J. Am. Chem. Soc. 2001, 123, 6441-6442
6441
Stereoselective Synthesis of Isomeric Functionalized
1,3-Dienes from Cyclobutenones
Masahiro Murakami,* Yasufumi Miyamoto, and
Yoshihiko Ito*
Department of Synthetic Chemistry and Biological Chemistry
Kyoto UniVersity, Yoshida, Kyoto 606-8501, Japan
ReceiVed March 12, 2001
To examine the effect of silicon on this rearrangement, substrate
57 was prepared by reaction of (n-Bu)2Cu(CN)Li2 with 2a
followed by treatment with acetic anhydride (eq 3). Unlike 3a,
The synthesis of organic compounds with control over stereo-
chemistry is a subject of continuing interest. As olefins are often
key starting materials for the construction of a wide variety of
complex molecules, methods for synthesizing them as pure
geometric isomers are especially important. In this report, we
describe a novel method for the stereoselective synthesis of
functionalized 1,3-butadiene derivatives from cyclobutenones via
a torquoselective electrocyclic ring-opening reaction of cy-
clobutene intermediates.1
This strategy emanates from our recent discovery of the
remarkable effect that silyl substituents have on the ring-opening
reaction of cyclobutenes.2 A silyl substituent at the 3-position
accelerates the electrocyclic reaction, and inter alia promotes
inward rotation despite the resulting steric congestion experienced
in the product. These intriguing effects were explained by the
electron-accepting interactions between the low-lying σ* orbital
of the silicon atom and the HOMO orbital of the opening
cyclobutene system, possible only in the inward transition state.3
As shown in eq 1, the starting silyl-substituted cyclobutenes
cyclobutene 5 was unreactive even in refluxing toluene (110 °C).
Ring-opening was observed at 140 °C to afford a mixture of E-6
and Z-6.7 In this case, the butyl and phenyl groups competed for
outward rotation.9 These results clearly demonstrate that the silyl
group of 3a plays the dual role of accelerating the ring-opening
reaction and controlling the torquoselectivity.
We surmised that isomeric 3-silyl-1-cyclobutenes such as 8
could be obtained by the 1,2-addition of silyllithium reagents to
cyclobutenones. Reaction of cyclobutenone 2a with silyllithium
7 in THF at -78 °C followed by treatment with acetic anhydride
did not, in fact, provide the expected cyclobutene derivative.
Instead, 2a was directly converted to a 1-silyl-1,3-diene having
Z-geometry (10a) in 87% yield (eq 4).7 The other stereoisomer
required for this strategy can be conveniently prepared from
cyclobutenones.4,5 Addition of a silyl nucleophile, either in a 1,4-
or 1,2-fashion, provides an efficient route to 3-silyl-1-cyclobutene,
which opens up to isomeric functionalized 1,3-diene.
To effect the 1,4-addition, cyclobutenone 2a was treated with
silylcuprate 16 at -78 °C for 5 min. The resultant 1,4-adduct was
trapped with acetic anhydride to afford 3-silyl-1-cyclobutene 3a
in 83% yield (eq 2).7 When heated in refluxing benzene for 2 h,
3a underwent a ring-opening reaction with unidirectional rotation
of the substituents. The silyl group rotated inward and the phenyl
group outward8 to furnish the 1-silyl-1,3-diene having Z-geometry
4a in 99% yield.7 The other stereoisomer was not detected.
was not detected. Stereoselective formation of 10a was explained
by assuming that the 1,2-addition of 7 to the carbonyl group was
followed by immediate and torquoselective ring-opening of the
1,2-adduct 8. The resulting lithium enolate 9 was trapped with
acetic anhydride to give 10a, a constitutional isomer of 4a.
As previously noted, the thermal ring-opening of cyclobutenes
3a is accelerated by the silyl substituent, but still requires heating
at 80 °C. Therefore, the direct ring-opening reaction of intermedi-
ate 8 at -78 °C was quite remarkable. As a comparison,
butyllithium was reacted with 2a. Unlike 8, the intermediate 1,2-
adduct 11 failed to undergo a ring-opening reaction at -78 °C,
and after aqueous workup, cyclobutenol 12 was obtained in 84%
yield (eq 5).7 However, when the reaction with butyllithium was
carried out at 0 °C, the intermediate 1,2-adduct 11 did undergo
spontaneous ring-opening to give 1,3-diene 13 (64% yield) after
treatment with acetic anhydride.7 On the other hand, ring-opening
(1) For an excellent review on torquoselective ring-opening reactions of
cyclobutenes, see: Dolbier, W. R., Jr.; Koroniak, H.; Houk, K. N.; Sheu, C.
Acc. Chem. Res. 1996, 29, 471.
(2) Murakami, M.; Miyamoto, Y.; Ito, Y. Angew. Chem., Int. Ed. 2001,
40, 189.
(3) A different explanation assuming geminal σ bond participation recently
appeared: Ikeda, H.; Kato, T.; Inagaki, S. Chem. Lett. 2001, 270.
(4) For the preparation of cyclobutenones, see: (a) Danheiser, R. L.;
Savariar, S. Tetrahedron Lett. 1987, 28, 3299. (b) Ammann, A. A.; Rey, M.;
Dreiding, A. S. HelV. Chim. Acta 1987, 70, 321.
(5) A cyclobutenone itself undergoes an electrocyclic ring-opening reac-
tion: (a) Danheiser, R. L.; Gee, S. K. J. Org. Chem. 1984, 49, 1672. (b)
Danheiser, R. L.; Nishida, A.; Savariar, S.; Trova, M. P. Tetrahedron Lett.
1988, 29, 4917 and references therein.
(6) Crump, R. A. N. C.; Fleming, I.; Hill, J. H. M.; Parker, D.; Reddy, N.
L.; Waterson, D. J. Chem. Soc., Perkin Trans. 1 1991, 3277.
(7) The products were satisfactorily characterized by 1H and 13C NMR and
elemental composition established by combustion analysis or HRMS. See
Supporting Information.
(9) Curry, M. J.; Stevens, I. D. R. J. Chem. Soc., Perkin Trans. 2 1980,
1391.
(8) Pomerantz, M.; Hartman, P. H. Tetrahedron Lett. 1968, 991.
10.1021/ja010639i CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/12/2001
Murakami
