A novel approach towards highly functionalized fluoroalkyl pyrazoles was developed by using fluoroalkyl amino reagents in combination with a variety of fluorinated ketimines. Tuneable introduction of fluoroalkyl groups in the 3- and 5-positions was possible by using vinamidinium intermediates or the corresponding enamino ketones after hydrolysis. These high-value building blocks can give rise to a large number of analogues for bioactivity screening and discovering new heterocyclic bioactive ingredients in various life science fields.
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http://dx.doi.org/10.1002/chem.201601621 | DOI Listing |
Org Biomol Chem
January 2025
College of Chemistry and Chemical Engineering, Northwest Normal University, 967 Anning East Road, Lanzhou 730070, P. R. China.
An efficient [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with trifluoromethyl-substituted alkenes was investigated to produce a variety of 3,5-bis(fluoroalkyl)pyrazoles/pyrazolines in moderate to good yields. This protocol features obvious advantages such as easily available and stable substrates, step economy, gram-scalability and simple operation, providing a novel and practical method for the preparation of 3,5-bis(fluoroalkyl)pyrazoles/pyrazolines.
View Article and Find Full Text PDFOrg Lett
July 2024
State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.
We disclose an efficient nickel catalytic system for expediting the coupling of alkynes with fluoroalkyl hydrazones and boronic acids, thus facilitating the synthesis of stereospecific α-fluoroalkyl-alkene derivatives. 3-Pyrazoles might be involved as key intermediates through a nitrogen-releasing process, enabling subsequent coupling with boronic acids to afford 1,2-difunctional alkenes in a highly efficient and step-economical fashion. This tandem platform demonstrates broad functional group tolerance, including complex natural products and drug-like molecules.
View Article and Find Full Text PDFMolecules
October 2023
Organisch-Chemisches Institut and Center for Multiscale Theory and Computation (CMTC), Universität Münster, Corrensstrasse 40, D-48149 Münster, Germany.
The in situ-generated -aryl nitrile imines derived from trifluoroacetonitrile smoothly undergo (3+2)-cycloadditions onto the enone fragment of the levoglucosenone molecule, yielding the corresponding, five-membered cycloadducts. In contrast to the 'classic' (Ph),(Ph) nitrile imine, reactions with fluorinated (CF),(Ar) analogues lead to stable pyrazolines in a chemo- and stereoselective manner. Based on the result of X-ray single crystal diffraction analysis, their structures were established as -cycloadducts with the location of the -Ar terminus of the 1,3-dipole at the α-position of the enone moiety.
View Article and Find Full Text PDFOrganometallics
April 2023
University of Michigan, Department of Chemistry, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
This report describes the reactions between -heterocyclic carbene copper(I) fluoroalkyl complexes and aryl halides bearing -directing groups. Pyridine, pyrazole, oxazoline, imine, and ester directing groups are shown to dramatically enhance the reactivity of aryl bromides and chlorides with (IPr)Cu-fluoroalkyl complexes (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; fluoroalkyl = difluoromethyl and pentafluoroethyl) to afford aryl-fluoroalkyl coupling products. This approach is leveraged to achieve the Cu-catalyzed directed fluoroalkylation of a series of aryl bromide substrates.
View Article and Find Full Text PDFOrg Biomol Chem
June 2023
Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Frontiers Science Center for Synthetic Biology (Ministry of Education), and Tianjin Collaborative Innovation Centre of Chemical Science and Engineering, Tianjin University, Tianjin 300072, P. R. of China.
Herein we describe the base-mediated [3 + 2] cycloaddition reaction of di/trifluoromethylated hydrazonoyl chlorides with fluorinated nitroalkenes. The reaction protocol provides a direct and facile strategy for the dual incorporation of a fluorine atom and fluoroalkyl group into pyrazole cores, thus allowing rapid access to a wide variety of densely functionalized 3-di/trifluoroalkyl-5-fluoropyrazoles in generally high yields with excellent regioselectivities. Furthermore, several drug-like 3-di/trifluoroalkyl-5-fluoropyrazoles have been synthesized, demonstrating potent inhibitory activities against cyclooxygenase 2 (COX-2).
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