Dimethylaminomethylphosphonic Acid Derivatives-Promoted CuI-Catalyzed Synthesis of Aryl Ethers

Abstract

An inexpensive and efficient catalyst system for synthesis of aryl ethers has been developed by using 20 mol% CuI as the catalyst, 30 mol% dimethylaminomethylphosphonic acid derivatives as the new ligands, K₂CO₃ as the base and toluene as the ­solvent. This is the first example using aminophosphonates as the ligands for Ullmann ether coupling reaction.

Key words

Ullmann reaction - aryl ether - copper-catalyzed - di­methylaminomethylphosphonic acid derivative

References and Notes

• 1a Evans DA. DeVries KM. In Glycopeptide Antibiotics, Drugs and the Pharmaceutical Sciences   Vol. 63:  Nagarajan R. Marcel Decker, Inc.; New York: 1994.  p.63-104  
• 1b Theil F. Angew. Chem. Int. Ed.  1999,  38:  2345 
• 1c Itokama H. Takeya K. Heterocycles  1993,  35:  1467 
• 1d Kase H. Masami K. Yamada K. J. Antibiot.  1987,  40:  450 
• 1e Williams DH. Acc. Chem. Res.  1984,  17:  364 
• 1f Pearson AJ. Bignan G. Zhang P. Chelliah M. J. Org. Chem.  1996,  61:  3940 
• 1g Janetka JW. Raman P. Satyshur K. Flentke GR. Rich DH. J. Am. Chem. Soc.  1997,  119:  441 
• 1h Nicolaou KC. Boddy CNC. Natarajan S. Yue T.-Y. Li H. Bräse S. Ramanjulu JM. J. Am. Chem. Soc.  1997,  119:  3421 
• 1i Boger DL. Patane MA. Zhou J. J. Am. Chem. Soc.  1994,  116:  8544 
• 2 Ullmann F. Ber. Dtsch. Chem. Ges.  1904,  37:  853 
• 3 Lindley J. Tetrahedron  1984,  40:  1433 
• For palladium-mediated ether synthesis, see:
• 4a Torraca KE. Huang X. Parrish CA. Buchwald SL. J. Am. Chem. Soc.  2002,  123:  10770 
• 4b Aranyos A. Old DW. Kiyomori A. Wolfe JP. Sadighi JP. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  4369 
• 4c Mann G. Hartwig JF. Tetrahedron Lett.  1997,  38:  8005 
• 4d Mann G. Incarvito C. Rheigold AL. Hartwig JF. J. Am. Chem. Soc.  1999,  121:  3224 
• 4e Shelby Q. Kataoka N. Mann G. Hartwig J. J. Am. Chem. Soc.  2000,  122:  10718 
• For some recent reports, see:
• 5a Marcoux J.-F. Doye S. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  10539 
• 5b Buck E. Song ZJ. Tschaen D. Dormer PG. Volante RP. Reider PJ. Org. Lett.  2002,  4:  1623 
• 5c Palomo C. Oiarbide M. Lopez R. Gomez-Bengoa E. Chem. Commun.  1998,  2091 
• 5d Ma D. Cai Q. Org. Lett.  2003,  5:  3799 
• 5e Fagan PJ. Hauptman E. Shapiro R. Casalnuovo A. J. Am. Chem. Soc.  2000,  122:  5043 
• 5f Gujadhur RK. Bates CG. Venkataraman D. Org. Lett.  2001,  3:  4135 
• 5g Cristau HJ. Cellier PP. Hamada S. Spindler JF. Tailefer M. Org. Lett.  2004,  6:  913 
• 6a Hardy TA. inventors; US Patent  4083897. 
• 6b Diel PJ. Maier L. Phosphorus Sulfur Relat. Elem.  1984,  20:  13 
• 9 Antilla JC. Klapars A. Buchwald SL. J. Am. Chem. Soc.  2002,  124:  11684 

7

Synthesis of Diisopropyl Dimethylaminomethyl-phosphonate (L ^¹ ).
The mixed solution of diisopropyl phosphite (22 mmol, 3.7 g), dimethylamine hydrochloride (22 mmol, 1.79 g) and Et₃N (22 mmol, 3.2 mL) in EtOH (30 mL) was added dropwise to 37% aq formaldehyde (1.8 mL), and the resulting solution was refluxed for 8 h. The ³¹P NMR spectroscopy showed that the starting material diisopropyl phosphite was almost quantitatively transferred into ligand L ^¹ (δ = 26.9 ppm). The solvent was removed by rotary evaporation, the residue was isolated by silica gel column chromatography using CHCl₃-MeOH (10:1) as eluent, and the pure L ^¹ was obtained as a colorless liquid. Yield 4.50 g, 92%. ³¹P NMR (121.5 MHz, CDCl₃): δ = 26.9 ppm. ¹H NMR (300 MHz, CDCl₃): δ = 4.78-4.71 (m, 2 H), 2.75 (d, J = 20.4 Hz, 2 H), 1.33 (s, 6 H), 2.41-2.38 (m, 12 H). ¹³C NMR (75 MHz, CDCl₃): δ = 70.2, 56.9, 47.4, 24.0. ESI-HRMS: m/z calcd for C₉H₂₃NO₃P [M + H]⁺: 224.1416; found: 224.1411.
Synthesis of Ethyl Dimethylaminomethylphosphonate (L ^² ).
The mixed solution of diethyl phosphite (22 mmol, 3.0 g), dimethylamine hydrochloride (22 mmol, 1.79 g) in EtOH (30 mL) was added dropwise to 37% aq formaldehyde (1.8 mL), and the resulting solution was refluxed for 6 h. The solvent was removed by rotary evaporation, the residue was dissolved in 5 mL of H₂O and 10 mL of EtOH. Then, LiOH (22 mmol, 0.53 g) was added, and the solution was stirred at 60 °C for 3 h. The solution was extracted with CH₂Cl₂, the aqueous phase was acidified with 3 M HCl to pH 3, and evaporated to dryness to provide a solid mixture. MeOH was added to the remaining solid, and the insoluble solid was filtrated. The filtrate was concentrated and dried over P₂O₅ in vacuo, and the desired product ethyl dimethylamino-methylphosphonate hydrochloride salt (L ^² ) was obtained in the form of a white solid. Yield 3.81 g, 85%. ³¹P NMR (121.5 MHz, CDCl₃): δ = 6.8 ppm. ¹H NMR (300 MHz, CDCl₃): δ = 8.98 (s, 1 H), 3.71-3.61 (m, 2 H), 2.80 (d, J = 20.4 Hz, 2 H), 2.59 (s, 6 H), 0.95 (t, J = 7.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 60.5, 55.2, 55.3, 45.3, 16.7. ESI-HRMS: m/z calcd for C₅H₁₅NO₃P [M + H]⁺: 168.0790; found: 168.0783.
Synthesis of Dimethylaminomethylphosphonic Acid (L ^³ ).
This compound was synthesized according to the known method.² Dimethylamine hydrochloride (50 mmol, 4.2 g), H₃PO₄ (50 mmol, 4.1 g) and 20 mL of HCl (6.5 M in H₂O) were added to a round-bottom flask fitted with a reflux condenser, and the solution was heated for 5 min. Then, 52 mmol (3.87 mL) of formaldehyde (36% aq solution) was added, and the solution was refluxed for 90 min. After removal of H₂O in vacuo, the residue was heated in 60 mL of EtOH to lead to the formation of a white solid. This solid was collected after filtration, and dried in vacuo to obtain dimethylaminomethyl phosphonic acid hydrochloride salt (L ^³ , 8.42 g, 96%). ³¹P NMR (121.5 MHz, DMSO-d ₆,): δ = 9.3 ppm. ¹H NMR (300 MHz, DMSO-d ₆): δ = 5.86 (s, 2 H), 3.30 (d, J = 12.7 Hz, 2 H), 2.83 (s, 6 H). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 54.7, 52.8, 44.8. ESI-HRMS: m/z calcd for C₃H₁₁NO₃P [M + H]⁺: 140.0477; found: 140.0481.

8

Characterization data of two representative compounds are shown as follows:
4-Nitrophenyl Phenyl Ether (3j) ⁹
Yellow solid; mp 58-60 °C (Lit.⁷ 60 °C). ¹H NMR (300 MHz, CDCl₃): δ = 8.17 (d, J = 9.27 Hz, 2 H), 7.42 (t, J = 7.89 Hz, 2 H), 7.25 (t, J = 7.56 Hz, 1 H), 7.08 (d, J = 7.82 Hz, 2 H), 7.00 (d, J = 8.85 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 163.5, 154.8, 142.7, 130.4, 126.0, 125.5, 120.6, 117.2. HRMS (EI): m/z calcd for C₁₂H₉NO₃ [M⁺]: 215.0582; found: 215.0574.
Bis(4-methoxyphenenyl)ether (3m) ^5b
White solid; mp 101-103 °C (Lit.^5b 102-103 °C). ¹H NMR (300 MHz, CDCl₃): δ = 6.92 (d, J = 9.27 Hz, 4 H), 6.85 (d, J = 9.27 Hz, 4 H), 3.79 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 155.4, 151.7, 119.6, 114.8, 55.8. HRMS (EI): m/z calcd for C₁₄H₁₄O₃ [M⁺]: 230.0943; found: 230.0949.