Palladium-Catalyzed Multiple Arylation of Thiophenes

Abstract

Secondary 2-thiophenecarboxamides efficiently undergo unique triarylation accompanied by formal decarbamoylation under palladium catalysis. 3-Substituted thiophenes, especially having an electron-withdrawing group, can also be triarylated.

Direct transition metal-catalyzed functionalization of heteroaromatic compounds

“…3 Furthermore, Miura reported a method for palladium-catalyzed multiple arylation of thiophenes 19 and 22 (Scheme 10). 25 Thiophene carboxamides were shown to undergo triarylation, accompanied by formal decarbamoylation in the presence of Pd(OAc) 2 , Buchwald's ligand (P(o-biphenyl)( t Bu) 2 ) or P( t Bu) 3 , and Cs 2 CO 3 in refluxing xylene. 25 3-Substituted thiophenes 19, bearing EWGs, can also be converted to triarylated products 21 in high yields.…”

“…25 Thiophene carboxamides were shown to undergo triarylation, accompanied by formal decarbamoylation in the presence of Pd(OAc) 2 , Buchwald's ligand (P(o-biphenyl)( t Bu) 2 ) or P( t Bu) 3 , and Cs 2 CO 3 in refluxing xylene. 25 3-Substituted thiophenes 19, bearing EWGs, can also be converted to triarylated products 21 in high yields. At the same time, selective diarylation can also be achieved in the presence of an excess of ArBr (Scheme 10).…”

“…30,31 Later, Kozikowski disclosed a methodology towards polycyclic indoles 43 featuring intramolecular cyclization of bromoaryl-bearing indoles 42 (Scheme 17). 32 It was demonstrated that intramolecular C-H arylation proceeded readily in the presence of Pd(PPh 3 ) 4 and KOAc in DMA, affording polycyclic products 43 in very good yields.…”

“…39 McClure reported a regioselective method for the C-5 arylation of furaldehyde 55 (Scheme 23). 40 In the presence of PdCl 2 , PCy 3 , Bu 4 NBr, and KOAc, a variety of 5-arylfurfurals 56 were obtained in high yields. The mechanistic rationale proposed included both Heck-type carbopalladation and electrophilic metalation pathways.…”

“…four distinct mechanisms have been proposed to date: electrophilic aromatic substitution (A), 3 C-H activation (B), 4 cross-coupling (C), 3 and Heck-type arylation (D) 5 (Scheme 2).…”