Nickel-Catalyzed Suzuki–Miyaura Reaction of Aryl Fluorides

Abstract

Two protocols for the nickel-catalyzed cross-coupling of aryl fluorides with aryl boronic esters have been developed. The first employs metal fluoride cocatalysts, such as ZrF(4) and TiF(4), which enable Suzuki-Miyaura reactions of aryl fluorides bearing electron-withdrawing (ketones, esters, and CF(3)), aryl and alkenyl groups as well as those comprising fused aromatic rings, such as fluoronaphthalenes and fluoroquinolines. The second protocol employs aryl fluorides bearing ortho-directing groups, which facilitate the difficult C-F bond activation process via cyclometalation. N-heterocycles, such as pyridines, quinolines, pyrazoles, and oxazolines, can successfully promote cross-coupling with an array of organoboronic esters. A study into the substituent effects with respect to both coupling components has provided fundamental insights into the mechanism of the nickel-catalyzed cross-coupling of aryl fluorides.

Facile Access to Fluoromethylated Arenes by Nickel‐Catalyzed Cross‐Coupling between Arylboronic Acids and Fluoromethyl Bromide

“…Furthermore,adecrease of the loading of NiCl 2 ·DME from 10 mol % to 5mol %and the use of L5 (5 mol %), DMAP (10 mol %), and K 2 CO 3 (2.0 equiv) in as olvent mixture of DME/1,4-dioxane [12] at 70 8 8Cp rovided 3a in ac omparable yield (entry 14). No product formation was observed in the absence of the nickel catalyst or the ligand L5,b ut 3a could be obtained in 51 %y ield without DMAP,t hus demonstrating the essential roles of both the nickel catalyst and the ligand L5 for the catalytic cycle (entries [15][16][17].…”

“…An increased concentration of NiCl 2 ·DME probably benefits the formation of ArÀAr species from arylboronic acids and thus results in aN i 0 species that can react with fluorinated substrates to generate some unidentified defluorinated products. [16] As imilar defluorination side reaction occurred when 1a was reacted with 2 under standard conditions with Ni(cod) 2 (10 mol %; cod = 1,4-cyclooctadiene) as the catalyst, leading to 3ain only 32 %yield (determined by 19 FNMR spectroscopy;for details, see Scheme S2 in the Supporting Information).…”

Activation and Formation of Aromatic C–F Bonds

“…Around the same time the above reaction was described, Chatani and coworkers communicated two methods of nickel-catalyzed Suzuki-Miyaura cross-coupling reactions using fluoride cocatalysts and (sp 2 ) hybridized N-containing directing groups [116]. Although a variety of functional groups and substituents were tolerated in the reactions, products were limited to having one remaining fluorine atom or none at all.…”

Palladium-Catalyzed Cross-Coupling Reactions of Perfluoro Organic Compounds

“…Thus, we started developing a base-free C-C bond formation reaction of 1 with arylboronates in the presence of a Pd(0) catalyst. We began by seeking an active species that could cleave the C-F bond of 1 without additives, because our original protocol using LiI eliminated the chance to generate a transition-metal fluoride intermediate in return for efficient C-F bond cleavage [41,[54][55][56]90]. As a result, the thermolysis of (η 2 -CF 2 =CF 2 )Pd(PCy 3 ) 2 (2b) in THF at 100 °C under a N 2 atmosphere underwent a C-F bond activation of 1 to give an expected trifluorovinylpalladium(II) fluoride (6) in 45% yield (Scheme 5).…”