Reductive Alkylation of Quinolines to N-Alkyl Tetrahydroquinolines Catalyzed by Arylboronic Acid

Priyanka Adhikari, Dipanjan Bhattacharyya, Sekhar Nandi, Pavan K. Kancharla and Animesh Das*

*Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India, Email: adasiitg.ac.in

P. Adhikari, D. Bhattacharyya, S. Nandi, P. K. Kancharla, A. Das, Org. Lett., 2021, 23, 2437-2442.

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Abstract

A boronic acid catalyzed one-pot tandem reduction of quinolines to tetrahydroquinolines followed by reductive alkylation with a carbonyl compound provides N-alkyl tetrahydroquinolines in the presence of Hantzsch ester under mild reaction conditions. The organoboron catalysts behave as both Lewis acids and hydrogen-bond donors.

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proposed mechanism

General procedure for synthesis of N-alkyl tetrahydroquinolines

In a reaction tube (15 mL), substituted quinoline (0.5 mmol), substituted aldehyde (0.5 mmol) or cyclic ketone (0.5 mmol), Hantzsch ester (1.75 mmol), 3-CF₃C₆H₄B(OH)₂ (25 mol%) and DCE (2 mL) were taken. Then the reaction tube was properly closed and placed in a preheated oil bath at 60 °C for 12 h with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in petroleum ether and ethyl acetate solvent system. After completion of the reaction, the reaction tube was brought to room temperature and the crude compound was purified through silica gel column chromatography.

Key Words

tetrahydroquinolines, Hantzsch ester

ID: J54-Y2021