Dual Incorporation of Trifluoromethyl and Cyano Groups into Pyrazole Pharmcophores via Silver-Catalyzed Cycloaddition Reaction of Trifluorodiazoethane  

作　　者：Cheng-Feng Gao Yin Zhou Hai Ma Yue Zhang Jing Nie Fa-Guang Zhang Jun-An Ma 

机构地区：[1]Department of Chemistry,Tianjin Key Laboratory of Molecular Optoelectronic Sciences,Frontiers Science Center for Synthetic Biology,Ministry of Education,Tianjin Collaborative Innovation Centre of Chemical Science and Engineering,Tianjin University,Tianjin 300072 [2]Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700

出　　处：《CCS Chemistry》2022年第12期3693-3704,共12页中国化学会会刊（英文）

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).

摘　　要：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.

关 键 词：PYRAZOLES trifluoromethyl group cyano group silver catalysis diazo reagents 

分 类 号：O62[理学—有机化学]