N,N-Dimethylglycine-Promoted Ullmann-Type Coupling Reactions of Aryl Iodides with Aliphatic Alcohols

Abstract

The Ullmann-type coupling reactions of aryl iodides and aliphatic alcohols occur at 110 °C with N,N-dimethylglycine as the ligand, giving aryl alkyl ethers in good to excellent yields.

Key words

cross-coupling - aliphatic alcohols - catalysis - ligands - aryl iodides

References and Notes

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8

N , N -Dimethylglycine-Promoted Coupling Reactions of Aryl Halides with Alcohols; General Procedure: A re-sealable tube or test tube with a removable cap was charged with CuI (10 mol%), N,N-dimethylglycine·HCl (20 mol%), Cs₂CO₃ (2 equiv), and aryl halide (if solid, 2 mmol). The tube was evacuated and backfilled with N₂ (3 cycles). Alcohol (2 mL) and aryl halide (if liquid, 2 mmol) were added by syringe at r.t. under nitrogen. The sealed or capped tube was put into the oil bath that was preheated to 110 °C and the reaction mixture was stirred for the time specified. The cooled mixture was partitioned between H₂O (10 mL) and EtOAc or Et₂O (20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc or Et₂O (10 mL) each time until TLC showed no trace of product left in the aqueous layer. The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated. Purification of the residue by flash chromatography on silica gel [2 × 20 cm, PE (30-60 °C)-EtOAc or Et₂O] gave the desired product.

9

4-Benzoxyanisole (Table 2, Entry 3): white solid; mp 60-62 °C (Lit. [6a] mp 63 °C). ¹H NMR (400 MHz, CDCl₃): δ = 7.25-7.43 (m, 5 H), 6.91 (d, J = 8.9 Hz, 2 H), 6.83 (d, J = 8.9 Hz, 2 H), 5.02 (s, 2 H), 3.77 (s, 3 H). MS (EI): m/z = 214 [M⁺], 123, 95, 92, 91, 65, 63, 41.

10

3-(3-Methylbut-2-enyloxy)pyridine (Table 2, Entry 20): yellow oil. ¹H NMR (500 MHz, CDCl₃): δ = 8.32 (s, 1 H), 8.21 (s, 1 H), 7.20 (s, 2 H), 5.46-5.49 (m, 1 H), 4.56 (d, J = 7.0 Hz, 2 H), 1.80 (s, 3 H), 1.75 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 155.0, 141.9, 139.0, 138.1, 123.8, 121.4, 119.0, 65.1, 25.8, 18.3. MS (EI): m/z = 163 [M⁺], 162, 95, 69, 68, 67, 41. HRMS (EI): m/z [M⁺] calcd for C₁₀H₁₃NO: 163.0997; found: 163.1002.