Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling
Abstract In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.1]pentylamines,...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54648-6 |
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| Summary: | Abstract In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.1]pentylamines, accessing analogs capable of mimicking ortho- and meta-substituted anilines remains challenging due to the lack of a versatile and modular synthetic methods. Herein, we present a modular approach to access a diverse array of saturated bioisosteres of anilines via photoelectrochemical-induced decarboxylative C(sp3)–N Coupling. The success of this reaction hinges on the merging the cooperative ligand-to-metal charge transfer (LMCT) with copper-catalyzed amination. Notably, this net-oxidative C(sp3)–N forming reaction operates under mild electrode potentials and proceeds through hydrogen evolution, eliminating the need for external chemical oxidants. Our research enables the facile decarboxylative amination of a set of sp3-rich small-ring cage carboxylic acids, thus offering a versatile bioisosteric replacement for ortho-, meta-, and para-substituted anilines and di(hetero)aryl amines. |
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| ISSN: | 2041-1723 |