the desired bromocyclohexane ent-7 was isolated in 35% yield,
and with an essentially undiminished e.r. of 94 : 6.
J. F. Ciccio, A. P. Rivera and J. D. Martin, J. Org. Chem., 1985,
50, 1261–1264; (g) A. Fukuzawa, M. Miyamoto, Y. Kumagai,
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1259–1262; (h) M. Suzuki, E. Kurosawa and K. Kurata, Phyto-
chemistry, 1988, 27, 1209–1210; (i) G. Corriero, A. Madaio,
L. Mayol, V. Piccialli and D. Sica, Tetrahedron, 1989, 45, 277–288.
8 The a-bromo-b,b-dimethylcyclohexane substructure can be con-
sidered the signature motif for a bromonium-ion induced polyene
cyclisation in naturally occurring compounds (see, for example,
ref. 4a–c). For a recent review on halogenating enzymes see:
A. Butler and M. Sandy, Nature, 2009, 460, 848–854 and references
cited therein.
9 For recent representative examples see: (a) A. L. Lane, L. Mular,
E. J. Drenkard, T. L. Shearer, S. Engel, S. Fredericq,
C. R. Fairchild, J. Prudhomme, K. Le Roch, M. E. Hay,
W. Aalbersberg and J. Kubanek, Tetrahedron, 2010, 66, 455–461;
(b) V. Constantino, E. Fattorusso, A. Mangoni, C. Perinu,
G. Cirino, L. De Gruttola and F. Roviezzo, Bioorg. Med. Chem.,
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In conclusion, we have shown that scalemic bromohydrins
of trisubstituted alkenes can be readily prepared by application
of the Sharpless dihydroxylation method, thereby giving
access to both enantiomeric series with high enantioselectivity.
Their tetrafluorobenzoate derivatives are excellent substrates
for the formation of scalemic bromonium ions of a trisubstituted
alkene from either 21 or 31 bromohydrins—or as a mixture—
on treatment with catalytic quantities of triflic acid, and
undergo enantiospecific regioselective cyclisation with a suitably
positioned nucleophile. This enantiospecific pathway is not
significantly perturbed by the addition of a trisubstituted
alkene. The above findings lay the groundwork for the develop-
ment of polyene cyclisations triggered by enantiomerically
pure bromonium ions. Further findings will be reported in
due course.
10 J. N. Carter-Franklin and A. Butler, J. Am. Chem. Soc., 2004, 126,
15060–15066.
11 An overall two-step mimic for this process has recently been
reported in cyclisations mediated by chiral mercury(II) complexes
in up to 81% ee: S. A. Snyder, D. S. Treitler and A. Schall,
Tetrahedron, 2010, 66, 4796–4804 and references cited therein.
12 Highly enantioselective (up to 95% ee) iodonium-induced polyene
cyclisations have been reported using stoichiometric quantities of a
phosphoramidite: A. Sakakura, A. Ukai and K. Ishihara, Nature,
2007, 445, 900–903. Attempts to extend this methodology for
asymmetric bromonium-induced polyene cyclisations gave only
poor enantiomeric excesses (36% ee).
13 D. C. Braddock, S. A. Hermitage, L. Kwok, R. Pouwer,
J. M. Redmond and A. J. P. White, Chem. Commun., 2009,
1082–1084.
14 For a recent demonstration that racemization of enantiopure
bromonium ions via olefin-to-olefin transfer is competitive with
We thank the EPSRC, Arrow Therapeutics and AstraZeneca
for a CASE award (to J. S. M.), and the EPSRC for further
financial support (EPSRC Grant no. EP/E058272/1).
Notes and references
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c
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Chem. Commun., 2011, 47, 9051–9053 9053