phosphonium monoperoxysulfate (TPPP) as the primary
7
oxidant. This oxidant is soluble in a variety of organic
Table 1. Catalytic Asymmetric Epoxidation of Various
solvents, and reactions can be performed over a range of
temperatures in the absence of water. Herein we report the
use of chloroform as the preferred solvent for the epoxidation
of several cis-alkenes using this system and the highly
enantioselective synthesis of the antihypertensive agent
levcromakalim 2 using this epoxidation as a key step.
a,8
cis-Alkenes Using TPPP in CHCl
3
Iminium salt 3 is one of our more enantioselective and
reactive epoxidation catalysts in the nonaqueous system for
trans- and trisubstituted alkene substrates. For example,
trans-stilbene, usually a very poor substrate under our
6
standard aqueous conditions, is epoxidized with 67% ee in
a
the presence of iminium salt 3 in chloroform solution to give
the (+)-(R,R) configured epoxide as the major enantiomer.
Several cis-alkenes were subjected to the same reaction
conditions (Table 1). Good enantiomeric excesses were also
Epoxidation conditions: iminium salt 3 (10 mol %), TPPP (2 equiv),
CHCl3, -40 °C, 24 h. Isolated yield. c Enantiomeric excesses were
b
1
determined by H NMR spectroscopy in the presence of (+)-Eu(hfc)3 (0.1
molar equiv) or by chiral HPLC on a Chiracel OD column. d Numbers in
parentheses refer to the ee obtained when acetonitrile was employed as
reaction solvent. e The absolute configurations of the major enantiomers
were determined by comparison of the sense of optical rotation with values
(4) Wang, Z.-X.; Shi, Y. J. Am. Chem. Soc. 1996, 118, 9806. Wang,
f
reported in the literature. Reaction time of 17 h.
Z.-X.; Tu, Y.; Frohn, M.; Shi, Y. J. Org. Chem. 1997, 62, 2328. Frohn,
M.; Shi, Y. J. Org. Chem. 1997, 62, 2328. Wang, Z.-X.; Shi, Y. J. Org.
Chem. 1997, 62, 8622. Wang, Z.-X.; Shi, Y. J. Org. Chem. 1998, 63, 3099.
Zhu, Y.; Tu, Y.; Yu, H.; Shi, Y. Tetrahedron Lett. 1998, 39, 7819. Warren,
J. D.; Shi, Y. J. Org. Chem. 1999, 64, 7675. Tian, H.; She, X.; Shu, L.;
Yu, H.; Shi, Y. J. Am. Chem. Soc. 2000, 67, 2435. Tian, H.; She, X.; Yu,
H.; Shu, L.; Shi, Y. J. Org. Chem. 2002, 67, 2435. Tian, H.; She, X.; Xu,
J.; Shi, Y. Org. Lett. 2001, 3, 1929. Cao, G. A.; Wang, Z.-X.; Tu, Y.; Shi,
Y. Tetrahedron Lett. 1998, 39, 4425. Frohn, M.; Zhou, X.; Zhang, J.-R.;
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Tetrahedron Lett. 1999, 40, 8721. Shu, L.; Shi, Y. J. Org. Chem. 2000, 65,
observed for cis-â-methyl styrene (70% ee) and dihydro-
naphthalene (82% ee). The level of enantioselectivity ob-
served was remarkable given that the corresponding reaction
carried out under our standard aqueous conditions with oxone
afforded dihydronaphthalene oxide in only 45% ee. The
enantiomeric excess for epoxidation of indene is somewhat
lower (61% ee) but is still much higher than other reported
ee’s for this epoxidation mediated by oxaziridinium salts.
Epoxidation of the non-aryl cis-hept-2-ene produced epoxide
with quantitative conversion but with low ee. Electron-
deficient alkenes are also poor substrates. It is interesting to
note that the enantiomeric excesses of epoxides generated
in chloroform are superior to those of epoxides generated in
acetonitrile.
8
807. Wu, X.-Y.; She, X.; Shi, Y. J. Am. Chem. Soc. 2002, 124, 8792.
Hickey, M.; Goeddel, D.; Crane, Z.; Shi, Y. Proc. Nat. Acad. Sci. U.S.A.
004, 101, 5794. Shi, Y. Acc. Chem. Res. 2004, 37, 488.
5) Picot, A.; Millet, P.; Lusinchi, X. Tetrahedron Lett. 1976, 17, 1573.
2
(
Hanquet, G.; Lusinchi, X.; Milliet, P. Tetrahedron Lett. 1987, 28, 6061.
Hanquet, G.; Lusinchi, X.; Milliet, P. Tetrahedron Lett. 1988, 29, 3941.
Boh e´ , L.; Hanquet, G.; Lusinchi, M.; Lusinchi, X. Tetrahedron Lett. 1993,
3
4, 7271. Boh e´ , L.; Lusinchi, M.; Lusinchi, X. Tetrahedron 1999, 55, 141.
Boh e´ , L.; Kammoun, M. Tetrahedron Lett. 2002, 43, 803. Aggarwal, V.
K.; Wang, M. F. J. Chem. Soc., Chem. Commun. 1996, 191. Armstrong,
A.; Ahmed, G.; Garnett, I.; Gioacolou, K. Synlett 1997, 1075. Armstrong,
A.; Ahmed, G.; Garnett, I.; Gioacolou, K.; Wailes, J. S. Tetrahedron 1999,
5
5, 2341. Minakata, S.; Takemiya, A.; Nakamura, K.; Ryu, I.; Komatsu,
We next turned our attention to the epoxidation of
benzopyran substrates. We were delighted to observe excel-
lent enantioselectivities in the epoxidations of 6-nitro,
6-chloro-, and 6-cyano-2,2-dimethylbenzopyrans (Table 1).
The epoxidation of 6-cyano-2,2-dimethylbenzopyran 9 was
M. Synlett 2000, 12, 1810. Wong, M.-K.; Ho, L.-M.; Zheng, Y.-S.; Ho,
C.-Y.; Yang, D. Org. Lett. 2001, 16, 2587. Lacour, J.; Monchaud, D.;
Marsol, C. Tetrahedron Lett. 2002, 43, 8257. Page, P. C. B.; Rassias, G.
A.; Bethell, D.; Schilling, M. B. J. Chem. Soc., Perkin Trans. 1 2000, 3325.
Page, P. C. B.; Rassias, G. A.; Barros, D.; Ardakani, A.; Buckley, B.;
Bethell, D.; Smith, T. A. D.; Slawin, A. M. Z. J. Org. Chem. 2001, 66,
6
926. Page, P. C. B.; Rassias, G. A.; Barros, D.; Ardakani, A.; Bethell, D.;
Merrifield, E. Synlett 2002, 4, 580.
6) Page, P. C. B.; Buckley, B. R.; Blacker, A. J. Org. Lett. 2004, 6,
543.
7) Page, P. C. B.; Barros, D.; Buckley, B. R.; Ardakani, A.; Marples,
B. A. J. Org. Chem. 2004, 69, 3595.
(8) In a control experiment formation of epoxide was not observed upon
treatment of 1,2-dihydronaphthalene with TPPP in chloroform even after
48 h at 0 °C.
(9) North, J. T.; Kronenthal, D. R.; Pullockaran, A. J.; Real, S. D.; Chen,
H. Y. J. Org. Chem. 1995, 60, 3397.
(
1
(
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