Synthesis of Benzofurans via 3 2 Cycloaddition Reactions

Despite its obvious limitation to the requisite preparation of copper(I) acetylides, this seminal work greatly influenced progress in the development of transition metal-catalyzed approaches for the preparation of benzofuran units, as well as other heterocyclic cores. Furthermore, since its original discovery, this protocol was featured in a number of syntheses of an array of multisubstituted benzofuran derivatives, including the preparation of various biologically active molecules and valuable intermediates [112-116]. 

This methodology was later extended by Owen [117] and Nilsson [78] to the employment of o-iodo- and -bromophenols and terminal acetylenes in the presence of stoichiometric amounts of Cu(I) oxide in pyridine or Cu(I) terf-butoxide to generate acetylide 55, allowing the achievement of typically higher or comparable yields (60-82%) of thecorresponding benzofurans 57. Ohemeng [118] and Scammells [119] effectively employed the first catalytic system in the synthesis of biologically active benzofuran derivatives, whereas Nilsson succeeded in the assembly of 

More recently, Bolm reported that the 3 + 2 synthesis of benzofurans from terminal alkynes and ortho-iodophenols could be achieved with a moderate efficiency in the presence of the FeCh-DMEDA [122] catalytic system [123]. 

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