Chem., 2004, 69, 8372–8381; For selected recent references on the
construction of carbocyclic aromatic systems by RCM, see:
(j) K. Yoshida, H. Takahashi and T. Imamoto, Chem.–Eur. J.,
2008, 14, 8246–8261; (k) K. Yoshida, T. Toyoshima and
T. Imamoto, Bull. Chem. Soc. Jpn., 2008, 81, 1512–1517;
(l) A. Grandbois and S. K. Collins, Chem.–Eur. J., 2008, 14,
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H. Takahashi and T. Imamoto, Chem. Asian J., 2006, 1, 611–613.
2 Recent reviews: (a) For
a special issue dedicated to olefin
metathesis, see: Adv. Synth. Catal., 2007, 349, 1–265;
(b) A. H. Hoveyda and A. R. Zhugralin, Nature, 2007, 450,
243–251; (c) K. C. Nicolaou, P. G. Bulger and D. Sarlah, Angew.
Chem., Int. Ed., 2005, 44, 4490–4527; (d) A. Furstner, Angew.
¨
Chem., Int. Ed., 2000, 39, 3012–3043; (e) S. K. Armstrong,
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3 (a) T. J. Donohoe, L. P. Fishlock and P. A. Procopiou, Org. Lett.,
2008, 10, 285–288; (b) T. J. Donohoe, L. P. Fishlock and
P. A. Procopiou, Synthesis, 2008, 2665–2667.
Fig. 2 Components of the pyridine and pyridazine core.
substituted pyridazines (24–27) bearing an alkyl group at each
possible position within the ring.
4 K. Yoshida, F. Kawagoe, K. Hayashi, S. Horiuchi, T. Imamoto
and A. Yanagisawa, Org. Lett., 2009, 11, 515–518.
5 S. M. Weinreb and S. M. Nahm, Tetrahedron Lett., 1981, 22,
3815–3818.
6 (a) S. B. Garber, J. S. Kingsbury, B. L. Gray and A. H
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Fig. 2 shows how the aromatic core of these two aromatic
heterocycle substrates has been constructed from three readily
accessible pieces. These components are readily available and
therefore this methodology enables complex substrates to be
assembled rapidly.
7 It has previously been demonstrated that 3-hydroxy pyridines exist
in equilibrium with the corresponding zwitterionic tautomer with
the ratio depending on the solvent. De Kowalewski and De Los
Santos disclosed a qualitative method for differentiating the
phenolic from the zwitterion structure for a series of 3-hydroxy-
pyridines; D. G. De Kowalewski and C. De Los Santos, J. Mol.
Struct., 1990, 221, 299–308. This approach involved comparison of
the observed chemical shift of C-3 in the 13C NMR spectrum with a
theoretical value. An analysis of compound 5 shows that this
species fails to satisfy the criteria set by the authors and so does
not indicate the predominance of the zwitterion for this particular
3-hydroxypyridine in (CD3)2SO.
To conclude, this paper has demonstrated the power of
RCM to make aromatic nitrogenous heterocycles, namely,
pyridines and, for the first time, pyridazines. A range of
functional groups and substitution patterns are compatible
with this sequence, and there are ample opportunities to
functionalise the products both before and after RCM.
We would like to thank the EPSRC and GlaxoSmithKline
for funding this project. The Clarendon Fund (University of
Oxford) is also thanked for support.
8 T. R. Hoye, C. S. Jeffrey, M. A. Tennakoon, J. Wang and H. Zhao,
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9 P. A. Evans, J. E. Robinson and J. D. Nelson, J. Am. Chem. Soc.,
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Notes and references
10 See: (a) T. Sato and I. Homma, Bull. Chem. Soc. Jpn., 1971, 44,
1885–1891. For an example of a related Mitsunobu reaction, see:
(b) A. G. Myers and B. Zheng, J. Am. Chem. Soc., 1996, 118,
4492–4493.
11 Z.-Y. J. Zhan, US Pat., 20 070 043 180, 2007. It is pertinent to note
that this catalyst was unsuccessful for the formation of C-4/C-5
disubstituted pyridazines (related to pyridine 8).
12 For the preparation and Pd-catalysed cross-coupling of related
pyridazine triflates, see: (a) D. Toussaint, J. Suffert and
C. G. Wermuth, Heterocycles, 1994, 38, 1273–1286; pyridazine
triflates 24–27 are contaminated with ca. 4–8% of a byproduct,
believed to be the corresponding N-triflated pyridazinone.
1H NMR monitoring of CDCl3 solutions of 24–27 shows gradual
conversion to this byproduct at room temperature. For a related
O - N rearrangement, see: (b) T. A. Engler and J. Wanner, J. Org.
Chem., 2000, 65, 2444–2457.
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and M. Bingham, Angew. Chem., Int. Ed., 2006, 45, 2664–2670.
For selected recent references on the construction of
heteroaromatic systems by RCM, see: (c) T. J. Donohoe,
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´ ´
Tetrahedron Lett., 2005, 46, 4035–4038; (h) Y. Chen, H. V. R. Dias
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This journal is The Royal Society of Chemistry 2009
3010 | Chem. Commun., 2009, 3008–3010