Benzofurans polysubstituted

Numerous polysubstituted benzofurans have thus been prepared,261,262,287,268 particularly nitro derivatives, some of which show anti-inflammatory and antibacterial activity.269... 

Complex benzofurans, such as N-substituted 3-oxo-l,3-dihy-drobenzofuro[2,3-c]pyrroles (95),263 or bacteriostatic substituted 5,6,7,8-tetrahydrobenzofuro[2,3-6]pyridines,270 4a-alkoxy-l,2,3,4,4a, 9b-hexahydrobenzofuro[3,2-c]pyridines and polysubstituted benzo-furo[3,2-c]pyridines,271 and other polyheterocyclic compounds with sulfur or nitrogen atoms272,273 have also been synthesized by this method. 

Scheme 13.12 Iron-catalysed nthesis of polysubstituted benzofuran via an oxidative coupling/annulation tandem process.

Based on the methodologies developed in this topic, this type of transformation was applied in the synthesis of various biologically active molecules and natural products as well, for example polysubstituted benzofurans as parasitic growth inhibitors optically active 2- and 3-indolylglycine derivatives benzofurans with antimicrobial activity and so on. ° ° ... 

Regioselective synthesis of polysubstituted benzofurans from phenols and alkynes using a Cu(OTf)2 catalyst and ZnClj as Lewis acid in O2 atmosphere in a one-pot procedure has been reported by Jiang et al. (Scheme 8.79). The transformation consists of a sequential nucleophihc addition of phenols to alkynes and oxidative cyclization. A wide variety of phenols and alkynes can be used in this reaction. The reaction might proceed via a Cu-catalyzed intermolecular nucleophilic addition and intramolecular Cu-catalyzed aryl C(sp )-H functionahzation [149]. 

Scheme 8.79 Regioselective synthesis of polysubstituted benzofurans from phenols and alkynes.

As shown in Scheme 9.23, Li and coworkers demonstrated that the combination of FeCl3 6H20 and di-tert- mty peroxide offers a novel and efficient method for the construction of polysubstituted benzofurans from the annulation reaction of simple phenols and P-ketoesters, which are expected to give coumarins in the well-known Pechmann condensation [28]. A variety of phenols reacted with P-ketoesters to provide a range of benzofuran products in moderate to excellent yields. 

Scheme 9.23 Construction of Polysubstituted Benzofurans through Annulation of Simple...

In 2009, Z. Li reported the preparation of polysubstituted benzofurans via a reaction between phenols and p-ketoesters. Using 10 mol% of FeCls 6H2O and 2 equiv. of fBuO)2 in DCE, 3 equiv. of phenol react with 1 equiv. of p-ketoester affording the resulting benzofurans in 20-75% yields (Scheme 4.36). The nature of the substituents on the phenol has a significant influence on the activity, with electron-donating p-substituents favoring the reaction. 

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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