3810
S. A. P. Quintiliano, L. F. Silva Jr. / Tetrahedron Letters 53 (2012) 3808–3810
azide group of 15 using 10% wt Pd/C in MeOH, under 2 atm of H2
produced the amine 16 in 43%, together with 13a, in 28% yield,
which is formed from a hydrogenolysis (Scheme 8). The triester
13a was recycled in the synthetic route. Using Pd/CaCO3 as cata-
lyst, only hydrogenolysis was observed.
References and notes
1. Dou, D.; Viwanathan, P.; Li, Y.; He, G.; Alliston, K. R.; Lushington, G. H.; Brown-
Clay, J. D.; Padmanabhan, R.; Groutas, W. C. J. Comb. Chem. 2010, 12, 836.
2. Maeda, H.; Suzuki, M.; Sugano, H.; Yamamura, M.; Ishida, R. Chem. Pharm. Bull.
1988, 36, 190.
3. (a) Grunewald, G. L.; Caldwell, T. M.; Li, Q.; Dahanukar, V. H.; McNeil, B.;
Criscione, K. R. J. Med. Chem. 1999, 42, 4351; (b) Dean, R. T.; Rapoport, H. J. Org.
Chem. 1978, 43, 2115.
4. (a) Al-Horani, R. A.; Desai, U. R. Tetrahedron 2012, 68, 2027; (b) Zhang, X.;
Zhang, J.; Zhang, L.; Feng, J.; Xu, Y.; Yuan, Y.; Fang, H.; Xu, W. Bioorg. Med. Chem.
2011, 19, 6015; (c) Zhang, Y.; Feng, J.; Jia, Y.; Wang, X.; Zhang, L.; Liu, C.; Fang,
H.; Xu, W. J. Med. Chem. 2011, 54, 2823; (d) Zhang, Y.; Feng, J.; Liu, C.; Zhang, L.;
Jiao, J.; Fang, H.; Su, L.; Zhang, X.; Zhang, J.; Li, M.; Wang, B.; Xu, W. Bioorg. Med.
Chem. 2010, 18, 1761; (e) Raghuraman, A.; Liang, A.; Krishnasamy, C.; Lauck, T.;
Gunnarsson, G. T.; Desai, U. R. Eur. J. Med. Chem. 2009, 44, 2626; (f) Cheng, S.;
Zhang, X.; Wang, W.; Zhao, M.; Zheng, M.; Chang, H. W.; Wu, J.; Peng, S. Eur. J.
Med. Chem. 2009, 44, 4904; (g) Azukizawa, S.; Kasai, M.; Takahashi, K.; Miike,
T.; Kunishiro, K.; Kanda, M.; Mukai, C.; Shirahase, H. Chem. Pharm. Bull 2008, 56,
335.
5. (a) Silva, L. F., Jr.; Siqueira, F. A.; Pedrozo, E. C.; Vieira, F. Y. M.; Doriguetto, A. C.
Org. Lett. 2007, 9, 1433; (b) Bianco, G. G.; Ferraz, H. M. C.; Costa, A. M.; Costa-
Lotufo, L. V.; Pessoa, C.; de Moraes, M. O.; Schrems, M. G.; Pfaltz, A.; Silva, L. F.,
Jr. J. Org. Chem. 2009, 74, 2561; (c) Kameyama, M.; Siqueira, F. A.; Garcia-
Mijares, M.; Silva, L. F., Jr.; Silva, M. T. A. Molecules 2011, 16, 9421.
6. Savard, J.; Brassard, P. Tetrahedron 1984, 40, 3455.
When 16 was subjected to a basic hydrolysis using LiOH fol-
lowed by a reflux in diluted acid to promote decarboxylation, the
tetrahydroisoquinoline 1 was produced in 77% yield (Scheme 9).
In conclusion, a new and practical route to obtain a functional-
ized 1-oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was
developed from the readily available dimedone. The synthesis is
ten step long and only three purifications by flash chromatography
are required through the whole sequence (see Supplementary data
for details). The key step is the reaction between the dimedone
derivative 8 and the chlorotetrolic ester 4, that gives a tetrasubsti-
tuted benzene through a Diels–Alder /retro- Diels–Alder process.
The sequence can be easily adapted to the synthesis of other 1-
oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids.
Acknowledgments
7. Olomucki, M.; Le Gall, J. Y.; Barrand, I. J. Chem. Soc., Chem. Commun. 1982, 1290.
8. Donner, C. D.; Gill, M. J. Chem. Soc., Perkin Trans. 1 2002, 938.
9. (a) Ibuka, T.; Mori, Y.; Aoyama, T.; Inubushi, Y. Chem. Pharm. Bull 1978, 26, 156;
(b) Langer, P.; Schneider, T.; Stoll, M. Chem. Eur. J. 2000, 6, 3204.
10. (a) Yoshino, T.; Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 14185; (b) Dai, M.;
Sarlah, D.; Yu, M.; Danishefsky, S. J.; Jones, G. O.; Houk, K. N. J. Am. Chem. Soc.
2007, 129, 645; (c) Yang, Z.-Q.; Geng, X.; Solit, D.; Pratilas, C. A.; Rosen, N.;
Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, 7881; (d) Ashburn, B. O.; Carter, R.
G. J. Org. Chem. 2007, 72, 10220.
The authors thank the support by CNPq, FAPESP, and CAPES.
Prof. N. P. Lopes (FCFRP-USP) is acknowledged for discussion.
Supplementary data
Supplementary data (spectroscopic data and detailed experi-
mental procedures) associated with this article can be found, in
11. Crisponi, G.; Casu, M.; Nurchi, V. M.; Cesare-Marincola, F.; Pivetta, T.; Silvagni,
R. Talanta 2002, 56, 441.