Synlett, Table of Contents Synlett 2022; 33(16): 1645-1654DOI: 10.1055/a-1896-3512 letter Iron-Catalyzed Synthesis of Pyrrolo[2,1-a]isoquinolines via 1,3-Dipolar Cycloaddition/Elimination/Aromatization Cascade and Modifications Xiao-Hui Chen a Laboratory of Asymmetric Synthesis, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing, 402160, P. R. of China , Yu-Yi Pan a Laboratory of Asymmetric Synthesis, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing, 402160, P. R. of China , Wei-Xun Wang b College of Chemistry and Environmental Engineering, Chongqing University of Arts and Sciences, Chongqing, 402160, P. R. of China , Hai-Lei Cui ∗ a Laboratory of Asymmetric Synthesis, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing, 402160, P. R. of China › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract We have developed an iron-catalyzed synthesis of pyrrolo[2,1-a]isoquinoline derivatives with tetrahydroisoquinolines, arylacyl bromides, and nitroolefins. Highly functionalized pyrrolo[2,1-a]isoquinolines can be obtained in moderate to good yields through a three-component N-alkylation/oxidative 1,3-dipolar cycloaddition/elimination/aromatization cascade. The obtained products in this study can be easily modified by easy chemical transformations to structurally complex molecules bearing privileged framework. Key words Key wordsiron catalysis - pyrrolo[2,1-a]isoquinoline - tetrahydroisoquinoline - nitroolefin - dipolar cycloaddition Full Text References References and Notes 1a Fan H, Peng J, Hamann MT, Hu JF. Chem. Rev. 2008; 108: 264 1b Banwell M, Lan P. In Targets in Heterocyclic Systems – Chemistry and Properties, Vol. 24. Attanasi OA, Gabriele B, Merino P, Spinelli D. 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These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures. 24 General Procedure for the Synthesis of Compounds 3 A suspension of tetrahydroisoquinoline hydrochloride 4 (0.3 mmol), arylacyl bromide 5 (0.3 mmol), nitroolefin 2 (0.2 mmol), FeCl3·6H2O (10 mol%), and K2CO3 (0.4 mmol) in PhCl (2 mL) was stirred at 120 °C for the indicated reaction time shown in the text under air atmosphere. Then the reaction mixture was cooled to rt and purified directly by a silica gel flash chromatography (hexane/EtOAc) to afford compound 3. Analytical Data for Typical CompoundsCompound 3a Yellow solid, 40.2 mg, 49% yield; purified by a silica gel flash chromatography (hexane/EtOAc = 9/1). 1H NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 7.3 Hz, 2 H), 7.21 (t, J = 7.4 Hz, 1 H), 7.12 (s, 1 H), 7.10–6.97 (m, 7 H), 6.78 (s, 1 H), 6.58 (s, 1 H), 4.55 (t, J = 6.8 Hz, 2 H), 3.94 (s, 3 H), 3.94 (s, 3 H), 3.10 (t, J = 6.8 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 187.6, 149.1, 148.3, 139.1, 135.9, 135.6, 135.5, 131.4, 129.9, 129.4, 127.5, 127.4, 127.3, 126.1, 125.3, 120.5, 111.1, 107.1, 105.3, 56.1, 56.0, 42.9, 28.7. ESI-HRMS: m/z calcd for C27H24NO3 + [M + H]+: 410.1751; found: 410.1758. Compound 3f Yellow solid, 49.5 mg, 60% yield; purified by a silica gel flash chromatography (hexane/EtOAc = 9/1). 1H NMR (400 MHz, CDCl3): δ = 7.69 (d, J = 7.5 Hz, 2 H), 7.33 (t, J = 7.4 Hz, 1 H), 7.19 (t, J = 7.6 Hz, 2 H), 7.11 (s, 1 H), 7.02 (d, J = 5.0 Hz, 1 H), 6.77 (s, 1 H), 6.67–6.62 (m, 1 H), 6.59 (s, 1 H), 6.54 (d, J = 3.3 Hz, 1 H), 4.45 (t, J = 6.7 Hz, 2 H), 3.95 (s, 3 H), 3.93 (s, 3 H), 3.07 (t, J = 6.7 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 187.5, 149.1, 148.4, 139.2, 137.4, 135.5, 131.8, 129.7, 127.7, 127.6, 127.2, 126.9, 125.2, 124.8, 120.3, 111.0, 107.0, 105.8, 56.1, 56.0, 43.1, 28.7. ESI-HRMS: m/z calcd for C25H22NO3S+ [M + H]+: 416.1315; found: 416.1320. Compound 3i Yellow solid, 66.5 mg, 75% yield; purified by a silica gel flash chromatography (hexane/EtOAc = 9/1). 1H NMR (400 MHz, CDCl3): δ = 7.51–7.46 (m, 2 H), 7.12 (s, 1 H), 7.05 (s, 5 H), 7.03–6.99 (m, 2 H), 6.78 (s, 1 H), 6.58 (s, 1 H), 4.55 (t, J = 6.8 Hz, 2 H), 3.94 (s, 3 H), 3.94 (s, 3 H), 3.10 (t, J = 6.7 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 186.1, 149.2, 148.4, 137.7, 137.6, 136.0, 135.9, 135.7, 131.3, 129.5, 127.74, 127.68, 127.0, 126.5, 125.5, 120.4, 111.1, 107.1, 105.5, 56.2, 56.1, 43.0, 28.7. ESI-HRMS: m/z calcd for C27H23ClNO3 + [M + H]+: 444.1361; found: 444.1369. Supplementary Material Supplementary Material Supporting Information
