Cp2TiCl2-catalyzed regio- and chemoselective one-step synthesis of γ-substituted allylsilanes from terminal alkenes using dianion-type zincate (SiSiNOL-Zn-ate)

Article abstract of DOI:10.1021/ja0541074

A regio-/chemoselective silylation reaction of various functionalized terminal alkenes in the presence of titanocene dichloride, based on a newly designed dianion-type zincate, was developed. The present silylation of terminal alkenes is a powerful tool f

Full text of DOI:10.1021/ja0541074

Published on Web 09/03/2005
Cp2TiCl2-Catalyzed Regio- and Chemoselective One-Step Synthesis of
γ-Substituted Allylsilanes from Terminal Alkenes Using Dianion-Type Zincate
(SiSiNOL-Zn-ate)
Shinji Nakamura, Masanobu Uchiyama,* and Tomohiko Ohwada
Graduate School of Pharmaceutical Sciences, The UniVersity of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received June 21, 2005; E-mail: uchiyama@mol.f.u-tokyo.ac.jp
Table 1. Screening of Zincates for Cp2TiCl2-Catalyzed Silylation
Allylsilanes are important intermediates for carbon-carbon and
of 1-Heptene (1a)a
carbon-heteroatom bond formation in organic synthesis because
of their easy handling, unique reactivities, and high regiocontrol-
lability.1 Methods currently available for their synthesis include
transition-metal-catalyzed silylmetalation of 1,3-dienes or allenes
and Wittig reactions.2 Unfortunately, however, many of these
reactions have significant disadvantages: low generality, low
chemoselectivity, the requirement for tedious multistep synthesis
of the precursor, and so on. We disclose here a chemo- and
regioselective direct preparation method of γ-substituted allylsilanes
from readily available terminal alkenes with various kinds of
functional groups, using a newly developed silylzincate (SiSiNOL-
Zn-ate) and catalytic Cp2TiCl2 system. We also demonstrate that
the resultant functionalized allylsilanes can be versatile allylating
reagents, providing basic architecture for functionalized materials.
Silylmetalation reaction of reactive unsaturated C-C bonds such
as alkynes, allenes, or dienes has been extensively utilized in organic
synthesis.3 However, its application to alkenes has not been well
developed due to low reactivity of the isolated C-C double bond.4
a The silylation was carried out using zincate (1.1 equiv), substrate (1.0
We have recently developed a dianion-type zincate (SiBNOL-
Zn-ate, Table 1 entry 6) that promotes chemo- and regioselective
silylzincation of functionalized terminal alkynes without any
transition-metal catalyst.6a To develop a new silylmetalation reaction
of terminal alkenes, we started with the design and screening of
suitable silylzincates by using 1-heptene (1a) as a model substrate.
However, all initial attempts using various silylzincates without any
catalyst were unsuccessful. Then, we focused on screening of
catalysts for the addition of the silylzincate to functionalized olefins.
After extensive experimentation, we found that the combination
of 5 mol % of Cp2TiCl2 and SiSiNOL-Zn-ate (Table 1, entry 7)
silylated 1a in good yield under mild conditions. Interestingly, this
silylation gave predominantly a γ-substituted allylsilane (2a, a Heck-
type addition product), and neither regioisomers nor saturated
alkylsilanes were observed at all.
equiv), and Cp2TiCl2 (5 mol %) in THF at room temperature for 18 h.
b Isolated yield.
Table 2. Silylation of Various Functionalized Terminal Alkenesa
Tamao and co-workers reported some excellent silyltitanation
reactions using a stoichiometric amount of Cp2TiCl2 and 2 equiv
of DMPSLi to acetylenes or 1,3-dienes,5 but no example using
alkenes as substrates has been reported to date. A Ti(III)-Si-active
species, Cp2TiSiMe2Ph, is proposed to be involved in those
silyltitanation reactions. Although the silylation mechanism in our
case is not clear yet, Zn-ate is essential for this catalytic silylation
at terminal alkenes; the yield of the allylsilane was less than 1%
when Zn(II) was omitted, and other metals such as Mg(II), Al(III),
V(II), Cr(II), Mn(II/III), Fe(II/III), Co(II/III), and Cu(I) could not
replace Zn(II). In addition, the coordination number and the nature
of the countercations were also critical for this silylation reaction.6
With optimized conditions in hand, we studied the scope of this
new protocol, and representative results are summarized in Table
2. In addition to terminal alkenes bearing simple alkyl chains, those
a Unless otherwise noted, the silylzincation was carried out using zincate
(1.1 equiv), substrate (1.0 equiv), and Cp2TiCl2 (5 mol %) in THF at room
temperature for 18 h. b Isolated yield. c The reaction was carried out under
reflux. d 3 equiv of zincate was used. e The reaction was carried out at 45
°C. f Vinylsilane was isolated in 18% yield (E/Z ) 64/36). g Vinylsilane
was isolated in 8% yield (E/Z ) 58/42). h Vinylsilane was isolated in 19%
yield (E/Z ) 50/50).
possessing a range of functional groups could be used: suitably
protected alcohols, amines, thiol, and ketones (entries 1-5, 14), as
well as cyclohexyl and aryl substitution (entries 11-13), are
tolerated in the reaction. A variety of electrophilic functional groups,
including a carbamate, carbonate, and ester, also caused no problems
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C O M M U N I C A T I O N S
Scheme 2. Reactivity of the Functionalized Allylsilanes
Scheme 1. Reactivity and Selectivity of the Present Silylation
(entries 8-10). Substrates containing a free O-H moiety, such as
aliphatic alcohols and carboxylic acid could also be utilized, and
no self-condensation was observed (entries 6, 7). To our knowledge,
this reaction is the first example of an efficient one-step synthesis
of γ-substituted allylsilanes with wide substrate generality.
Some characteristic aspects of the regio- and stereoselectivity
of this silylation can be drawn from the data in Table 2. (1)
Regioselectivity of addition: the silylation reaction occurs with very
high regiospecifically for monosubstituted alkenes (no regio isomer
was detected), probably due to the steric effect. (2) Direction of
â-elimination (allyl/vinyl selectivity): as evidenced by entries 1-10,
the reactions with terminal alkenes containing any functional group
distal from the reaction site (the double bond) gave the allylsilanes
preferentially over the corresponding vinylsilanes. On the other
hand, in the case of terminal alkenes containing bulky substituents,
such as a cyclohexyl, benzyl, or cyclic ketal group, near the reaction
site, the allyl/vinyl selectivity showed a declining trend. (3)
Stereoselectivity: the E/Z ratios of the allylsilanes were almost
constant (except for entry 12), with Z isomers as the major
component. (4) Isomerization of double bond: no movement of
the C-C double bond of allylsilanes was observed at all, even when
a carbonyl or phenyl moiety was present. Isomerization to give
conjugated products often occurs in Ru- and Pd-catalyzed reactions.7
To investigate the chemoselectivity of this silylation, the reac-
tivities of this system with various alkenes were next examined
(Scheme 1). The functional group specificity of this silylation is
very high, and internal olefins (3 or 4) or 1,1′-disubstituted alkenes
(5 or 6) did not react at all. On the other hand, the reaction of
styrene (7) provides both alkylsilane and vinylsilane with a
quantitative conversion yield. The alkyl/vinyl ratio depends on the
reaction temperature to some extent, and when the reaction was
carried out at 45 °C, the corresponding vinylsilane and alkylsilane
were obtained in 88% and 12% yields, respectively. In the
competitive reaction of internal alkenes in 1,5-heptadiene (8) using
SiSiNOL-Zn-ate and 5 mol % of Cp2TiCl2, silylation at the terminal
alkene proceeded with complete selectivity. In addition, no isomer-
ization of olefins was observed at all.
Finally, the potential use of the functionalized allylsilanes
produced in this work was examined (Scheme 2).8 The resultant
γ-substituted allylsilanes can be utilized as allylating agents in the
presence of Lewis acids with high chemo- and regioselectivity. The
allylsilanes also react with m-CPBA or BH3‚THF to give the
corresponding oxidized products in moderate to high yields with
high regioselectivities. These multifunctionalities can easily be
further transformed in various ways, so that the synthetic value of
γ-substituted allylsilanes would be greatly extended by the present
approach.
In conclusion, we have developed a new method for the chemo-
and regioselective silylation reaction of functionalized terminal
alkenes, utilizing a catalyst system comprising catalytic Cp2TiCl2
and a dianion-type Zn(II) ate complex (SiSiNOL-Zn-ate). The
method provides a simple and direct route for the synthesis of
regiocontrolled γ-substituted allylsilanes from various functionalized
terminal alkene precursors. Efforts to expand the scope of the
reaction and to elucidate the reaction pathway with the help of
theoretical and spectroscopic studies are in progress in our
laboratory.
Acknowledgment. This research was partly supported by
Grants-in-Aid for Young Scientists (A) from JSPS (to M.U.). We
are also grateful for a JSPS Research Fellowship for Young
Scientists (to S.N.). We thank Prof. M. Suginome (Kyoto Univer-
sity) for his valuable comments.
Supporting Information Available: Experimental procedures and
characterizations. This material is available free of charge via the
Internet at http://pubs.acs.org.
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