Harnessing the Untapped Potential of Fluoroalkynes

Two novel approaches to the generation of fluoroalkynes will be explored. (1) Elimination reactions of fluoroalkenes: A fluoroalkene derivative bearing a good leaving group Z, and an anion-precursor group Y will act as a precursor for fluoroalkyne generation. Treatment with an appropriate reagent (e.g. fluoride when Y=SiMe3) will lead to elimination via an ionic or radical pathway to generate the fluoroalkyne under mild conditions. This approach has good precedent for the generation of reactive compounds through the many methods used for the formation of benzyne compounds.6 Photochemically initiated elimination processes will also be explored. (2) Nucleophilic substitution of activated alkyne derivatives: This approach will build upon the method recently developed in the Årstad group for fluorination of aromatics via nucleophilic displacement of a sulfonium salt (X=SAr2 as shown, unpublished work). A preliminary DFT calculation by MJP suggests this reaction should be feasible (activation energy of 71 kJmol-1; the corresponding activation energy for fluorination of an arylsulfonium salt was calculated to be 80 kJmol-1). An alternative approach using an iodonium salt will also be investigated. The fluoroalkynes will be generated in the presence of suitable trapping agents which can undergo cyclisation reactions with the reactive triple bond, e.g. diynes (alkyne/nitrile cyclotrimerization to give benzenes/pyridines/pyrimidines), dienes (Diels-Alder reactions to give cyclic aliphatics) or azides/nitrones (1,3-dipolarcycloadditions to give heterocycles). Potential reaction pathways will be explored computationally to select the most suitable trapping agents. The use of metal salts to trap the fluoroalkyne as a stable complex [e.g. Cu(I)], or activate it for reaction with less reactive partners [e.g. Au(I)] will also be studied.