Synthesis of Functionalized 4-Fluoropyridazines

A route to 4-fluoropyridazines by a [2+1]/[3+2] cycloaddition sequence between an acetylenic derivative, a difluorocarbene source, and a diazo compound is reported. This approach is highly modular and compatible with a broad range of functional groups. The protocol does not require the isolation of any reactive intermediates and, thus, allows for 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 nucleophilic aromatic substitution (SNAr) to displace the fluoro group to give a wider range of 3,4,6-trisubstituted pyridazines. As a result of increasing interest in functionalized pyridazines as well as fluorinated derivatives, this efficient and concise approach to 4-fluoropyridazines should be of value to medicinal chemists.