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

Dnyaneshwar Nighot, Arvind Kumar Jain, Mandeep Singh, Varun Rawat
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Abstract


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.

Keywords


oxoisoindoline; cyclization; diastereoselectivity; enantioselectivity; Sonogashira coupling.

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