Nickel-Catalyzed Cross-Electrophile [2+4] Annulation of Benzynes

Abstract

Cross-electrophile coupling (XEC) reactions have emerged as powerful tools for C–C bond formation, whereas annulation employing arynes provides unique approaches to polycyclic arenes. Herein, we report a nickel-catalyzed cross-electrophile [2+4] annulation using benzynes and a 1-bromo-2-(2-chlorovinyl)arenes as C-2 and C-4 synthons, respectively. This proof-of-concept study not only provides a new method for synthesizing polysubstituted phenanthrenes, but also substantiates the feasibility of merging XEC reaction and aryne chemistry.

Key words

benzynes - [2+4] annulation - nickel catalysis - phenanthrenes - reductive cross-coupling - cross-electrophile coupling

Publication History

Received: 12 October 2024

Accepted after revision: 09 January 2025

Accepted Manuscript online:
09 January 2025

Article published online:
18 February 2025

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• 13 2-Methoxy-9-(trifluoromethyl)phenanthrene (3aa); Typical Procedure A Schlenk tube equipped with a stirrer bar was charged with NiBr₂·diglyme (7.0 mg, 0.02 mmol, 10 mol%), Zn (39 mg, 0.6 mmol, 3 equiv), and 3,4,7,8-tetramethyl-1,10-phenanthroline (L6) (5.7 mg, 0.024 mmol, 12 mol%). The tube was then evacuated and filled with nitrogen (three cycles), then anhyd NMP (1.0 mL), (Z)-1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)benzene (1a) (56.8 mg, 0.2 mmol, 1.0 equiv), and 2-(trimethylsilyl)phenyl triflate (2a) (119.2 mg, 0.4 mmol, 2.0 equiv) were added successively under N₂. The mixture was stirred at 40 °C for 20 h and then was quenched by addition of H₂O. The aqueous phase was extracted with EtOAc (3 × 20 mL), and the combined organic phases were washed with brine, dried (Na₂SO₄), filtered, and concentrated in vacuo. The crude materials were purified by column chromatography (silica gel, PE–EtOAc) to give a white solid; yield: 40.0 mg (72%). ¹H NMR (500 MHz, CDCl₃): δ = 8.64 (d, J = 8.3 Hz, 1 H), 8.58 (d, J = 9.0 Hz, 1 H), 8.21 (d, J = 8.4 Hz, 1 H), 8.11 (s, 1 H), 7.70 (ddd, J = 7.6, 6.9, 1.2 Hz, 1 H), 7.63 (ddd, J = 8.2, 6.9, 1.3 Hz, 1 H), 7.39 (dd, J = 9.0, 2.7 Hz, 1 H), 7.32 (d, J = 2.7 Hz, 1 H), 3.97 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 158.8, 131.1, 130.9, 127.4, 126.5 (q, J = 6.3 Hz), 126.5, 126.1, 125.8, 125.19 (q, J = 29.8 Hz), 125.16 (q, J = 2.7 Hz), 124.7, 124.3 (q, J = 273.5 Hz), 122.7, 119.6, 109.6, 55.5. ¹⁹F NMR (471 MHz, CDCl₃): δ = –60.25 (s, 3 F). HRMS (ESI): m/z [M⁺] calcd for C₁₆H₁₁F₃O: 276.0757; found: 276.0769.