1362
LETTERS
SYNLETT
As can be seen the best results are found using HMDS, presumably due
to greater steric congestion. Different bases with pair matched and
mismatched were used, but failed to improve the stereoselectivity of the
double bond formation.
materials 6a and 7a with Monte Carlo Search was completed, the
torsion angles were constrained so that both the breaking C-H bond (0°
and 180°) and the breaking C-O bond were lined up with Π orbitals of
the double bond (90°) based on the Hammond Postulate. Relative
energy values of the rotameric transition states thus obtained are
consistent with experimental results, so the transition state with lowest
energy was expected to lead to the major product on each case. This
gives confidence that similar calculations might be used to predict the
results of related reactions.
This reaction has been extended to other protecting groups of the 1,2
diol functionality. The acetone ketal of 6a, was removed and changed
for cyclohexanone ketal, methoxy ethers, acetates and tert-
butyldimethylsilyl derivatives. All these compounds when treated with
n-BuLi gave aproximately the same yields and ratio in selectivity of
dienes 8a and 9a.
Compounds 6b and 7b only led to 8b by treatment with n-BuLi under
the same conditions in 85 and 80% yield respectively (Scheme 3). These
results can be explained in a similar manner as previously. The more
favoured transition states would be Ib and IIIb which would lead to the
These results can be understood by the assumption that the preferred
conformations of transition states, which are responsible in the reaction,
are Ia and IIa for compound 6a and IIIa and IVa for compound 7a. In
4,5
same stereochemistry for ∆ . The stereochemistry of the double bond
Scheme 5 the Newman projection for C -C of 6a and 7a has been
3’ 2’
between C2-C3 can be explained by the same reasons as in the case
above. Thus, a new way of obtaining α,β-γ,δ-unsaturated sulfones with
good control over the double bond geometry has been obatined (Scheme
7).
represented. As can be seen, the steric congestion is a bit higher in Ia
than in IIa, in agreement with the experimental result of 25:75 ratio for
compounds 8a and 9a. In the case of the conformers of 7a, IVa is more
crowded than IIIa due to steric repulsion between the groups and this
explains the observed stereoselectivity and the ratio in this case 85:15 in
favour of 8a.
Scheme 7
Further studies of the extension of this methodology to the synthesis of
related compounds will be reported in due course.
Acknowledgments. The authors thank the CICYT, Junta Castilla y
Leon (SA 44-96) and M.E.C. for financial support and Dr. D. Craig for
helpful discussions.
Scheme 5
To study the stereoselectivity observed in the second double bond, the
transition states for 6a and 7a are represented on Scheme 6. They are Va
and VIa for the former and VIIa and VIIIa for the latter. As can be
observed, the conformers VIa and VIIIa are crowded, this explainins
References and Notes
(1) a) Simpkins, N. S. Sulphones in Organic Synthesis. Pergamon
Press, Oxford 1993. b) Arce, E., Carreño, M. C.; Cid, M. B.and
Garcia Ruano, J. L. Tetrahedron Asymm. 1995, 6, 1757. c) Garcia
Ruano, J. L.; Maestro, M. C. and Sánchez Sancho, F. Tetrahedron
Asymm. 1995, 6, 2299. d) Clasby, M. C.; Craig, D.; Slawin, A. M.
Z.; White, A. J. P. and Williams, D. J. Tetrahedron 1995, 51, 1532;
and references cited therein. e) Takano, S. Sugihara, Y. and
Ogasawara, K. Tetrahedron Lett. 1993, 34, 845; and references
cited therein.
1
why an E geometry was obtained for ∆ in both compounds.
(2) a)Westwell, A. D. and Rayner C. M Tetrahedron Asymm. 1994, 5,
355. b) Hardinger, S. A. and Fuchs, P. L. J. Org. Chem. 1987, 52,
2739. c) Carr, R. V. C.; Williams, R. V. and Paquette, L. A. J. Org.
Chem. 1983, 48, 4976.
(3) a)Backwall, J. E.; Löfstrom, C.; Maffei, M.; Larger, V.
Tetrahedron Lett. 1992, 33, 2417 and references cited therein. b)
Padwa, A., Gareau, Y.; Harrison, B.; Rodriguez, A. J. Org. Chem.
1992, 57, 3540.
(4) Urones, J. G.; Díez, D. M.; Marcos, I. S.; Basabe, P.; Lithgow, A.
M.; Moro, R. F.; Garrido, N. M. and Escarcena, R. Tetrahedron,
1995, 51, 3691.
Scheme 6
(5) Kierstead, R. W.; Faraone, A.; Mennona, F.; Mullin, J.; Guthrie,
R. W.; Crowley, H.; Simko, B. and Blaber, L. C. J. Med. Chem.
1983, 26, 1561. The same results could be obtained starting from
solketal, but the oxidation was more troublesome.
On the other hand, we have tried to explain the observed experimental
results carring out molecular modeling calculations. The theoretical
study was done with the MacroModel Program , version 6.0, using the
11
(6) Thompson, C. M. Tetrahedron Lett. 1987, 28, 4243.
12
MM2* force field . After a full conformational search of starting
Urones, Julio G.
