Mild niobium-catalyzed [2 + 2 + 2] cycloaddition of sila-triynes: Easy access to polysubstituted benzosilacyclobutenes

Article abstract of DOI:10.1021/ol503663k

A new and efficient synthesis of highly sensitive benzosilacyclobutenes has been developed. For the first time, these compounds can be synthesized in very high yields by a mild, unprecedented intramolecular niobium-catalyzed [2 + 2 + 2] cycloaddition of easily accessible tetrasubstituted sila-triynes. An easy access to highly functionalized benzosilacyclobutenes enlarging the number of potential applications in organic and material chemistry is described.

Full text of DOI:10.1021/ol503663k

Letter
pubs.acs.org/OrgLett
Mild Niobium-Catalyzed [2 + 2 + 2] Cycloaddition of Sila-triynes:
Easy Access to Polysubstituted Benzosilacyclobutenes
Cedric Simon, Muriel Amatore, Corinne Aubert, and Marc Petit*
́
́ ́
Sorbonne Universites, UPMC UNIV Paris 06, Institut Parisien de Chimie Moleculaire, UMR CNRS 8232, Case 229, 4 Place Jussieu,
75252 Paris Cedex 05, France
S
* Supporting Information
ABSTRACT: A new and efficient synthesis of highly sensitive
benzosilacyclobutenes has been developed. For the first time, these
compounds can be synthesized in very high yields by a mild,
unprecedented intramolecular niobium-catalyzed [2 + 2 + 2]
cycloaddition of easily accessible tetrasubstituted sila-triynes. An
easy access to highly functionalized benzosilacyclobutenes enlarging
the number of potential applications in organic and material chemistry is described.
ilacycles have become an important class of molecules in
materials chemistry and recent organic chemistry. They
Scheme 1. (a) Grignard Approaches to
Benzosilacyclobutenes. (b) Proposed [2 + 2 + 2]
Cycloaddition Approach
S
can be found in the literature as precursors for more elaborate
silicon-containing molecules,1 or they have direct applications
because of their intrinsic optical properties.2 Due to their ring
strain and Lewis acidity, small silacycles have been used in a
wide range of chemical transformations.3 For instance, the
more specific silacyclobutanes and benzosilacyclobutenes have
been used in ring-opening polymerization (ROP) to afford
polycarbosilane polymers4 with interesting features. Silacyclo-
butanes and benzosilacyclobutenes have also been described
in ring expansion chemistry by reaction with several transition
metals such as Ni,5 Pd,6 Pt,7 and Co8 to afford larger silicon-
containing cycles or rare polycyclic compounds bearing a
silicon atom at the ring junction.8 In each case, the same Si−
C bond activation strategy has been employed to generate a
metallacycle intermediate that can be trapped with different
unsaturated molecules (carbonyls, alkynes, alkenes, etc.).
However, the range of applications of the benzene-fused
silacyclobutanes has been limited by the poor variability of the
substitution on these molecules. Indeed, the downside of their
high reactivity is unfortunately the low stability of these
molecules during their synthesis.9,10a Thus, only a few
synthetic approaches have been described in the literature.
The most significant, by Gilman,10a Kang,10b and de Boer,10c
all start with 2-bromobenzyl bromide derivatives in the
presence of sensitive polyhalosilanes and magnesium yielding
to the desired benzosilacyclobutenes in poor to moderate
yields (Scheme 1a). To the best of our knowledge, until now,
no modulation of the substitution on the aromatic moiety has
been reported making the development of alternative and
more practical synthetic routes highly desirable. In this paper,
we propose to use the well-known [2 + 2 + 2] cycloaddition
of newly synthesized sila-triynes to provide highly function-
alized benzosilacyclobutenes (Scheme 1b).
sila-triyne 1a. However, an oxidative addition occurred
immediately during the reaction and after ring expansion;
the only compound formed is the sila-polycyclic compound
3a in 41% yield (Scheme 2). Even if this proof of concept is
very appealing, the [2 + 2 + 2] approach appears
challenging.11 Indeed, we have to find the right catalyst to
allow efficient cyclotrimerization and preserve the integrity of
the newly formed benzosilacyclobutene.
Recently, we discovered that the [Co(R)(PMe3)4] family of
cobalt complexes was able to catalyze the cycloaddition of
triynes and enediynes at room temperature with a different
reactivity compared to the CpCo(L)2 type of complexes.12
Thus, we decided to screen (Table 1) this family of
In the course of studying the reactivity of benzosilacyclo-
butenes toward cobalt,8 we discovered that this sila-cycle
could be generated as an intermediate by cycloaddition of the
Received: December 19, 2014
© XXXX American Chemical Society
A
DOI: 10.1021/ol503663k
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
high sensitivity to acidic medium, compound 2b could be
isolated after silica gel chromatography only with a moderate
yield of 26% (Table 1, entry 6). In this transformation, the
cationic rhodium was also not efficient, and no conversion
was observed (Table 1, entry 7).13 Finally, the less known and
rarely used low-valent niobium catalyst NbCl3·DME was the
most efficient of all catalysts in the trial with both a
conversion and a NMR yield of 76% (Table 1, entry 8).14
However, once again, the corresponding benzosilacyclobutene
was isolated in a poor 28% yield, justifying an optimization of
the reaction and purification conditions. With this promising
result in hand, we next focused on developing a more efficient
niobium-catalyzed process to reach full conversion in order to
avoid complicated chromatography. Optimizations of the
workup, degassing procedures, catalyst loading, and concen-
tration led us to the optimal conditions of 5 mol % catalyst in
2 h with a concentration of 0.8 M. Pure product can be
isolated after a simple filtration on an alumina pad, with an
excellent 97% yield (see the Supporting Information).
Scheme 2. First Evidence of a Possible Synthesis of
Benzosilacyclobutenes by [2 + 2 + 2] Cycloaddition
Table 1. Screening of [2 + 2 + 2] Cycloaddition Catalysts
To establish that our methodology is a real breakthrough in
the synthesis of highly functionalized benzosilacyclobutenes,
we wish to demonstrate that the substitution on the silicon
atom but also on the aromatic moiety could be easily
modulated. Thus, we had to develop an efficient synthesis of
the acyclic starting sila-triynes incorporating a tri- or
tetrasubstituted silicon atom. We first thought of using our
previously published strategy on the synthesis of dissymmetric
silicon tethers.15 However, the use of THF to generate some
of the requisite lithiated nucleophiles was not compatible with
the formation of the bromosilane in the presence of NBS.
Therefore, we decided to use the 2,4,6-trimethoxyphenyl
(TMOP) as protecting group for chlorosilane in order to
develop a flexible synthesis of the sila-triynes.16 Thus,
precursors 1b−m owning tri- or tetrasubstituted silanes can
be prepared using that approach (Scheme 3). The hydro-
silylation of 1-hexene and 1,5-hexadiene with the commer-
cially available methyldichlorosilane 4 delivers the correspond-
ing dissymmetric disubstituted dichlorosilanes 5. Next, two
successive monosubstitutions were performed using first the
bulky Li-TMOP reagent and then the requisite lithium
derivatives giving selectively compounds 6 or 7. From
compounds 6 or 7 ,two approaches were developed for the
introduction of the other triple bonds. The first one using a
THP as protecting group allowed the formation of
compounds 1f,g after a sequence: deprotection of TMOP
(in the presence of nonaqueous HCl), nucleophilic sub-
stitution, alcohol deprotection, Parikh−Doering oxidation, and
Colvin homologation.17,18 With the removal of the TMOP
group at the very beginning, this strategy allows the
purification of each in termediate. However, introduction of
the R3 group on the silylacetylene moiety is done at the
beginning of the synthesis, and varying this group requires all
of the steps to be repeated. Thus, a second approach has then
been developed and centered on the use of TBS as protecting
group. Therefore, the alcohol can be deprotected in the first
step using TBAF, followed by an oxidation and homologation
with Ohira−Bestmamnn reagent (OBR) allowing the
formation of a common intermediate 8.19 Then, introduction
of the last alkyne moiety can be carried out after TMOP
replacement by a chlorine atom. This strategy is more
divergent; however, due to the low stability of the Si-TMOP
bond toward acidic medium all the sequence starting from the
b
yield of 2b
time conversion
(%) (NMR
a
a
entry catalyst (mol %)
solvent
toluene
(h)
NMR
yield, %)
1
2
3
4
5
6
7
8
CoH(PMe3)4
(10 mol %)
12
NR
nd
nd
10
nd
CoMe(PMe3)4
(10 mol %)
toluene
DCE
12
20
30
12
24
12
NR
22
CoCI(PMe3)3
(20 mol %)
CoCI(PPh3)3
(20 mo l%)
toluene
toluene
DCE
13
c
d
Co(PMe)3
(10 mol %)
50
nd
a
RhCI(PPh3)3
(20 mol %)
82
NR
76
26 (61)
[Rh(cod)2]·BF4
(20 mol %)
DCE
nd
a
NbCI3·DME
(20 mol %)
DCE
2
28 (76)
a
1
Yield and conversion measured by H NMR analysis using 1,3,5-
trimethoxybenzene as internal standard. After chromatography on
silica gel. Several compounds were observed on the basis of the
(CH3)2Si resonances. Compound obtained in a mixture of
b
c
d
undetermined silicon compounds.
complexes together with other metals able to catalyze the
cycloaddition of triynes at room temperature in order to avoid
a subsequent nondesired oxidative addition and degradation of
the very sensitive benzosilacyclobutenes.
We initially chose the substrate 1b as model substrate, and
using the above family of cobalt(I) catalysts, no desired
compound or only a small amount was formed (Table 1,
entries 1−3). In the case of ClCo(PR3)3, changing the
trimethylphosphine to triphenylphosphine did not improve
the conversion (Table 1, entry 4). Finally, the cobalt(0)
catalyst Co(PMe3)4 allows the observation of the desired
compound in 50% yield by NMR analysis, but it could never
be obtained in a pure form (Table 1, entry 5). Extensive
screening of room temperature-reactive nickel and ruthenium
catalysts did not allow the formation of compound 2b. By
using Wilkinson’s catalyst, a conversion of 82% and a yield of
61% could be measured by NMR monitoring but due to its
B
DOI: 10.1021/ol503663k
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
Scheme 3. Synthesis of Sila-triyne Precursors
silanes 4 or 5 has to be done without any purification for
overall better yields.20
substituted benzosilacyclobutene 2n in a very good 82% yield
(Scheme 4).
Having in hand a straightforward synthesis21 of precursors
and an efficient cycloaddition, we next tested all our substrates
under the optimal conditions (Table 2). Variations on the
Scheme 4. Synthesis of Fully Substituted
Benzosilacyclobutene
Table 2. Scope
entry
1
R1
R2
R3
isolated yield (%)
1
1c
Id
1e
1f
Me
Ph
Me
Ph
H
H
H
H
H
Ph
84
78
2
In summary, we have developed a versatile synthesis of the
very sensitive benzosilacyclobutenes that features ease of
operation, good yields, and a large scope of substrates. Indeed,
this approach allows for the first time the formation of highly
functionalized benzosilacyclobutenes in high yields (63−97%)
compared to the few reported syntheses (20−58%). This new
and efficient access to strained sila-cycles from new acyclic
sila-triynes demonstrates the high potential of the scarcely
used niobium-catalyzed [2 + 2+2] cycloaddition. Work toward
the use of these new substituted sila-cycles to reach more
complex sila-molecules with biological relevance is under
investigation and will be reported in due course.
a
3
i-Pr
Me
Me
Me
Me
Me
Me
Me
Me
Me
i-Pr
94
4
hexyl
1 -hexene
Me
85
77
97
63
65
80
72
96
89
5
1g
1b
1h
1i
6
7
Me
p-MeOC6H4
p-CF3C6H4
SiMe3
8
Me
9
1j
Me
10
11
12
1k
1l
Me
cyclopropyl
cyclohexyl
n-pentyl
Me
1m
Me
a
Reaction was run for 3 h.
ASSOCIATED CONTENT
* Supporting Information
■
S
silicon atom do not affect the reactivity, and even with bulky
isopropyl substituents a very good yield is obtained (Table 2,
entries 1−3). Silicon atom with four different substituents can
be employed in this process, and introduction of an alkene
moiety does not interfere in the cyclotrimerization of the sila-
triyne (Table 2, entry 5). The substitution on the silylated
alkyne was also studied and appeared to have no significant
influence on the cycloaddition. Aromatic groups bearing
electron-donating or electron-withdrawing groups (Table 2,
entries 7 and 8), as well alkyl groups (Table 2, entries 10−12)
and even a trimethylsilyl group, can be added on this position
(Table 2, entry 9).
Experimental procedures and physical properties of com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: marc.petit@upmc.fr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the CNRS, MRES, Emergence-
UPMC-2011 research program, which we gratefully acknowl-
edge.
The fully substituted sila-triyne 1n was finally obtained
from substrate 1m after a Sonogashira coupling. The latter
submitted to our optimal conditions of [2 + 2 + 2]
cycloaddition allows the unprecedented formation of a fully
■
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DOI: 10.1021/ol503663k
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Letter
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