Room-Temperature Direct β-Arylation of Thiophenes and Benzo[b]thiophenes and Kinetic Evidence for a Heck-type Pathway

Abstract

The first example of a regioselective β-arylation of benzo[b]thiophenes and thiophenes at room temperature with aryl iodides as coupling partners is reported. This methodology stands out for its operational simplicity: no prefunctionalization of either starting material is required, the reaction is insensitive to air and moisture, and it proceeds at room temperature. The mild conditions afford wide functional group tolerance, often with complete regioselectivity and high yields, resulting in a highly efficient catalytic system. Initial mechanistic studies, including 13C and 2H KIEs, suggest that this process occurs via a concerted carbo-palladation across the thiophene double bond, followed by a base-assisted anti-elimination.

Computational exploration of Pd‐catalyzed C–H bond activation reactions

“…As shown in Figure 7, for Pd(II)-catalyzed β-arylation of benzo[b]thiophenes developed by the Larrosa group, the carbopalladation is followed by an anti-β-hydride elimination or base-assisted E2 elimination. [50] This Heck-type mechanistic pathway is supported by both the experimental KIEs and DFT calculations. The carbopalladation step has a free energy barrier of 22.4 kcal/mol.…”

Room‐Temperature Gold‐Catalysed Arylation of Heteroarenes: Complementarity to Palladium Catalysis

“…The successful α‐arylation of brominated pyrrole 15 a and furan 15 l are also significant, as there are no other published examples of C−H arylation of these or other ring‐halogenated pyrroles/furans. The regioselective arylation of brominated thiophenes 15 o and 15 p and benzo[ b ]thiophenes 15 q and 15 r under such mild conditions is also likely to find application in the preparation of functional organic materials …”

“…The regioselective arylation of brominated thiophenes 15 o [14] and 15 p [14] and benzo [b]thiophenes 15 q [15] and 15 r under such mild conditions is also likely to find application in the preparation of functional organic materials. [16,17] As af urther illustration of practical advance, the state-of-theart in Pd-catalysed CÀHa rylation of some of the heteroarenes employedi nt he current work are presented in Ta ble 1( i.e.,f or 15 c, [18] 15 n, [19] 15 o,p, [14] 15 q, [16] 15 r, [20] and 15 s [21] ). [22] Althoughc atalyst loadingsi ns ome cases are < 1mol %, all of the procedures require an excess of one couplingpartner (typically the heteroarene), elevated temperatures (80-160 8C), and, almosti nvariably,a ni nert atmosphere.…”

Regioselective synthesis of C3 alkylated and arylated benzothiophenes

“…However, C3 C–H functionalization is underdeveloped. In the absence of a directing group, direct C–H arylation at C3 of benzothiophenes is traditionally accomplished with palladium catalysts and coupling partners such as aryl-halides16171819, -borons2021, -silanes22, -sulfonyl chlorides23 and-iodoniums24 (Fig. 1bi).…”