Synlett 2007(2): 0243-0246  
DOI: 10.1055/s-2007-968010
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Hui Zhang*a, Dawei Maa,b, Weiguo Caoa
a Department of Chemistry, Shanghai University, 99 Shangda Lu, Shanghai 200444, P. R. of China
b State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. of China
e-Mail: yehao7171@shu.edu.cn;
Further Information

Publication History

Received 17 August 2006
Publication Date:
24 January 2007 (online)

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.

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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.

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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.

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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.