A CONVENIENT 5-<i>exo-dig</i> CYCLIZATION ROUTE TO DIASTEREOMERICALLY PURE METHYL (2<i>S</i>)-2-(1-BENZYL-3-OXO-1,3-DIHYDRO-2<i>H</i>-ISOINDOL-2-YL)-3-METHYLBUTANOATE

Аннотация

A robust method toward the synthesis of diastereomerically pure methyl (2S)-2-(1-benzyl-3-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-methylbutanoate has been described. The key reactions in the synthesis are: HATU-mediated coupling, Pd-catalyzed Sonogashira coupling, base-mediated 5-exo-dig cyclization, and catalytic hydrogenation. The diastereomeric mixture is subjected to trituration with heptane to furnish both diastereomers in moderate yields. The relative stereochemistry was confirmed by the single crystal X-ray diffractometry. The key feature of the method is the simplicity of the diastereomeric separation.