Journal of Organic Chemistry 2010-09-03

Diastereoselective one-pot tandem synthesis of 3-substituted isoindolinones: a mechanistic investigation.

Marcus Angelin, Martin Rahm, Andreas Fischer, Tore Brinck, Olof Ramström

Index: J. Org. Chem. 75(17) , 5882-7, (2010)

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Abstract

The mechanism of a base-catalyzed one-pot reaction of 2-cyanobenzaldehyde and primary nitroalkanes, to produce 3-substituted isoindolinones, has been investigated. A route starting with a nitroaldol (Henry) reaction, followed by a subsequent cyclization and rearrangement, was supported by intermediate analogue synthesis and DFT calculations. Direct diastereoselective crystallization from the reaction mixture was also achieved and studied for a number of substrates. Furthermore, the 3-substituted isoindolinones are an interesting group of compounds, both present important natural products, as well as being precursors to other valuable building blocks.