Regioselective [3+2] cycloaddition of di/trifluoromethylated hydrazonoyl chlorides with fluorinated nitroalkenes: a facile access to 3-di/trifluoroalkyl-5-fluoropyrazoles

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).

Automated summary

Here, we report a base-mediated [3 + 2] cycloaddition reaction between di/trifluoromethylated hydrazonoyl chlorides and fluorinated nitroalkenes. This reaction provides a direct and easy approach to incorporate both a fluorine atom and fluoroalkyl group into pyrazole cores, leading to the synthesis of a diverse range of densely functionalized 3-di/trifluoroalkyl-5-fluoropyrazoles with high yields and excellent regioselectivities. Moreover, several drug-like 3-di/trifluoroalkyl-5-fluoropyrazoles have been synthesized and shown to exhibit potent inhibitory activities against cyclooxygenase 2 (COX-2).