Beyond conventional construction of the phthalimide core: a review

Phthalimides are a privileged structural motif frequently found in natural products, pharmaceuticals and organic materials. The most common strategy for their synthesis involves the condensation of phthalic acids/anhydrides with primary amines. However, the target-oriented synthesis of functionalized phthalimides has presented long-standing challenges to the synthetic community. The present review emphasizes the different strategies exploited in the past decade (2010-2021) towards the construction of the phthalimide core beyond conventional routes, which are classified as: (1) the carbonylative cyclization of aromatic amides, (2) the carbonylative cyclization of o-dihaloarenes/o-haloarenes, (3) the cyclization of isocyanate/isocyanide with arenes, (4) cyclization involving maleimides and (5) miscellaneous synthesis. Most of the reactions discussed in this review involve readily available starting materials, cheap catalysts, and are one-pot processes that are environmentally benign with operational simplicity. Interesting mechanisms of representative transformations have also been highlighted. Some of the methodologies have been useful in the gram-scale synthesis of biologically active and fluorescent phthalimide frameworks.

Automated summary

This review highlights different strategies used in the past decade (2010-2021) for constructing the phthalimide core, including various cyclization methods. Most of the discussed reactions involve readily available starting materials, cheap catalysts, and environmentally friendly one-pot processes. Some of the methodologies have been useful in the gram-scale synthesis of biologically active and fluorescent phthalimide frameworks.