Potassium tert-Butoxide Promoted Intramolecular Mizoroki–Heck-Type Radical Cyclization: Photoluminescence Properties and Application in Live Cancer-Cell Imaging

Abstract

Privileged indole-fused phenanthridinones were synthesized by an inexpensive potassium tert-butoxide-promoted intramolecular Mizoroki–Heck-type radical cyclization. This method offers high atom- and step-economic C–C bond formation. An array of the synthesized compounds showed good photoluminescence properties, and could be successfully applied as fluorescent bioprobes for imaging of living cancer cells.

Key words

transition-metal-free reaction - C–H bond functionalization - potassium tert-butoxide - Mizoroki–Heck reaction - phenanthridinones - indoles

Publikationsverlauf

Eingereicht: 18. Januar 2022

Angenommen nach Revision: 25. Februar 2022

Accepted Manuscript online:
25. Februar 2022

Artikel online veröffentlicht:
25. April 2022

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• 17 3-(2-(2-Bromophenyl)-1H-indol-1-yl)-5,5-dimethylcyclohex-2-en-1-ones 2a–n; General ProcedureA suspension of the appropriate cyclohexanone 1 (1.0 equiv), CuI (0.2 equiv), l-proline (0.4 equiv), and K₂CO₃ (2.0 equiv) in DMSO under N₂ was stirred at 100 °C for 3 h. The mixture was then diluted with H₂O and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, PE–EtOAc (7:3)].3-[2-(2-Bromophenyl)-1H-indol-1-yl]-5,5-dimethylcyclohex-2-en-1-one (2a)Yellow viscous liquid; yield: 276 mg (92%). ¹H NMR (400 MHz, CDCl₃): δ = 7.67 (t, J = 7.7 Hz, 2 H), 7.50 (d, J = 8.2 Hz, 1 H), 7.37 (d, J = 6.3 Hz, 2 H), 7.31–7.22 (m, 3 H), 6.76 (s, 1 H), 6.26 (s, 1 H), 2.28 (s, 2 H), 2.21 (s, 2 H), 0.87 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.21, 155.61, 137.65, 136.61, 134.22, 133.30, 132.47, 130.31, 128.64, 127.39, 124.43, 124.35, 123.46, 121.70, 121.25, 111.25, 108.42, 50.96, 44.14, 33.22, 27.94.7,7-Dimethyl-7,8-dihydroindolo[1,2-f]phenanthridin-5(6H)-ones 3a–m; General ProcedureA solution of the appropriate cyclohexanone 2 (1.0 equiv), t-BuOK (2.0 equiv), and 1,10-phen (0.5 equiv) in DMF was stirred at 120 °C under N₂ until the reaction was complete (TLC). The mixture was then diluted with H₂O and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, PE–EtOAc (8:2)].7,7,12-Trimethyl-7,8-dihydroindolo[1,2-f]phenanthridin-5(6H)-one (3d)Yellow solid; yield: 50 mg (63%); mp 159–161 °C. ¹H NMR (400 MHz, CDCl₃): δ = 9.24 (d, J = 8.3 Hz, 1 H), 7.97 (d, J = 7.8 Hz, 1 H), 7.84 (d, J = 8.7 Hz, 1 H), 7.53–7.39 (m, 3 H), 7.08 (d, J = 8.7 Hz, 1 H), 7.04 (s, 1 H), 3.29 (s, 2 H), 2.53 (s, 2 H), 2.51 (s, 3 H), 1.16 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.82, 149.09, 136.48, 133.08, 131.88, 131.85, 128.29, 127.12, 126.77, 125.80, 124.46, 123.25, 123.00, 120.79, 116.15, 112.00, 96.62, 52.32, 44.00, 32.29, 28.62, 21.49. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₂₂NO: 328.1701; found: 328.1700.