Synthesis of a library of tricyclic azepinoisoindolinones

Abstract

Hydrozirconation of 1-hexyne, the addition to in situ prepared N-acyliminium species, and ring-closing metathesis (RCM) were key steps in the preparation of a tricyclic isoindolinone scaffold. An unusual alkene isomerization process during the RCM was identified and studied in some detail. Chemical diversification for library synthesis was achieved by a subsequent alkene epoxidation and zinc-mediated aminolysis reaction. The resulting library products provided selective hits among a large number of high-throughput screens reported in PubChem, thus illustrating the utility of the novel scaffold.

Keywords

• chemical diversity
• epoxide aminolysis
• hydrozirconation
• isoindolinones
• metathesis
• N-acyliminium ion