Modular Synthesis of 4-Acylquinolines via Cycloaddition of 1,3-Enynes and Nitrosoarenes

Xiao Li; Chenxin Diao; Wangqing Kong

doi:10.1055/a-2229-1963

Synlett, Table of Contents

Synlett 2024; 35(15): 1807-1812
DOI: 10.1055/a-2229-1963

letter

Modular Synthesis of 4-Acylquinolines via Cycloaddition of 1,3-Enynes and Nitrosoarenes

Xiao Li

,

Chenxin Diao

,

Wangqing Kong ∗

Abstract

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Abstract

Herein, we disclose a FeBr₂-promoted cycloaddition of readily available 1,3-enynes and nitrosoarenes, providing a promising platform for the synthesis of privileged 4-acylquinoline scaffolds. This simple, one-pot process is characterized by high atom-economy, broad substrate-scope, and excellent functional-group tolerance. A possible reaction mechanism was proposed, involving processes such as [4+2] cycloaddition, ring opening, aromatization, and dehydroaromatization.

Key words

4-acylquinolines - cycloaddition - 1,3-enynes - nitrosoarenes - modular synthesis

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References

References and Notes

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14 Cycloaddition of 1,3-enynes and nitrosoarenes; Typical Procedure for Phenyl(3-(trifluoromethyl)quinolin-2-yl)methanone (3aa): An oven-dried 10-mL vial equipped with a PTFE-coated stir bar was charged with FeBr₂ (6.5 mg, 0.03 mmol), nitrosobenzene 2a (0.2 mmol, 21.4 mg), (3-(trifluoromethyl)but-3-en-1-yn-1-yl)benzene 1a (0.1 mmol, 19.6 mg) and anhydrous MeCN (1.3 mL) in an atmosphere of air. The reaction mixture was stirred at 80 °C for 48 hours, then concentrated under vacuum, and the residue was purified by chromatography on silica gel, eluting with petroleum ether/EtOAc (20:1→1:1) to afford 4-acylquinoline 3aa. Characterization data for 3aa: ¹H NMR (400 MHz, CDCl₃): δ = 9.21 (s, 1 H), 8.26 (d, J = 8.6 Hz, 1 H), 7.90–7.84 (m, 1 H), 7.77 (d, J = 7.0 Hz, 2 H), 7.67–7.54 (m, 3 H), 7.51–7.45 (m, 2 H). ¹³C NMR (151 MHz, CDCl₃): δ = 194.0, 149.2, 146.3 (q, J = 3.9 Hz), 144.7 (q, J = 2.4 Hz), 136.0, 134.8, 132.1, 130.1, 129.7, 129.0, 128.7, 126.1, 123.8, 123.3 (q, J = 274.6 Hz), 119.6 (q, J = 32.0 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –56.96. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₁F₃NO⁺: 302.0787; found: 302.0776. For experimental protocols, characterization data, and copies of NMR spectra of all products, see the Supporting Information.
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Supplementary Material

Supporting Information