A copper-catalyzed decarboxylative amination/hydroamination sequence of propargylic carbamates with various nucleophiles is described for the first time. It features an earth-abundant metal catalyst, mild reaction conditions, and high efficiency. Further treatments of the resultant key intermediates using an acid or a base in one pot enable the controllable and divergent synthesis of two types of functionalized indoles. Moreover, experiments to demonstrate the synthetic potential of this methodology are performed.
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http://dx.doi.org/10.1002/anie.201605900 | DOI Listing |
Nat Commun
January 2025
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai, 200240, China.
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.
View Article and Find Full Text PDFOrg Lett
January 2025
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Org Lett
October 2024
Department of Otolaryngology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei 430071, China.
A copper-catalyzed decarboxylative aminomethylation of indole-3-carboxylic acids with 1,2-oxazetidines has been developed, enabling the rapid synthesis of structurally diverse 3-aminomethylindoles in good to excellent yields. Remarkably, an unprecedented decarboxylative aminomethylation/cyclization cascade was further achieved by a combination of copper and iron salts to construct complex γ-carbolines with high efficiency. It is worth noting that one of the obtained products proved to be a good dual-emissive luminogen, exhibiting both aggregation-caused quenching and aggregation-induced emission.
View Article and Find Full Text PDFOrg Biomol Chem
October 2024
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, P. R. China.
The first successful copper-catalyzed decarboxylative cyclization reaction of ethynylbenzoxazinones and thiols has been developed. A rarely studied α-addition process to a copper-allenylidene intermediate promoted this reaction. Using this protocol, a range of 2-thiomethylene indole compounds have been obtained.
View Article and Find Full Text PDFJ Org Chem
September 2024
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
Decarboxylative C(sp2)-heteroatom cross-coupling reactions hold extraordinary potential for the sustainable preparation of biologically active scaffolds. Herein, we report a copper sulfate/1,10-phenathroline catalytic system for the decarboxylative intramolecular C(sp2)-O, C(sp2)-S, and C(sp2)-N coupling reactions leading to the construction of a series of benzo[]furans, benzo[]thiophenes, and indole derivatives from the corresponding coumarins, thiocoumarins, or quinolones, respectively. Our mechanistic study based on benzo[]furan formation suggests a three-step process of the transformations, which consists of (i) base-mediated hydrolytic ring opening of coumarin, (ii) copper-oxygen co-initiated radical decarboxylation, and (iii) copper-catalyzed C-heteroatom cross coupling.
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