Metal-catalyzed couplings benzofurans

Transition metal-catalyzed cross-coupling and C-H activation have become an important method for the formation of carbon-carbon bonds in the synthesis of furan and benzofuran containing pharmaceutical compounds. The reaction conditions required for these transformations are generally mild and tolerant of a number of different functional groups including ethers, esters, and amines to name a few. 

The synthesis of benzofurans and related compounds from ortho-iodophenol and copper] I) acetylides via a coupling-cydization reaction (vide infra) was introduced by Castro in the 1960s [75-77] and stimulated the development of many contemporary transition metal-catalyzed synthetic approaches toward the assembly of the benzofuran unit. In a subsequent report from Castro s group, it was proposed that the formation of the benzofuran core occurs in a stepwise fashion with the intermediacy of ortho-alkynylphenol, which, upon activation by the Cu(I) salt promoter, undergoes subsequent cydoisomerization [77]. 

Transition-metal-mediated C—X bond formation by intramolecular reactions with alkynes is a powerful strategy for the construction of heteroarene rings such as pyridines, pyrroles, and furans. Because of the wide availability of Sonogashira coupling of various haloarenes with terminal alkynes, these transformations provide efficient routes to synthesize fused heteroarenes, including isoquinolines, indoles, and benzofurans. In this chapter the construction of aromatic rings by transition-metal-catalyzed or transition-metal-mediated intramolecular C—X bond formation between C—X or X—H and alkynes is described. As shown in Scheme 19.1, Section... 

Guo et al. [24] reported iron-catalyzed tandem oxidative coupling and annulation of phenols and p-keto esters, furnishing polysubstituted benzofurans 38 (Scheme 5.20). The combination of FeClj 6HjO and (t-BuO) offers an efficient catalytic oxidative system. The iron catalyst demonstrates dichotomous catalytic behavior in this transformation, which is a transition metal catalyst in the oxidative coupling step and a Lewis acid in the condensation. 

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