M. Córdoba et al. / Tetrahedron Letters 52 (2011) 1738–1741
1741
272.1188. Anal. Calcd for C18H13N3: C, 79.68; H, 4.83; N, 15.49. Found: C,
79.36; H, 5.09; N, 15.62.
RD06/0016/0016) for financial support and the Universidad de
Alcalá (UAH) for a studentship (M.C.).
12. (a)Microwaves in Organic Synthesis; Loupy, A., Ed.; Wiley-VCH: Weinheim,
2002; (b) Tierney, J.; Lidstrom, P. Microwave Assisted Organic Synthesis;
Blackwell: Oxford, 2004; (c) Hayes, B. L. Aldrichim. Acta 2004, 37, 66–76; (d)
Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250–6284; (e) Kappe, C. O.;
Stadler, A. Microwaves in Organic and Medicinal Chemistry; Wiley-VCH:
Weinheim, 2005; (f) Kappe, C. O.; Dallinger, D. Nat. Rev. Drug Disc. 2006, 5,
51–63; (g) de la Hoz, A.; Díaz-Ortiz, A.; Moreno, A.; Sánchez-Migallón, A.;
Prieto, P.; Carrillo, J. R.; Vázquez, E.; Gómez, M. V.; Herrero, M. A. Comb. Chem.
High Throughput Screening 2007, 10, 877–902; (h) Kappe, C. O. Chem. Soc. Rev.
2008, 37, 1127–1139; (i) Santagada, V.; Frecentese, F.; Perissutti, E.; Fiorino, F.;
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References and notes
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14. Method C: N-(50-iodopyridin-20-yl)pyridinium aminide 6 (0.02 g, 0.07 mmol),
DABCO (0.05 g, 0.42 mmol), PdCl2(PPh3)2 (5 mol %), acetonitrile (1 mL) and the
corresponding acetylene 7 (0.14 mmol) were placed in a standard CEM 10 mL
pressurized reaction vial. The reaction mixture was then magnetically stirred
and irradiated in the microwave system at 60 °C for 10 min. The solvent was
removed under vacuum and the product was purified by chromatography on
silica gel, using ethanol as eluent. The products were finally crystallized from a
suitable solvent and characterized.
5. Ren, T. Chem. Rev. 2008, 108, 4185–4207.
N-[5-(Trimethylsilanylethynyl)pyridin-2-yl]pyridinium aminide (8a): orange solid
6. (a) Carceller, R.; García-Navío, J. L.; Izquierdo, M. L.; Alvarez-Builla, J.; Fajardo,
M.; Gómez-Sal, P.; Gago, F. Tetrahedron 1994, 50, 4995–5012; (b) Burgos, C.;
Delgado, F.; García-Navío, J. L.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron
1995, 51, 8649–8654; (c) Martínez-Barrasa, V.; Delgado, F.; Burgos, C.; García-
Navío, J. L.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2000, 56, 2481–2490;
(d) Reyes, M. J.; Delgado, F.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2002,
58, 8573–8579; (e) Reyes, M. J.; Burgos, C.; Izquierdo, M. L.; Alvarez-Builla, J.
Tetrahedron 2004, 60, 1093–1097; (f) Castillo, R.; Izquierdo, M. L.; Alvarez-
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8713–8715; (b) Reyes, M. J.; Castillo, R.; Izquierdo, M. L.; Alvarez-Builla, J.
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M. L.; Alvarez-Builla, J. Tetrahedron 2008, 64, 1351–1370; (d) Córdoba, M.;
Castillo, R. R.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2010, 66, 2624–
2632.
(46%, ethyl acetate/hexane), mp 139–141 °C; IR (KBr) m
max (cmꢀ1): 2143, 1591,
1465, 1381, 1291, 1139, 862, 841; 1H NMR (300 MHz, CD3OD): d 8.72 (2H, dd,
J = 6.9 and 1.3 Hz, H2(6)), 8.13 (1H, tt, J = 7.7 and 1.3 Hz, H4), 7.86 (2H,
dd, J = 7.7 and 6.9 Hz, H3(5)), 7.77 (1H, dd, J = 2.1 and 0.9 Hz, H60), 7.35 (1H, dd,
J = 8.8 and 2.1 Hz, H40), 6.43 (1H, dd, J = 8.8 and 0.9 Hz, H30), 0.22 (9H, s, CH3);
13C NMR (75 MHz, CD3OD): d 165.0 (C20), 151.4 (C60), 145.2 (C2(6)), 140.5 (C40),
139.0 (C4), 128.7 (C3(5)), 111.3 (C30), 107.0 (C50), 105.5 (Cb„), 93.5 (C „), 0.2
a
(CH3). MS (EI, m/z): 267 (54, M+), 266 (100), 125 (14); HRMS (APCI-TOF): calcd
for
C
15H18N3Si: [M+H]+ 268.1270, found 268.1271. Anal. Calcd for
C
15H17N3Siꢁ1/2H2O: C, 65.18; H, 6.56; N, 15.20. Found: C, 65.39; H, 6.39; N,
15.18.
15. (a)Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic
&
Professional: London, 1998; (b)Aqueous-phase Organometallic Catalysis,
Concepts and Applications; Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH:
Weinheim, 1998; (c) Lubineau, A.; Auge, J. In Modern Solvents in Organic
Synthesis; Knochel, P., Ed.; Springer: Berlin, 1999.
8. García, D.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J. Org. Lett. 2004, 6,
4175–4178.
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Moltó, J.; Nájera, C. Eur. J. Org. Chem. 2005, 4073–4081; (d) Liang, B.; Dai, M.;
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Nájera, C. Tetrahedron 2005, 61, 12168–12176; (f) Inoue, N.; Sugimoto, O.;
Tanji, K. Heterocycles 2007, 72, 665–671; (g) Guan, J. T.; Weng, T. Q.; Yu, G.-A.;
Liu, S. H. Tetrahedron Lett. 2007, 48, 7129–7133; (h) Lipshutz, B. H.; Chung, D.
W.; Rich, B. Org. Lett. 2008, 10, 3793–3796; (i) Bakherad, M.; Keivanloo, A.;
Bahramian, B.; Hashemi, M. Tetrahedron Lett. 2009, 50, 1557–1559.
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Green Chem. 2008, 10, 563–570; (c) Komáromi, A.; Tolnai, G. L.; Novák, Z.
Tetrahedron Lett. 2008, 49, 7294–7298.
9. (a) Li, J.-H.; Liu, W.-J. Org. Lett. 2004, 6, 2809–2811; (b) Li, J.-H.; Zhang, X.-D.;
Xie, Y.-X. Synthesis 2005, 5, 804–808; (c) Li, J.-H.; Hu, X.-C.; Liang, Y.; Xie, Y.-X.
Tetrahedron 2006, 62, 31–38; (d) Li, J.-H.; Hu, X.-C.; Xie, Y.-X. Tetrahedron Lett.
2006, 47, 9239–9243; (e) Li, J.-H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.;
Zhang, M.-B.; Hu, X.-C. J. Org. Chem. 2007, 72, 2053–2057.
10. (a) Li, J.-H.; Liang, Y.; Xie, Y.-X. J. Org. Chem. 2005, 70, 4393–4396; (b) Luque, R.;
Macquarrie, D. J. Org. Biomol. Chem. 2009, 7, 1627–1632.
11. (a) Method A: The acetylene 7 (0.48 mmol) was added to a solution of N-(50-
iodopyridin-20-yl)pyridinium aminide
6 (0.07 g, 0.24 mmol) and DABCO
(0.16 g, 1.43 mmol) in dry acetonitrile (5 mL) and the reaction mixture was
vigorously stirred for 45 min at room temperature to give a purple solution.
Pd(AcO)2 (5 mol %) was then added. The mixture was stirred at 40 °C until
starting material was no longer detected by TLC. The inorganic salts were
filtered off through Celite. The filtrate was evaporated in vacuo and the product
was purified by chromatography on silica gel, using ethanol as eluent, and
crystallized from a suitable solvent and characterized.; (b) Method B: A round-
bottomed flask was charged with N-(50-iodopyridin-20-yl)pyridinium aminide
18. Method D: N-(50-iodopyridin-20-yl)pyridinium aminide 6 (0.02 g, 0.07 mmol),
DABCO (0.05 g, 0.42 mmol), PdCl2(PPh3)2 (10 mol %), water (1 mL) and the
corresponding acetylene 7 (0.28 mmol) were placed in a standard Biotage
Initiator microwave vial. The reaction mixture was then magnetically stirred
and irradiated in the microwave system at 70 °C for 20 min. The solvent was
removed under vacuum and the product was purified by chromatography on
silica gel, using ethanol as eluent. The products were finally crystallized from a
suitable solvent and characterized.
6
(0.07 g, 0.24 mmol), caesium carbonate (0.47 g, 1.43 mmol) and DABCO
(10 mol %). The mixture was flushed with argon for 10 min. Dry acetonitrile
(5 mL), the corresponding acetylene 7 (0.48 mmol) and Pd(AcO)2 (5 mol %)
were added. The mixture was stirred at room temperature until starting
material was no longer detected by TLC. The inorganic salts were filtered
off through Celite. The filtrate was evaporated in vacuo and the product
was purified by chromatography on silica gel, using ethanol as eluent,
N-[5-(3-Thiophenylethynyl)pyridin-2-yl]pyridinium aminide (8c): orange solid
(34%, ethyl acetate/hexane), mp 130–132 °C; IR (KBr) m
max (cmꢀ1): 2193, 1593,
1479, 1464, 1384, 1141, 774; 1H NMR (300 MHz, CD3OD): d 8.74 (2H, dd, J = 6.9
and 1.3 Hz, H2(6)), 8.11 (1H, tt, J = 7.7 and 1.3 Hz, H4), 7.86 (2H, dd, J = 7.7 and
6.9 Hz, H3(5)), 7.83 (1H, dd, J = 2.3 and 0.7 Hz, H60), 7.52 (1H, dd, J = 3.1
and 1.0 Hz, H200), 7.43 (1H, dd, J = 8.9 and 2.3 Hz, H40), 7.42 (1H, dd, J = 4.9 and
3.1 Hz, H500), 7.15 (1H, dd, J = 4.9 and 1.0 Hz, H400), 6.49 (1H, dd, J = 8.9 and
and crystallized from
a
suitable solvent and characterized.N-[5-
(Phenylethynyl)pyridin-2-yl]pyridinium aminide (8d): orange solid (method A
13
0.7 Hz, H30); C NMR (75 MHz, CD3OD): d 164.8 (C20), 150.7 (C60), 145.1
45%, method B 66%, ethyl acetate/hexane), mp 46–48 °C; IR (KBr)
m
max (cmꢀ1):
(C2(6)), 140.2 (C40), 138.8 (C4), 130.6 (C400), 128.6 (C3(5)), 128.3 (C200), 126.5
2924, 2852, 2204, 1587, 1459, 1380, 1131, 815, 755, 690; 1H NMR (300 MHz,
CD3OD): d 8.75 (2H, dd, J = 6.9 and 1.3 Hz, H2(6)), 8.13 (1H, tt, J = 7.7 and
1.3 Hz, H4), 7.87 (3H, m, H3(5) and H60), 7.45 (3H, m, H200(600) and H40), 7.34
(3H, m, H300(500) and H400), 6.50 (1H, dd, J = 8.9 and 1.0 Hz, H30); 13C NMR
(75 MHz, CD3OD): d 164.9 (C20), 150.9 (C60), 145.2 (C2(6)), 140.3 (C40), 138.9
(C4), 132.0 (C200(600)), 129.4 (C300(500)), 128.7 (C3(5) and C400), 125.4 (C100), 111.5
(C500), 124.2 (C300), 111.5 (C30), 107.5 (C50), 88.2 (C „), 85.0 (Cb„). MS (EI, m/z):
a
277 (69, M+), 276 (100), 171 (69), 170 (34), 145 (16), 127 (36), 79 (41), 52 (38);
HRMS (ESI-TOF, CH3OH): calcd for C16H12N3S: [M+H]+ 278.07317, found
278.07464. Anal. Calcd for C16H11N3S: C, 69.29; H, 4.00; N, 15.15; S, 11.56.
Found: C, 69.65; H, 4.17; N, 15.04; S, 11.29.
(C30), 107.2 (C50), 89.9 (C „), 89.0 (Cb„). MS (EI, m/z): 271 (74, M+), 270 (100),
19. (a) Chen, G.; Zhu, X.; Cai, J.; Wan, Y. Synth. Commun. 2007, 37, 1355–1361; (b)
Guan, J. T.; Yu, G.-A.; Chen, L.; Weng, T. Q.; Yuan, J. J.; Liu, S. H. Appl. Organomet.
Chem. 2009, 23, 75–77.
a
165 (68), 164 (75), 139 (25), 138 (36), 135 (37), 114 (21), 79 (38), 52 (31);
HRMS (ESI-TOF, CH3OH): calcd for C18H14N3: [M+H]+ 272.1188, found