2046
C. H. Müller et al.
LETTER
(2) (a) Trost, B. M.; Yasukata, T. J. Am. Chem. Soc. 2001, 123,
7162. (b) Markham, J. P.; Staben, S. T.; Toste, F. D. J. Am.
Chem. Soc. 2005, 127, 9708. (c) Trost, B. M.; Xie, J. J. Am.
Chem. Soc. 2006, 128, 6044. (d) Trost, B. M.; Xie, J. J. Am.
Chem. Soc. 2008, 130, 6231. (e) Trost, B. M.; Xie, J.;
Maulide, N. J. Am. Chem. Soc. 2008, 130, 17258. (f) Toste,
F. D.; Kleinbeck, F. J. Am. Chem. Soc. 2009, 131, 9178.
(3) Zhang, E.; Fan, C.-A.; Tu, Y.-Q.; Zhang, F.-M.; Song, Y.-L.
J. Am. Chem. Soc. 2009, 131, 14626.
(4) (a) Zhang, Q.-W.; Fan, C.-A.; Zhang, H.-J.; Tu, Y.-Q.; Zhao,
Y.-M.; Gu, P.; Chen, Z.-M. Angew. Chem. Int. Ed. 2009, 48,
8572. (b) Liang, T.; Zhang, Z.; Antilla, J. C. Angew. Chem.
Int. Ed. 2010, 49, 9734.
tion became even slower and yield and enantioselectivity
dropped significantly (24%, 52% ee, Table 2, entry 8).
The cyclopentene derivatives proved to be in general
much less reactive compared to the cyclohexanes
(Table 2, entries 9–11). Even with the electron-rich mi-
grating phenyl groups higher reaction temperatures had to
be used. The enantioselectivities were also not as good as
those obtained for the cyclohexane derivatives (37–40%
ee). If the migrating aryl group contained an electron-
withdrawing group such as fluorine no rearrangement
could be observed and heating to elevated temperatures
led only to decomposition of the starting material. The
lower reactivity of the cyclopentenes compared to the cy-
clohexenes is puzzling, but has been observed before in
related semipinacol rearrangements of cyclohexene and
cyclopentene epoxides.17
(5) Wang, B.-M.; Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q.; Chen,
W.-M. Synlett 2003, 1497.
(6) For examples of halogen-induced semipinacol
rearrangements in natural product synthesis, see: (a) Fan,
C.-A.; Tu, Y.-Q.; Song, Z.-L.; Zhang, E.; Shi, L.; Wang, M.;
Wang, B.-M.; Zhang, S.-Y. Org. Lett. 2004, 6, 4691.
(b) Dake, G. R.; Fenster, M. D. B.; Hurley, P. B.; Patrick,
B. O. J. Org. Chem. 2004, 69, 5668. (c) Hu, X.-D.; Tu,
Y.-Q.; Zhang, E.; Gao, S.-H.; Wang, S.-H.; Wang, A.-X.;
Fan, C.-A.; Wang, M. Org. Lett. 2006, 8, 1823. (d) Hurley,
P. B.; Dake, G. R. J. Org. Chem. 2008, 73, 4131.
(e) Reisman, S. E.; Ready, J. M.; Weiss, M. M.; Hasuoka,
A.; Hirata, M.; Tamaki, K.; Ovaska, T. V.; Smith, C. J.;
Wood, J. L. J. Am. Chem. Soc. 2008, 130, 2087.
In summary, we present a new enantioselective catalyst
system for bromine-induced semipinacol rearrangements
at nonactivated double bonds in cyclic systems. Under the
optimised reaction conditions using the commercially
available (DHQD)2Pyr catalyst the products containing
all-carbon quaternary chiral centres are available in good
yields and good enantioselectivities.
(7) Reviews on enantioselective halogenation reactions:
(a) French, A. N.; Bissmire, S.; Wirth, T. Chem. Soc. Rev.
2004, 33, 354. (b) Chen, G.; Ma, S. Angew. Chem. Int. Ed.
2010, 49, 8306. (c) Castellanos, A.; Fletcher, S. P. Chem.
Eur. J. 2011, 17, 5766. (d) Tan, C. K.; Zhou, L.; Yeung,
Y.-Y. Synlett 2011, 1335.
(8) Enantioselective halolactonisation reactions: (a) Ning, Z.;
Jin, R.; Ding, J.; Gao, L. Synlett 2009, 2291. (b)Whitehead,
D. C.; Yousefi, R.; Jaganathan, A.; Borhan, B. J. Am. Chem.
Soc. 2010, 132, 3298. (c) Veitch, G. E.; Jacobsen, E. N.
Angew. Chem. Int. Ed. 2010, 49, 7332. (d) Zhou, L.; Tan,
C. K.; Jiang, X.; Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc.
2010, 132, 15474. (e) Murai, K.; Matsushita, T.; Nakamura,
A.; Fukushima, S.; Shimura, M.; Fujioka, H. Angew. Chem.
Int. Ed. 2010, 49, 9174. (f) Zhang, W.; Zheng, S.; Liu, N.;
Werness, J. B.; Guzei, I. A.; Tang, W. J. Am. Chem. Soc.
2010, 132, 3664. (g) Tan, C. K.; Zhou, L.; Yeung, Y.-Y.
Org. Lett. 2011, 13, 2738.
(9) Other enantioselective halogen additions to the double
bond: (a) Kang, S. H.; Sung, B. L.; Park, C. M. J. Am. Chem.
Soc. 2003, 125, 15748. (b) Sakakura, A.; Ukai, A.; Ishihara,
K. Nature (London) 2007, 445, 900. (c) Cai, Y.; Liu, X.;
Hui, Y.; Jiang, J.; Wang, W.; Chen, W.; Lin, L.; Feng, X.
Angew. Chem. Int. Ed. 2010, 49, 6160. (d) Hennecke, U.;
Müller, C. H.; Fröhlich, R. Org. Lett. 2011, 13, 860.
(e) Jaganathan, A.; Garzan, A.; Whitehead, D. C.; Staples,
R. J.; Borhan, B. Angew. Chem. Int. Ed. 2011, 50, 2593.
(f) Zhou, L.; Chen, J.; Tan, C. K.; Yeung, Y.-Y. J. Am.
Chem. Soc. 2011, 133, 9164. (g) Nicolaou, K. C.; Simmons,
N. L.; Ying, Y.; Heretsch, P. M.; Chen, J. S. J. Am. Chem.
Soc. 2011, 133, 8134.
Typical Experimental Procedure for the Enantioselective Bro-
mination–Semipinacol Rearrangement
Compound 1a (79.2 mg, 0.30 mmol), (DHQD)2Pyr (13.2 mg, 0.015
mmol), and Na2CO3 (3.2 mg, 0.03 mmol) were placed in an argon-
filled Schlenk flask with a rubber septum. Toluene (3 mL) and
CHCl3 (3 mL) were added, and the mixture was cooled to –10 °C.
Recrystallised N-bromoacetamide (49.7 mg, 0.36 mmol) was add-
ed, and the reaction mixture was stirred at –10 °C until full conver-
sion was reached (TLC control). Sat. Na2S2O3 solution (5 mL) was
added, the phases were separated, and the aqueous phase was ex-
tracted with CH2Cl2 (2 × 5 mL). The combined organic phases were
dried over MgSO4, the solvent was evaporated, and the crude prod-
uct was purified by flash chromatography to provide the product 2a
(80 mg, 0.23 mmol, 78%, 90% ee) as a white crystalline solid.
Supporting Information for this article is available online at
Acknowledgment
Financial support by the ‘Fonds der chemischen Industrie’ and the
WWU Münster is gratefully acknowledged. We thank Prof. A.
Studer (WWU Münster) for generous support and comments on the
manuscript.
References and Notes
(1) Selected reviews: (a) Snape, T. J. Chem. Soc. Rev. 2007, 36,
1823. (b) Overman, L. E. Tetrahedron 2009, 65, 6432.
(c) Leemans, E.; D’Hooghe, M.; De Kimpe, N. Chem. Rev.
2011, 111, 3268.
(10) Wang, M.; Wang, B. M.; Shi, L.; Tu, Y.-Q.; Fan, C.-A.;
Wang, S. H.; Hu, X. D.; Zhang, S. Y. Chem. Commun. 2005,
5580.
(11) Chen, Z.-M.; Zhang, Q.-W.; Chen, Z.-H.; Li, H.; Tu, Y.-Q.;
Zhang, F.-M.; Tian, J.-M. J. Am. Chem. Soc. 2011, 133,
8818.
(12) Li, H.; Zhang, F.-M.; Tu, Y.-Q.; Zhang, Q.-W.; Chen, Z.-M.;
Chen, Z.-H.; Li, J. Chem. Sci. 2011, DOI: 10.1039/
C1SC00295C.
Synlett 2011, No. 14, 2043–2047 © Thieme Stuttgart · New York