Palladium-catalyzed Tsuji-Trost-type reaction of benzofuran-2-ylmethyl acetates with nucleophiles

The palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-2-ylmethyl acetate with N, S, O and C soft nucleophiles has been investigated. The success of the reaction is dramatically influenced by the choice of catalytic system: with nitrogen based nucleophiles the reaction works well with Pd-2(dba)(3)/dppf, while with sulfur, oxygen and carbo-nucleophiles [Pd(eta(3)-C3H5)Cl](2)/XPhos is more efficient. The regiochemical outcome shows that the nucleophilic substitution occurs only on the benzylic position of the eta(3)-(benzofuryl)methyl complex. The high to excellent yields and the simplicity of the experimental procedure make this protocol a versatile synthetic tool for the preparation of 2-substituted benzo[b]furans.

Automated summary

The palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-2-ylmethyl acetate with N, S, O and C soft nucleophiles was investigated, showing different catalytic systems have significant effects on the reaction outcome, with nucleophilic substitution only occurring at the benzylic position.