The Organometallic Fluorine Chemistry of Palladium and Rhodium: Studies toward Aromatic Fluorination

Although springing from two established fields, organometallic chemistry and fluorine chemistry, organometallic fluorine chemistry is still in its early stages. However, developments in this area are expected to provide new tools for the synthesis of selectively fluorinated organic compounds that have been in high demand. Selectively fluorinated organic molecules currently account for up to 40% of all agrochemicals and 20% of all pharmaceuticals on the market. Our research efforts have been focused on the development of new organometallic and catalytic methods for the selective introduction of fluorine and the CF(3) group into the aromatic ring. Monofluorinated and trifluoromethylated aromatic compounds are still made by the old technologies that employ stoichiometric quantities of hazardous and costly materials. In this Account, we describe our studies toward the development of safe, catalytic alternatives to these methods. We have synthesized, characterized, and studied the reactivity of the first aryl palladium(II) fluoride complexes. We have demonstrated for the first time that a Pd-F bond can be formed in a soluble and isolable molecular complex: this bond is more stable than previously thought. Toward the goal of fluoroarene formation via Ar-F reductive elimination, we have studied a number of sigma-aryl Pd(II) fluorides stabilized by various P, N, and S ligands. It has been established that numerous conventional tertiary phosphine ligands, most popular in Pd catalysis, are unlikely to be useful for the desired C-F bond formation at the metal center because of the competing, kinetically preferred P-F bond-forming reaction. A metallophosphorane mechanism has been demonstrated for the P-F bond-forming processes at Rh(I) and Pd(II), which rules out the possibility of controlling these reactions by varying the amount of phosphine in the system, a most common and often highly efficient technique in homogeneous catalysis. The novel F/Ph rearrangement of the fluoro analogue of Wilkinson's catalyst (Ph(3)P)(3)RhF and P-F bond-forming reactions at Pd(II) are insensitive to phosphine concentration and, because of the small size of fluorine, occur even with bulky phosphine ligands. These observations may guide further efforts toward metal-catalyzed nucleophilic fluorination of haloarenes. We have also developed aryne-mediated and CuF(2)/TMEDA-promoted aromatic fluorination reactions. The formation of fluoroarenes from the corresponding iodo- and bromoarenes in the presence of the CuF(2)/TMEDA system is the first example of a transition metal-mediated fluorination of nonactivated aryl halides in the liquid phase. Progress has also been made toward the development of aromatic trifluoromethylation. We have found unexpectedly facile and clean benzotrifluoride formation as a result of Ph-CF(3) reductive elimination from (Xantphos)Pd(Ph)CF(3). This observation demonstrates for the first time that the notoriously strong and inert metal-CF(3) bond can be easily cleaved (at 50-80 degrees C) as a result of reductive elimination to produce the desired aryl-trifluoromethyl bond, the only previously missing link of the catalytic loop. Our study of the novel complex (Ph(3)P)(3)RhCF(3) has led to a rationale for the long-puzzling strong trans influence (electron donation) of the CF(3) group which, in complete contrast, is known to be an electron acceptor in organic chemistry.