Organic Letters
Letter
failed to give the expected intramolecular cyclization either neat
C.; Meldal, M. J. Org. Chem. 2002, 67, 3057. (c) Meldal, M.; Tornøe,
C. W. Chem. Rev. 2008, 108, 2952. (d) Haldon
́
, E.; Nicasio, M. C.;
or in solution under different conditions. Instead, polymer
15
Perez, P. J. Org. Biomol. Chem. 2015, 13, 9528.
(
́
products with a polycationic backbone were produced. In
contrast, when the reaction was repeated using the 2-azidoethyl
triflate 16 in a 0.3 M solution of MeCN at 30 °C, a clean
tandem N-alkylation/cycloaddition reaction took place to give
the hexaazaindacenium salt 17 in 73% yield, via intramolecular
3) (a) Aizpurua, J. M.; Fratila, R. M.; Monasterio, Z.; Per
́
ez-Esnaola,
N.; Andreieff, E.; Irastorza, A.; Sagartzazu-Aizpurua, M. New J. Chem.
2
2
014, 38, 474. (b) Obadia, M. M.; Drockenmuller, E. Chem. Commun.
016, 52, 2433.
(4) (a) Aizpurua, J. M.; Sagartzazu-Aizpurua, M.; Monasterio, Z. In
1
,5-ring closure. A computational analysis yielded an activation
Topics in Heterocyclic Chemistry; Dehaen, W., Bakulev, V. A., Eds.;
Springer-Verlag; Heidelberg, 2014; Vol. 40, pp 211−268. (b) Mercs,
L.; Albrecht, M. Chem. Soc. Rev. 2010, 39, 1903.
(5) For selected references, see: (a) Zhang, L.; Chen, X.; Xue, P.;
Sun, H. H. Y.; Williams, I. D.; Sharpless, K. B.; Fokin, V. V.; Jia, G. J.
Am. Chem. Soc. 2005, 127, 15998. (b) Lamberti, M.; Fortman, G. C.;
Poater, A.; Broggi, J.; Slawin, A. M. Z.; Cavallo, L.; Nolan, S. P.
Organometallics 2012, 31, 756. (c) Smith, C. D.; Greaney, M. F. Org.
Lett. 2013, 15, 4826. (d) Li, Y.; Qi, X.; Lei, Y.; Lan, Y. RSC Adv. 2015,
‡
−1
barrier of ΔG = 18.8 kcal·mol for the [3 + 2] cycloaddition
step to 17, whereas the analogous intermolecular cycloaddition
of 1d with methyl azide was 8 kcal·mol higher in energy (see
SI, Figure S7). Interestingly, the tetrahydrohexaazaindacenium
salt 17 could be further N-alkylated with methyl triflate to
afford the nonsymmetrically substituted bis-triazolium salt 18 in
−1
84% yield. It can be confidently anticipated that such novel
dicationic triazolium salts might constitute excellent precursors
5
, 49802. (e) Hong, L.; Lin, W.; Zhang, F.; Liu, R.; Zhou, X. Chem.
of triazole dicarbenes and, therefore, of novel chelating ligands
Commun. 2013, 49, 5589. (f) Thomas, J.; Jana, S.; John, J.; Liekens, S.;
Dehaen, W. Chem. Commun. 2016, 52, 2885.
(6) This approach was first implemented by Koguchi on N-(3,4-
dimethoxybenzyl)-1,2,3-triazolium salts, but the conditions required
16
for transition metal complexation.
In summary, we have shown that a variety of 1,5-substituted
,2,3-triazoles incorporating “click”-compatible functional
1
groups can be easily synthesized starting from 1-pivaloyl-
oxymethyl-1,2,3-triazoles and functionalized alcohols, following
a one-pot site-selective N-alkylation/N-dealkylation sequence.
The method, which is metal-free and operationally very simple,
takes advantage of the electrophilicity enhancement generated
by the triazolium moiety on the pivaloyloxymethyl intermedi-
ates. We have also found that bis(1,2,3-triazoles) with a hitherto
unknown combination of 1,5-/1,4-substitution patterns can be
efficiently synthesized by combining the former methodology
with CuAAC reactions or thermal intramolecular azide−alkyne
for the oxidative dealkyltion of the benzyl group [Ce(NH ) (NO ) ,
4 2 3 6
DMF, 120 °C, 13−24 h] were incompatible with functionalized
substituents. (a) Koguchi, S.; Izawa, K. Synthesis 2012, 44, 3603.
(b) Koguchi, S.; Izawa, K. ACS Comb. Sci. 2014, 16, 381.
(
7) (a) Loren, J. C.; Krasinski, A.; Fokin, V. V.; Sharpless, K. B.
̌
́ ́
D.; Vianello, R.; Zinic, B. Eur. J. Org.
Synlett 2005, 2847. (b) Saftic,
Chem. 2015, 2015, 7695.
8) Yacob, Z.; Liebscher, J. In Topics in Heterocyclic Chemistry;
(
Dehaen, W., Bakulev, V. A., Eds.; Springer-Verlag; Heidelberg, 2014;
Vol. 40, pp 167−201.
(9) Obadia, M. M.; Mudraboyina, B. P.; Serghei, A.; Montarnal, D.;
Drockenmuller, E. J. Am. Chem. Soc. 2015, 137, 6078.
[
3 + 2] cycloadditions.
(
1
(
10) (a) Hanack, M.; Fuchs, K.-A.; Collins, C. J. J. Am. Chem. Soc.
983, 105, 4008. (b) Bolje, A.; Kosmrlj, J. Org. Lett. 2013, 15, 5084.
11) Bouffard, J.; Keitz, B. K.; Tonner, R.; Guisado-Barrios, G.;
ASSOCIATED CONTENT
* Supporting Information
■
S
Frenking, G.; Grubbs, R. H.; Bertrand, G. Organometallics 2011, 30,
2617.
(12) (a) Angell, Y.; Burgess, K. Angew. Chem., Int. Ed. 2007, 46, 3649.
(
b) Gonzal
Corona, D.; Cuevas-Yan
13) Janka, M.; Anderson, G. K.; Rath, N. P. Organometallics 2004,
́
ez, J.; Per
́
ez, V. M.; Jimen
́
ez, D. O.; Lopez-Valdez, G.;
̃
ez, E. Tetrahedron Lett. 2011, 52, 3514.
Preparation procedures; NMR spectra of compounds 1b,
(
1
f−g, 1j−k, 2a−m, 6−9, 11−13, 15, and 17−18; NMR
2
3, 4382.
studies of the N-dealkylation of 2n and carbene
energies for structures D, E (PDF)
(14) Monasterio, Z.; Sagartzazu-Aizpurua, M.; Miranda, J. I.; Reyes,
Y.; Aizpurua, J. M. Org. Lett. 2016, 18, 788.
(15) Mudraboyina, B. P.; Obadia, M. M.; Abdelhedi-Miladi, I.;
Allaoua, I.; Drockenmuller, E. Eur. Polym. J. 2015, 62, 331.
(
16) (a) Aizpurua, J. M.; Sagartzazu-Aizpurua, M.; Monasterio, Z.;
AUTHOR INFORMATION
■
*
Azcune, I.; Mendicute, C.; Miranda, J. I.; García-Lecina, E.; Altube, A.;
Fratila, R. M. Org. Lett. 2012, 14, 1866. (b) Guisado-Barrios, G.;
Bouffard, J.; Donnadieu, B.; Bertrand, G. Organometallics 2011, 30,
Notes
6
017.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Gobierno Vasco (Project_KK-2015/00101) and
́
Universidad del Pais Vasco UPV/EHU (GIU15/31) for
financial support and SGIker UPV/EHU for NMR facilities.
Grants from Gobierno Vasco to A.I. and UPV/EHU to Z.M.
are acknowledged. M.Sci. Alberto F. Montiel is thanked for
technical assistance.
REFERENCES
1) Schulze, B.; Schubert, U. S. Chem. Soc. Rev. 2014, 43, 2522.
2) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
■
(
(
Angew. Chem., Int. Ed. 2002, 41, 2596. (b) Tornøe, C. W.; Christensen,
D
Org. Lett. XXXX, XXX, XXX−XXX