Iodonium-Induced Cyclization of N-Allenylindoles and N-Allenylpyrroles: An Access to Iododihydropyrido[1,2-a]indoles and Dihydroindolizines

Abstract

The formation of iodinated dihydropyrido[1,2-a]indoles and dihydroindolizines was achieved by an iodocarbocyclization reaction of N-allenylindoles and N-allenylpyrroles. This transformation proceeded under very mild conditions using N-iodosuccinimide as the electrophilic iodine source to deliver the products via a 6-endo cyclization process. Careful choice of the solvent and concentration were mandatory to obtain the cyclization in good yields.

Keywords

electrophilic iodocyclization - allenes - NIS - indoles - pyrroles

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• 17 General Procedure for the Iodocyclization of Allenyl Substrates To a dry flask equipped with a magnetic stir bar were added the allenyl substrate (0.2 mmol, 1 equiv) and CH₃CN (5 mL); then NIS (0.24 mmol, 1.2 equiv) dissolved in CH₃CN (5 mL) was added. After stirring at room temperature for 10 min, TLC analysis showed complete conversion of the substrate, and the reaction mixture was quenched with sat. aq Na₂S₂O₃ (5 mL). The aqueous phase was extracted with EtOAc (2 × 10 mL), the combined organic layers were washed with brine, dried over MgSO₄, filtered, and concentrated under reduced pressure to afford the crude product, which was then purified by flash chromatography to give the desired cyclized compound. Compound 2b was obtained as a colorless oil in 75% yield (53.4 mg). R_f = 0.38 (petroleum ether/dichloromethane = 95:5). ¹H NMR (300 MHz, CDCl₃): δ = 7.57 (dd, J = 6.7, 1.5 Hz, 1 H), 7.26–7.09 (m, 3 H), 4.57 (s, 2 H), 2.44 (s, 3 H), 2.14 (s, 3 H), 1.62 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 134.7 (Cq), 133.6 (Cq), 130.2 (Cq), 129.5 (Cq), 120.9 (CH), 119.5 (CH), 117.9 (CH), 115.9 (Cq), 108.6 (CH), 104.5 (Cq), 46.8 (CH₂), 40.7 (Cq), 30.5 (2CH₃), 28.5 (CH₃), 10.9 (CH₃). APCI-MS: m/z = 352 [M + H]⁺.