Synthesis of functionalized 4-fluoropyridazines

A route to novel 4-fluoropyridazines by a [2+1]/[3+2]-cycloaddition sequence between acetylenic derivatives, a difluorocarbene source and diazo compounds is reported. This sequence features high modularity, broad functional group compatibility, and does not require the isolation of any reactive intermediates, thus allowing access to a wide range of 4-fluoropyridazines in a single synthetic step from simple alkynes. Furthermore, these fluorinated compounds can be easily diversified by an aromatic nucleophilic substitution (SNAr) of the fluorine atom, to give a wider range of 3,4,6-trisubstituted pyridazines. Given the increasing interest in functionalized pyridazines as well as fluorinated derivatives, this efficient and concise approach to 4-fluoropyridazines, should be of interest for medicinal chemists.