Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 2 69Yamanaka and coworkers have studied 65a-c an approach to thesynthesis of 2-substituted indoles in presence of a Copper-Palladiumcatalyst. Essentially, this procedure allowed the use of copper (I) incatalytic amounts and did not require prior preparation and isolation ofcopper(I) acetylide. Palladium then catalyzed the coupling between the aryliodide and the copper (I) acetylide. Conditions to achieve only the couplingreaction or both coupling and cyclization have been studied in depthshowing the important role of the R group on the aniline (scheme 2.22).HINHRR= Ms, CO 2 EtR= Alkyl, Aryl.+HR'PdCl 2 (PPh 3 ) 2CuI, TEA, 120°sealed tubeR'NRR=MsR'NHR EtO - Na +R=CO 2 EtHNHR'Scheme 2.22.: Influence of activating groups in the Yamanaka cyclization.In particular, when R is a mesyl group, 2-substituted indoles can bedirectly obtained, while with less electron withdrawing R groups, such asCO 2 Et the reaction affords the intermediate, uncyclized coupling product.This, in turn, can be transformed into the heteroannulated compound by theaction of a base.2.4.2.2. Cacchi's procedure for the synthesis of 2-substitutedbenzo[b]furanes using Palladium catalyst.Cacchi and coworkers 66 reported a procedure for the synthesis of 2-substituted benzo[b]furanes from 1-alkynes using a Copper-Palladiumcatalyst. The reaction of 2-hydroxyaryl or 2-hydroxyheteroaryl halides withseveral 1-alkynes in the presence of a base, bistriphenylphosphine Pd (II)diacetate and Copper (I) iodide in DMF at RT or 60° C leads to 2-substituted benzo[b]furanes in usually good yields (scheme 2.23).