Scheme 1
Scheme 2
conversions that we wished to exploit for the purposes of
synthesizing the oak lactones (1).
Chevtchouk et al. (Scheme 1, eq 3) prepared both (4S,5S)
and (4S,5R) isomers of 1 with the key step being the Baeyer-
Villiger ring expansion of dialkyl-substituted cyclobu-
tanones.7
Thus we explored the possibility of preparing both cis-
and trans-1 enantiomerically pure, from a common dioxine.
All four isomers were sought for a full sensory evaluation
of their impact on beverages. This has surprisingly been
lacking from the literature given the known importance of
these compounds to the perceived aroma of beverages
fermented and/or stored in oak barrels. Therefore, the strategy
used for the syntheses of 1 was devised so that both the
naturally occurring isomers of 1, as well as their correspond-
ing enantiomers, could be prepared in an enantiomerically
pure manner. To facilitate resolution of diastereomers by
chromatography, a chiral ester group was introduced that did
not feature in the final products.
The synthesis of dioxine 9 (Scheme 3) was accomplished
by the [4 + 2] cycloaddition reaction between 1-phenylocta-
1,3-diene (8) and singlet oxygen. Diene 8 was prepared in
82% yield by a Wittig reaction between the ylide derived
from 1-iodopentane and cinnamaldehyde. This reaction
actually produced a 3:1 mixture of the (E,E)- and (E,Z)-
isomers of 8; however, the latter was observed to isomerize
into the former under the conditions of photolysis, obviating
the separation of the two stereoisomers. The photolysis was
conducted in dichloromethane, with illumination from two
tungsten halogen lamps (500 W) and with Rose Bengal
present as a photosensitizer,14 to give the desired dioxine 9
as a racemate in 79% yield.
1,2-Dioxines 2 have proven to be extremely versatile
starting materials (Scheme 2). They behave as if they are,
in effect, masked cis-γ-hydroxy enones 3 into which they
are converted by treatment with either base or a cobalt-based
catalyst.8 The ring-opened form, 3, can be converted into
cyclopropanes 4 in a highly diastereoselective manner by
reaction with stabilized phosphorus ylides.9 Subsequently,
it was discovered that the use of sterically hindered ylides
altered the regiochemistry and gave rise to a different class
of cyclopropanes 5.10 1,2-Dioxines can be converted into
disubstituted pyrroles or thiophenes,11 or the γ-hydroxy enone
equivalent can be transformed into more complex substituted
tetrahydrofurans 612 or furanones 7.13 It was the last of these
(7) Chevtchouk, T.; Ollivier, J.; Salaun, J. Tetrahedron: Asymmetry 1997,
8, 1011-1014.
(8) Kimber, M. C.; Taylor, D. K. The Reactivity, Synthesis and
Application of γ-Hydroxy Enones in Organic Synthesis. In Trends Org.
Chem. 2001, 9, 53-68.
(9) (a) Avery, T. D.; Haselgrove, T.; Rathbone, T. J.; Taylor, D. K.;
Tiekink, E. R. T. J. Chem. Soc., Chem. Commun. 1998, 333-334. (b) Avery,
T. D.; Taylor, D. K. Tiekink, E. R. T. J. Org. Chem. 2000, 65, 5531-
5546. (c) Avery, T. D.; Jenkins, N. F.; Kimber, M. C.; Lupton, D. W.;
Taylor, D. K. J. Chem. Soc., Chem. Commun. 2002, 28-29.
(10) (a) Avery, T. D.; Greatrex, B. W.; Taylor, D. K.; Tiekink, E. R. T.
J. Chem. Soc., Perkin Trans. 1 2000, 1319-1321. (b) Avery, T.; Fallon,
G.; Greatrex, B. W.; Pyke, S. M.; Taylor, D. K.; Tiekink, E. R. T. J. Org.
Chem 2001, 66, 7955-7966.
(11) Hewton, C. E.; Kimber, M. C.; Taylor, D. K. Tetrahedron Lett.
2002, 43, 3199-3201.
(12) Greatrex, B. W.; Kimber, M. C.; Taylor, D. K.; Tiekink, E. R. T.
J. Org. Chem. 2003, 68, 4239-4246.
(13) Greatrex, B. W.; Kimber, M. C.; Taylor, D. K.; Fallon, G.; Tiekink,
E. R. T. J. Org. Chem. 2002, 67, 5307-5314.
(14) Lamberts, J. J. M.; Schumacher, D. R.; Neckers, D. C. J. Am. Chem.
Soc. 1984, 106, 5879-5883.
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