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 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. On the basis of these results, we have developed a catalytic process that converts aryl bromides and aryl triflates into the corresponding fluorinated arenes by using simple fluoride salts. We expect this method to allow the introduction of fluorine atoms into advanced, highly functionalized intermediates.

Figure 1

Metal Catalyzed Aryl Fluorination

Figure 2

Ligands for the Successful Reductive Elimination of Ar-F

Figure 3

Preparation of and Reductive Elimination From [2·PdAr(F)] Complexes

Figure 4. X-Ray Structure of Complex 4

(ORTEP drawing at 50% probability, hydrogen atoms omitted for clarity)

Figure 5

Catalytic Conversion of Aryl Bromide 8 to Aryl Fluoride 7