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

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