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DOI: 10.1055/s-0028-1083508
Deoxygenation of Pyridine N-Oxides by Palladium-Catalysed Transfer Oxidation of Trialkylamines
Publication History
Publication Date:
01 October 2008 (online)
![](https://www.thieme-connect.de/media/synlett/200817/lookinside/thumbnails/10.1055-s-0028-1083508-1.jpg)
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.
Key words
deoxygenation - homogeneous catalysis - palladium - pyridine N-oxides - ligand effects
-
1a
Toganoh M.Fujino K.Ikeda S.Furuta H. Tetrahedron Lett. 2008, 49: 1488 -
1b
Singh SK.Reddy MS.Mangle M.Ganesh KR. Tetrahedron 2006, 63: 126 -
1c
Yoo BW.Choi JW.Yoon CM. Tetrahedron Lett. 2005, 47: 125 -
1d
Sanz R.Escribano J.Fernandez Y.Aguado R.Pedrosa MR.Arnaiz FJ. Synlett 2005, 1389 -
1e
Kumar S.Saini A.Sandhu JS. Tetrahedron Lett. 2005, 46: 8737 -
1f
Ilias M.Barman DC.Prajapati D.Sandhu JS. Tetrahedron Lett. 2002, 43: 1877 -
1g
Boruah M.Konwar D. Synlett 2001, 795 -
1h
Nicolau KC.Koumbis AE.Snyder SA.Simonsen KB. Angew. Chem. Int. Ed. 2000, 39: 2529 -
1i
Keith JM.
J. Org. Chem. 2006, 71: 9540 -
1j
Bjorsvik H.-R.Gambarotti C.Jensen VR.Gonzalez RR. J. Org. Chem. 2005, 70: 3218 -
1k
Chandrasekhar S.Reddy CR.Rao RJ.Rao JM. Synlett 2002, 349 -
1l
Hwu JR.Tseng WN.Patel HV.Wong FF.Horng D.-N.Liaw BR.Lin LC. J. Org. Chem. 1999, 64: 2211 -
1m
Rosenau T.Potthast A.Ebner G.Kosma P. Synlett 1999, 623 -
2a
Mandal PK.McMurray JS. J. Org. Chem. 2007, 72: 6599 -
2b
Fessard TC.Motoyoshi H.Carreira EM. Angew. Chem. Int. Ed. 2007, 46: 2078 -
2c
Leclerc J.-P.Fagnou K. Angew. Chem. Int. Ed. 2006, 45: 7781 -
2d
Mori A.Mizusaki T.Miyakawa Y.Ohashi E.Haga T.Maegawa T.Monguchi Y.Sajiki H. Tetrahedron 2006, 62: 11925 -
2e
Rahaim RJ.Maleczka RE. Synthesis 2006, 3316 -
2f
Campeau L.-C.Rousseaux S.Fagnou K. J. Am. Chem. Soc. 2005, 127: 18020 -
2g
Rahaim RJ.Maleczka RE. Org. Lett. 2005, 7: 5087 -
2h
Zacharie B.Moreau N.Dockendorff C. J. Org. Chem. 2001, 66: 5264 -
2i
Xu S.Xi X.Shi J.Cao S. J. Mol. Catal. A: Chem. 2000, 160: 287 -
2j
Islam SM.Palit BK.Mukherjee DK.Saha CR. J. Mol. Catal. A: Chem. 1997, 124: 5 -
2k
Petrini M.Ballini R.Rosini G. Synthesis 1987, 713 -
3a
Clarke ML.Fuentes JA. Angew. Chem. Int. Ed. 2007, 46: 930 -
3b
Fuentes JA.Clarke ML.Slawin AMZ. New J. Chem. 2008, 32: 689
References and Notes
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-¹. 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-¹. 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.
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.