Bai et al.
COMMUNICATION
Organic Chemistry, Chinese Academy of Sciences, Shanghai, 2012
(in Chinese).
5.00-4.96 (m, 2H), 3.81 (s, 3H), 3.58 (t, J=9.6 Hz,
1H), 3.11-3.08 (m, 1H), 3.07 (s, 3H), 2.97(s, 3H), 0.91
(d, J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
175.42, 159.66, 143.46, 139.68, 129.46, 120.66, 115.34,
114.38, 111.43, 55.08, 53.46, 40.26, 37.38, 35.65, 16.24.
FT-IR (film) ν: 1642 cm−1; LRMS−ESI m/z 270 ([M+
Na]+); HRMS-ESI calcd for C15H21NNaO2 ([M+Na]+)
270.1464, found 270.1458.
[7] (a) FDA approved new drug to alleviate moderate to severe pain.
November 24th, 2008, see: http: //www/fda.org/bbs/topics/NEWS/
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Van Hove, L.; Rauschkolb, C.; Steup, A.; Lange, B.; Lange, A.;
Etropolski, M. Expert Opin. Pharmacol. 2010, 11, 1787; (d)
Riemsma, R.; Forbes, C.; Harker, J.; Worthy, G.; Misso, K.; Schafer,
M.; Kleijnen, J.; Sturzebecher, S. Curr. Med. Res. Opin. 2011, 27,
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[8] (a) Buschmann, H.; Strassburger, W.; Friderichs, E. EP 693475 A1,
1996; (b) Tzschentke, T. M.; de Vry, J.; Terlinden, R.; Hennies,
H.-H.; Lange, C.; Strassburger, W.; Haurand, M.; Kolb, J.;
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Drugs Future 2006, 31, 1053.
[9] (a) Zhang, Q.; Li, J.-F.; Tian, G.-H.; Zhang, R.-X.; Sun, J.; Suo, J.;
Feng, X.; Fang, D.; Jiang, X.-R.; Shen, J.-S. Tetrahedron: Asymme-
try 2012, 23, 577; Other asymmetric syntheses of Tapentadol are
also reported, see: (b) Sun, Z.-K.; Liu, Y.-J.; Li, H.-H.; Wang, M.-J.;
Zhang, N.-Y.; Wang, Z.-S. WO 2011026314 A1, 2010 [Chem. Abstr.
2010, 154, 310327]; (c) Marom, E.; Mizhiritskii, M. WO
2011080736 A1, 2011 [Chem. Abstr. 2011, 155, 152232].
[10] Preparation of allylic alcohol: Kumar, S. P.; Nagaiah, K. Tetrahe-
dron Lett. 2007, 48, 1391; (b) Allylic amine 2 can also be synthe-
sized from the reductive amination of commercially available
3-methoxycinnamaldehyde (Haung, S.-H.; Dai, J.; Lin, Z. and Hong,
R. unpublished results).
[11] (a) Yoon, T. P.; Dong, V. M.; MacMillan, D. W. C. J. Am. Chem.
Soc. 1999, 121, 9726, and references cited therein; (b) Yoon, T. P.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2001, 123, 2911.
[12] Ma, H.; Feng, W.; Liang, Y. Chin. J. Pharm. 2010, 41, 641.
[13] The original discovery, see: (a) Bestmann, H. J.; Seng, F. Angew.
Chem., Int. Ed. 1963, 2, 393; Recent developments and applications,
see: (b) Dong, D.-J.; Li, H.-H.; Tian, S.-K. J. Am. Chem. Soc. 2010,
132, 5018; (c) Fang, F.; Li, Y.; Tian, S.-K. Eur. J. Org. Chem. 2011,
1084; (d) Dong, D.-J.; Li, Y.; Wang, J.-Q.; Tian, S.-K. Chem.
Commun. 2011, 47, 2158.
[14] The detailed mechanistic study on aza-Belluš-Claisen rearrangement
remains largely unexplored and awaits further in-depth investigation.
For discussion on the mechanism of Claisen rearrangement, see: (a)
Rehbein, J.; Hiersemann, M. In The Claisen Rearrangement, Eds.:
Hiersemann, M.; Nubbemeyer, U., Wiley-VCH, 2007, Chapter 11, p.
525; (b) Gajewski, J. J. Acc. Chem. Res. 1997, 30, 219.
[15] An Ireland-Claisen rearrangement was first disclosed in the synthe-
sis of Tapentadol, see: Vlaskova, R.; Hajicek, J.; Zezula, J. WO
2012089181 A1, 2012. In this patent, anti-isomer was obtained in
excellent stereochemistry control from the E-allylic alcohol. How-
ever, the detailed reaction conditions were not disclosed for the gen-
eration of E-enolate, which was clearly required if the desired [3,
3]-sigmatropic rearrangement crosses over the chair-like transition
state. After chemically resolving the corresponding acid, an extra
step to install dimethylamine was necessary in the patent synthesis.
The spectra data of anti-3 and synthetic rac-Tapentadol in our syn-
thesis are identical with the reported data in ref. [15] and ref. [12],
respectively.
Anti-3: 1H NMR (400 MHz, CDCl3) δ: 7.17 (t, J=
8.0 Hz, 1H), 6.80-6.70 (m, 3H), 5.95 (dt, J1=17.2, J2
=9.6 Hz, 1H), 5.17-5.10 (m, 2H), 3.77 (s, 3H), 3.55 (t,
=10.0 Hz, 1H), 3.09-3.04 (m, 1H), 2.77 (s, 3H), 2.73
(s, 3H), 1.17 (d, J=6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 175.31, 159.56, 144.90, 139.07, 129.32,
119.88, 116.78, 113.40, 111.79, 55.20, 53.97, 40.44,
37.21, 35.55, 16.48. FT-IR (film) ν: 1637 cm−1;
LRMS-ESI m/z 270 ([M+Na]+); HRMS-ESI calcd for
C15H21NNaO2 ([M+Na]+) 270.1464, found 270.1467.
Acknowledgement
Financial support for this work was generously pro-
vided by CAS (to R. Hong, No. KGCX2-YW-201) and
the Young Teachers Program of Universities in Shang-
hai (to S.-H. Huang, No. yyy11015). We thank Dr. Lili
Zhu for great assistance during the manuscript prepara-
tion and Dr. Hanqing Dong and Prof. Dr. Minghua Xu
for helpful discussions.
References
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[2] Recent reviews and monographs on the Claisen rearrangement, see:
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Wiley-VCH, Weinheim, 2007; (b) MajumdarAuthor Vitae, K. C.;
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J. Am. Chem. Soc. 1972, 94, 5897; (b) Review: Chai, Y.; Hong, S.-P.;
Lindsay, H. A.; MacFarland, C.; McIntosh, M. C. Tetrahedron 2002,
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Chin. J. Chem. 2013, 31, 317—320