10.1002/ejoc.201900187
European Journal of Organic Chemistry
FULL PAPER
5-(1H-indol-2-yl)-3-phenylisoxazole (4m´): General procedure F is
employed with 3-phenylisoxazol-5-yl trifluoromethanesulfonate 3c (0.1
mmol, 29 mg), indole-2-boronic acid pinacol ester 9l (0.12 mmol, 29 mg),
Na2CO3 (0.14 mmol, 15 mg), Pd(PPh3)4 (0.005 mmol, 6 mg) and dioxane
(1 mL). Purification by flash column chromatography (SiO2, gradient: Hex
– 95:5 Hex:AcOEt – 9:1 Hex:AcOEt) affords the title compound as a
brown solid: 24 mg, 92%. 1H (500 MHz, CDCl3) δ: 8.75 (s, 1H), 7.87-7.85
(m, 2H), 7.68-7.66 (m, 1H), 7.49-7.43 (m, 4H), 7.30-7.27 (m, 1H), 7.18-
7.14 (m, 1H), 7.02-7.02 (m, 1H), 6.82 (s, 1H). 13C (125 MHz, CDCl3) δ:
164.0, 163.2, 137.0, 130.4, 129.2, 129.0, 128.4, 127.1, 125.3, 124.5,
121.8, 121.2, 111.7, 103.8, 97.6. M. P.: 191 -193 ºC. IR (ATR, cm-1):
3414, 3102, 3054, 1620, 1577, 1490, 1440, 1395, 1343, 1287, 1249,
1090. HRMS (ESI+): Calcd. for [C17H12N2O+H]+: 261.1022, found:
261.1018.
Acknowledgments
A. A. G. F. acknowledges a Ph.D. Fellowship from Fapesp
(2017/ 22164-6); A. F. S. is thankful to Capes for a Ph.D.
Fellowship; C. Y. O. Jr. is grateful to CNPq for a Ph.D.
Fellowship (140554/ 2017-3); V. S. is grateful for an
Undergraduate Fellowship from SAE-Unicamp and I. D. J.
acknowledges Fapesp for a Research Grant (2017/ 24017-0).
Keywords: Heterocycles
•
Isoxazoles
•
Isoxazolones
•
Nucleophilic Substitutions • Cross-Coupling
[1]
For selected examples, see: a) A. G. Griesback, M. Franke, J. Neudörfl,
H. Kotaka, Beilstein J. Org. Chem. 2011, 7, 127-134. b) Y. Ge, W. Sun,
B. Pei, J. Ding, Y. Jiang, T.-P. Loh, Org. Lett. 2018, 20, 2774-2777. c) K.
I. Mikhailov, E. E. Galenko, A. V. Galenko, M. S. Novikov, A. Yu. Ivanov,
G. L. Starova, A. F. Khlebnikov, J. Org. Chem. 2018, 83, 3177-3187. d)
J. O. Ruvinskaya, N. V. Rostovskii, I. P. Filippov, A. F. Khlebnikov, M. S.
Novikov, Org. Biomol. Chem. 2018, 16, 38-42. e) K. Okamoto, A.
Nanya, A. Egushi, K. Ohe, Angew. Chem. Int. Ed. 2018, 57, 1039-1043.
f) S. Pusch, T. Opatz, Org. Lett. 2014, 16, 5430-5433. g) S.Pusch, D.
Schollmeyer, T. Opatz, Org. Lett. 2016, 18, 3043-3045. h) E. E.
Galenko, V. A. Bodunov, A. V. Galenko, M. S. Novikov, A. F.
Khlebnikov, J. Org. Chem. 2017, 82, 8568-8579.
5-(benzo[b]thiophen-2-yl)-3-phenylisoxazole (4n´): General procedure
F is employed with 3-phenylisoxazol-5-yl trifluoromethanesulfonate 3c
(0.1 mmol, 29 mg,), benzo[b]thiophen-2-ylboronic acid 9m (0.12 mmol,
23 mg), Na2CO3 (0.14 mmol, 15 mg), Pd(PPh3)4 (0.005 mmol, 6 mg) and
dioxane (1 mL). Purification by flash column chromatography (SiO2,
gradient: Hex – 95:5 Hex:AcOEt – 9:1 Hex:AcOEt) affords the title
compound as a white solid: 13 mg, 46%. 1H (400 MHz, CDCl3) δ: 7.89-
7.84 (m, 4H), 7.79 (s, 1H), 7.50-7.45 (m, 3H), 7-42-7.7.34 (m, 2H), 6.80
(s, 1H). 13C (100 MHz, CDCl3) δ: 165.5, 163.3, 140.4, 139.7, 130.4,
129.3, 129.2, 129.0, 127.1, 126.1, 125.3, 124.9, 123.9, 122.7, 99.0. M.
P.: 157 -159 ºC. IR (ATR, cm-1): 3117, 3054, 1602, 1498, 1463, 1439,
1396, 1331, 1254, 1201, 1072, 1023. HRMS (ESI+): Calcd. for
[C17H10NOS+H]+: 278.0634, found: 278.0630.
[2]
[3]
For reviews, see: a) P. G. Baraldi, A. Barco, S. Benetti, G. P. Pollini, D.
Simoni, Synthesis 1987, 10, 857-869. b) F. Liu, A. G. Myers, Curr. Opin.
Chem. Biol. 2016, 32, 48-57. For selected examples, see: c) C. Sun, Q.
Wang, J. D. Brubaker, P. M. Wright, C. D. Lerner, K. Noson, M. Charest,
D. R. Siegel, Y.-M. Wang, A. G. Myers, J. Am. Chem. Soc. 2008, 130,
17913-17927.
For a review, see: a) A. Sysak, B. Obminska-Mrukowicz, Eur. J. Med.
Chem. 2017, 137, 292-309. For selected examples, see: b) D. Simoni,
R. Rondanin, R. Baruchello, M. Rizzi, G. Grisolia, M. Eleopra, S.
Grimaudo, A. Di Cristina, M. R. Pipitone, M. R. Bongiorno, M. Aricò, F.
P. Invidiata, M. Tolomeo, J. Med. Chem. 2008, 51, 4796-4803. c) M.
Mączyński, S. Borska, K. Mieszala, M. Kocięba, E. Zaczyńska, I.
Kochanowska, M. Zimecki, Molecules 2018, 23, 1545-1558. d) A.
Kamal, J. S. Reddy, M. J. Ramaiah, D. Dastagiri, E. V. Bharathi, M. A.
Azhar, F. Sultana, S. N. C. V. L. Pushpavalli, M. Pal-Bhadra, A. Juvekar,
S. Sen, S. Zingde, Eur. J. Med. Chem. 2010, 45, 3924-3937. e) S. S.
Panda, P. V. R. Chowdary; B. S. Jayashree, Indian J. Pharm Sci. 2009,
71, 684-687. f) S. Marwaha, H. Uvell, O. Salin, A. E. G. Lindgren, J.
Silver, M. Elofsson, A. Gylfe, Antimicrob. Agents Chemother. 2014, 58,
2968-2971.
3-phenyl-5-vinylisoxazole (4o´): General procedure F is employed with
3-phenylisoxazol-5-yl trifluoromethanesulfonate 3c (0.1 mmol, 29 mg),
vinylboronic acid 2-methyl-2,4-pentanediol ester 9n (95%, 0.25 mmol, 41
mg), Na2CO3 (0.14 mmol, 15 mg), Pd(PPh3)4 (0.005 mmol, 6 mg) and
dioxane (1 mL). Purification by flash column chromatography (SiO2,
gradient: Hex - 95:5 Hex:AcOEt – 9:1 Hex:AcOEt) affords the title
compound as an yellow solid: 6 mg, 35%. 1H (500 MHz, CDCl3) δ:28
7.80-7.78 (m, 2H), 7.45-7.42 (m, 3H), 6.65 (dd, J = 11.4 Hz, J = 17.8 Hz,
1H), 6.50 (s, 1H), 6.05 (d, J = 17.8 Hz, 1H), 5.58 (d, J = 11.4 Hz, 1H). 13
C
(125 MHz, CDCl3) δ: 169.0, 162.9, 130.2, 129.3, 129.1, 127.0, 122.6,
120.9, 99.7. M. P.: 37 - 38 ºC. IR (ATR, cm-1): 2850, 1664, 1564, 1509,
1466, 1403, 1297, 1227, 1260, 1081, 1027, 999, 961. HRMS (ESI+):
Calcd. for [C11H9NO +H]+: 172.0757, found: 172.0757.
[4]
[5]
For a recent review, see: F. Hu, M. Szostak, Adv. Synth. Catal. 2015,
357, 2583-2614.
For selected examples, see: a) F. Himo, T. Lovell, R. Hilgraf, V. V.
Rostovtsev, L. Noodleman, K. B. Sharpless, V. V. Fokin, J. Am. Chem.
Soc. 2005, 127, 210-216. b) T. V. Hansen, P. Wu, V. V. Fokin, J. Org.
Chem. 2005, 70, 7761-7764. c) S. Grecian, V. V. Fokin, Angew. Chem.
Int. Ed. 2008, 47, 8285-8287. d) J. S. Oakdale, R. K. Sit, V. V. Fokin,
Chem. Eur. J. 2014, 20, 11101-11110.
(E)-3-phenyl-5-(prop-1-en-1-yl) isoxazole (4p´): General procedure F is
employed with 3-phenylisoxazol-5-yl trifluoromethanesulfonate 3c (0.1
mmol, 29 mg), trans-prop-1-en-1-ylboronic acid 3o (0.25 mmol, 22 mg),
Na2CO3 (0.14 mmol, 15 mg), Pd(PPh3)4 (0.005 mmol, 6 mg) and dioxane
(1 mL). Purification by flash column chromatography (SiO2, gradient: Hex
– 95:5 Hex:AcOEt – 9:1 Hex:AcOEt) affords the title compound as a
white solid: 15 mg, 81%. 1H (500 MHz, CDCl3) δ: 7.79-7.77 (m, 2H),
7.44-7.41 (m, 3H), 6.61-6.54 (m, 1H), 6.37-66.34 (m, 1H), 6.65 (s, 1H),
1.93 (dd, J = 6.8 Hz, J = 1.6 Hz, 3H). 13C (125 MHz, CDCl3) δ: 169.3,
162.7, 134.0, 130.0, 129.5, 129.0, 127.0, 117.3, 97.9, 18.9. M. P.: 60 - 61
ºC. IR (ATR, cm-1): 2850, 1664, 1564, 1509, 1466, 1403, 1297, 1227,
1260, 1081, 1027, 999, 961. HRMS (ESI+): Calcd. for [C12H11NO+H]+:
186.0913, found: 186.0912.
[6]
[7]
For selected examples, see: a) J. P. Waldo, R. C. Larock, Org. Lett.
2005, 7, 5203-5205. b) T. Okitsu, K. Sato, T. M. Potewar, A. Wada, J.
Org. Chem. 2011, 76, 3438-3449. c) I. Cikotiene, Eur. J. Org. Chem.
2012, 2766-2773.
For selected examples, see: a) S. Tang, J. He, Y. Sun, L. He, X. She,
Org. Lett. 2009, 11, 3982-3985. b) D. Xiang, X. Xin, X. Liu, R. Zhang, J.
Yang, D. Dong, Org. Lett. 2012, 14, 644-647. c) S. Samai, T. Chanda,
H. Ila, M. S. Singh, Eur. J. Org. Chem. 2013, 4026-4031.
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