Synthesis of Heterodiarylmethanes via Metallaphotoredox Decarboxylative Arylation

Abstract

A metallaphotoredox-catalyzed synthesis of heterodiarylmethanes using mild reaction conditions, commercially available substrates, and bench-stable catalysts is demonstrated. Moderate yields are obtained, and further derivatization of the newly formed benzylic position is shown.

Key words

metallaphotoredox - decarboxylative arylation - heterodiarylmethanes - photochemistry

• References and Notes

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• 18 Representative Experimental Procedure: 3-(Naphthalen-2-ylmethyl)pyridine (3a) To a vial charged with 2-(naphthalen-2-yl)acetic acid (100 mg, 532 μmol), 3-bromopyridine (57.5 μL, 585 μmol), dtbbpy (14.6 mg, 53.2 μmol), NiCl₂(glyme) (11.9 mg, 53.2 μmol), K₂CO₃ (225 mg, 1.59 mmol), and {Ir[dF(CF₃)ppy]₂(dtbpy)}PF₆ (5.96 mg, 5.32 μmol) was added anhydrous DMF (10.6 mL, 0.05 M). The headspace of the vial was purged with nitrogen for 10 s, placed in a Penn PhD Photoreactor M2 equipped with a 450 nm blue LED light and left to stir for 16 h under irradiation. To the reaction was added saturated NaHCO₃ and was extracted with EtOAc (3×), the combined organic layers were washed with water (4×) then brine, dried over anhydrous Na₂SO₄, filtered, and evaporated. The residue was purified on a 10 g silica gel column using a Biotage Isolera automated purification system with a gradient elution of EtOAc/heptanes (0–100%) and a flow rate of 36 mL/min over 20 min to afford the title product 3a as a tan solid. Yield 64 mg (55%). ¹H NMR (400 MHz, CDCl₃): δ = 8.58 (d, J = 1.7 Hz, 1 H), 8.49 (dd, J = 4.9, 1.4 Hz, 1 H), 7.84–7.76 (m, 3 H), 7.63 (s, 1 H), 7.57 (d, J = 7.9 Hz, 1 H), 7.50–7.42 (m, 2 H), 7.31–7.27 (m, 2 H), 4.16 (s, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 150.3, 147.8, 137.4, 136.7, 136.6, 133.7, 132.3, 128.6, 127.8, 127.7, 127.4, 127.3, 126.4, 125.8, 123.7, 39.3. LC–MS (ESI): m/z [M + H]⁺ = 220.1, t _R = 1.17 min; 5–100% MeCN/H₂O (0.1% of 10 mM ammonium formate buffer) over 3 min.