Assessment of the Intermediacy of Arylpalladium Carboxylate Complexes in the Direct Arylation of Benzene: Evidence for C−H Bond Cleavage by “Ligandless” Species

Abstract

Palladium-catalyzed direct arylations of benzene have been proposed to occur by the generation of a phosphine-ligated arylpalladium pivalate complex LPd(Ar)(OPiv) and reaction of this complex with benzene. We have isolated an example of the proposed intermediate and evaluated whether this complex reacts with benzene to form the biaryl products of the catalytic process. In contrast to the proposed mechanism, no biaryl product was formed from cleavage of the benzene C-H bond by LPd(Ar)(OPiv). However, reactions of LPd(Ar)OPiv with benzene and additives that displace or consume the phosphine ligand formed the arylated products in good yield, suggesting that a "ligandless" arylpalladium(II) carboxylate complexes undergoes the C-H cleavage step. Consistent with this conclusion, we found that reactions catalyzed by Pd(OAc) 2 without ligand occur faster than, and with comparable selectivities to, reactions catalyzed by Pd(OAc) 2 and phosphine ligand.Direct arylation, the reaction of aryl halides with arenes or heteroarenes to form biaryl or aryl-heteroaryl products, is an attractive alternative to traditional cross-coupling because it occurs without the need to prepare organometallic or main-group reagents. 1 Early efforts to develop this process focused on the direct arylation of heteroarenes, 2 arenes with directing groups 3 and electron-deficient arenes. 4 In 2006, the direct arylation of benzene was reported by Lafrance and Fagnou. 5 Substoichiometric amounts of pivalic acid were used in the reported catalyst system, and this carboxylic acid was proposed to function as a proton shuttle during the aryl C-H cleavage step. 6 Despite the improvements in the reaction scope, little experimental information on the mechanism of this reaction is available, especially on the mechanism of the cleavage of the C-H bonds in arenes. Phosphine-ligated arylpalladium carboxylates LPd(Ar)(OCOR) are typically proposed to react with heteroarenes or arenes to form biarylpalladium complexes through a concerted metallation-deprotonation (CMD) pathway. 7 DFT calculations of this pathway have been conducted, and these studies suggested that arylpalladium acetates are competent to undergo C-H cleavage with various heteroarenes.8 Indeed, a recent report from Fagnou's group showed that the reaction of Pd(PtBu 3 )(Ph)(OAc) with 4-nitropyridine Noxide formed the arylated product. 9 However, arylpalladium pivalate complexes have not been studied either experimentally or theoretically, and the reactions of isolated arylpalladium carboxylate complexes with arenes have not been conducted. We report the synthesis and characterization of the phosphine-ligated arylpalladium pivalate complexes Pd(PtBu 3 )(Ar)(OPiv). Inconsistent with previous proposals, the reaction of isolated Pd(PtBu 3 )(Ar)(OPiv) with benzene does not form Ar-Ph products. However, reactions conducted with additives that displace or consume the phosphine ligand promote the formation of the arylated products, and these results and others reported herein imply the involvement o...

Mechanism Selection for Regiocontrol in Base‐Assisted, Palladium‐Catalysed Direct CH Coupling with Halides: First Approach for Oxazole‐ and Thiazole‐4‐Carboxylates

“…It should be noted that direct arylation of 1 a was also successfully achieved without ligand and only in the presence of the PivOH additive and occurred selectively at the C5 position to provide 5 a in 40 % yield (Table 7, entries 18 and 19) 20. Importantly, we also noted that the selectivity could be highly improved by reducing the temperature of the reaction, but the extent of completion dramatically decreased in the majority of cases, even when carrying out the direct phenylation over a 36 h period 18c…”

“…The competitive S E Ar‐type mechanism was yet again discarded through additional competitive direct C5 phenylation between 2‐phenylthiazole‐4‐carboxylates with 4‐CN and 4‐OMe ( 4 b , c ) substitution, which revealed that EWG model was slightly more reactive than the EDG model (Table 2, entry 7) 5. Also notable was that, in contrast to observations for the oxazole‐4‐carboxylate series, direct arylation of 2 a failed without ligand even in the presence of PivOH additive (Table 11, entries 19 and 20) 20. The novel procedures designed for C2‐ and C5‐selective CMD direct arylation of 2 a with bromides and chlorides in dioxane are summarised in Scheme .…”

Computational Studies of Heteroatom‐Assisted CH Activation at Ru, Rh, Ir, and Pd as a Basis for Heterocycle Synthesis and Derivatization

“…For example, Hartwig and Tan have shown that the Pd(OAc) 2 -catalyzed direct arylation of 2-bromotoluenes and benzene proceeds more efficiently in DMA solvent in the absence of added phosphine ligands [54]. A preformed dianionic dimer, [ArPdBr 2 ] 2 2− , was also active.…”

Mechanistic Studies on Direct Arylation of Pyridine N-Oxide: Evidence for Cooperative Catalysis between Two Distinct Palladium Centers

“…Phosphine-ligated arylpalladium carboxylate complexes LPd(Ar)(OC(O)R) are typically proposed to react with heteroarenes or arenes to form biarylpalladium complexes through a concerted metallation-deprotonation (CMD) pathway, 7 but we recently reported that a “ligandless” species is involved in the direct arylation of benzene, 8 not the proposed phosphine-ligated complex.…”