Direct arylations palladium pivalate

Scheme 9.32 Proposed mechanism of palladium-catalyzed direct arylations with pivalic acid as additive.

They were able to extend the scope of the direct arylation to simple, completely unactivated arenes, such as benzenes by development of a palladium-pivalic acid co-catalyst system (Scheme 28) [48]. 

Scheme 9.31 Palladium-catalyzed direct arylations of arenes with the aryl bromide 94 and pivalic acid as additive.

Fagnou and co-workers disclosed an effective palladium-catalyzed protocol for direct arylations of unactivated arenes using aryl bromides.A catalytic system comprising of [Pd(OAc)2] and DavePhos as ligand, along with substoichiometric amounts of pivalic acid 78, generated a highly active catalyst for the arylation of simple arenes like benzene 6 (Scheme 20). 

Coupling Reactions. Palladium pivalate is an effective catalyst for mild and efficient direct arylation reactions. One account described the intramolecular arylation phenolic ethers (eq 1). Initial optimization with Pd(OAc)2 in conjunction with electron-deficient phosphines led to the desired biphenyl in low yield. Upon the addition of carboxylic acid additives, the yield improved markedly with the optimal additive being pivalic acid. Indeed it was determined that the additive was not needed when Pd(OPiv)2 was errqtloyed as a catalyse although improved yields were observed when the title compound was used in conjunction with the acid additive. The role of the pivalate is believed to be that of a proton shuttle in a concerted metallation-deprotonation (CMD) sequence. A further advantage of using Pd(OPiv)2 was the rate enhancement of the arylation with most reactions complete in less than 6 h (vs. 12 or more hours with Pd(OAc)2). The catalyst was applied to a range of electron-rich and -deficient arenes with good to excellent yields. 

Thiophenes could be directly arylated under phosphine-free, pivalate-mediated conditions with low catalyst loading using a bis(alkoxo)palladium(II) complex (eq 16). ... 

O/t/20-arylation of benzoic acids is often preferable to ortho-arylation of benzamides if conversion of the amide moiety to other functional groups is desired. However, only a few reports have dealt with the orf/io-functionalization of free benzoic acids due to challenges that involve such transformations. The reactions can be complicated by decarboxylation of the product and the starting material. Despite those difficulties, several methods for direct o/t/io-arylation of benzoic acids have been developed. Yu has shown that arylboronates are effective in arylation of benzoic acids under palladium catalysis [59], The reactions require the presence of palladium acetate catalyst, silver carbonate oxidant, and benzoquinone. Even more interestingly, the procedure is applicable to the arylation of unactivated sp3 C-H bonds in tertiary carboxylic acids such as pivalic acid (Scheme 13) if aryl iodide coupling partner is used. Aryl trifluoroborates can also be used [60],... 

The Ar-H functionalization approach has also been used in the preparation of polymers. For instance, a diketopyrrolopyrrole-based polymer was prepared via a palladium-catalyzed direct C-H (hetero)arylation reaction between a di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-l,4-dione and 4,7-dibromo-2,l,3-benzothiadiazole (eq31). The reaction was conducted using palladium acetate as the catalyst and pivalic acid as an additive. A survey of different phosphines demonstrated that molecular weights of the same order and similar polydispersity indexes (PDI) were obtained using tri-terf-butylphosphonium and tri-ferf-cyclohexyl tetrafluoroborate. ... 

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