Regio- and stereoselective synthesis of multisubstituted vinylsilanes via zirconacycles

Article abstract of DOI:10.1021/ol901236s

Image Persented A series of novel multisubstituted vinylsilanes are prepared regio- and stereoselectively by carbozirconation of various alkynylsilanes through zirconacycles such as zirconacyclopropenes and zirconacyclopentenes and the subsequent transformation of the formed alkenylzirconocene complexes.

Full text of DOI:10.1021/ol901236s

ORGANIC
LETTERS
2009
Vol. 11, No. 16
3546-3549
Regio- and Stereoselective Synthesis of
Multisubstituted Vinylsilanes via
Zirconacycles†
Yasushi Nishihara,* Daisuke Saito, Kenki Tanemura, Shintaro Noyori, and
Kentaro Takagi
DiVision of Chemistry and Biochemistry, Graduate School of Natural Science and
Technology, Okayama UniVersity, 3-1-1 Tsushimanaka, Kita-ku,
Okayama 700-8530, Japan
ynishiha@cc.okayama-u.ac.jp
Received June 2, 2009
ABSTRACT
A series of novel multisubstituted vinylsilanes are prepared regio- and stereoselectively by carbozirconation of various alkynylsilanes through
zirconacycles such as zirconacyclopropenes and zirconacyclopentenes and the subsequent transformation of the formed alkenylzirconocene complexes.
Carbon-carbon double bonds are essential structural con-
stituents in organic molecules and controlling the regio- and
stereoselectivity of the multisubstituted olefins has been one
of the central issues in synthetic organic chemistry.1 Along
this line, we have succeeded in synthesizing various multi-
substituted olefins in regio- and stereoselective manners via
Suzuki-Miyaura coupling for vinylboronates derived from
alkynylboronates and a low-valent ziroconocene complex.2
On the other hand, vinylsilanes3 have received increased
attention due to the lower toxicity of organosilicon compounds
that are suitable for Hiyama coupling.4 Originally, heteroatom-
functionalized vinylsilanes such as halosilanes,5 oxysilanes,6
silanols,7 cyclic silyl ethers,8 and polysiloxanes9 were necessary
owing to efficient reactivity.10 However, these vinylsilanes in
general are difficult to handle from the standpoint of their
chemical stability. Recently, several disclosures have demon-
strated the synthetic potential of more stable, all-carbon-
substituted silyl groups for Hiyama coupling, including meth-
ylsilacyclobutanes,11dimethylphenyl-,12benzyldimethyl-,132-dimethyl-
(4) (a) Hiyama, T.; Hatanaka, Y. Pure Appl. Chem. 1994, 66, 1471–
1478. (b) Hiyama, T. In Metal-Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter
10, pp 421-454. (c) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64,
1684–1688. (d) Denmark, S. E.; Neuville, L.; Christy, M. E. L.; Tymonko,
S. A. J. Org. Chem. 2006, 71, 8500–8509.
† This work is dedicated to Prof. John M. Birmingham on the occasion
of his 80th birthday.
(1) (a) Denmark, S. E.; Amburgey, J. J. Am. Chem. Soc. 1993, 115,
10386–10387. (b) Shimizu, M.; Nakamaki, C.; Shimono, K.; Schelper, M.;
Kurahashi, T.; Hiyama, T. J. Am. Chem. Soc. 2005, 127, 12506–12507.
(2) Nishihara, Y.; Miyasaka, M.; Okamoto, M.; Takahashi, H.; Tane-
mura, K.; Inoue, E.; Takagi, K. J. Am. Chem. Soc. 2007, 129, 12634–12635.
(3) For recent reports for utility of vinylsilanes in organic synthesis,
see: (a) Gordillo, A.; de Jesus, E.; Lopez-Mardomingo, C. J. Am. Chem.
Soc. 2009, 131, 4584–4585. (b) Sugiyama, A.; Ohnishi, Y.; Nakaoka, M.;
Nakao, Y.; Sato, H.; Sakaki, S.; Nakao, Y.; Hiyama, T. J. Am. Chem. Soc.
2008, 130, 12975–12985. (d) Zhang, H.; Song, Z.; Wang, C.; Bruneau, C.;
Xi, Z. Tetrahedron Lett. 2008, 49, 624–627. (e) Xi, Z.; Zhang, W.-X. Synlett
2008, 2557–2570. (f) Li, D.; Liu, G.; Hu, Q.; Wang, C.; Xi, Z. Org. Lett.
2007, 9, 5433–5436. (g) Park, J.-W.; Jun, C.-H. Org. Lett. 2007, 9, 4073–
4076.
(5) Sato, K.; Kira, M.; Sakurai, H. Tetrahedron Lett. 1989, 30, 4375–
4378.
(6) Li, L.; Navasero, N. Org. Lett. 2004, 6, 3091–3094.
(7) (a) Hirabayashi, K.; Takahisa, E.; Nishihara, Y.; Mori, A.; Hiyama,
T. Bull. Chem. Soc. Jpn. 1998, 71, 2409–2417. (b) Hirabayashi, K.;
Kawashima, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Org. Lett. 1999, 1,
299–301. (c) Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.;
Nishihara, Y.; Hiyama, T. J. Org. Chem. 2000, 65, 5342–5349. (d) Denmark,
S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835–846, and references
cited therein.
(8) Denmark, S. E.; Pan, W. T. Org. Lett. 2001, 3, 61–64.
(9) Denmark, S. E.; Butler, C. R. Org. Lett. 2006, 8, 63–66.
10.1021/ol901236s CCC: $40.75
Published on Web 07/22/2009
 2009 American Chemical Society

Table 1. Effect of Reaction Parameters on Hiyama Coupling of the Benzyldimethylsilyl-Substituted Vinylsilane 2aa
.
run
catalyst
Pd(dba)2
Pd(dba)2
Pd(dba)2
2a (equiv)
PhI (equiv)
TBAF (equiv)
time/h
yield/%b
E/Zc
1
2
3
4
5
6
1.0
1.5
1.5
1.2
1.0
1.0
1.5
1.0
1.0
1.5
1.0
1.0
1.0
1.5
1.5
1.0
1.5
1.5
2.2
3.3
2.2
1.2
2.2
2.2
1.5
2.2
2.2
24
1
1
1
24
1
24
24
24
76
66
77
94
<1
<1
59
33
<1
16:84
0:100
0:100
0:100
n/a
Pd(dba)2
Pd(PPh3)4
Pd(dba)2/2 PtBu3
CpPd(π-ally)
Pd(acac)2
n/a
7
97:3
100:0
n/a
8d
9d
Ni(acac)2
a All reactions employed vinylsilane 2a (0.1 mmol) and 1.0-1.5 equiv of iodobenzene in THF (0.5 mL, 0.2 M) at 0 °C. TBAF (1.2-3.3 equiv) was
added, and the mixture was stirred for 10 min followed by addition of 5 mol % of the catalyst. The mixture was then stirred at room temperature. b GC yields
c
1
(combined for both isomers of 3). Determined by GC-MS with internal standard of (E)- and (Z)-stilbenes and/or H NMR of the crude reaction mixture.
d Reaction was conducted at 50 °C.
2-thienyl-,14 2-pyridyldimethyl-,15 allyldimethyl-,16 and reusable
[2-(hydroxymethyl)phenyl]dimethylsilanes.17 Although di- or
trisubstituted vinylsilanes have been utilized for Hiyama
coupling, few examples are shown to synthesize the stereode-
fined multisubstituted vinylsilanes. Herein, we report the
extension of our vinylboronate synthesis using a zir-
conocene complex to a new, versatile procedure for the
regio- and stereospecific one-pot formation of a variety
of multisubstituted vinylsilanes.
To the best of our knowledge, zirconacyclopropenes as the
intermediate species are believed to be fleeting and difficult
to observe,20 although related complexes are known.21
Similarly, analogous vinylsilanes 2b-d were obtained in a
stereoselective (Z)-manner. The perfect control of the ster-
eochemistry of (Z)-vinylsilanes 2 by hydrosilylation of
terminal alkynes has been known to be difficult.22 Obtained
1
(Z)-vinylsilanes 2 are fully characterized by GC-MS, H,
and 13C NMR spectra as well as elemental analyses.
The starting alkynylsilanes 1a-d were prepared by the
reaction of phenylacetylene with EtMgBr, followed by
addition of various chlorosilanes in good to excellent yields.18
Addition of benzyldimethylsilyl (BDMS)-substituted alky-
nylsilane 1a to Cp2ZrCl2/2EtMgBr (Takahashi’s reagent)19
afforded (Z)-benzyldimethyl(2-phenylethenyl)silane (2a),
upon hydrolysis, in 82% yield with a perfect stereoselectivity
as shown in Scheme 1. Deuterium labeling of the intermedi-
ate zirconacycle by DCl/D2O workup of the reaction mixture
showed the presence of two deuterium atoms (>95%
incorporation) in 2a-d2, indicative of the formation of
zirconacyclopropene A bearing two zirconium-carbon bonds.
Scheme 1
.
Zirconocene-Mediated Synthesis of (Z)-Vinylsilanes
2a-d with Different Silyl Groups
(10) For reviews, see: (a) Denmark, S. E.; Sweis, R. F. Chem. Pharm.
Bull. 2002, 50, 1531–1541. (b) Denmark, S. E.; Ober, M. E. Aldrichim.
Acta 2003, 3675–85.
With access to the stereodefined (Z)-vinylsilane 2a in hand,
we turned to Hiyama coupling, expecting retention of the
stereochemistry of the coupled products. The results from
our survey of catalysts, an amount of tetrabutylammonium
(11) Denmark, S.; Choi, J. J. Am. Chem. Soc. 1999, 121, 5821–5822.
(12) Anderson, J. C.; Anguille, S.; Bailey, R. Chem. Commun. 2002,
2018–2019.
(13) Trost, B. M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003, 5,
1895–1898.
(14) Hosoi, K.; Nozaki, K.; Hiyama, T. Chem. Lett. 2002, 138–139.
(15) Itami, K.; Nokami, T.; Yoshida, J. AdV. Synth. Catal. 2002, 344,
441–451, and references cited therein.
(20) For example, see: (a) Takahashi, T.; Swanson, D. R.; Negishi, E.
Chem. Lett. 1987, 623–626. (b) Buchwald, S. L.; Nielsen, R. B. Chem.
ReV. 1988, 88, 1047–1058. (c) Johnson, S. A.; Liu, F. Q.; Suh, M. C.;
Zurcher, S.; Haufe, M.; Mao, S. S. H.; Tilley, T. D. J. Am. Chem. Soc.
2003, 125, 4199–4211. (d) Imabayashi, T.; Fujiwara, Y.; Nakao, Y.; Sato,
H.; Sakaki, S. Organometallics 2005, 24, 2129–2140.
(16) (a) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2004, 126, 13942–
13944. (b) Li, L.; Navasero, N. Org. Lett. 2006, 8, 3733–3736.
(17) Nakao, Y.; Imanaka, H.; Sahoo, A. K.; Yada, A.; Hiyama, T. J. Am.
Chem. Soc. 2005, 127, 6952–6953.
(18) Doyle, M. M.; Jackson, W. R.; Perlmutter, P. Aust. J. Chem. 1989,
42, 1907–1918.
(21) Miller, A. D.; McBee, J. L.; Tilley, T. D. J. Am. Chem. Soc. 2008,
130, 4992–4999.
(19) Takahashi, T.; Nitto, Y.; Seki, T.; Saburi, M.; Negishi, E. Chem.
Lett. 1990, 2259–2262.
(22) Mori, A.; Takahisa, E.; Kajiro, H.; Hirabayashi, K.; Nishihara, Y.;
Hiyama, T. Chem. Lett. 1998, 443–444.
Org. Lett., Vol. 11, No. 16, 2009
3547

fluoride (TBAF), and temperatures are collected in Table 1.
We first conducted the reaction 2a with iodobenzene under
Denmark’s reaction conditions, e.g., TBAF/Pd(dba)2/THF,23
yielding stilbenes 3 in 76% yield with a mixture of E/Z
isomers (84:16 ratio) (run 1). We found that various ratios
of 2a and iodobenzene, TBAF provided the predominant
formation of (Z)-3 with a shorter reaction time (1 h) in up
to 94% yield (runs 2-4). The mild reaction conditions would
lead to a general process that retains the stereochemistry of
3. When Pd(dba)2 was replaced with other palladium
catalysts, almost no product was formed (runs 5 and 6).
Interestingly, if the Pd(II) precursors such as CpPd(π-allyl)
and Pd(acac)2 were employed, 3 was formed in moderate
yields, albeit mostly (E)-isomers (runs 7 and 8). Other
fluoride sources such as KF and CsF did not show improve-
ment over TBAF at all.
The lack of stereoselectivity observed in runs 1, 7, and 8
probably results from the isomerization of the vinylsilanol
and/or vinylsiloxane intermediates derived from 2a under
the coupling conditions. Isomerization of the product (Z)-3
was excluded because no isomerization of (Z)-3 into (E)-3
was observed by GC-MS when the once isolated (Z)-3 was
refluxed in THF in the presence of with Pd(dba)2 and/or
TBAF. We found that 1.2 equiv of TBAF was enough for
complete conversion of 2a, which was then used throughout.
Since BDMS-vinylsilane 2a was found to undergo Hiyama
coupling with retention of stereochemistry in the presence
of TBAF, couplings of other synthesized vinylsilanes 2b-d
with iodobenzene were performed under optimized reaction
conditions.
debenzylation smoothly at 0 °C by activation of TBAF to
form vinylsilanol in situ in the presence of the contaminating
water.26 Then, the generated silanols can form a reactive
fluorosilicate with the assistance of a fluoride ion.27 Thus,
our investigations were focused on the regio- and stereose-
lective preparation of multisubstituted vinylsilanes with the
most active BDMS group, expecting synthesis of multisub-
stituted olefins by a simple Hiyama coupling.
To achieve a one-pot synthesis of trisubstituted vinylsilanes
directly from alkynylsilanes without isolation of zircona-
cycles, we chose the zircono-allylation reaction.28 Starting
from Takahashi protocol in the presence of alkynylsilanes,
the added allyloxytrimethylsilane rapidly reacted with the
intermediate zirconacyclopropene to form the transient
zirconacylopentene B. It is well-known that a trimethylsilyl
group direct zirconocene-mediated oxidative couplings such
that it adopt the R-positions.29 The following ꢀ-siloxy
abstraction proceeds to form the alkenylzirconocene inter-
mediate C, in which hydrolysis (or deuterolysis) of the
remaining Zr-C bond can afford trisubstituted vinylsilanes
4a-c in moderate yields (Scheme 3). It is noteworthy that
this protocol does not need any additive running the reaction
owing to the selective formation of zirconacyclopropene,
although the original zircono-allylation reaction required the
addition of PMe3 to stabilize the zirconacyclopropene inter-
mediate.
Scheme 3
.
Regio- and Stereoselective Synthesis of Tri- and
Tetrasubstituted Vinylsilanes 4-12
The results are shown in Scheme 2. (Z)-Dimethyl(2-
phenylethenyl)-2-thienylsilane (2b) provided 3 stereoselec-
tively in 81% yield, whereas 2c (R ) Ph) and 2d (R ) Me)
23,24
were unreacted. The usage of another activator KOSiMe3
did not improve the yield of 3.
Scheme 2
.
Hiyama Coupling of (Z)-Vinylsilanes 2a-d with
Iodobenzene
The regioselectivity in vinylsilanes 4a-c was determined
by NMR data. In 1H NMR spectra, the presence of a singlet
in the double-bond region (around 5.8 ppm) is indicative
that the vinyl hydrogen located in the R-position of the silyl
groups. The successful transformation of the transient
alkenylzirconocene species into trisubstituted vinylsilanes
This is the first example to show the comparison of the
effect of the all-carbon-substituted silyl groups of a class of
(Z)-vinylsilanes for Hiyama coupling.25 Among four types
of (Z)-vinylsilanes, the BDMS group is found to be most
reactive under the present conditions because it can undergo
(25) Other Hiyama coupling for retention of configuration of (Z)-
vinylsilanes: Tris(trimethylsilyl)vinylsilanes: Wnuk, S. F.; Garcia, P. I., Jr.
Org. Lett. 2004, 6, 2047–2049. Diethoxymethyvinylsilanes: Mori, A.;
Takahisa,; Yamamura, Y.; Kato, T; Mudalige, A. P.; Kajiro, H.; Hirabayashi,
K.; Nishihara, Y.; Hiyama, T. Organometallics 2004, 23, 1755–1765.
(26) Denmark, S.; Wehrli, D.; Choi, J. Org. Lett. 2000, 2, 2491–2494.
(27) Denmark, S. E.; Sweis, R. F.; Wehrli, D. J. Am. Chem. Soc. 2004,
126, 4865–4875.
(23) Denmark, S. E.; Tymonko, S. A. J. Am. Chem. Soc. 2005, 127,
8004–8005.
(24) Potassium trimethylsilanolate has found use for activation of
vinylsilanes: (a) Anderson, J. C.; Munday, R. H. J. Org. Chem. 2004, 69,
8971–8974. (b) Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2001, 123,
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R. Tetrahedron Lett. 1993, 34, 4811–4814.
6439–6440
.
3548
Org. Lett., Vol. 11, No. 16, 2009

encouraged us to investigate the one-pot synthesis of
tetrasubstituted vinylsilanes. The transient C could be
converted into functionalized tetrasubstituted vinylsilanes by
couplings with various electrophiles. The various reactions
are also summarized in Scheme 3. The reaction with various
aryl iodides in the presence of CuCl and a catalytic amount
Since zirconacyclopropene has two Zr-C bonds, one
might consider that it may be utilized as an intermediate for
the double arylation reaction. The formed in situ zircona-
cyclopropene was treated with 2 molar equiv of iodobenzene
in the presence of a stoichiometric amount of Ni(cod)2 to
give the desired products 14, albeit in low yield (Scheme
5).36
30
of Pd(PPh3)4 gave the corresponding cross-coupled prod-
ucts 6-8 in good yields. The reaction with iodomethane,31
alkynyl iodide,32 and benzyl chloride afforded the corre-
sponding products 9-11 in 73, 58, and 71% yield, respec-
tively. When C was treated with additional allyl chloride in
the presence of CuCl,33 double allylation of alkynylsilane
1a was accomplished to give 12 in 73% yield. The stereo-
chemistry of tetrasubstituted vinylsilanes 5-12 was deter-
mined by a comparison of spectroscopic data of 9 with those
of the analogous TMS-containing vinylsilane.34
Scheme 5
.
Nickel-Mediated Double Arylation of Alkynylsilane
1a
Scheme 4
.
Zircono-esterification of Alkynylsilane 1a
In summary, we have developed a direct, regio- and
stereoselective synthesis of tri- and tetrasubstituted vinylsi-
lanes by a one-pot zirconocene-mediated carbometalation of
alkynylsilanes and the subsequent transformation with vari-
ous electrophiles. This method is potentially applicable to
the regio- and stereoselective synthesis of multisubstituted
olefins. Current efforts to expand the scope of coupling
partners on zirconacycles as well as to elucidate the Hiyama
coupling of the produced tri- and tetrasubstituted vinylsilanes
are in progress.
Since the cross-coupling of sterically hindered trisubstituted
benzyldimethylvinylsilanes is known to proceed,13,23 we at-
tempted a Hiyama coupling of the synthesized trisubstituted
vinylsilanes 4a with iodobenzene. Unfortunately the reaction
did not proceed at all under the conditions described in Table
1. Several trials to realize the successful Hiyama coupling
of tri- or tetrasubstituted vinylsilanes have been failed.
Zirconocene-mediated transformations for alkynes are ver-
satile methods to tolerate a wide range of functional groups
such as the ester group.35 The reaction of alkynylsilane 1a with
Takahashi’s reagent and chloroformate, followed by hydrolysis
resulted in the formation of hydroesterification product 13 in
53% yield in a single step (Scheme 4).
Acknowledgment. We gratefully thank Prof. Hiroshi
Nakazawa and Dr. Masumi Itazaki at Osaka City University
for measurements of elemental analyses and Prof. Tamotsu
Takahashi at Hokkaido University for a generous gift of
Cp2ZrCl2. This work was supported by a Grant-in-Aid for
Scientific Research on Priority Areas “Advanced Molecular
Transformations of Carbon Resources” from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan. Y.N. also acknowledges the Japan Securities Scholar-
ship Foundation, Mitsubishi Chemical Corporation Fund, and
the Kurata Memorial Hitachi Science and Technology
Foundation.
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Supporting Information Available: Experimental pro-
cedures as well as characterization data for all vinylsilanes.
This material is available free of charge via the Internet at
http://pubs.acs.org.
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OL901236S
(36) The analogous titanium-alkyne complexes gave the diarylated
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