In their structural multiplicity and in the extent to which they occur in nature the derivatives of benzofuran are significantly lesser than the isoelectronic analogue indoles. However, these heterocyclic compounds show a variety of pharmacological properties, and change of their structure offers a high degree of diversity that has proven useful for the search of new therapeutic agents. The broad spectrum of pharmacological activity in individual benzofurans indicates that this series of compounds is of an undoubted interest. From this point of view, synthetic methods may be of very useful aid in the production of specific structures characterized by given pharmacological qualities. Moreover from a drug discovery perspective, synthesis of chiral functionalized substituted benzofurans could be more interesting because they might constitute starting materials for the production of biologically active compounds. Taking into account the actual tendency directed toward the development of enantiomerically pure drugs, indeed there is a limited number of papers related to the preparation of enantiomers of benzofuran containing compounds, likely because of difficulties in their preparation with conventional methods. In this context, new approaches seem to expand the potentiality of the synthesis of substituted benzofurans, providing also convenient routes to enantiopure 2-substituted benzofurans.