Copper-catalyzed vinylsilane allylation

Article abstract of DOI:10.1002/ejoc.201301360

Soft reaction conditions, particularly important in total synthesis, have dragged many researchers into the field of silylated organic compounds. Hereby, we describe a new copper-catalyzed vinylsilane transformation. Various vinylsilanes were allylated by using a copper(I) salt, and this led to the formation of polysubstituted 1,4-dienes bearing sensitive moieties such as halogens, ketones, and aldehydes. Hereby is described a new copper-catalyzed vinylsilane transformation. Various vinylsilanes were allylated by using copper(I) salts, and this led to the formation of polysubstituted 1,4-dienes bearing sensitive moieties such as halogens, ketones, and aldehydes. TBAT = tetrabutylammonium difluorotriphenylsilicate. Copyright

Full text of DOI:10.1002/ejoc.201301360

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201301360
Copper-Catalyzed Vinylsilane Allylation
Loïc Cornelissen,[a] Sébastien Vercruysse,[a] Ayoub Sanhadji,[a] and Olivier Riant*[a]
Keywords: Copper / Silicon / Vinylsilanes / Allylation / Cross-coupling
Soft reaction conditions, particularly important in total syn-
thesis, have dragged many researchers into the field of sil-
ylated organic compounds. Hereby, we describe a new cop-
per-catalyzed vinylsilane transformation. Various vinylsil-
anes were allylated by using a copper(I) salt, and this led to
the formation of polysubstituted 1,4-dienes bearing sensitive
moieties such as halogens, ketones, and aldehydes.
metals. Although palladium cross-coupling methodologies
have been used for decades,[7] copper-catalyzed vinylsilane
transformations have also recently started to emerge as
powerful tools. Takeda showed that a Brook rearrangement
might be used to promote the formation of a vinylcopper
species, which could be captured by various electrophiles.[8]
Shibasaki et al. reported the (diphosphine)copper(I)-cata-
lyzed enantioselective transfer of vinylsilanes to aldehydes
for the straightforward preparation of enantiomerically en-
riched allylic alcohols.[9] Chiral N-heterocyclic carbenes
have also been used to promote the conjugated addition of
vinylsilanes onto α,β-unsaturated carbonyl compounds with
high enantioselectivities, as recently shown by Hoveyda et
al.[10]
Over the past few years, copper-catalyzed allylic substitu-
tion has emerged as a powerful strategy to insert various
nucleophiles into a carbon backbone.[11] Among others, it
is nowadays possible to graft magnesium-,[12] lithium-,[13]
zinc-,[14] boron-,[15] and silylboronate-containing[16] nucleo-
philes enantioselectively. Copper-catalyzed allylation reac-
tions of a vinyl moiety to form 1,4-dienes from vinylalumi-
num[17] and vinylboron[18] reagents have also recently been
developed. The resulting 1,4-diene fragments are useful in-
termediates and are also present in several natural-product
structures.[19]
Introduction
Functional-group compatibility and soft reaction condi-
tions are of utmost importance in organic synthesis. Al-
lowing sensitive groups to remain unprotected usually leads
to much shorter and efficient synthetic pathways. Organo-
silicon compounds have been shown to be perfect candi-
dates to meet these criteria, as they are stable under various
conditions.[1] Supported by the recent development of
highly efficient hydrosilylation and silylcupration catalysts
(Scheme 1),[2] vinylsilanes have proven to be reagents of
choice for the introduction of unsaturation into complex
organic frameworks. Although the more common way to
synthesize β-(E)-vinylsilanes uses platinum-catalyzed hydro-
silylation of alkynes,[3] cross-metathesis with the use of
ruthenium catalysts[4] might be used as well; β-(Z)- and α-
vinylsilanes can be obtained by iridium-[5] and ruthenium-
catalyzed[6] hydrosilylation, respectively.
Herein we wish to describe our first results regarding a
new and robust methodology that uses simple copper salts
as efficient catalysts for the allylation of various vinylsilanes
by using allyl bromides as electrophilic partners. β-(E)-
Vinylsilanes, easily available from the corresponding alk-
ynes, were used as models for the initial optimizations.
These β-(E)-vinylsilanes bear different base- and nucleo-
phile-sensitive moieties, including halogens, esters, and
ketones.
Scheme 1. Formation of different vinylsilanes by using transition-
metal catalysis.
The lack of reactivity induced by the stable nature of
vinylsilanes has been overcome by the use of transition
[a] Institute of Condensed Matter and Nanosciences, Molecules,
Solids and Reactivity (IMCN/MOST) – Université catholique
de Louvain
Place Louis Pasteur 1, bte L4.01.02, 1348 Louvain-la-Neuve,
Belgium
Results and Discussion
E-mail: Olivier.riant@uclouvain.be
http://www.uclouvain.be/en-201510.html
We started our experiments with model vinylsilane 1a
bearing a triethoxysilane group acting as an activated sili-
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301360.
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
35

L. Cornelissen, S. Vercruysse, A. Sanhadji, O. Riant
SHORT COMMUNICATION
con moiety (Table 1). The initial idea was to promote trans-
Although model substrate 1a was considered to be quite
metalation between the silicon atom and the copper(I) sensitive because of the presence of a carbonyl group and
source to generate a vinylcopper(I) intermediate that should because of the leaving ability of the benzoyl moiety, it was
then be easily captured by the electrophile. We found that important to test the limits of the functional-group compat-
without any activating agent, no reaction was observed ibility. Using the optimal conditions (Table 1, Entry 6), six
(Table 1, Entry 1). Several nucleophilic bases were tested to other vinylsilanes were allylated by using allyl bromide (Fig-
activate the silane and facilitate the migration of the vinylic ure 1). A change from the benzoyl group to a more robust
fragment to the copper atom. Both cesium fluoride and so- benzyl group led to better results, and product 2b was iso-
dium tert-butoxide did not promote the reaction (Table 1, lated in 98% yield. Shortening the tether between the olefin
Entries 2 and 3), and this left the vinylsilane unchanged. and the functional group did not influence the reactivity, as
The use of tetrabutylammonium fluoride (TBAF) as a fluor- shown with tosylamine 2c. A highly hindered and chelating
ide source gave only the protodesilylated products, as this vinylsilane also reacted accordingly, as revealed by diethyl
reagent always contains various amounts of water.[20]
malonate 2d, which was obtained in 89% yield. The pres-
ence of an aryl bromide was tolerated and gave correspond-
ing diene 2e in 80% yield. A vinylsilane bearing a more
polar phthalimide group was easily allylated to give 2f in
85% yield. Interestingly, the presence of a ketone was fully
tolerated as shown by the formation of 2g in 86% yield.
Table 1. Initial optimization of the coupling reaction to afford 2a.
Entry Solvent
CuI salt
(equiv.)
Activating agent
(equiv.)
Yield
[%][a]
1
2
3
4
5
6
7
8
9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
CuI (1.1)
CuI (1.1)
CuCl (1.1)
CuI (1.1)
CuI (1.1)
CuI (0.2)
CuI (0.1)
CuI (0.2)
CuI (0.2)
–
–
–
–
–
60
87
CsF (1.2)
NaOtBu (1.2)
TBAT (1.2)
TBAT (2.4)
TBAT (2.4)
TBAT (2.4)
TBAT (2.4)
TBAT (2.4)
TBAT (2.4)
86 (84[b]
53
)
56[c]
74
DMF
MeCN
10
–
[a] Determined by analysis of the crude reaction mixture by 1H
NMR spectroscopy by using an internal standard. [b] Yield of the
isolated product. [c] Conversion [%].
However, the use of tetrabutylammonium difluorotri-
phenylsilicate (TBAT) as an anhydrous fluorine source with
a stoichiometric amount of copper(I) iodide allowed us to
observe the formation of desired allylated product 2a in a
modest 60% yield (Table 1, Entry 4). This could be im-
Figure 1. Substrate scope of the vinylsilane allylation. Yields of iso-
lated products are given in parentheses.
Optimization experiments including varying the CuI
proved to 87% yield (Table 1, Entry 5) if 2.4 equiv. of TBAT source led us to choose copper(I) thiophenecarboxylate
was used under the same reaction conditions. To evaluate (CuTC) to explore the electrophile scope. Although no
the capacity of the copper(I) reagent to act as a catalyst, major difference was observed, CuTC provided the best
the loading of copper(I) iodide was evaluated. The use of γ/α selectivity over CuI and various other copper(I) sources.
20 mol-% of CuI (Table 1, Entry 6) allowed us to keep a Providing the best results in the first stage of the substrate
satisfactory 86% yield. However, reducing the catalytic exemplification (Figure 1), vinylsilane 1b was also used for
loading to 10 mol-% led to a decreased 53% yield (Table 1, the electrophile screening (Figure 2). Cinnamyl bromide led
Entry 7). THF, used as a less-coordinating solvent, was to the formation of 3a in 93% yield with γ/α = 84:16. Re-
tested, and this resulted in a poor 56% conversion (Table 1, placing the aryl group by an alkyl group such as cyclohexyl
Entry 8), which indicates that relatively strong stabilization gave 3b in a good 89% yield with only a slight decrease in
was required. DMF, in contrast, acting as a much stronger selectivity.
coordinating solvent, did not give better results than aceto-
Aryl moieties bearing halogen substituents led to the for-
nitrile, and the product was obtained in only 74% yield mation of aryl bromide 3c and aryl chloride 3d in 86 and
(Table 1, Entry 9). A control reaction was also performed 76% yield, respectively, and no major change in the γ/α
without added copper and did not lead to any substrate selectivity. An electron-rich substituent such as a thiophene
conversion (Table 1, Entry 10). The use of 0.2 equiv. of CuI induced a decrease in the yield to a moderate 67% for 3e
in acetonitrile (Table 1, Entry 6) was chosen as optimal with and a slight increase in selectivity. Surprisingly, the presence
86% yield.
of an aldehyde in the aryl moiety allowed the formation of
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Copper-Catalyzed Vinylsilane Allylation
The mixture of isomers was allylated under our standard
conditions to provide desired polysubstituted diene 7 in a
satisfactory 73% yield. Notably, no 1,4- or 1,2-addition
onto the carbonyl group was observed.
Figure 4. Trisubstituted alkene synthesis.
Conclusions
An efficient catalytic method to functionalize vinylsilanes
with allylic electrophiles has been developed. Broad func-
tional-group compatibility was possible by using a cop-
per(I) reagent and allyl bromides. The allylation reactions
proceeded even in the presence of esters, ketones, and alde-
hydes with yields up to 98%. α-Vinylsilanes showed inter-
esting reactivity, as they delivered the corresponding α-ole-
fins in good yields. Finally, the use of a trisubstituted vinyl-
silane showed the extent of this method, which led to the
construction of polysubstituted 1,4-dienes. Further studies
concerning the copper-catalyzed functionalization and ap-
plications of vinylsilanes are ongoing and will be reported
in due time.
Figure 2. Electrophile scope of the vinylsilane allylation. Yields of
isolated products are given in parentheses.
desired product 3f in 79% yield, which is very satisfactory
considering the sensitive nature of such an electrophile. The
selectivity was still within standards with γ/α = 82:18, and
the aldehyde group remained intact. No 1,4- to 1,3-diene
isomerization was observed during any workup and chro-
matographic separation.
Experimental Section
As α-olefins are important building blocks in organic
synthesis, it was interesting to know whether or not α-vinyl-
silanes would react under our standard conditions. Both 4a
and 4b were synthesized from the corresponding alkynes
according to the Trost and Ball method[6] with α/β(E+Z) =
90:10 and 92:8, respectively. The mixture of isomers was
allylated under the previous optimal conditions (Figure 3).
Benzoyl-bearing vinylsilane 4a was successfully allylated to
α-olefin 5a in 90% yield. Benzyl-functionalized vinylsilane
4b smoothly afforded 5b in 97% yield (Figure 3). In both
cases, the α/β(E+Z) ratio remained unchanged, and no
isomerization took place.
General Method: To a solution of the vinylsilane (0.20 mmol,
1.0 equiv.) in MeCN (2 mL) was added the allylic bromide
(0.40 mmol, 2.0 equiv.) and the copper(I) salt (0.04 mmol,
0.2 equiv.). TBAT (0.48 mmol, 2.4 equiv.) was added, and the re-
sulting mixture was stirred at room temperature for 16 h. The sol-
vent was removed in vacuo to afford a dark brown oil. This oil
was diluted with a minimum amount of CH2Cl2 (0.5 mL), filtered
through a short pad of silica, and eluted with diethyl ether (25 mL).
The ethereal solution was concentrated under reduced pressure to
afford the crude product, which was purified by flash chromatog-
raphy by using CH2Cl2 in petroleum ether to afford the desired
olefin.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, characterization data, and copies of the
1H and 13C NMR spectra of all key intermediates and final prod-
ucts.
Acknowledgments
Financial support from the Fonds de la Recherche Scientifique
(FRS-FNRS), the Fonds pour la formation à la Recherche dans
l’Industrie et dans l’Agriculture (FRIA), and the Université Catho-
lique de Louvain is gratefully acknowledged. Steve Dierick is grate-
fully acknowledged for his help concerning the hydrosilylations.
Figure 3. α-Vinylsilane allylation reactions. Yields of isolated prod-
ucts are given in parentheses.
Using internal alkynes to perform the ruthenium-based
hydrosilylation led to the formation of trisubstituted β-(Z)-
vinylsilanes such as α,β-unsaturated ketone 6 (Figure 4).
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L. Cornelissen, S. Vercruysse, A. Sanhadji, O. Riant
SHORT COMMUNICATION
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Received: September 8, 2013
Published Online: November 19, 2013
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