Facile and Direct Synthesis of 1-Phenyl-Substituted β-Benzofused Oxygen Heterocycles from Benzoxaboroles and Salicylaldehydes under Amine Catalysis

Abstract

A facile and metal-free approach for the construction of structurally diverse 1-phenyl-substituted β-benzofused oxygen heterocycles is described. This method employs stable benzoxaboroles, salicylaldehydes, and a catalytic amount of amine to deliver biologically relevant 1-phenyl-substituted β-benzofused oxygen heterocycle scaffolds under mild conditions. The reaction proceeds via a tetracoordinate borate intermediate with a catalytic amount of amine through intramolecular cyclization. The method exhibits broad functional group compatibility and accommodates five-, six-, and seven-membered benzoxaborole homologues, providing unified access to 1-phenyl-substituted β-benzofused oxygen heterocycles encompassing 1,3-dihydroisobenzofuran, isochroman, and benzoxepine frameworks. The synthetic utility is further underscored by a concise derivatization to a complex tetracyclic polycycle. This work establishes a practical platform for accessing challenging 1-phenyl-substituted β-benzofused oxygen heterocycles that would otherwise be difficult to obtain.