Synthesis of a library of tricyclic azepinoisoindolinones

作者：Bettina Miller, Shuli Mao, Kara M. George Rosenker, Joshua G. Pierce, Peter Wipf · 发表于：Beilstein Journal of Organic Chemistry · 年份：2012 · DOI：10.3762/bjoc.8.120 · 被引用次数：22 · 研究领域：Synthetic Organic Chemistry Methods、Synthesis and pharmacology of benzodiazepine derivatives、Advanced Synthetic Organic Chemistry

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.