Stereoselective synthesis of multisubstituted alkenes via conformationally labile alkenyllithium species

Article abstract of DOI:10.1021/ol050114l

(Chemical Equation Presented) Stereoselective synthesis of tri- and tetrasubstituted alkenylsilanes has been realized by the selective intramolecular silicon migration in the rapidly equilibrating alkenyllithium species. Subsequent copper- and palladium-m

Full text of DOI:10.1021/ol050114l

ORGANIC
LETTERS
2005
Vol. 7, No. 5
909-911
Stereoselective Synthesis of
Multisubstituted Alkenes via
Conformationally Labile Alkenyllithium
Species
Shigeru Yamago,*,† Kazuyoshi Fujita,‡ Masaki Miyoshi,‡ Masashi Kotani,† and
Jun-ichi Yoshida‡
DiVision of Molecular Material Science, Graduate School of Science, Osaka City
UniVersity, Osaka 558-8585, Japan, and Department of Synthetic Chemistry and
Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Nishikyo-ku, Kyoto 615-8510, Japan
yamago@sci.osaka-cu.ac.jp
Received January 19, 2005
ABSTRACT
Stereoselective synthesis of tri- and tetrasubstituted alkenylsilanes has been realized by the selective intramolecular silicon migration in the
rapidly equilibrating alkenyllithium species. Subsequent copper- and palladium-mediated coupling with allyl and aryl halides provides tri- and
tetrasubstituted alkenes possessing all different carbon-substituents with complete stereoselectivity.
Alkenylmetal species play crucial roles in the stereoselective
synthesis of multisubstituted alkenes, which are ubiquitous
and essential structural constituents in organic molecules.1
Since the stereochemical outcome of the alkenes depends
critically on the stereochemistry of alkenylmetal species, its
isomerization usually results in the loss of stereochemical
purity. Therefore, configurationally labile alkenylmetal spe-
cies have not been considered as important synthetic precur-
sors for stereochemically defined multisubstituted alkenes,2
because reactivity of (E)- and (Z)-isomers of alkenylmetals
are almost identical. We, however, are interested in the
possibility to use rapidly equilibrating alkenylmetal species
for stereoselective synthesis of multisubstituted alkenes. We
envisaged that discrimination of the reactivity between (E)-
and (Z)-isomers of alkenylmetal species becomes possible
if one isomer could selectively react with an electrophile by
intramolecular reaction (Scheme 1). We report here the
Scheme 1
† Osaka City University.
‡ Kyoto University.
(1) (a) Marek, I.; Normant, J. F. Metal-catalyzed Cross-coupling Reac-
tions; Diederich, F., Stang, P. J., Eds.; Wiley-VHC: Weinhein, Germany,
1998; pp 271-337. (b) Knochel, P. ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press:
Oxford, UK, 1991; Vol. 4, pp 865-950. (c) Negishi, E. Chem. Eur. J. 1999,
5, 411. (d) Inoue, S.; Honda, K. J. Synth. Chem. Soc. Jpn. 1993, 51, 894.
(e) Normant, J. F.; Alexakis, A. Synthesis 1981, 841.
highly efficient synthesis of multisubstituted alkenes based
on this new synthetic strategy. Although one example for
the stereoselective synthesis of trisubstituted homoallyl
(2) (a) Ma, S.; Negishi, E. J. Org. Chem. 1997, 62, 784. (b) Cummins,
C. H.; Gordon, E. J. Tetrahedron Lett. 1994, 35, 8133.
10.1021/ol050114l CCC: $30.25
© 2005 American Chemical Society
Published on Web 02/08/2005

alcohol through alkene isomerization has been reported,3 its
synthetic scope as well as explicit mechanism have not been
clarified. We now demonstrate that the current strategy
provides a powerful route for varieties of tri- and tetrasub-
stituted alkenes with defined stereochemistry.4,5
Table 1. Synthesis of Tri- and Tetrasubstituted Alkenylsilanesa
Our initial finding for the stereoselective synthesis of
multisubstituted alkenes was obtained when E-1a (R1 ) R3
) R4 ) Ph, R2 ) H, 96% E)5b was treated with butyllithium
(1.1 equiv) in THF at -72 to 0 °C for 0.5 h (Scheme 2).6
Scheme 2
After usual hydrolytic workup, we isolated alkenylsilane
(Z)-2a as an exclusive isomer in almost quantitative yield
(Table 1, entry 1). The structure of 1a and 2a was confirmed
by X-ray crystallographic analysis5b and by NMR analysis
based on NOE, respectively, revealing that olefin isomer-
ization as well as silicon migration from oxygen to carbon
took place. As transmetalation from tellurium to lithium takes
place with retention of stereochemistry through a hypervalent
tellurium intermediate,7 the result could be explained by the
initial formation of (Z)-alkenyllithium (Z)-3, which subse-
quently isomerized to the (E)-isomer,8 followed by the silicon
(3) (a) Gais, H.-J.; Mu¨ller, H.; Decker, J.; Hainz, R. Tetrahedron Lett.
1995, 36, 7433. (b) Marumoto, S.; Kuwajima, I. J. Am. Chem. Soc. 1993,
115, 9021.
(4) Recent representative example for tri- and tetrasubstituted alkenes.
(a) Itami, K.; Mineno, M.; Muraoka, N.; Yoshida, J. J. Am. Chem. Soc.
2004, 126, 11778. (b) Carbometalation route: Kennedy, J. W.; Hall, D. G.
J. Am. Chem. Soc. 2002, 124, 898. (c) Itami, K.; Nokami, T.; Ishimura, Y.;
Matsudo, T.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 11577.
(d) Yamanoi, S.; Seki, K.; Matsumono, T.; Suzuki, K. J. Organomet. Chem.
2001, 624, 143. (e) Takahashi, T.; Xi, C.; Ura, Y.; Nakajima, K. J. Am.
Chem. Soc. 2000, 122, 3228. (f) Shirakawa, E.; Yamasaki, K.; Yoshida,
H.; Hiyama, T. J. Am. Chem. Soc. 1999, 121, 10221. (g) Urabe, H.; Hamada,
T.; Sato, F. J. Am. Chem. Soc. 1999, 121, 2931. (h) Ramachandran, P. V.;
Reddy, M. V. R.; Rudd, M. T.; Tetrahedron Lett. 1999, 40, 627. (i)
Stu¨demann, T.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1997, 36, 93. (j)
Ikeda, S.; Kondo, K.; Sato, Y. J. Org. Chem. 1996, 61, 8248. (k) Brown,
S. D.; Armstrong, A. W. J. Am. Chem. Soc. 1996, 118, 6331. (l) Wittig
reaction route: Denmark, S. E.; Amburgey, J. J. Am. Chem. Soc. 1993,
115, 10386. (m) Other routes: Shindo, M.; Matsumoto, K.; Mori, S.;
Shishido, K. J. Am. Chem. Soc. 2002, 124, 6840.
(5) Our interest in organotellurium compounds in organic synthesis: (a)
Yamago, S. Synlett 2004, 1875, and references therein. (b) Yamago, S.;
Miyoshi, M.; Miyazoe, H.; Yoshida, J. Angew. Chem., Int. Ed. 2002, 41,
1407. (c) Yamago, S.; Kokubo, K.; Hara, O.; Masuda, S.; Yoshida, J. J.
Org. Chem. 2002, 67, 8584.
(6) (a) Seebach, D.; Beck, A. K. Chem. Ber. 1975, 108, 314. (b) Luppold,
E.; Mu¨ller, E.; Winter, W. Z. Naturforsch. 1976, 31b, 1654. (c) Hirao, T.;
Kambe, N.; Ogawa, A.; Miyoshi, M.; Murai, S.; Sonoda, N. Angew. Chem.,
Int. Ed. Engl. 1987, 26, 1187. (d) Ogawa, A.; Tsuboi, Y.; Yokoyama, K.;
Ryu, I.; Sonoda, N. J. Org. Chem. 1994, 59, 1600.
a Butyllithium (1.1-1.2 equiv) was added to a THF solution of 1 (ca.
0.5 M solution) at -72 °C, and the resulting solution was slowly warmed
to 0 °C over 0.5 h. b Performed with 2.2 equiv of buthyllithium.
migration from oxygen to carbon to 4 (Scheme 2).9 Trans-
metalation to the corresponding alkenylcopper species by
10
the reaction of 1a with Me2Cu(CN)Li2 or Me2CuLi
(8) (a) Wardell, J. L. In ComprehensiVe Organometallic Chemistry;
Wilkinson, G., Stones, F. G. A., Abel, E. W., Eds.; Pergamon Press: Oxford,
UK, 1982; Vol. 1, pp 42-120. (b) Bauer, W.; Feigel, M.; Mu¨ller, G.;
Schleyer, P. R. J. Am. Chem. Soc. 1988, 110, 6033. (c) Knorr, R.; von
Roman, T. Angew. Chem., Int. Ed. Engl. 1984, 23, 366. (d) Zweifel, G.;
Murray, R. E.; On, H. P. J. Org. Chem. 1981, 46, 1292. (e) Knorr, R.;
Lattke, E. Tetrahedron Lett. 1977, 45, 3969. (f) Panek, B. L.; Neff, E. J.;
Chu, H.; Panek, M. G. J. Am. Chem. Soc. 1975, 97, 3996.
(7) . (a) Reich, H. J.; Bevan, M. J.; Gudmundsson, B. O¨ .; Puckett, C. L.
Angew. Chem., Int. Ed. 2002, 41, 3436. (b) Reich, H. J.; Green, D. P.;
Phillips, N. H. J. Am. Chem. Soc. 1991, 113, 1414. See also ref 6d.
(9) (a) Kim, K. D.; Magriotis, P. A. Tetrahedron Lett. 1990, 31, 6137.
(b) Lautens, M.; Delanghe, P. H. M.; Goh, J. B.; Zhang, C. H. J. Org.
Chem. 1995, 60, 4213.
910
Org. Lett., Vol. 7, No. 5, 2005

reagents6d,11 in Et2O also afforded (Z)-2a as an exclusive
product in 74 and 81% yields, respectively.
Scheme 3
The present reaction is generally applicable to alkenyl-
telluride 1 bearing different R1, R2, R3, and R4 groups and
afforded the resulting (Z)-alkenylsilane 2 in good to excellent
yields (Table 1).12 Most notably, (Z)-isomers of both tri- and
tetrasubstituted alkenes were exclusively formed regardless
of the geometrical purity of the starting alkenyltellurides in
all cases, indicating that both the (E)- and (Z)-isomers of
alkenyllithium species generated from 1 gave the same
product. The reaction also tolerates a variety of R3 and R4
groups to give the secondary and tertially alcohols efficiently.
Although hydroxyl group-directed carbometalation of pro-
pargyl alcohol derivatives has been widely used for the
stereoselective synthesis of multisubstituted alkenes,13 the
applicability of this method is limited to primary alcohols.
Therefore, the current method provides a stereoselective
synthetic route to highly substituted allyl alcohols with
defined alkene geometry. The current reaction exhibited high
functional group selectivities, and arylbromide function was
retained to the product (entry 3). We could also utilize a
variety of silyl groups, and 2c also formed upon starting from
1c (entry 11).
Several control experiments further supported the reaction
pathway as depicted in Scheme 1. First, isomerization of
alkenyllithium species was ascertained by the experiments
using 5 (>99% E), which resulted in the formation of an
83:17 mixture of (E)- and (Z)-isomers of 614 upon treatment
of butyllithium followed by hydrolysis. The result is con-
sistent with the fact that R-aryl-substituted alkenyllithiums
isomerize at low temperature in a polar solvent such as THF8
and clearly indicates the role of the silicon migration as the
stereochemistry-determining step. Second, intramolecular
silicon migration is ascertained by the scrambling experi-
ments. Thus, treatment of an equimolar amount of 1b and
1c with butyllithium resulted in the selective formation of
(Z)-2b (59%) and (Z)-2c (64%), and no silicon-scrambled
products were detected. Therefore, selective intramolecular
silyl group migration from (E)-3 to 4 shifts the equilibrium
between (Z)- and (E)-isomers of 3, thus providing 2 as a
single stereoisomer regardless of the stereochemistry of 1.15
The virtue of the current method is the ease of the
transformation of silyl groups to other functionalities (Scheme
3). We are pleased to find that the coupling reaction de-
veloped by Takeda could be nicely applied to this system.16
Thus, alkenylsilane 2b was transformed directly to skipped
diene 7 upon transmetalation from silicon to copper followed
by the treatment with allyl chloride. Further transformation
from copper to palladium also enabled alkenyl-aryl coupling
reaction to give vicinally aryl-substituted alkene 8 in excellent
yield. In both transformations, the stereochemistry of the
alkenyl carbon was retained in the products. Therefore, the
stereoselective synthesis of tetrasubstituted alkenes possess-
ing all different carbon substituents could be easily achieved.4a
In summary, we have developed a new stereoselective
synthesis of tri- and tetrasubstituted alkenes using confor-
mationally labile alkenyllithium species. Furthermore, silyl
group in the products serves as useful surrogate of reactive
alkenylmetal species with defined structure for further
synthetic transformations. Because alkenyllithiums are also
prepared by the transmetalation from alkenylstannanes or
alkenyliodides, or carbometalation, a variety of synthetic
routes would be feasible. In addition, an internal electrophile
would not be limited to the silyl groups. Exploration of such
possibilities is now in progress.
Acknowledgment. This work was partly supported by a
Grant-in-Aid for Scientific Research from the Japan Society
for the Promotion of Science.
Supporting Information Available: Preparations and
reactions of alkenyltellurides and transformation of alkenyl-
silanes. This material is available free of charge via the
Internet at http://pubs.acs.org.
(10) Chieffi, A.; Comasseto, J. V. Tetrahedron Lett. 1994, 35, 4063.
(11) Mariano, J. P.; Joao, F. T.; Comasseto, J. V. Synlett 1993, 761.
(12) Tetrasubstituted alkenyltellurides were prepared from easily available
enals bearing phenyltellanyl moiety. See: (a) Prim, D.; Fuss, A.; Kirsh,
G.; Silva, A. M. J. Chem. Soc., Perkin Trans. 2 1999, 1175. (b) Minkin, V.
I.; Sadekov, I. D.; Rivkin, B. B.; Zakharov, A. V.; Nivorozhkin, V. L.;
Kompan, O. E.; Struchkov, Y. T. J. Organomet. Chem. 1997, 536, 233.
(13) Fallis, A. G.; Forgione, P. Tetrahedron 2001, 57, 5899.
OL050114L
(15) An alternative mechanism, in which the stereochemistry is deter-
mined by selective hydrolysis of pentavalent cyclic silicate intermediate,
could not be rigorously ruled out.
(16) (a) Taguchi, H.; Ghoroku, K.; Tadaki, M.; Tsubouchi, A.; Takeda,
T. J. Org. Chem. 2002, 67, 8450. (b) Taguchi, H.; Ghoroku, K.; Tadaki,
M.; Tsubouchi, A.; Takeda, T. Org. Lett. 2001, 3, 3811.
(14) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya,
Y. J. Am. Chem. Soc. 1989, 111, 4392.
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