Bulky Phosphane Ligand for Monoselective Ruthenium-Catalyzed, Directed o-C–H Arylation with Challenging Aryl Chlorides

Abstract

Functionalized aryl chlorides are more economically attractive but usually much more difficult as substrates in metal-mediated couplings than the corresponding bromides and iodides. A catalyst prepared from a bulky (biaryl)diphenyl phosphane and a common ruthenium source (1:1) mediates selective direct monoarylations of arenes bearing 2-pyridyl and related ortho-directing groups in good yields. Sequential arylations to heterodiarylated products also proceed in satisfactory yields.

Key words

ruthenium - C–H activation - arylations - aryl chlorides - phosphanes - heterocycles

• References and Notes

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• 24 Experimental Procedure Two runs were set side by side. A Schlenk tube was loaded with [RuCl₂(p-cymene)]₂ (3.1 mg, 5 μmol, 1 mol%), L3 (3.9 mg, 10 μmol, 2 mol%), and K₂CO₃ (173 mg, 1.25 mmol). The tube was backfilled with Ar (3×). Under light backflow of Ar, NMP (0.5 mL) was added, followed by 1a (86 μL, 93 mg, 0.6 mmol) and p-chloroanisole (2a; 62 μL, 71 mg, 0.5 mmol). The tube was sealed and the reaction mixture was stirred at 120 °C for 24 h. After cooling to r.t., under light backflow of Ar, o-chlorotoluene (2k; 59 μL, 63.3 mg, 0.5 mmol) was added, the tube was sealed, and the reaction mixture was stirred 140 °C for 24 h. After cooling to r.t., the reaction mixtures from both tubes were combined in H₂O (40 mL) and EtOAc (20 mL). The organic phase was separated and washed with H₂O (3 × 30 mL), dried (MgSO₄), filtered, and concentrated under reduced pressure. Compounds 3aa (65.3 mg, 25%; PE–EtOAc, 20:1), 4aa (64.6 mg, 18%; PE–EtOAc, 4:1), and 5 (214.4 mg, 61%; PE–EtOAc, 4:1) were sequentially isolated after flash chromatography. Compound 5: white solid, mp 107–108 °C. ¹H NMR (600 MHz, CDCl₃): δ = 8.26 (d, J = 4.6 Hz, 1 H), 7.46 (dt, J = 7.6, 4.1 Hz, 2 H), 7.27 (s, 1 H), 7.08–6.96 (m, 7 H), 6.85 (dd, J = 11.4, 6.4 Hz, 2 H), 6.69 (d, J = 8.5 Hz, 2 H), 3.74 (s, 3 H), 2.05 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 158.8, 158.0, 148.2, 141.5, 141.2, 141.0, 134.7, 134.0, 130.7–130.4 (multiple carbons), 129.3–128.8 (multiple carbons), 127.8, 126.7, 126.1, 124.7, 120.7, 113.1, 113.1, 55.1, 20.3. ESI-HRMS: m/z [M + H]⁺ calcd for C₂₅H₂₂NO⁺: 352.1696; found: 352.1698.