Efficient One-Pot Synthesis of 3-Substituted Phthalides via Additive Arylation of Organozinc Intermediate

: In recent years substitution at the third position on phthalides has been proven a valuable synthetic intermediate for the development of active molecules. We reported a direct and efficient one-pot method for the synthesis of 3-aryl Phthalides performed by the addition of organo-zinc reagent on methyl-2-formylbenzoate; reagent formed in-situ by the reaction between diethylzinc and different aryl boronic acid derivatives without using any kind of ligand. The possible mechanism involved a coordinated zinc carbonyl transition state, arylation, and followed by the intramolecular cyclization. The substituents groups in boronic having different electronic and steric properties played an important role in the reaction completion time and yield. The structure elucidation and confirmation of the synthesized compounds were done by using H-NMR analytical data. The method can be useful for the synthesis of various scaffolds and intermediates in the search of potentially active compounds.