One Pot Access to 2′‐Aryl‐2,3′‐Bithiophenes via Twofold Palladium‐Catalyzed C−X/C−H Coupling Associated to a Pd‐1,4‐Migration

Abstract

The reactivity of 1,2‐dihalobenzenes in palladium catalyzed polyheteroarylation via C−H bond functionalization was investigated. The first catalytic cycle using thiophene as the heteroarene gives the expected 2‐(2‐bromophenyl)thiophenes. In the course of the second catalytic cycle, in the presence of heteroarenes having a free C3‐position, a partial Pd‐1,4‐migration occurred giving rise to aryl‐substituted biheteroarenes such as 2′‐aryl‐2,3′‐bithiophenes as well as the expected 1,2‐di(thiophen‐2‐yl)benzenes. The best selectivities in favor of the formation of 2′‐aryl‐2,3′‐bithiophenes were obtained with electron‐rich 1,2‐dihalobenzenes. A wide variety of thiophene derivatives bearing useful functions such as formyl, acetyl, cyclopropylmethanone, 2‐methyl‐1,3‐dioxolane, ester, nitrile or chloro was tolerated allowing to prepare poly‐functionalized 2′‐aryl‐2,3′‐bithiophenes. Moreover, this one pot preparation of 2′‐aryl‐2,3′‐bithiophenes employs a low loading of an air stable commercially available palladium source associated to an inexpensive base.

Scope and Limitations of the Palladium-Catalyzed Direct 1,2-Diheteroarylation of 1,2-Dihalobenzene Derivatives

“…However, this Pd 1,4-migration is influenced by the electronic properties of the 1,2-dihalobenzene and is favored by electron-rich benzene derivatives. 11 Consequently, the presence of electron-withdrawing substituents on the 1,2-dihalobenzene was expected to allow, in some cases, the formation of 1,2-diheteroarylated benzenes with quite good selectivities and yields. Therefore, we investigated the selectivity of the reaction using a variety of 4-substituted-2-bromo-1-iodobenzenes (the C–Br bond is in a meta -position with respect to the 4-substituent) (Scheme 5 ).…”

“…The a : c selectivity of this reaction appears to be linked to the Hammett σ m constants. 11 13 In the presence of 1,2-dimethylimidazole and imidazo[1,2- a ]pyrazine, only the formation of products 35 and 36 was observed. With such heteroarenes the Pd 1,4-migration appears to be less favored.…”

“…10b We have recently reported that with 1,2-dihalobenzenes a partial Pd 1,4-migration occurred during the reaction leading to a mixture of 1,2-diheteroarylated benzenes and aryl-substituted biheteroarenes such as 2′-aryl-2,3′-bithiophenes (Scheme 1b ). 11 12 Such a Pd 1,4-migration may proceed by oxidative addition of the thienyl C3–H bond with the formation of a Pd(IV) intermediate, followed by reductive elimination (Scheme 1b , bottom). 12 However, mechanisms proceeding via Pd(II) intermediates have also been proposed.…”

“…Firstly, we studied the reactivity of heteroarenes bearing a substituent at the C3 position in order to block the Pd 1,4-migration previously observed with several heteroarenes (see Scheme 1b ). 11 We thus reacted 2-bromo-1-iodobenzene (1 equiv.) with 2-isopropyl-4-methylthiazole (3 equiv.)…”