
January 2025
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China.
A Ni-catalyzed protocol for the regioselective and stereoselective three-component fluoroalkylthiolation of alkynes with fluoroalkyl halides and thiosulfonates is presented. This reductive difunctionalization provides an efficient strategy for the rapid construction of fluoroalkyl-incorporated vinylthioethers under mild conditions in moderate to good yields.
View Article and Find Full Text PDFJ Org Chem
December 2024
College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001, Zhejiang, China.
In this work, a switchable synthesis of β-ketosulfone and α-chloroketone through a radical difunctionalization of alkenes is reported. The transformation works well under iron peroxo species/photoredox dual catalysis and an open-flask atmosphere, and the reaction is highlighted with good yields and a broad reaction scope. Mechanism studies show that the reaction is initiated by a formal [4 + 2] cyclization of the sulfonyl radical in a regioselective manner.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Org Lett
December 2024
School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255000, Shandong, P. R. China.
A nickel-catalyzed intermolecular three-component 1,1-difunctionalization of unactivated alkenes with quinoxaline/naphthoquinone and arylboronic acids via organometallic-radical relay is developed. This efficient protocol provides a new method to access a variety of arylalkanes in moderate to good yields with a broad substrate scope and excellent functional group tolerance. The mechanistic studies provide insights into the mechanism and origin of chemo- and regioselectivity as well as confirm the generation of functionalized benzylic radicals.
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