Palladium‐Catalysed Direct Polyarylation of Pyrrole Derivatives

Abstract

International audienceThe palladium-catalysed direct polyarylation of 1-methylpyrrole and 1-phenylpyrrole was studied. As the C2 and C5 positions of pyrroles are more reactive for C-H bond functionalisation than the C3 and C4 positions, the formation of 2,5-diarylpyrroles was found to proceed selectively in the presence of 3 equiv. of a variety of aryl bromides. The sequential C2 arylation followed by C5 arylation to prepare non-symmetrically substituted 2,5-diarylpyrroles was also studied. For the synthesis of such pyrroles, higher yields were obtained for the couplings with electron-deficient aryl bromides. The tetraarylation of 1-methylpyrrole was also achieved. From 4 equiv. of 3,5-bis(trifluoromethyl) bromobenzene, the 2,3,4,5-tetraarylated pyrrole was obtained in good yield

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

“…[135] Higher yields of symmetrically substituted 2,5-di-A C H T U N G T R E N N U N G arylpyrroles 192 were obtained when 44a was used as substrate instead of 44b. [135] In 2011, Ackermann and Lygin accomplished the site selective directing group assisted diarylation of 2-pyridyl-and 2-pyrimidyl-substituted pyrroles 193a and 193b at C-2 and C-5 with 4-bromoanisole using metaxylene as the solvent, K 2 CO 3 as the base and a catalyst system composed of 2.5 mol% [RuCl 2 A C H T U N G T R E N N U N G (p-cymene)] 2 and 30 mol% 1-adamantylcarboxylic acid [(1-Ad)COOH], obtaining the triarylated pyrroles 194a and 194b in good yields (Scheme 99). [136] Notably, the [RuCl 2 …”

“…[134] More recently, Doucet and co-workers developed a synthetically useful protocol to prepare unsymmetrically substituted 2,5-diarylpyrroles 191 which involved the sequential C-2 arylation of 1-methylpyrrole (44a) and 1-phenylpyrrole (44b) followed by C-5 arylation using aryl bromides as coupling partners, PdA C H T U N G T R E N N U N G (OAc) 2 (0.5 mol%) as the catalyst precursor, KOAc as the base, and DMA as the solvent. [135] The scope of this sequential arylation is illustrated in Scheme 97. As shown in this scheme, higher yields of compounds 191 were obtained when the C-5 arylation reactions were performed using aryl bromides more electron-poor than those employed for the C-2 arylation of pyrroles 44a and 44b.…”

“…[135] Ackermann and Lygin also discovered that the protocol used for the site selective arylation of compounds 193a, b and 195 was not limited to pyrroles and that the most efficient catalysis in direct arylation of N-substituted indoles 196a, b with aryl chlorides could be achieved with (1-Ad) 2 P(O)H (Ad = adamantyl) as the preA C H T U N G T R E N N U N G liA C H T U N G T R E N N U N G gand instead of (1-Ad)COOH. As shown in Scheme 101, the direct arylation of compounds 196a, b, in which the 2-pyridyl-and 2-pyrimidyl substituents also served as powerful directing groups, provided C-2 arylated derivatives 197a, b in good yields.…”

“…As shown in Scheme 101, the direct arylation of compounds 196a, b, in which the 2-pyridyl-and 2-pyrimidyl substituents also served as powerful directing groups, provided C-2 arylated derivatives 197a, b in good yields. [135] Remarkably, the pyrimidyl group of compounds 197b could be efficiently removed by treatment with sodium ethoxide on DMSO at 100 8C under a nitrogen atmosphere for 24 h to give free NH-indoles 198 (Scheme 102). [135] In recent years, several studies have also been carried out on the direct arylation reaction of 1,2-disubstituted pyrroles.…”

“…[135] Remarkably, the pyrimidyl group of compounds 197b could be efficiently removed by treatment with sodium ethoxide on DMSO at 100 8C under a nitrogen atmosphere for 24 h to give free NH-indoles 198 (Scheme 102). [135] In recent years, several studies have also been carried out on the direct arylation reaction of 1,2-disubstituted pyrroles. LiØgault, Fagnou and co-workers established that treatment of 2-substituted N-methoxymethylpyrroles 68 and 2-substituted N-benzylpyrroles 199 with equimolar amounts of aryl bromides, 1.5 equiv.…”