Synthesis of Polycyclic Indolone and Pyrroloindolone Heterocycles via the Annulation of Indole- and Pyrrole-2-Carboxylate Esters with Arynes

Abstract

A mild and general method for the synthesis of a variety of polycyclic indolone and pyrroloindolone heterocycles via the reaction of indole- and pyrrole-2-carboxylate esters with arynes has been developed.

Keywords

arynes - indolones - pyrroloindolones - pyrroloindoles - indoles - annulation reactions

References and Notes

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12

Representative Experimental Procedure - 5 H -Indolo[1,2- a ]indol-5-one (10a)
To a solution of ethyl 1H-indole-2-carboxylate 9a (76 mg, 0.40 mmol) and TMAF (94 mg, 1.0 mmol) in THF (4 mL) was added 2-(trimethylsilyl)phenyl trifluoromethane-sulfonate (2a, 107 µL, 0.44 mmol) in an oven-dried 8 mL glass vial. The reaction mixture was stirred at r.t. for 1 h, monitored by TLC. The solvent was evaporated, the residue was diluted with H₂O (2 mL) and extracted with CH₂Cl₂ (3 × 2 mL; the organic phase was separated using an organic phase separator cartridge). The solvent was evaporated and the product was purified by Combi-flash (ISCO) on silica gel column (10 g) using a gradient elution of 0-2% EtOAc-hexanes over 3 min, followed by 2-4% EtOAc-hexanes over 25 min) to afford the title product (66 mg, 75% yield) as a solid. ^¹H NMR (500 MHz, acetone-d ₆): δ = 7.80 (d, 1 H, J = 8.4 Hz), 7.74 (d, 1 H, J = 8.1 Hz), 7.70 (d, 1 H, J = 7.9 Hz), 7.66-7.60 (m, 2 H), 7.50-7.44 (m, 1 H), 7.21 (s, 1 H), 7.19 (d, 1 H, J = 7.3 Hz), 7.18-7.13 (m, 1 H). ^¹³C NMR (126 MHz, acetone-d ₆): δ = 181.5, 146.3, 136.7, 136.5, 135.0, 133.6, 130.0, 128.9, 125.7, 125.4, 124.9, 122.9, 112.8, 112.5, 108.0. HRMS (ESI, MH⁺): m/z calcd for C₁₅H₁₀NO: 220.0757; found: 220.0755.