Synthesis of 4-fluoroalkyl-substituted pyridazines from fluorinated diazodiketones

Two approaches are reported for the preparation of 3,4,6-trisubstituted pyridazines from fluoroalkyl-containing diazodiketones: the sequence of Wittig/Staudinger/diaza-Wittig and Staudinger/Wittig/diaza-Wittig reactions. The implementation of the Wittig reaction at the first stage gives rise to considerably higher yields of the targeted pyridazines than through initial phosphazines. In both approaches the final stages of the synthesis (the formation of vinylphosphazines and the subsequent diaza-Wittig reaction) occur as a tandem process. RF-activated carbonyls are much more reactive in Wittig olefination of diazodicarbonyl and 1,3-dioxophosphazine molecules, than non-fluorinated acyl and aroyl carbonyl groups (RFCO ≫ COAlk, COAr), and as a result non-fluorinated diazodiketones and their phosphazines do not produce pyridazines under the same conditions.

Graphical abstractThe synthesis of 4-fluoroalkyl-containing 3,4,6-trisubstituted pyridazines from fluorinated diazodiketones using Wittig, Staudinger, diaza-Wittig or Staudinger, Wittig, diaza-Wittig reaction sequences is described. Figure optionsDownload full-size imageDownload as PowerPoint slide