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Synlett 2023; 34(11): 1241-1246
DOI: 10.1055/a-2030-7826
DOI: 10.1055/a-2030-7826
letter
Special Edition Thieme Chemistry Journals Awardees 2022
Organophotoredox-Catalyzed Oxidative C(sp2)–H Alkylation of N-Heteroarenes with Dihydroquinazolinones by C–C Cleavage
This work was supported by SERB, India (File: SRG/2021/000572). P.P.M. and A.P. thank the Ministry of Education, India for their Prime Minister’s Research Fellowship. S.D. thanks UGC, India for research fellowship.
Dedicated to Professor Matthias Beller on his 60th birthday
Abstract
We report a visible-light-mediated, organophotoredox-catalyzed, C(sp2)–H alkylation of N-heteroarenes with dihydroquinazolines, prepared from aliphatic ketones, under oxidative conditions. This protocol represents a metal-free approach to the effective construction of C–C bonds through a Minisci-type reaction, formally activating the native C–H bond of the N-heteroarene and an α-C–C bond of a readily available ketone. The mild nature of this method accommodates a wide variety of N-heteroarenes and ketones, tolerating a wide range of functional groups.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2030-7826.
- Supporting Information
Publication History
Received: 24 December 2022
Accepted after revision: 08 February 2023
Accepted Manuscript online:
08 February 2023
Article published online:
09 March 2023
© 2023. Thieme. All rights reserved
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- 16 Compounds 3; General Procedure In a heat-gun-dried Schlenk tube equipped with a Teflon-coated stirrer bar, the appropriate N-heteroarene 1 (0.2 mmol, 1.0 equiv), dihydroquinazolinone substrate 2 (0.5 mmol, 2.5 equiv), 4CzIPN (0.004 mmol, 2 mol%), and K2S2O8 (0.4 mmol, 2.0 equiv) were dissolved in anhyd DMF (1 mL) under an inert atmosphere. The mixture was stirred at rt for 18 h in the presence of light from blue LEDs. The reaction was then quenched by the addition of aq Na2CO3 (2 mL) and extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with H2O (5 mL) and brine (5 mL), and the solvents were removed under reduced pressure. The crude residue was purified by flash column chromatography (silica gel, PE–EtOAc).2-Cyclohexyl-4-methylquinoline (3aa)Colorless liquid; yield: 73%. 1H NMR (500 MHz, CDCl3): δ = 8.15 (d, J = 8.4 Hz, 1 H), 8.03 (d, J = 8.3 Hz, 1 H), 7.75 (ddd, J = 8.3, 6.9, 1.4 Hz, 1 H), 7.60 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 7.26 (s, 1 H), 2.98 (tt, J = 12.1, 3.4 Hz, 1 H), 2.75 (s, 3 H), 2.10–2.12 (m, 2 H), 1.98 (dt, J = 12.8, 3.0 Hz, 2 H), 1.77–1.81 (m, 1 H), 1.62 (qd, J = 12.6, 3.1 Hz, 2 H), 1.62 (qt, J = 12.8, 3.3 Hz, 2 H), 1.44 (tt, J = 12.8, 3.6 Hz, 1 H). 13C NMR (126 MHz, CDCl3): δ = 166.7, 147.8, 144.4, 129.7, 129.1, 127.2, 125.5, 123.7, 120.4, 47.8, 33.0, 26.7, 26.3, 19.0.4-Methyl-2-(1-phenylcyclopropyl)quinoline (3af)Colorless liquid; yield: 77%. 1H NMR (500 MHz, CDCl3): δ = 8.03 (d, J = 8.5 Hz, 1 H), 7.90 (d, J = 8.3 Hz, 1 H), 7.67 (ddd, J = 8.4, 6.9, 1.3 Hz, 1 H), 7.48 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 7.43–7.45 (m, 2 H), 7.36–7.39 (m, 2 H), 7.28–7.30 (m, 1 H), 6.95 (s, 1 H), 2.55 (s, 3 H), 1.81 (dd, J = 6.2, 3.5 Hz, 2 H), 1.36 (dd, J = 6.5, 3.8 Hz, 2 H). 13C NMR (126 MHz, CDCl3): δ = 163.9, 147.8, 144.0, 143.6, 130.3, 129.8, 129.1, 128.7, 126.8, 126.7, 125.5, 123.7, 122.1, 32.3, 18.8, 17.3.(4-Cyclohexylquinolin-2-yl)(piperidin-1-yl)methanon (3da)Colorless liquid; yield: 51%. 1H NMR (500 MHz, CDCl3): δ = 8.01–8.31 (m, 2 H), 7.70 (t, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.7 Hz, 1 H), 7.51 (s, 1 H), 3.78–3.80 (m, 2 H), 3.47–3.49 (m, 2 H), 3.30–3.36 (m, 1 H), 2.00–2.02 (m, 2 H), 1.91–1.94 (m, 2 H), 1.82–1.85 (m, 1 H), 1.67–1.74 (m, 4 H), 1.49–1.61 (m, 6 H), 1.29–1.37 (m, 1 H). 13C NMR (126 MHz, CDCl3): δ = 168.3, 154.8, 154.6, 147.2, 130.9, 129.4, 127.0, 126.8, 123.1, 116.8, 48.5, 43.4, 39.3, 33.6, 27.0, 26.7, 26.4, 25.7, 24.8.1-Cyclohexyl-6-(4-methoxyphenyl)isoquinoline (3ha)White solid; yield: 76%; mp 118 °C. 1H NMR (500 MHz, CDCl3): δ = 8.48 (d, J = 5.7 Hz, 1 H), 8.26 (d, J = 8.9 Hz, 1 H), 7.93 (d, J = 1.6 Hz, 1 H), 7.80 (dd, J = 8.8, 1.8 Hz, 1 H), 7.66–7.68 (m, 2 H), 7.50 (d, J = 5.7 Hz, 1 H), 7.03–7.05 (m, 2 H), 3.88 (s, 3 H), 3.57 (tt, J = 11.7, 3.2 Hz, 1 H), 1.93–2.01 (m, 4 H), 1.80–1.88 (m, 3 H), 1.50–1.57 (m, 2 H), 1.38–1.44 (m, 1 H). 13C NMR (126 MHz, CDCl3): δ = 165.7, 160.0, 142.5, 141.9, 137.0, 132.8, 128.7, 126.4, 125.5, 125.2, 124.5, 119.2, 114.6, 55.6, 41.8, 32.8, 27.1, 26.4.