In Situ Generation of Difluoromethyl Diazomethane for [3+2] Cycloadditions with Alkynes†
Corresponding Author
Dr. Pavel K. Mykhailiuk
Enamine Ltd. Matrosova 23, 01103 Kyiv (Ukraine) http://www.enamine.net
Taras Shevchenko National University of Kyiv, Chemistry Department, Volodymyrska 64, 01601 Kyiv (Ukraine)
Enamine Ltd. Matrosova 23, 01103 Kyiv (Ukraine) http://www.enamine.netSearch for more papers by this authorCorresponding Author
Dr. Pavel K. Mykhailiuk
Enamine Ltd. Matrosova 23, 01103 Kyiv (Ukraine) http://www.enamine.net
Taras Shevchenko National University of Kyiv, Chemistry Department, Volodymyrska 64, 01601 Kyiv (Ukraine)
Enamine Ltd. Matrosova 23, 01103 Kyiv (Ukraine) http://www.enamine.netSearch for more papers by this authorAll chemicals were provided by Enamine Ltd. I am grateful to Dr. S. Shishkina for X-ray studies, to Prof. T. Brigaud for insightful comments on the reaction mechanism, to R. Iminov, B. Chalyk, V. Arkhipov, and O. Mashkov for their help with managing this work, and to C. Thinnes and Dr. V. Kubyshkin for proofreading the manuscript.
Graphical Abstract
A new reagent: The elusive chemical reagent CF2HCHN2 was generated in situ for the first time and further reacted with alkynes in a [3+2] cycloaddition reaction. This transformation constitutes a novel and efficient approach to agrochemically important difluoromethylated pyrazoles.
Abstract
A novel approach to agrochemically important difluoromethyl-substituted pyrazoles has been developed based on the elusive reagent CF2HCHN2, which was synthesized (generated in situ) for the first time and employed in [3+2] cycloaddition reactions with alkynes. The reaction is extremely practical as it is a one-pot process, does not require a catalyst or the isolation of the potentially toxic and explosive gaseous intermediate, and proceeds in a common solvent, namely chloroform, in air. The reaction is also scalable and allows for the preparation of the target pyrazoles on gram scale.
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