Fluoride-Assisted Synthesis of 1,4,5,6-Tetrahydropyridazines via [4 + 2] Cyclodimerization of in Situ-Generated Azoalkenes Followed by a C–N Bond Cleavage

An unexpected CsF-assisted C–N
bond cleavage was exploited
to synthesize highly functionalized and biologically important 1,4,5,6-tetrahydropyridazine
derivatives from α-halo N-acylhydrazones in
excellent yields. The extrusion of nitrogen and the [4 + 2] cycloaddition
between in situ-generated azoalkenes is a key reaction in the process.
The identified methodology is suitable for synthesizing a wide variety
of analogues of tetrahydropyridazines, which are prevalent in many
medicinally important small molecules. The reaction conditions are
mild, high-yielding, and amenable for the gram scale.