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.

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

References and Notes

1a Yamazaki N. Washio I. Shibasaki Y. Mitsuru Ueda M. Org. Lett.  2006,  8:  2321 

1b Asano M. Inoue M. Katoh T. Synlett  2005,  2599 

1c Jiang H. Leger J.-M. Huc I. J. Am. Chem. Soc.  2003,  125:  3448 

1d Bolm C. Hildebrand JP. Muñiz K. Hermanns N. Angew. Chem. Int. Ed.  2001,  40:  3284 

1e Gu WX. Jing XB. Pan XF. Chan ASC. Yang TK. Tetrahedron  2000,  41:  6079 

1f Matsumoto Y. Uchida W. Nakahara H. Yanagisawa I. Shibanuma T. Nohira H. Chem. Pharm. Bull.  2000,  48:  428 

1g Cao B. Haengsoon Park H. Joullie MM. J. Am. Chem. Soc.  2002,  124:  520 

1h Temal-Laïb T. Chastanet J. Zhu J. J. Am. Chem. Soc.  2002,  124:  583 

1i Kawata S. Hirama M. Tetrahedron Lett.  1998,  39:  8707 

1j Thompson A. Delaney A. James M. Hamby J. Schroeder M. Spoon T. Crean S. Showalter HDH. Denny W. J. Med. Chem.  2005,  48:  4628 

2 Lindley J. Tetrahedron  1984,  40:  1433 

For some recent reports on palladium-catalyzed aryl ether synthesis, see:

3a Vorogushin AV. Huang X. Buchwald SL. J. Am. Chem. Soc.  2005,  127:  8146 

3b Kataoka N. Shelby Q. Stambuli J. Hartwig J. J. Org. Chem.  2002,  67:  5553 

3c Kuwabe S. Torraca KE. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  12202 

3d Prim D. Campagna J.-M. Joseph D. Andrioletti B. Tetrahedron  2002,  58:  2041 

3e Hartwig JF. Angew. Chem. Int. Ed.  1998,  37:  2046 

3f Palucki M. Wolfe J. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  3395 

3g Torraca K. Huang X. Parrish C. Buchwald S. J. Am. Chem. Soc.  2001,  123:  10770 

4 an der Heiden MR. Frey GD. Plenio H. Organometallics  2004,  23:  3548 

For some recent reviews on copper-catalyzed Ullmann-type reaction, see:

5a Kunz K. Scholz U. Ganzer D. Synlett  2003,  2428 

5b Frlan R. Kikelj D. Synthesis  2006,  2271 

5c Beletskaya I. Cheprakov A. Coord. Chem. Rev.  2004,  248:  2337 

5d Ley S. Thomas A. Angew. Chem. Int. Ed.  2003,  42:  5400 

6a Wolter M. Nordmann GE. Buchwald SL. Org. Lett.  2002,  4:  973 

6b Job G. Buchwald SL. Org. Lett.  2002,  4:  3703 

6c Hosseinzadeh R. Tajbakhsh M. Mohadjerani M. Alikarami M. Synlett  2005,  1101 

6d Manbeck GF. Lipman A. Stockland RA. Freidl A. Hasler A. Stone J. Guzei I. J. Org. Chem.  2005,  70:  244 

7a Ma D. Zhang Y. Yao J. Wu S. Tao F. J. Am. Chem. Soc.  1998,  120:  12459 

7b Ma D. Xia C. Org. Lett.  2001,  3:  2583 

7c Ma D. Cai Q. Zhang H. Org. Lett.  2003,  5:  2453 

7d Ma D. Cai Q. Org. Lett.  2003,  5:  3799 

7e Zhang H. Cai Q. Ma D. J. Org. Chem.  2005,  70:  5164 

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.