A Versatile Palladium/Triphosphane System for Direct Arylation of Heteroarenes with Chloroarenes at Low Catalyst Loading

Direct Arylation of Heteroaromatic Compounds with Congested, Functionalised Aryl Bromides at Low Palladium/Triphosphane Catalyst Loading

“…We then focused our efforts to provide an efficient palladium-catalysed methodology for the challenging intermolecular arylation of functionalised aryl chlorides by using systems that incorporated modified ferrocenyl triphosphanes (Scheme 1). [20] A further screening of the scope of the palladium catalytic systems with associated ligands L1 and L2 (Scheme 2) used in these promising C À H direct activation/functionalisation reactions revealed that these auxiliaries were moderately efficient in the coupling of hindered aryl bromides, such as 2-bromotoluene ( Table 1, entries 1 and 2). We had also observed that the coupling of selected heteroaromatic compounds with some ortho-substituted electron-deficient aryl bromides proceeds very efficiently when PdA C H T U N G T R E N N U N G (OAc) 2 was used as a catalyst in the absence of any ligand L (Table 2, entries 5 and 8, arylation of 2-n-butyl furane and 2-n-butylthiophene).…”

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

“…of tetrabutylammonium bromide (TBAB) and the air-stable catalyst system consisting of a mixture of 5 mol% PdA C H T U N G T R E N N U N G (OAc) 2 and 0.5 mol% of the constrained ferrocenyl triphosphane ligand 1,1',2-tris(diphenylphosphino)-3',4-di-tert-butylferrocene (L1) (Scheme 5). [21] Notably, the ligand-free conditions were totally inefficient, but the air-stable PdA C H T U N G T R E N N U N G (OAc) 2 /L1 catalyst system also enabled the C-5 arylation of 2-substituted thiophenes 13, 2-propylthiazole (14a) and 1-methyl-2-formylpyrrole (15) (Figure 3) with aryl chlorides. [21] However, an unsatisfactory result was obtained when the C-5 arylation of free-NH 2 furfurylamine (16) was attempted with 4-bromobenzotrifluoride in DMA at 150 8C using KOAc as the base and 2 mol% PdClA C H T U N G T R E N N U N G (C 3 H 5 )A C H T U N G T R E N N U N G (dppb) as the catalyst.…”

“…[21] Notably, the ligand-free conditions were totally inefficient, but the air-stable PdA C H T U N G T R E N N U N G (OAc) 2 /L1 catalyst system also enabled the C-5 arylation of 2-substituted thiophenes 13, 2-propylthiazole (14a) and 1-methyl-2-formylpyrrole (15) (Figure 3) with aryl chlorides. [21] However, an unsatisfactory result was obtained when the C-5 arylation of free-NH 2 furfurylamine (16) was attempted with 4-bromobenzotrifluoride in DMA at 150 8C using KOAc as the base and 2 mol% PdClA C H T U N G T R E N N U N G (C 3 H 5 )A C H T U N G T R E N N U N G (dppb) as the catalyst. [22] In fact, the reaction produced a mixture of compounds 17 and 18 which were isolated in 67 and 28 % yield, respectively (Scheme 6).…”

“…[42] On this subject it is worth noting that in a recent discussion of the parameters that govern the activation barriers of the C À H bond in heteroarenes, Gorelsky included furan in a class (Class II) for which heteroarene-catalyst electronic interaction energies define the most reactive C À H bonds and he reported that in arylation of furan Ca À H bonds are more reactive than Cb À H bonds in the CMD process due to more negative interaction energy at the Ca site. [45] We believe it is also useful to point out that, although intermolecular direct C-2 or C-5 arylation reaction of furans are strongly favoured, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]41,42,46] successful intermolecular Pd-catalyzed C-4 arylations of furan substrates have been described. Thus, in 2009, Zhu and co-workers found that 2,5-diaryl-3-fluorofurans 65 underwent C-4 arylation with a variety of aryl bromides in NMP at 110-120 8C in the presence of KOAc as the base and a catalytic amount of PdCl 2 A C H T U N G T R E N N U N G (PPh 3 ) 2 (Scheme 28).…”

“…[19] Even after 2009, Doucet and co-workers conducted an intense and fruitful activity in the area of the Pdcatalyzed intermolecular arylations of furan derivatives with (hetero)aryl halides. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] They investigated the reaction of 2-substituted furans with 2-, 3-and 4-bromobenzylacetamides using PdClA C H T U N G T R E N N U N G (C 3 H 5 )A C H T U N G T R E N N U N G (dppb) [35] [dppb = 1,4-bis(diphenylphosphino)butane] as the catalyst, KOAc as the base and DMA as the solvent and found that the couplings at 150 8C gave site selectively the required 5-arylated derivatives 11 in high yields (Scheme 4). [20] Interestingly, the protocol used for the synthesis of compounds 11 proved to be suitable for the high yielding direct arylation of 2-substituted thiophenes, pyrroles, thiazoles and imidazoles with bromobenzylacetamide derivatives.…”