PAPER
Oxidation of 2,5-Dialkylpyrroles with CAN
1151
HRMS (EI): m/z [M·+] calcd for C13H17NO6: 283.1056; found:
283.1138.
13C NMR (125 MHz, CDCl3): d = 11.4, 20.9, 33.5, 51.7, 52.8, 53.5,
113.3, 131.6, 134.3, 135.1, 136.5, 165.5, 165.7, 175.1.
HRMS (EI): m/z [M·+] calcd for C13H17NO6: 283.1056; found:
283.1049.
Diethyl 5,6-Bis-ethoxycarbonyl-4,7-dioxodecanedioate (18)
Sodium metal (61 mmol, 1.4 g) was reacted with EtOH (20 mL) and
diethyl 3-oxoadipate (17; 61 mmol, 13.2 mL) was added. The reac-
tion mixture was stirred for 1 h, then EtOH was removed in vacuum,
the residue was suspended in anhydrous Et2O (70 mL) and a solu-
tion of I2 (30.5 mol, 7.78 g) in anhydrous THF (30 mL) was added
dropwise with vigorous stirring until the reaction mixture started to
become purple. The reaction mixture was filtered and solvent was
evaporated. Crystallization of the residue (EtOAc–hexanes) afford-
ed pure product.
22
Yield: 8.48 g (67%); yellow oil.
1H NMR (400 MHz, CDCl3): d = 2.17 (s, 3 H, CH3), 2.52 (t, J = 7.8
Hz, 2 H, CH2CH2), 2.87 (t, J = 7.8 Hz, 2 H, CH2CH2), 3.64 (s, 3 H,
CH3CO2), 3.68 (s, 3 H, CH3CO2), 3.81 (s, 3 H, CH3CO2), 3.82 (s,
3 H, CH3CO2), 3.86 (s, 3 H, CH3CO2), 7.39 (s, 1 H, C=CH).
13C NMR (125 MHz, CDCl3): d = 11.1, 21.0, 33.3, 51.5, 51.7, 52.8,
53.4, 53.7, 113.6, 129.0, 131.5, 134.2, 135.3, 136.8, 162.4, 162.7,
165.1, 165.5, 172.8.
Yield: 5.35 g (31%); white crystals.
IR (KBr): 1185, 1295, 1267, 1379, 1713, 1723, 1736, 2992, 3449
cm–1.
HRMS (EI): m/z [M·+] calcd for C19H23NO10: 425.1322; found:
425.1328.
1H NMR (500 MHz, CDCl3): d = 1.24 (t, J = 7.1 Hz, 6 H,
2 × CH3CH2), 1.26 (t, J = 7.1 Hz, 6 H, 2 × CH3CH2), 2.50–2.56 (m,
2 H, 2 × CHHCH2), 2.59–2.65 (m, 2 H, 2 × CHHCH2), 2.95–3.01
(m, 2 H, 2 × CH2CHH), 3.25–3.31 (m, 2 H, 2 × CH2CHH), 4.12 (q,
J = 7.1 Hz, 4 H, 2 × CH3CH2CO2), 4.16 (q, J = 7.1 Hz, 4 H,
2 × CH3CH2CO2), 4.51 (s, 2 H, 2 × CH).
13C NMR (125 MHz, CDCl3): d = 13.9, 14.1, 27.9, 38.2, 57.1, 60.6,
62.2, 166.8, 172.1, 201.8.
HRMS (ESI): m/z [M + Na+] calcd for C20H30O10Na: 453.1731;
found: 453.1750.
Dimethyl 2-Formyl-5-(2-methoxycarbonylethyl)pyrrole-3,4-di-
carboxylate (24)
Dimethyl 2-(2-methoxycarbonylethyl)-5-methylpyrrole-3,4-dicar-
boxylate (23; 1 mmol, 283 mg) was dissolved in a mixture of MeOH
(20 mL) and H2O (10 mL). CAN (8.2 mmol, 4.5 g) was added and
the resulting mixture was stirred at r.t. for 3 h. Subsequently, H2O
(200 mL) was added, the layers were separated and the aqueous lay-
er was extracted with CH2Cl2 (100 mL). The combined organic lay-
ers were washed with H2O (10 mL), dried (Na2SO4) and
concentrated. Column chromatography (silica; CH2Cl2–EtOAc,
9:1) afforded the pure product.
Anal. Calcd for C20H30O10: C, 55.81; H, 7.02. Found: C, 55.13; H,
6.98.
Yield: 125 mg (42%); yellowish oil.
Diethyl 2,5-Bis(2-ethoxycarbonylethyl)pyrrole-3,4-dicarboxy-
late (19)
1H NMR (500 MHz, CDCl3): d = 2.74 (t, J = 6.3 Hz, 2 H, CH2CH2),
3.21 (t, J = 6.3 Hz, 2 H, CH2CH2), 3.70 (s, 3 H, CH3CO2), 3.84 (s,
3 H, CH3CO2), 3.92 (s, 3 H, CH3CO2), 9.78 (s, 1 H, CHO), 9.08 (br
s, 1 H, NH).
13C NMR (125 MHz, CDCl3): d = 21.6, 32.8, 51.8, 52.2, 52.5, 114.5,
124.4, 130.3, 142.2, 163.9, 173.8, 179.8, 200.1.
Diethyl 5,6-bis-ethoxycarbonyl-4,7-dioxodecanedioate (18; 6.65
mmol, 2.86 g) and NH4OAc (133 mmol, 10 g) were dissolved in
AcOH (50 mL) and stirred at 25 °C for 20 h. Subsequently, AcOH
was evaporated and H2O (50 mL) was added to the residue. The sus-
pension was extracted with CH2Cl2 (2 × 30 mL). The organic layer
was dried (Na2SO4) and the solvent was evaporated to directly ob-
tain the pure product.
HRMS (EI): m/z [M·+] calcd for C13H15NO7: 297.0849; found:
297.0831.
Yield: 1.5 g (55%).
1H NMR (200 MHz, CDCl3): d = 1.26 (t, J = 7.0 Hz, 6 H,
2 × CH3CH2), 1.32 (t, J = 7.2 Hz, 6 H, 2 × CH3CH2), 2.65 (t, J = 6.2
Hz, 4 H, 2 × CH2CH2), 3.04 (t, J = 6.2 Hz, 4 H, 2 × CH2CH2), 4.12
(q, J = 7.2 Hz, 4 H, 2 × CH3CH2CO2), 4.16 (q, J = 7.0 Hz, 4 H,
2 × CH3CH2CO2), 9.41 (br s, 1 H, NH).
Acknowledgment
We thank the Ministry of Science and Higher Education (Project 3
T09A 12429) the Volkswagen Foundation and the US Air Force for
financial support.
13C NMR (50 MHz, CDCl3): d = 12.5, 14.2, 21.2, 33.8, 60.1, 60.8,
112.4, 135.1, 165.2, 173.8.
References
HRMS (EI): m/z [M·+] calcd for C20H29NO8: 411.1893; found:
411.1878.
(1) (a) Larionov, O. V.; de Meijere, A. Angew. Chem. Int. Ed.
2005, 44, 5664. (b) Garg, N. K.; Caspi, D. D.; Stoltz, B. M.
J. Am. Chem. Soc. 2005, 127, 5970. (c) Dhawan, R.;
Arndtsen, B. A. J. Am. Chem. Soc. 2004, 126, 468.
(d) Donohoe, T. J.; Sintim, H.; Sisangia, L.; Harling, J. D.
Angew. Chem. Int. Ed. 2004, 43, 2293. (e) Fürstner, A.
Angew. Chem. Int. Ed. 2003, 42, 3582. (f) Hoffmann, H.;
Lindel, T. Synthesis 2003, 1753. (g) Handy, S. T.; Zhang, Y.
Org. Prep. Proced. Int. 2005, 37, 411. (h) Walsh, C. T.;
Garneau-Tsodikova, S.; Howard-Jones, A. R. Nat. Prod.
Rep. 2006, 23, 517. (i) Rossi, R.; Bellina, F. Tetrahedron
2006, 62, 7213.
Dimethyl 2-(2-Methoxycarbonylethyl)-5-methylpyrrole-3,4-di-
carboxylate (23)
L-Glutamic acid 5-monomethyl ester (21; 4.83 g, 30 mmol) was sus-
pended in Ac2O (30 mL), and dimethyl acetylenedicarboxylate (20;
60 mmol, 7.3 mL) was added. The reaction mixture was stirred at
140 °C for 1 h, then concentrated and purified by column chroma-
tography (silica; CH2Cl2–MeOH, 100:0→99:1→98:2) to afford the
pure desired product 23 and the by-product 22.
Yield: 2.58 g (30%); yellowish oil.
(2) (a) Baran, P. S.; Richter, J. M.; Lin, D. W. Angew. Chem. Int.
Ed. 2005, 44, 609. (b) Naumovski, L.; Ramos, J.; Sirisawad,
M.; Chen, J.; Thieman, P.; Lecane, P.; Magda, D.; Wang, Z.;
1H NMR (500 MHz, CDCl3): d = 2.36 (s, 3 H, CH3), 2.68 (t, J = 6.6
Hz, 2 H, CH2CH2), 3.03 (t, J = 6.6 Hz, 2 H, CH2CH2), 3.69 (s, 3 H,
CH3CO2), 3.80 (s, 6 H, 2 × CH3CO2), 9.08 (br s, 1 H, NH).
Synthesis 2009, No. 7, 1147–1152 © Thieme Stuttgart · New York