Copper-mediated oxidative [3+2]-annulation of nitroalkenes and pyridinium imines: efficient synthesis of 3-fluoro- and 3 nitro-pyrazolo[1,5-a]pyridines

An efficient route to pyrazolo[1,5-a]pyridines by Cu(OAc)2∙H2O-promoted oxidative [3+2]-annulation of nitroalkenes with in situ generated pyridinium imines was developed. The reaction with α-fluoronitroalkenes provides the first preparative synthesis of 3-fluoro-pyrazolo[1,5-a]pyridines. The cycloaddition with α-unsubstituted nitroalkenes opens access to 3 nitro-pyrazolo[1,5-a]pyridines in excellent yields. Broad scope of transformation was demonstrated. Both electron-rich and electron-deficient nitroalkenes as well as different aminopyridinium salts can be used for the assembly of target pyrazolo[1,5-a]pyridines. The related aza-heterocycles, namely, pyrazolo[1,5-a]-pyrazines and pyrazolo[1,5-a]pyridazines were successfully prepared via the present methodology. Possible mechanism of the reaction is discussed.