Formation of ArF from LPdAr(F): Catalytic Conversion of Aryl Triflates to Aryl Fluorides

Abstract

Despite increasing pharmaceutical importance, fluorinated aromatic organic molecules remain difficult to synthesize. Present methods require either harsh reaction conditions or highly specialized reagents, making the preparation of complex fluoroarenes challenging. Thus, the development of new and general methods for their preparation that overcome the limitations of those techniques currently in use is of great interest. We have prepared [LPd(II)Ar(F)] complexes where L is a biaryl monophosphine ligand and Ar is an aryl group, and identified conditions under which reductive elimination occurs to form an Ar-F bond. Based on these results, we have developed a catalytic process that converts aryl bromides and aryl triflates into the corresponding fluorinated arenes using simple fluoride salts. We expect this method to allow the introduction of fluorine atoms into advanced, highly functionalized intermediates.

Recent advances in green fluorine chemistry

“…In 2013, Mazzotti et al developed palladium-III -catalyzed fluorination of aryl boronic acids ( Figure 5). 21 Unlike the previously reported Pd-mediated fluorination, 13,19 the C-F bond formation presented here seems to proceed without the formation of organopalladium complexes. The author proposed a single-electron-transfer (SET) mechanism involving a well-defined Pd III 3 .…”

“…12 The first Pd-catalyzed aryl fluorination involving Pd 0 /Pd II was reported in 2009. 13 To achieve the reductive elimination process from a Pd II complex, a sterically demanding, electron-rich biarylmonophosphine ligand (tBuBrettPhos) is needed ( Figure 2). It was believed that this ligand not only …”

In vitro efficiency of 9-(N-cinnamoylbutyl)aminoacridines against blood- and liver-stage malaria parasites

“…2); the compounds were chosen according to: (i) their antiplasmodial activity against the erythrocytic stage, 6c being the most active; (ii) their prospective propensity to present low cytotoxicity, 6d being the most active compound complying with lead-likeness properties, 13 Lipinski's Rule of Five, 14 and Veber filter, 15 and (iii) their likelihood of good metabolic stability, solubility and bioavailability, the cinnamic ring of 6f being substituted with a fluorine atom, which is known for its ability to increase the aforementioned properties when incorporated into aromatic organic compounds. 16 Remarkably, the three test compounds were more potent than primaquine (PQ), the reference drug for the parasite liver stage, and compounds 6d and 6f were non-toxic to Huh7 human hepatoma cells in vitro at up to 5 lM, as shown by cell confluency analysis ( Fig. 2).…”

Synthesis of fluorinated oxygen- and sulfur-containing heteroaromatics

“…Buchwald et al have developed a general method for the conversion of aryl triflates to aryl fluorides using Pd-mediated catalysis [76]. In a typical example, triflate 119 reacted with caesium fluoride in the presence of [(cinnamyl)PdCl] 2 and the tBuBrettPhos ligand to furnish fluoroflavone 120 in 63% yield along with a small amount (2%) of the defluorinated byproduct (Scheme 35).…”