The Versatility of the Aryne–Imine–Aryne Coupling for the ­Synthesis of Acridinium Photocatalysts

Dedicated to Prof. Shunichi Fukuzumi on the occasion of his 70th Birthday

Abstract

The increasing use of acridinium photocatalysts as sustainable alternative to precious metal-based counterparts encourages the design and efficient synthesis of distinct catalyst structures. Herein, we report our exploration of the scope of the aryne–imine–aryne coupling reaction combined with a subsequent acridane oxidation for a short two-step approach towards various acridinium salts. The photophysical properties of the novel photocatalysts were investigated and the practical value was demonstrated by a cation-radical accelerated nucleophilic aromatic substitution reaction.

Key words

acridinium salts - aryne - organocatalysis - photoredox catalysis - synthesis

• References and Notes

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• 25 General Procedure A for the Synthesis of Kobayashi Aryne PrecursorsAryne precursors were prepared according to a modified literature procedure.²¹ To a solution of the corresponding o-bromophenol (1 equiv) in anhydrous THF (0.3 mol L^–1) was added HMDS (2 equiv) under an Ar atmosphere. The reaction mixture was stirred at reflux for 2 h. After cooling to room temperature, the crude product was attained by removing the solvent in vacuo and was used for the next step without isolation. The crude material of the first step was dissolved in anhydrous THF (0.3 mol L^–1) under an Ar atmosphere and cooled to –78 °C. n-BuLi (1.1 equiv) was added dropwise to the mixture, and the reaction was stirred for 1 h at –78 °C. After that, Tf₂O (1.2 equiv) was added dropwise to the mixture at –78 °C, and the reaction was stirred for another hour. The reaction mixture was quenched with cold saturated aqueous NaHCO₃ at –78 °C and warmed to room temperature. The aqueous layer was extracted with MTBE three times, the combined organic layers were dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (from cyclohexane to cyclohexane/EtOAc (100:1)) to afford the aryne precursors.General Procedure B for the Synthesis of IminesThe amine (1.5 equiv or 1 equiv) and the corresponding aldehyde (1 equiv) were dissolved in dry toluene (0.1 mol L^–1 aldehyde concentration). p-TsOH·H₂O (0.05 equiv) and 4 Å molecular sieves were added to the obtained solution. The reaction mixture was stirred at reflux for 18 h. The solvent was removed under reduced pressure (5 mbar) to yield the desired imine. When aniline was used as a substrate, the excess of aniline was removed afterwards under high vacuum (<0.1 mbar, 60 °C).General Procedure C for the Acridinium Salt SynthesisThe reaction flask charged with CsF (8 equiv) was evacuated at 100 °C for 2 h and cooled to room temperature before imine (1 equiv), dry acetonitrile (0.1 mol L^–1 imine concentration) and benzyne precursor (2.2 equiv or 2.5 equiv) were added. The reaction progress was monitored by NMR spectroscopy. After the reaction was completed, the acetonitrile was removed in vacuo. The residue was dissolved in dichloromethane and washed with water. The organic layer was dried over Na₂SO₄, the solvent was evaporated, and the crude product was subjected to silica gel column chromatography [starting from Et₂O/cyclohexane (1:100) to Et₂O/cyclohexane (1:10)]. The obtained acridane was then dissolved in CH₂Cl₂ (0.1 mol L^–1), and nitrosonium tetrafluoroborate (2 equiv) was added. The reaction was monitored by NMR spectroscopy and after its completion, the reaction mixture was diluted with CH₂Cl₂ and washed with water twice. The organic layer was dried over Na₂SO₄, and the solvent was removed under reduced pressure. The residue was triturated with Et₂O (upon sonification), the obtained precipitate collected and washed several times with Et₂O