The dual incorporation of two important functional groups—trifluoromethyl and cyano moieties into one heterocyclic core in a single-step reaction represents an appealing but largely unaddressed synthetic challenge.He...The dual incorporation of two important functional groups—trifluoromethyl and cyano moieties into one heterocyclic core in a single-step reaction represents an appealing but largely unaddressed synthetic challenge.Here we demonstrate that a silver-catalyzed[3+2]cycloaddition reaction of dicyanoalkenes with trifluorodiazoethane(CF_(3)CHN2)could render a facile construction of a unique category of pyrazoles that are simultaneously adorned by trifluoromethyl and cyano groups.Changing the location pattern of the cyano group in starting dicyanoalkene material allows regiodivergent access to two series of previously elusive trifluoromethyl cyanopyrazoles with an exquisite level of regiocontrol.Thus,this method could be applied in the preparation of cyano-analogues of CF_(3)-containing drugs(Celecoxib)and agrochemicals(Penthiopyrad and Fluazolate).Notably,several cyano-analogues of Celecoxib demonstrate enhanced inhibitory activity towards cyclooxygenase-2(COX-2),thereby laying a good foundation for developing new lead-based antiinflammatory agents.展开更多
基金This work is supported by the National Natural Science Foundation of China(grant nos.92156025,21901181,and 21961142015)the National Key Research and Development Program of China(grant nos.2019YFA0905100 and 2021YFF0701700)Tianjin Municipal Science and Technology Commission(grant no.19JCQNJC04700).
文摘The dual incorporation of two important functional groups—trifluoromethyl and cyano moieties into one heterocyclic core in a single-step reaction represents an appealing but largely unaddressed synthetic challenge.Here we demonstrate that a silver-catalyzed[3+2]cycloaddition reaction of dicyanoalkenes with trifluorodiazoethane(CF_(3)CHN2)could render a facile construction of a unique category of pyrazoles that are simultaneously adorned by trifluoromethyl and cyano groups.Changing the location pattern of the cyano group in starting dicyanoalkene material allows regiodivergent access to two series of previously elusive trifluoromethyl cyanopyrazoles with an exquisite level of regiocontrol.Thus,this method could be applied in the preparation of cyano-analogues of CF_(3)-containing drugs(Celecoxib)and agrochemicals(Penthiopyrad and Fluazolate).Notably,several cyano-analogues of Celecoxib demonstrate enhanced inhibitory activity towards cyclooxygenase-2(COX-2),thereby laying a good foundation for developing new lead-based antiinflammatory agents.
