Transfer Hydrogenation of N- and O-Containing Heterocycles Including Pyridines with H3N-BH3 Under the Catalysis of the Homogeneous Ruthenium Precatalyst
Tarun Bhatt, Kishore Natte*
*Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502 285, Telangana, India, Email:
kishore.natte
chy.iith.ac.in
T. Bhatt, K. Natte, Org. Lett., 2024, 26, 866-871.
DOI: 10.1021/acs.orglett.3c04051
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Abstract
A transfer hydrogenation protocol for the reduction of quinolines, quinoxalines, pyridines, pyrazines, indoles, benzofurans, and furan derivatives with borane-ammonia (H3N-BH3) as the hydrogen source and a commercially available RuCl3·xH2O precatalyst provides the corresponding alicyclic heterocycles in very good isolated yields.
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Details
This study presents a novel transfer hydrogenation protocol using borane−ammonia (H3N−BH3) as the hydrogen source and RuCl3·xH2O as the catalyst for the selective reduction of N- and O-containing heterocycles, including pyridines. The method efficiently converts quinolines, quinoxalines, pyridines, pyrazines, indoles, benzofurans, and furan derivatives into their corresponding alicyclic heterocycles with high yields. This process is significant for synthesizing key pharmaceutical intermediates like donepezil and flumequine. The protocol is scalable and operates under mild conditions, making it economically favorable and sustainable. The study highlights the challenges in reducing functionalized pyridines and demonstrates the method's broad substrate scope and functional group tolerance. The RuCl3·xH2O catalyst's effectiveness is compared with other Ru-based catalysts, showing superior performance. The research also explores the solvent effects and confirms that isopropanol acts as a solvent rather than a hydrogen donor. This ligand-free catalytic system offers a safer, low-cost alternative to traditional hydrogenation methods, contributing to advancements in synthetic organic chemistry and pharmaceutical manufacturing.
Key Words
tetrahydroquinolines, piperidines, borane-ammonia
ID: J54-Y2024
