Synthesis of Isocoumarins with Different Substituted Patterns via Passerini–Aldol Sequence

An efficient combination between
the Passerini three-component
reaction and aldol condensation has been developed for the synthesis
of bicyclic isocoumarins with different substituted patterns via solvent-dependent
domino pathways. These two operationally friendly methods simultaneously
install C–O and C–C bonds in a one-pot manner, allowing
the utilization of low-cost and readily accessible 2-formylbenzoic
acid, isocyanides, and arylglyoxals. Mechanisms of formation of different
substituted isocoumarin derivatives are also proposed.