Stereoselective formation of formal exo Diels-Alder adducts of silyloxydienes and allenecarboxylates [1]

Full text of DOI:10.1021/ja9841660

J. Am. Chem. Soc. 1999, 121, 3529-3530
3529
Communications to the Editor
Scheme 1
Stereoselective Formation of Formal Exo
Diels-Alder Adducts of Silyloxydienes and
Allenecarboxylates
Michael E. Jung* and Nobuko Nishimura1
Department of Chemistry and Biochemistry
UniVersity of California, Los Angeles, California 90095-1569
ReceiVed December 4, 1998
For a projected total synthesis of the novel naturally occurring
phosphatase inhibitor, dysidiolide 1,2 we envisioned an intermo-
lecular Diels-Alder cycloaddition of the vinylcyclohexene 2 with
a highly substituted dienophile 3 which could be forced to occur
in the normally less favorable exo mode to give an adduct such
as 4. This compound would possess many of the structural and
work and that of others.6 However, we have now shown that
thermolysis of the purified cyclobutane 8 in toluene at 120 °C
for 4 d gave only the exo cycloadduct 7x. Thus heating the diene
5 and dienophile 6 in toluene for 4 d gave only the two [4 + 2]
cycloadducts 7n and 7x in 14 and 58% yields, respectively.
Although we had observed the thermal rearrangement of a [2 +
2] cycloadduct into a [4 + 2] cycloadduct before,6ab this is the
first case where the stereochemical course of this process could
be determined.
The mechanism of the rearrangement of simple 3-ethenylmeth-
ylenecyclobutanes I has been proposed to involve an initial bond
homolysis to give a bis(allylic) diradical II which then recombines
at the termini to give the 4-methylenecyclohexene III.7 Indeed it
was shown that the divinyl compound I (R ) CHdCH2) had a
lower activation energy for this reaction (Ea ) 27.3 kcal/mol)
than did the parent I (R ) H) (Ea ) 35.7 kcal/mol).7a We believe
that the substitution in our case may cause the reaction to proceed
through a zwitterionic rather than a diradical pathway although
the latter can certainly not be ruled out.
stereochemical features of the desired natural products and thereby
perhaps simplify its total synthesis.3 However, all attempts at
carrying out such a cycloaddition with 2 using Fisher carbene
complexes4 3 [Z ) C(OMe)dCr(CO)5], which would have given
the exo adducts, or the simple acid chloride 3 (Z ) COCl), which
would have given more of the endo adducts, unfortunately gave
only starting material, presumably due to the steric hindrance of
these dienophiles. We proposed using R-methyl allenecarboxylates
as the dienophiles in order to decrease this steric hindrance with
a subsequent reduction of the exocyclic double bond to give
compounds such as 4. We report herein the thermal cycloaddition
of silyloxydienes 2 (X ) OSiR3) and allenecarboxylates which
ultimately afford the formal exo Diels-Alder adducts 4.
Heating a solution of E-4-methyl-2-silyloxybutadiene 55 with
ethyl 2-methylbuta-2,3-dienoate 6 in toluene at 120 °C (sealed
tube) for 14 h afforded, after chromatographic separation, a
mixture of three compounds, the endo Diels-Alder product 7n
(18%), the exo Diels-Alder product 7x (28%), and the [2 + 2]
cycloadduct 8 (22%) (Scheme 1). The isolation of [2 + 2]
cycloadducts from dienes and allenes was precedented in our own
The reasons for the interesting stereochemical course of the
reaction are not known. However, we suggest the following
hypothesis: cleavage of the strained C-C bond of the cyclobutane
syn to the ester8 in IV would generate the zwitterion V, rotation
about the indicated C-C bond would give a different conformer
of the zwitterion VI, and final coupling of the zwitterion at the
termini would then give the product VII (which corresponds to
the exo cycloadduct 7x). We are currently trying to lend some
computational evidence to this hypothesis.9
(6) (a) Jung, M. E.; Node, M.; Pfluger, R.; Lyster, M. A.; Lowe, J. A., III.
J. Org. Chem. 1982, 47, 1150. (b) Jung, M. E.; Lowe, J. A., III; Lyster, M.
A.; Node, M.; Pfluger, R.; Brown, R. W. Tetrahedron 1984, 40, 4751. (c)
Spitzner, D.; Klein, I. Liebigs Ann. Chem. 1990, 63. (d) Angew. Chem. 1982,
94, 639. In reference c, Spitzner and Klein report that their [2 + 2] cycloadduct
does not rearrange to the [4 + 2] cycloadduct on heating.
(7) (a) Dolbier, W. R., Jr.; Mancini, G. J. Tetrahedron Lett. 1975, 2141.
(b) Dolbier, W. R., Jr.; Piedrahita, C. A.; Al-Sader, B. H. Tetrahedron Lett.
1979, 2957.
(8) We believe that the anion syn to the ester should be more stable than
that syn to the methyl group, and thus, this determines which of the otherwise
symmetrical C-C bonds of the cyclobutane ring is broken preferentially.
Weiler showed several years ago that deprotonation of 3-methylbut-2-enoic
acid salts with butyllithum in THF/HMPA gave nearly exclusively the anion
syn to the acid. Harris, F. L.; Weiler, L. Tetrahedron Lett. 1985, 26, 1939.
(9) Jung, M. E.; Houk, K. N., unpublished results.
(1) Recipient of the Award for Excellence in First Year Graduate Study,
University of California, Los Angeles, CA, 1997.
(2) Gunasekera, S. P.; McCarthy, P. J.; Kelly-Borges, M.; Lobkovsky, E.;
Clardy, J. J. Am. Chem. Soc. 1996, 118, 8759.
(3) (a) Corey, E. J.; Roberts, B. E. J. Am. Chem. Soc. 1997, 119, 12425.
(b) Boukouvalas, J.; Cheng, Y. X.; Robichaud, J. J. Org. Chem. 1998, 63,
228. (c) Magnuson, S. R.; Sepp-Lorenzino, L.; Rosen, N.; Danishefsky, S. J.
J. Am. Chem. Soc. 1998, 120, 1615. (d) Brohm, D.; Waldmann, H. Tetrahedron
Lett. 1998, 39, 3998.
(4) Wulff, W. D.; Bauta, W. E.; Kaesler, R. W.; Lankford, P. J.; Miller, R.
A.; Murray, C. K.; Yang, D. C. J. Am. Chem. Soc. 1990, 112, 3642.
(5) This diene was prepared by silylation of the kinetic enolate of E-3-
penten-2-one.
10.1021/ja9841660 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/24/1999

3530 J. Am. Chem. Soc., Vol. 121, No. 14, 1999
Communications to the Editor
Scheme 2
As a closer model for the synthesis of dysidiolide, we carried
out the cycloaddition of the (silyloxyvinyl)cyclohexene 9 with
the allenecarboxylate 6 under similar conditions and obtained
analogous results, namely, the formation of the endo and exo [4
+ 2] cycloadducts 10n and 10x in 15 and 27% yield, respectively,
along with 18% of the [2 + 2] cycloadduct 11 (Scheme 2).
Thermolysis of 11 for several days afforded 10x exclusively in
good yield. As before, when the diene and dienophile were heated
in a sealed tube for an extended period, only the [4 + 2]
cycloadducts 10n and 10x were isolated in 18 and 55% yield,
respectively. Thus, one can obtain a reasonable yield of the desired
exo adduct 10x by this reaction.
Scheme 3
Hydrogenation of 10x over Pd(OH)2/C gave in 89% yield an
approximate 2:1 mixture of the dihydro compounds 12ab10 which
were separated by chromatography and converted to the two trans
decalones 13ab in 80-90% yield (Scheme 3).10 Compounds 12a
and 13a have the required stereochemistry at the ring juncture
and two methyl-bearing carbons for dysidiolide. Further work on
this project is under way in our laboratories.
Acknowledgment. We thank the National Institutes of Health (GM
72684) and the Agricultural Division of American Cyanamid Company
for generous financial support. We also thank Professors Houk (UCLA),
Dolbier (Florida), and Weiler (British Columbia) for helpful discussions.
(10) The structures of all of the products were assigned by careful analysis
of the high field proton NMR spectra, using coupling constants, 2D and nOe
techniques heavily. Hydrolysis of the minor Diels-Alder adduct, 10n, afforded
a crystalline enone, the structure of which was confirmed by single-crystal
X-ray analysis. We thank Dr. Kenneth Hardcastle of the California State
University, Northridge for that data.
Supporting Information Available: Experimental procedures and
spectral data for all new compounds (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
JA9841660