Palladium-Catalyzed Cascade Reaction for the Synthesis of Substituted Isoindolines

摘要

Isoindoline heterocycles have demonstrated potential in medicinal chemistry as they exhibit activity across diverse biological targets. They are present in molecules which act as bronchodilaters, N-methyl-D-aspartate agonists, multidrug resistance reversal agents, and fibrinogen receptor antagonists. While several approaches to the synthesis of unsubstituted or monosubstituted isoindolines have been reported, few methods exist to produce disubstituted isoindolines with high diastereoselectivity. In addition, there are no diastereoselective methods for the synthesis of 1,3-disubstituted isoindolines that allow for incorporation of readily available boronic acids, which are practical building blocks in medicinal chemistry. Synthetic methods for isoindoline synthesis that provide straightforward introduction of substitutents on the heterocycle would enable preparation of families of biologically significant compounds.