Multicomponent Synthesis of 3-Arylmethyl-2,5-diarylthiophenes

Abstract

Pseudo Five-Component Synthesis of 3-(Hetero)arylmethyl-2,5-di(hetero)aryl-Substituted Thiophenes via Sonogashira-Glaser Cyclization Sequence Synthesis 2014, 46, 3415-3422. Multicomponent Synthesis of 3-Arylmethyl-2,5-diarylthiophenes Significance: Reported is the synthesis of 3-arylmethyl-2,5-diarylthiophenes using a palladiumcatalyzed multicomponent reaction involving aryl iodides, thiophenols, and TMS acetylene. This reaction was initially developed using a sequential protocol with a solvent exchange, which was transmuted into the one-pot sequence shown. The use of anhydrous DMSO was not necessary, and the reaction could be carried out under aerobic conditions with no formation of furan byproducts. A proposed mechanism for the reaction is supported by the formation of A as a 1:2 mixture of E/Z isomers in the absence of strong base. This mixture isomerizes into the Z isomer on standing in indirect sunlight for an extended time (one year), therefore equilibration of the E/Z mixture under microwave heating is a reasonable proposal.Comment: 3-Substituted thiophenes are important as intermediates for the synthesis of π-conjugated materials, such as oligomers and polymers, for use in electronic devices. The current method provides 3-arylmethyl-2,5-diarylthiophenes using a convenient and efficient alternative to sequential cross-coupling methods, particularly as it avoids 2,5-diarylthiophenes, which are apparently poorly soluble. The reaction was optimized with respect to temperature, solvent, base, and fluoride source. A reaction involving conventional oil-bath heating does not appear to have been tested for comparison, which would strengthen the utility of the method for those without access to a microwave. The reactions were carried out on 2 mmol scales, which is enough to make the reported yields robust. The scope of the reaction was modestly examined. Although a range of groups were tolerated, the yields varied dramatically, even between seemingly very similar systems such as Ar 2 = 4-Tol, Ar 1 = 2-Tol (84% yield) and Ar 2 = 4-Tol, Ar 1 = 3-Tol (33% yield), and Ar 2 = 4-Tol, Ar 1 = 4-Tol (41% yield).Ar 1 I