PAPER
Synthesis of 3-Indolecarboxylates
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13C NMR: d = 163.9 (+), 161.2 (+), 140.3 (+), 132.3 (–), 125.0 (+),
122.4 (–), 108.4 (–), 106.6 (–), 80.0 (+), 53.2 (–), 28.5 (–).
HRMS: m/z [M + H]+ calcd for C15H19N2O: 243.1497; found:
243.1492.
Anal. Calcd for C13H16N2O3: C, 62.89; H, 6.50; N, 11.28. Found: C,
62.85; H, 7.19; N, 10.97.
41
Yield: 10 mg (10%); pale-yellow solid; mp 51–52 °C.
HRMS: m/z [M + H]+ calcd for C13H17N2O3: 249.1239; found:
249.1234.
IR (neat): 2228, 1619, 1479, 1213, 1072 cm–1.
1H NMR (600 MHz): d = 8.00 (d, J = 9.0 Hz, 1 H), 7.58 (s, 1 H),
7.44 (dd, J = 9.0, 3.0 Hz), 7.34 (d, J = 3.0 Hz, 1 H), 3.99 (s, 3 H),
2.97 (t, J = 7.8 Hz, 2 H), 1.79 (pent, J = 7.8 Hz, 2 H), 1.44 (sext,
J = 7.8 Hz, 2 H), 0.97 (t, J = 7.8 Hz, 3 H).
5-Methoxyindol-3-yl Phenyl Sulfone (33)
Reaction of 23 (100 mg, 0.31 mmol), Pd(dba)2 (15 mg, 0.02 mmol),
dppp (11 mg, 0.02 mmol) and phen (10 mg, 0.04 mmol) in DMF (5
mL), as described for 3 (120 °C, 6 atm CO, 72 h), gave 33 after
chromatography (hexanes–EtOAc, 9:1).
13C NMR (150 MHz): d = 159.6, 159.3, 144.2, 131.2, 125.7, 125.2,
124.0, 117.2, 102.1, 55.9, 38.4, 31.9, 22.5, 13.9.
Yield: 65 mg (74%); pale-yellow solid; mp 91 °C.
HRMS: m/z [M + H]+ calcd for C15H17N2O: 241.1341; found:
241.1335.
IR (neat): 1506, 1487, 1293, 1213, 1144, 909, 732 cm–1.
1H NMR: d = 9.36 (br s, 1 H), 7.99 (dd, J = 7.7, 1.2 Hz, 1 H), 7.79
(s, 1 H), 7.56–7.39 (m, 4 H), 7.32 (d, J = 2.5 Hz, 1 H), 7.28 (d,
J = 9.2 Hz, 1 H), 6.90 (dd, J = 8.9, 2.5 Hz, 1 H), 3.82 (s, 3 H).
Acknowledgment
This work was supported by research grants from the National Sci-
ence Foundation (CHE 0611096), the National Institute of General
Medical Sciences, National Institutes of Health (RO1 GM57416)
and the American Chemical Society Petroleum Research Fund
(40665-AC1). NSF-EPSCoR (Grant #1002165R) is gratefully
acknowledged for the funding of a 600 MHz Varian Inova NMR
and a Thermo-Finnegan LTQ-FT Mass Spectrometer and the NMR
and MS facilities in the C. Eugene Bennett Department of Chem-
istry at West Virginia University.
13C NMR: d = 156.0 (+), 143.2 (+), 132.5 (–), 131.1 (+), 130.2 (–),
129.0 (–), 126.5 (–), 124.3 (+), 115.8 (+), 114.4 (–), 113.1 (–), 100.9
(–), 55.8 (–).
Anal. Calcd for C15H13NO3S: C, 62.70; H, 4.56; N, 4.87. Found: C,
63.13; H, 4.41; N, 4.49.
HRMS: m/z [M + Na]+ calcd for C15H13NO3S: 310.0514; found:
310.0508.
Ethyl 2-Propylindole-3-carboxylate (37)
Reaction of ethyl 2-(2-nitrophenyl)hexenoate (130 mg 0.44 mmol),
Pd(dba)2 (14 mg, 0.02 mmol), dppp (10 mg, 0.02 mmol) and phen
(11 mg, 0.04 mmol) in DMF (5 mL), as described for 3 (120 °C, 6
atm CO, 72 h), gave 37 after chromatography (hexanes–EtOAc,
9:1).
References
(1) (a) Kuethe, J. T.; Davies, I. W. Tetrahedron 2006, 62,
11381. (b) Clawson, R. W. Jr.; Deavers, R. E. III;
Akhmedov, N. G.; Söderberg, B. C. G. Tetrahedron 2006,
62, 10829. (c) Davies, I. W.; Smitrovich, J. H.; Sidler, R.;
Qu, C.; Gresham, V.; Bazaral, C. Tetrahedron 2005, 61,
6425. (d) Söderberg, B. C. G.; Hubbard, J. W.; Rector, S. R.;
O’Neil, S. N. Tetrahedron 2005, 61, 3637. (e) Söderberg,
B. C.; Shriver, J. A. J. Org. Chem. 1997, 62, 5838.
(f) Akazome, M.; Kondo, T.; Watanabe, Y. J. Org. Chem.
1994, 59, 3375. (g) Tollari, S.; Cenini, S.; Crotti, C.;
Gianella, E. J. Mol. Catal. 1994, 87, 203.
(2) For reactions using Fe(CO)5, Ru3(CO)12 or Rh6(CO)16
catalysts under CO, see: Crotti, C.; Cenini, S.; Rindone, B.;
Tollari, S.; Demartin, F. Chem. Commun. 1986, 784.
(3) For reactions using catalytic amounts of selenium under CO,
see: Nishiyama, Y.; Maema, R.; Ohno, K.; Hirose, M.;
Sonoda, N. Tetrahedron Lett. 1999, 40, 5717.
(4) For reactions using catalytic amounts of MoO2Cl2(dmf)2
with PPh3 as oxygen acceptor, see: Sanz, R.; Escribano, J.;
Pedrosa, M. R.; Aguado, R.; Arnaiz, F. J. Adv. Synth. Catal.
2007, 349, 713.
(5) Kuethe, J. T.; Wong, A.; Davies, I. W. Org. Lett. 2003, 5,
3721.
(6) Kuethe, J. T.; Wong, A.; Qu, C.; Smitrovich, J.; Davies, I.
W.; Hughes, D. L. J. Org. Chem. 2005, 70, 2555.
(7) Scott, T. L.; Söderberg, B. C. G. Tetrahedron 2003, 59,
6323.
(8) Dantale, S. W.; Söderberg, B. C. G. Tetrahedron 2003, 59,
5507.
(9) Scott, T. L.; Yu, X.; Gorunatula, S. P.; Carrero-Martínez, G.;
Söderberg, B. C. G. Tetrahedron 2006, 62, 10835.
(10) Söderberg, B. C.; Chisnell, A. C.; O’Neil, S. N.; Shriver, J.
A. J. Org. Chem. 1999, 64, 9731.
Yield: 96 mg (84%); pale-yellow solid; mp 108 °C.
IR (neat): 2965, 2925, 1726, 1267, 1118, 1973, 740 cm–1.
1H NMR (600 MHz): d = 8.28 (s, 1 H), 8.06 (dd, J = 7.8, 1.2 Hz,
1 H), 7.24 (dd, J = 7.8, 1.2 Hz, 1 H), 7.13 (m, 2 H), 4.33 (q, J = 7.2
Hz, 2 H), 3.07 (t, J = 7.8 Hz, 2 H), 1.71 (sext, J = 7.8 Hz, 2 H), 1.37
(t, J = 7.2 Hz, 3 H), 0.94 (t, J = 7.2 Hz, 3 H).
13C NMR (150 MHz): d = 165.9, 148.2, 144.5, 134.5, 127.3, 122.3,
121.7, 121.5, 110.5, 59.4, 29.9, 22.5, 14.6, 14.0.
HRMS: m/z [M + H]+ calcd for C14H18NO2: 232.1338; found:
232.1333.
3-Cyano-2-pentyl-5-methoxyindole (40) and 2-Butyl-4-cyano-6-
methoxyquinoline (41)
Reaction of 39 (110 mg, 0.40 mmol), Pd(dba)2 (16 mg, 0.02 mmol),
dppp (15 mg, 0.02 mmol) and phen (19 mg, 0.03 mmol) in DMF (5
mL), as described for 3 (120 °C, 6 atm, 72 h), gave 40 and 41 (in
order of elution), after chromatography (hexanes–EtOAc, 8:2).
40
Yield: 40 mg (45%); pale-yellow solid; mp 98–99 °C.
IR (neat): 3249, 2210, 1477, 1221 cm–1.
1H NMR (600 MHz): d = 8.44 (br s, 1 H), 7.24 (d, J = 8.4 Hz, 1 H),
7.09 (d, J = 2.4 Hz, 1 H), 6.86 (dd, J = 9.0, 2.4 Hz, 1 H), 3.86 (s,
3 H), 2.92 (t, J = 7.8 Hz, 2 H), 1.78 (pent, J = 7.2 Hz, 2 H), 1.38–
1.35 (m, 4 H), 0.90 (t, J = 7.2 Hz, 3 H).
13C NMR (150 MHz): d = 155.8, 149.2, 129.2, 128.6, 116.5, 113.7,
112.1, 100.7, 84.9, 55.8, 31.2, 28.7, 27.6, 22.3, 13.9.
(11) For a recent review, see: Humphrey, G. R.; Kuethe, J. T.
Chem. Rev. 2006, 106, 2875.
(12) Allen, G. R. Jr. Org. React. 1973, 20, 337.
Anal. Calcd for C15H18N2O: C, 74.35; H, 7.49; N, 11.56. Found: C,
73.88; H, 8.04; N, 11.45.
Synthesis 2008, No. 6, 903–912 © Thieme Stuttgart · New York