Synthesis and Comparison of the Reactivity of Allyl Fluorides and ...

3
Chapter One
frequently conducted in either high boiling solvents, which aid solubility of the ionic
fluorides, or in anhydrous solvents, which diminish the chances of stray hydrogen bonds
forming, which occur due to the high hydration energy (123 kcal/mol) of fluoride. [13]
Alternatively, TBAF (tetrabutylammonium fluoride) is often used as it provides a soluble
source of the fluoride ion, with nucleophilicity enhanced by the presence of the bulky
organic cation (Scheme 1.2). One disadvantage is the extreme hydroscopic nature of the
fluorinating agent, which may consequently lead to inconsistent results if water is present.
Scheme 1.2 Fluorinations using KF and TBAF
Another source of fluoride is anhydrous HF. However, HF has a low boiling point, high
vapour pressure and is corrosive and toxic, therefore, HF/base complexes, such as
pyridinium poly(hydrogen fluoride) [15] and triethylamine tris(hydrogen fluoride) [16] have
been developed as safer alternatives (Scheme 1.3).
Scheme 1.3 Fluorination using pyridinium poly(hydrogen fluoride)
Recent work by Buchwald [17] has demonstrated that aryl fluorides, which are important in a
number of pharmaceutical and agrochemical products, can be synthesised using CsF in a
palladium catalysed reaction from aryl triflates. Initial work was conducted using aryl
bromides and AgF, however, these were limited to electron poor substrates with ortho
directing substituents. Therefore, aryl triflates were used with AgF. Only trace amounts of
fluorinated product were obtained, however, with CsF, yields increased. Therefore reaction
conditions were honed and it was found that the reaction proceeded best with CsF,
[(cinnamyl)PdCl]2 (2 mol %) and t-BuBrettPhos (1) (6 mol %) in toluene. The use of t-
BuBrettPhos (1) as a ligand was integral in the reaction as it was found to promote
reductive-elimination of the Ar-F due to its size, as well as prevent formation of unwanted
dimeric [LPdAr(F)]2 complexes (Scheme 1.4). A variety of aryl triflates were evaluated,