Synlett 2008(17): 2579-2582  
DOI: 10.1055/s-0028-1083508
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Deoxygenation of Pyridine N-Oxides by Palladium-Catalysed Transfer ­Oxidation of Trialkylamines

José A. Fuentes, Matthew L. Clarke*
School of Chemistry, University of St Andrews, EaSTCHEM, St Andrews, Fife, KY16 9ST, UK
Fax: +44(1334)463808; e-Mail: mc28@st-andrews.ac.uk;
Further Information

Publication History

Received 21 July 2008
Publication Date:
01 October 2008 (online)

Abstract

A convenient and chemoselective method for deoxygenation of pyridine N-oxide derivatives by transfer oxidation of triethylamine-catalysed by [Pd(OAc)2]/dppf is described.

    References and Notes

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4

Synthesis of Pyridine N -Oxide 2 (Scheme 1)
Aryl bromide 1 (67 mg, 0.29 mmol), Pd(OAc)2 (1.9 mg, 3 mol%), and a stirring bead were placed in a 5 mL microwave process vial that was placed under a nitrogen atmosphere before the addition of dry DMF (4 mL), Et3N (0.12 mL, 0.87 mmol), and isobutyl acrylate (0.13 mL, 0.87 mmol). The reaction mixture was heated by microwave irradiation at 140 ˚C for 60 min. After being cooled to ambient temperature, the reaction mixture was concentrated under reduced pressure. The crude mixture was purified by chromatography on a SiO2 column using EtOAc-MeOH (8:1) as eluent to give the corresponding coupling product 2 (74 mg, 0.27 mmol, 92%) as a yellow solid; mp 149-151 ˚C. IR (KBr): 3065, 2959, 2876, 1718, 1692, 1639, 1605, 1569, 1525, 1399 cm. ¹H NMR (300 MHz, CDCl3): δ = 0.91 (d, J = 6.7 Hz, 6 H, CH3), 1.94 (m, 1 H, CH), 2.26 (s, 3 H, CH3), 3.94 (d, J = 6.7 Hz, 2 H, CH2), 6.38 (d, J = 16.0 Hz, 1 H, =CH), 7.41 (d, J = 16.0 Hz, 1 H, =CH), 7.43 (d, J = 8.8 Hz, 1 H, ArCH), 8.33 (s, 1 H, ArCH), 8.39 (d, J = 8.8 Hz, 1 H, ArCH), 9.98 (br s, 1 H, NH). ¹³C NMR (75 MHz, CDCl3): δ = 19.5, 25.4, 28.2, 71.5, 114.7, 121.6, 126.8, 127.0, 136.6, 138.5, 144.9, 166.3, 169.3. MS (TOF-ES): m/z (%) = 301.1 (100) [M + Na]+. HRMS (TOF-ES): m/z [M + Na]+ calcd for C14H18N2O4Na: 301.1164; found: 301.1173.
Synthesis of Compound 3 (Scheme 1) To aryl bromide 1 (134 mg, 0.58 mmol) and [Pd(dippf)Cl2] (10.4 mg, 3 mol%) in a 5 mL microwave process vial were added dry DMF (4 mL), Et3N (0.24 mL, 1.74 mmol), and isobutyl acrylate (0.35 mL, 1.74 mmol). The reaction mixture was heated by microwave irradiation at 140 ˚C for 60 min. After being cooled to ambient temperature, the reaction mixture was concentrated under reduced pressure. The crude mixture was purified by chromatography on a SiO2 column using EtOAc-hexane (3:1) as eluent to give the corresponding coupling product 3 (130 mg, 0.47 mmol, 81%) as a white solid; mp 112-114 ˚C. IR (KBr): 3245, 3095, 2959, 2876, 1720, 1687, 1641, 1604, 1586, 1542, 1369 cm. ¹H NMR (300 MHz, CDCl3): δ = 0.91 (d, J = 6.7 Hz, 6 H, CH3), 1.94 (m, 1 H, CH), 2.17 (s, 3 H, CH3), 3.93 (d, J = 6.7 Hz, 2 H, CH2), 6.38 (d, J = 16.0 Hz, 1 H, =CH), 7.56 (d, J = 16.0 Hz, 1 H, =CH), 7.82 (dd, J = 8.7, 2.3 Hz, 1 H, ArCH), 8.19 (d, J = 8.7 Hz, 1 H, ArCH), 8.31 (d, J = 2.3 Hz, 1 H, ArCH), 8.58 (br s, 1 H, NH). ¹³C NMR (75 MHz, CDCl3): δ = 19.2, 24.8, 27.8, 70.8, 113.9, 118.7, 126.5, 136.6, 140.3, 148.2, 152.5, 166.7, 168.9. MS (TOF-ES): m/z (%) = 263.1 (14) [M + H]+, 285.0(100) [M + Na]+. HRMS (TOF-ES): m/z [M + Na]+ calcd for C14H18N2O3Na: 285.1215; found: 285.1206.

5

General Procedure for the Deoxygenation of Pyridine N -Oxides
Pyridine N-oxide (0.29 mmol), Pd(OAc)2 (1.9 mg, 3 mol%), dppf (4.8 mg, 3 mol%), and a stirring bead were placed in a 5 mL microwave process vial that was then put under a nitrogen atmosphere. Dry MeCN (2.5 mL) and Et3N (0.12 mL, 0.87 mmol) were then added by syringe. The reaction mixture was heated by microwave irradiation at the temperature and time indicated in Tables  [¹] and  [²] . After NMR analysis, the solvent was concentrated under reduced pressure. The crude mixture was purified by chromatog-raphy on SiO2 using EtOAc as eluent to afford the corresponding deoxygenated products. The spectral data for the isolated material was in accord with the literature data, and authentic samples.