FULL PAPERS
could be obtained after column chromatography on silica
gel (pentane:EtOAc; 5:1) as a white solid; yield: 0.052 g
(0.212 mmol, 69%).
New York, 2007; c) S. E. Denmark, J. J. Cottell, Nitro-
nates, in: The Chemistry of Heterocyclic Compounds:
Synthetic Applications of 1,3-Dipolar Cycloaddition
Chemistry Toward Heterocycles and Natural Products,
(Eds.: A. Padwa, W. H. Pearson), John Wiley & Sons,
New York, 2002, Vol. 59, pp 83–167.
Methyl 3-(2,6-Dimethyl-4-ethylphenyl)-1,2,4-oxadiazole-5-
carboxylate (12l): The 1,2,4-oxadiazole 12l was prepared ac-
cording to GP2 from methyl cyanoformate (11j, 0.06 mL,
0.782 mmol, 3.00 equiv.), AgOTf (0.004 g, 5.0 mol%) and ni-
tronate 4m (0.080 g, 0.261 mmol, 1.00 equiv.) in chloroben-
zene (1.5 mL). The solution was stirred for 1 h at 1008C and
the product could be obtained after column chromatography
on silica gel (pentane:EtOAc; 5:1) as a colourless liquid;
yield: 0.047 g (0.182 mmol, 70%).
Methyl 3-[5-(2fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoate
(18): The 1,2,4-oxadiazole 18 was prepared according to
GP2 from 2-fluorobenzonitrile (11l, 0.21 mL, 1.94 mmol,
3.00 equiv.), AgOTf (0.008 g, 5.0 mol%) and the nitronate
4g (0.200 g, 0.647 mmol, 1.00 equiv.) in chlorobenzene
(5.0 mL). The solution was stirred for 1 h at 1008C and the
product could be obtained after column chromatography on
silica gel (pentane:EtOAc; 15:1) as a white solid; yield:
0.138 g (0.462 mmol, 71%).
[2] V. A. Tartakovsky, S. L. Ioffe, A. D. Dilman, A. A.
Tishkov, Russ. Chem. Bull. 2001, 50, 1936–1948.
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D. Seebach, Helv. Chim. Acta 1981, 64, 2264–2271.
[4] T. Ooi, K. Doda, K. Maruoka, J. Am. Chem. Soc. 2003,
125, 2054–2055.
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17, 3194–3197; b) L. Dong, C. Geng, P. Jiao, J. Org.
Chem. 2015, 80, 10992–11002; c) K. B. G. Torssell, A. C.
Hazell, R. G. Hazell, Tetrahedron 1985, 41, 5569–5575.
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Competition eExperiment (Scheme 4): Nitrile Oxide
15 versus Silyl Nitronate 4l
[9] a) S. H. Watterson, J. Guo, S. H. Spergel, C. M. Lange-
vine, R. V. Moquin, D. R. Shen, M. Yarde, M. E. Cvijic,
D. Banas, R. Liu, S. J. Suchard, K. Gillooly, T. Taylor,
S. RexRabe, D. J. Shuster, K. W. McIntyre, G. Corne-
lius, C. D’Arienzo, A. Marino, P. Balimane, L. Salter-
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2016, 59, 2820–2840; b) L. L. Xu, X. Zhang, Z. Y. Jiang,
Q. D. You, Bioorg. Med. Chem. 2016, 24, 3540–3547;
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The competition experiment was carried out according to
GP2 with methyl cyanoformate (11j, 10.0 mL, 0.065 mmol,
1.00 equiv.), AgOTf (0.9 mg, 5.0 mol%), the nitrile oxide 15
(0.010 g, 0.065 mmol, 1.00 equiv.) and the silyl nitronate 4l
(0.020 g, 0.065 mmol, 1.00 equiv.) in chlorobenzene
(0.40 mL). The reaction mixture was stirred for 1 h at 1008C
and monitored by GC. Oxadiazole 12k (Rt =15.03 min;
40%), oxadiazole 12l (Rt =15.27 min; 46%) and oxadiazole
16 (Rt =15.53 min; 13%) were formed.
Regioselectivity Studies (Scheme 5): Nitrile Oxide 15
with Cyanomethyl Ester 11j
[10] Y. Li, H. Zhu, K. Chen, R. Liu, A. Khallaf, X. Zhang,
J. Ni, Org. Biomol. Chem. 2013, 11, 3979–3988.
The 1,2,4-oxadiazole 12k and 1,2,3-oxadiazole 16 were pre-
pared according to GP2 from methyl cyanoformate (11j,
0.15 mL, 1.86 mmol, 3.00 equiv.), AgOTf (0.008 g, 5.0 mol%)
and nitrile oxide 15 (0.100 g, 0.620 mmol, 1.00 equiv.) in
chlorobenzene (3.0 mL). The solution was stirred for 1 h at
1008C and the products could be obtained as a mixture (12k
and 16) after column chromatography on silica gel (pen-
[11] a) O. Francesangeli, V. Stanic, S. I. Torgova, A. Strigaz-
zi, N. Scaramuzza, C. Ferrero, I. P. Dolbnya, T. M.
Weiss, R. Berardi, L. Muccioli, S. Orlandi, C. Zannoni,
Adv. Funct. Mater. 2009, 19, 2592–2600; b) Q. Li, L. S.
Cui, C. Zhong, X. D. Yuan, S. C. Dong, Z. Q. Jiang,
L. S. Liao, Dyes Pigm. 2014, 101, 142–149.
[12] J. C. Jochims, in: Comprehensive Heterocyclic Chemis-
try II, (Ed.: R. C. Stor), Pergamon Press, Oxford, 1996,
Vol. 4, pp 179–228.
A
a colourless solid; yield: 0.098 g
[13] K. Hemming, in. Science of Synthesis, (Eds.: R. C.
Storr, T. L. Gilchrist), Georg Thieme Verlag, Stuttgart,
2004, Vol. 13, pp 127–184.
[14] Recent examples: a) K. Luki, V. Kishore, J. Heterocycl.
Chem. 2014, 51, 256–261; b) P. K. Gupta, K. Hussain,
M. Asad, R. Kant, R. Mahar, S. K. Sukla, K. Hajela,
New J. Chem. 2014, 38, 3062–3070.
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft is
greatfully acknowledged.
[15] N. Nishiwaki, K. Kobiro, S. Hirao, J. Sawayama, K.
Saigo, Y. Ise, Y. Okajima, M. Ariga, Org. Biomol.
Chem. 2011, 9, 6750–6754.
[16] a) C. Grundmann, R. Richter, J. Org. Chem. 1968, 33,
476–478; b) M. L. McIntosh, M. R. Naffziger, B. O.
Ashburn, L. N. Zakharov, R. G. Carter, Org. Biomol.
Chem. 2012, 10, 9204–9213; c) O. Altintas, M. Glassner,
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References
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nates in Organic Synthesis, VCH, Weinheim 1988, p 60;
b) Nitrile Oxides, Nitrones, and Nitronates in Organic
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Adv. Synth. Catal. 0000, 000, 0 – 0
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