N-heterocyclic carbene-catalyzed atroposelective synthesis of N-Aryl phthalimides and maleimides via activation of carboxylic acids.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38982037.
- Also identified by DOI 10.1038/s41467-024-49799-5 and PMC identifier 11233592.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Traditionally, N-aryl phthalimides are synthesized by the condensation of phthalic anhydride and aniline derivatives, usually proceeding under harsh conditions. The alternative mild and organocatalytic strategies for their synthesis are underdeveloped. Herein, we demonstrate the organocatalytic atroposelective synthesis of N-aryl phthalimides via the traditional N-C<sub>C=O</sub> disconnection under mild conditions. The in-situ acid activation of phthalamic acid and subsequent N-heterocyclic carbene (NHC)-catalyzed atroposelective amidation allowed the synthesis of well-decorated N-aryl phthalimides in excellent yields and enantioselectivities. Mechanistic studies reveal the addition of NHC to the in situ generated isoimides, thus introducing a unique mode of generating acylazoliums. Interestingly, both enantiomers of the product can be accessed from the same phthalic anhydride and aniline using the same NHC pre-catalyst. Moreover, this strategy has been extended to the atroposelective synthesis of N-aryl maleimides.