Palladium-Catalyzed Homocoupling of Highly Fluorinated Arylboronates: Studies of the Influence of Strongly vs Weakly Coordinating Solvents on the Reductive Elimination Process

Abstract

C−C reductive elimination from [PdL 2 (C 6 F 5 ) 2 ] to form polyfluorinated biaryls has been a challenge for over 50 years. Thus, palladium-catalyzed homocoupling of arylboronates (Ar F − Bpin) containing two ortho-fluorine substituents is very difficult, as the reaction typically stops at the [PdL 2 (Ar F ) 2 ] stage after two transmetalation steps. The transmetalated complexes cis-[Pd-and cis-[Pd(MeCN) 2 (2,6-C 6 F 2 H 3 ) 2 ] (3e) have been isolated from the reaction of Ar F −Bpin with Pd(OAc) 2 in acetonitrile solvent, with no homocoupling observed. However, catalytic homocoupling proceeds smoothly in a "weakly coordinating" arene solvent as long as no ancillary ligands or coordinating solvents are present. DFT computations reveal that the active catalyst formed by arene solvent coordination leads to an overall reduced barrier for the reductive elimination step compared to the formation of stable [PdL 2 (Ar F ) 2 ] complexes in the presence of a donor ligand or solvent L.

Fluorinated Aryl Boronates as Building Blocks in Organic Synthesis

“…However, if the aryl groups contain two ortho ‐fluorine substituents, homocoupling products were not observed. In 2020, Radius and Marder et al [116] . reported an efficient palladium‐catalyzed homocoupling reaction of aryl pinacol boronates containing two ortho ‐fluorine groups.…”

“…As mentioned in section 4.2, the palladium‐catalyzed homocoupling of aryl pinacol boronates to generate symmetrical fluorinated biaryls with two ortho ‐fluorines in each ring must be conducted in arene solvents to reduce the energy barrier of the reductive elimination step [116] . It was previously mentioned in section 4.3.2 and Table 3 that Bulfield and Huber reported optimized conditions for constructing polyfluorobiphenyls via Suzuki‐Miyaura cross‐coupling of fluorinated aryl‐boronic acid derivatives and fluorinated aryl halides, using a combination of [Pd 2 (dba) 3 ] and phosphine ligands in good to excellent yields; [123] however, the reaction failed to couple pentafluorophenyl boronic acid derivatives with 1,2,4,5‐tetrafluoro‐3‐iodobenzene (Table 3, entry 4).…”

Crystal structure of bis(1,8-dibenzoyl-7-methoxynaphthalen-2-yl)terephthalate: Terephthalate phenylene moiety acts as bidentate hydrogen acceptor of bidirectional C-H···π non-classical hydrogen bonds

“…Weak interactions in the solid of organic molecular substances have acquired interests and the revaluation in the scientific area over the last two decades [1][2][3]. Indeed, weak interactions have been established as essential features in influencing the chemical, physical, and biological activity properties of materials [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], by determining their threedimensional single molecular structure and spatial organization of molecular assembly. A number of papers and reviews have been dedicated to the crystallographic and theoretical study and consequently the analysis of halogen interactions and nonclassical hydrogen bonds such as C-H•••X (X = Polar atom) and C-H•••π hydrogen bonds have drastically increased over recent years, emphasizing the applicability and usefulness of weak interactions to scientific disciplines [22][23][24][25][26][27][28][29][30].…”

Copper‐Catalyzed Oxidative Cross‐Coupling of Electron‐Deficient Polyfluorophenylboronate Esters with Terminal Alkynes

“…Very recently, we reported optimized conditions for the Suzuki–Miyaura cross‐coupling of Ar F Bpin with aryl iodides and bromides using a combination of CuI and phenanthroline as a catalyst precursor to generate cross‐coupled products in moderate to excellent yields [20c] . We have recently reported the palladium‐catalyzed homocoupling of fluorinated arylboronates, [20d] and the borylation of aryl chlorides, using NHC‐stabilized nickel(0) complexes [20e] or a readily prepared NHC‐stabilized Cu catalyst [20f] . Inspired by these results, we attempted to develop a Cu‐catalyst system for the oxidative cross‐coupling of Ar F Bpin compounds with terminal alkynes.…”