Communication
Organic & Biomolecular Chemistry
80% deuterium in compound 6de and a triplet for the pyrazole method can be used for both the synthesis of 1,4,5-tri or
C-4 was observed in 13C-NMR (Scheme 3). This result confirms 1,3,4,5-tetrasubstituted pyrazoles and allows for the construc-
that the 1,3-allyl migration indeed proceeds via an aza-Claisen tion of functionalized pyrazoles.
rearrangement followed by proton elimination and finally
protodeauration.
Next to alkynyl aldehydes, different alkynyl ketones (2c and
2d) were used in combination with the hydrazine salts
Conflicts of interest
(Table 3). Previously it was already mentioned that due to the There are no conflicts to declare.
instability of the N,N-diallyl hydrazine, very low yields were
obtained when an alkynyl ketone is used. However, with the
hydrazine salts no substantial loss in yield (22–79%) could be
detected compared to the alkynyl aldehydes. Therefore, it can
Acknowledgements
be concluded that the oxalic acid in the reaction medium This work was supported by grants from Ghent University:
avoids the degradation of the hydrazine enabling the hydra- “Bijzonder Onderzoeksfonds”.
zone formation and the gold-catalyzed cyclization to occur.
Furthermore, in contrast to the alkynyl aldehydes no 1,3-allyl
migration is possible, only the 1,4-allyl migration was detected.
Notes and references
Similar as for the alkynyl aldehydes, lower conversions
were obtained when R1 is a benzyl or phenyl group, and the
1 J. Britton and T. F. Jamison, Angew. Chem., Int. Ed., 2017,
56, 8823–8827.
methyl substituent for R2 (compound 1d) showed that the
allyl migration proceeds through
rearrangement.
a
[3,3]-sigmatropic
2 M. J. Naim, O. Alam, F. Nawaz, M. J. Alam and P. Alam,
J. Pharm. BioAllied Sci., 2016, 8, 2–17.
In conclusion, a novel method for the synthesis of polysub-
stituted pyrazoles starting from N-allyl-N-aryl/alkyl hydrazines
was developed. These polysubstituted pyrazoles can be pre-
pared in a one-pot procedure involving a domino reaction of
hydrazone formation, gold-catalyzed 5-endo-dig cyclization and
a subsequent [3,3]-sigmatropic rearrangement. The present
3 J. Elguero, 3.01 - Pyrazoles A2 - Katritzky, Alan R, in
Comprehensive Heterocyclic Chemistry II, ed. C. W. Rees and
E. F. V. Scriven, Pergamon, Oxford, 1996, pp. 1–75.
4 L. Yet, 4.01
Comprehensive
-
Pyrazoles A2
Heterocyclic
-
Katritzky, Alan R, in
Chemistry III, ed.
C. A. Ramsden, E. F. V. Scriven and R. J. K. Taylor, Elsevier,
Oxford, 2008, pp. 1–141.
5 J. D. Kirkham, S. J. Edeson, S. Stokes and J. P. A. Harrity,
Org. Lett., 2012, 14, 5354–5357.
Table 3 Synthesis of tetra-substituted pyrazolesa,b
6 P. Fricero, L. Bialy, A. W. Brown, W. Czechtizky, M. Méndez
and J. P. A. Harrity, J. Org. Chem., 2017, 82, 1688–1696.
7 B. R. Vaddula, R. S. Varma and J. Leazer, Tetrahedron Lett.,
2013, 54, 1538–1541.
8 H. S. Chandak, N. P. Lad and D. S. Dange, Green Chem.
Lett. Rev., 2012, 5, 135–138.
9 S. Guo, J. Wang, D. Guo, X. Zhang and X. Fan, Tetrahedron,
2012, 68, 7768–7774.
10 S. Guo, J. Wang, D. Guo, X. Zhang and X. Fan, RSC Adv.,
2012, 2, 3772–3777.
11 L. Mertens, K. J. Hock and R. M. Koenigs, Chem. – Eur. J.,
2016, 22, 9542–9545.
12 C. Zhang, J. Huang, L. Qiu and X. Xu, Org. Lett., 2016, 18,
6208–6211.
13 M. Zora, A. Kivrak and C. Yazici, J. Org. Chem., 2011, 76,
6726–6742.
14 J. Qian, Y. Liu, J. Zhu, B. Jiang and Z. Xu, Org. Lett., 2011,
13, 4220–4223.
15 Y. D. Dhage, H. Daimon, C. Peng, T. Kusakabe,
K. Takahashi, Y. Kanno, Y. Inouye and K. Kato, Org. Biomol.
Chem., 2014, 12, 8619–8626.
16 T. Kusakabe, H. Sagae and K. Kato, Org. Biomol. Chem.,
2013, 11, 4943–4948.
17 Y. Suzuki, S. Naoe, S. Oishi, N. Fujii and H. Ohno, Org.
Lett., 2012, 14, 326–329.
a Reactions were carried out by mixing 1 (1 equiv.), 2 (1 equiv.) and
AuCl3 (10 mol%) in ethyl acetate in the presence of molecular sieves
(4 Å). b Isolated yields.
9362 | Org. Biomol. Chem., 2018, 16, 9359–9363
This journal is © The Royal Society of Chemistry 2018