Green and Facile Assembly of Diverse Fused N -Heterocycles Using Gold-Catalyzed Cascade Reactions in Water

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 5; p. 988
• Main Authors: Jia, Xiuwen, Li, Pinyi, Liu, Xiaoyan, Lin, Jiafu, Chu, Yiwen, Yu, Jinhai, Wang, Jiang, Liu, Hong, Zhao, Fei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11-03-2019; MDPI
• Subjects: Acids; alkynoic acids; amine nucleophiles; Antiinfectives and antibacterials; Benzene; Carbon; Cascade chemical reactions; cascade reaction; Catalysis; Catalysts; Chemical reactions; Functional groups; fused N-heterocycles; Gold; gold catalysis; Indoles; Naphthalene; Pyridines; Selectivity; Solvents; alkynoic acids; gold catalysis; amine nucleophiles; fused N-heterocycles; cascade reaction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24050988

The present study describes an AuPPh₃Cl/AgSbF₆-catalyzed cascade reaction between amine nucleophiles and alkynoic acids in water. This process proceeds in high step economy with water as the sole coproduct, and leads to the generation of two rings, together with the formation of three new bonds in a single operation. This green cascade process exhibits valuable features such as low catalyst loading, good to excellent yields, high efficiency in bond formation, excellent selectivity, great tolerance of functional groups, and extraordinarily broad substrate scope. In addition, this is the first example of the generation of an indole/thiophene/pyrrole/pyridine/naphthalene/benzene-fused N-heterocycle library through gold catalysis in water from readily available materials. Notably, the discovery of antibacterial molecules from this library demonstrates its high quality and potential for the identification of active pharmaceutical ingredients.