Copper-catalyzed Hiyama cross-coupling using vinylsilanes and benzylic electrophiles

Article abstract of DOI:10.1039/c4cc02923b

Allylbenzene derivatives are ubiquitous frameworks in organic chemistry. Herein is described an efficient copper-catalyzed cross-coupling reaction using vinylsilanes and benzyl bromides, leading to the synthesis of allylbenzenes. This methodology allows the use of cis, trans and 1,1′-disubstituted vinylsilanes as well as a large number of sensitive moieties. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc02923b

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Copper-catalyzed Hiyama cross-coupling using
vinylsilanes and benzylic electrophiles†
Cite this: Chem. Commun., 2014,
50, 8018
L. Cornelissen, V. Cirriez, S. Vercruysse and O. Riant*
Received 20th April 2014,
Accepted 3rd June 2014
DOI: 10.1039/c4cc02923b
www.rsc.org/chemcomm
Allylbenzene derivatives are ubiquitous frameworks in organic
chemistry. Herein is described an efficient copper-catalyzed cross-
coupling reaction using vinylsilanes and benzyl bromides, leading to
the synthesis of allylbenzenes. This methodology allows the use of
cis, trans and 1,10-disubstituted vinylsilanes as well as a large number
of sensitive moieties.
Scheme 1 Copper-catalyzed benzylation of vinylsilanes.
as benzylic electrophiles. Herein is described an efficient method to
synthesize allylbenzenes from readily available vinylalkoxysilanes10–13
(Scheme 1). This methodology uses low copper loadings, requires
no ligands, and uses TBAT (tetrabutylammonium difluorotri-
phenylsilicate) as an activating agent.
The optimization started under similar conditions as previously
reported, leading to a promising 70% conversion14 of the model
vinylsilane (1a) to the desired product (2a) (Table 1, entry 1). The
remaining 30% was identified as dimers and protodesilylated
alkenes. Importantly, no isomerization of the alkene into a styrene
was observed. Other common copper(I) sources were then evaluated.
The bulkiness of the NHC IPr (1,3-bis(2,6-diisopropylphenyl)-
imidazol-2-ylidene) ligand reduced the conversion (Table 1,
entry 2), as did the use of CuTC (copper(I) thiophenecarboxylate).
Vinylsilane-based cross-coupling reactions have emerged as a
powerful and versatile tool to introduce insaturations in complex
organic frameworks.1 The low toxicity, low cost, ready availability
and high chemical stability of silylated molecules led to the devel-
opment of various palladium-based cross-coupling reactions.2
Namely, the Hiyama3 and Hiyama–Denmark4 reactions have proven
to be useful in many cases. More recently, Tsubouchi and Takeda
proposed a copper-catalyzed reaction between an alkenylsilane
and various C(sp3) electrophiles, promoted by the intramolecular
coordination of an alkoxide.5
The coupling of a vinyl-metal and a benzylic electrophile
leads to the formation of allylbenzene derivatives. Allylbenzenes
are ubiquitous in organic chemistry, especially as pharmacolo-
gically active molecules.6 The relative instability of allylbenzenes,
due to the prompt isomerization of the alkene into a styrene,
makes efficient procedures quite rare, compared to other cross-
coupling products. Although the more common ways to synthe-
size allylbenzenes require palladium catalysts,7 non-noble metal
catalysis emerged.8
Table 1 Initial experiments
Our group recently developed an efficient copper-catalyzed
methodology to synthesize 1,4-dienes from vinylsilanes.9 This
very mild method proved to be compatible with many func-
tional groups ranging from halides to aldehydes.
These encouraging results led us to apply this copper-
catalyzed transformation to more challenging substrates such
Reaction time/
temperature
Entry
CuI salt
Conversiona
1
2
3
4
5
6
7
8
9
CuI (20%)
IPrCu(dbm) (20%)
CuTC (20%)
CuF(PPh)3ꢀ2MeOH (20%)
Cu(MeCN)4PF6 (20%)
Cu(MeCN)4PF6 (10%)
Cu(MeCN)4PF6 (10%)
Cu(MeCN)4PF6 (10%)
Cu(MeCN)4PF6 (5%)
16 h/r.t.
16 h/r.t.
16 h/r.t.
16 h/r.t.
16 h/r.t.
16 h/r.t.
32 h/r.t.
16 h/40 8C
16 h/40 1C
70
61
73
60
84
Institute of Condensed Matter and Nanosciences, Molecules, Solids and Reactivity
93 (80b)
91 (88b)
92 (91b)
76
´
(IMCN/MOST) – Universite catholique de Louvain, Place Louis Pasteur 1, bte
L4.01.02, 1348 Louvain-la-Neuve, Belgium. E-mail: Olivier.riant@uclouvain.be;
Web: http://www.uclouvain.be/en-201510.html
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc02923b
Determined by analysis of the crude mixture by 1H NMR. Isolated yield.
a
b
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The presence of methanol in the copper(I) fluoride catalyst led
to the protodesilylation of the vinylsilane, hence reducing the
conversion to 60% (Table 1, entry 4). Still using 20% of the
catalyst, cationic copper(I) Cu[MeCN]4PF6 led to the best conver-
sion of 84% (Table 1, entry 5). Reducing the copper loading to
10% led to an improvement (Table 1, entry 6) in the conversion.
The isolated yield however, was surprisingly low compared to the
conversion. This might indicate an incomplete reaction, as
the activated silicate is lost during the work-up. Longer reaction
time indeed improved the yield to 88% (Table 1, entry 7). To
our delight, gently heating the solution to 40 1C overnight gave
the best results. The desired product (2a) was obtained in 91%
isolated yield (Table 1, entry 8). However, it was not possible to
further reduce the catalytic loading without loss of conversion
(Table 1, entry 9).
With optimal conditions in hand (Table 1, entry 8), model
vinylsilane (1a) was coupled with various benzylic electrophiles
(Scheme 2) in order to determine the scope of the reaction. The
presence of a methyl in the para position gave the desired
product (2b) in excellent yield. Bulkiness at the ortho position
seems to have little impact on the reaction, as shown by (2c).
Fluorinated aromatic groups were tolerated, as shown by (2d)
and the trifluoromethylated (2e). Interestingly, brominated (2f)
gave the cross-coupling product in 88% yield, without any
Scheme 3 Vinylsilane scope. Isolated yields are given within brackets.
degradation of the aromatic bromine, as would be expected because of the very acidic allylbenzyl hydrogen, no styrene
for palladium-based catalysts. Yield of the reaction using derivatives were observed at any moment. Globally, all of the
electron-poor nitrile (2g) dropped to 83%. This drop was not a desired products were obtained in high yields, ranging from
surprise since a small part of TBAT reacted with the p-cyanobenzyl electron-rich, electron-poor and hindered substrates, leading to
bromide to give the corresponding benzylic fluoride. Electron- a large array of different allylbenzenes.
rich anisole (2h) as well as the ester-substituted (2i) proceeded
Various vinylsilanes were benzylated under our optimal
in 87% and 88% yields, respectively. No addition of the conditions (Scheme 3) to collect information on the limitations
vinylsilane on the carbonyl was observed. It must be noted that of this methodology. b-(E)-Vinylsilanes bearing a tosylamine or
although electron-poor allylbenzenes tend to easily isomerize a benzoyl group gave the desired products (3a) and (3b) in
excellent yields. The more hindered and chelating malonate
(3c) resulted in a slight drop in yield. Phthalimide (3d) was fully
tolerated in 87% yield. Although 1,1-disubstituted allylbenzenes
are present in the natural world, very few methods exist to
synthesize them. Benzyl and benzoyl protected 1,1-disubstituted
alkenes (3e) and (3f) were synthesized in 70% and 58% yields,
respectively, which is acceptable considering the bulkiness of
such vinylsilanes. (Z)-Trisubstituted alkene (3g) was obtained
in 51% yield, confirming that steric hindrances might have a
negative effect on the reactivity of the vinylsilanes. Overall, all
of the b-(E)-vinylsilanes led to high yields, no matter how
sensitive the functional groups were, while other more bulky
vinylsilanes led to reduced yields.
The synthesis of (Z)-alkenes deserves special attention
since very few practical methods exist to obtain such substrates.
b-(Z)-Vinylsilane Z-(4) was obtained directly from phenyl-
acetylene according to Faller et al.13 It was benzylated with
the meta-methylester substituted benzyl bromide to form the
desired product Z-(5a) in an excellent 92% yield (Scheme 4). The
presence of a bromide in the ortho position gave the desired
product Z-(5b) in 75% yield. Such a compound would be very
tedious to synthesize by conventional alkyne reductions and
Scheme 2 Electrophile scope. Isolated yields are given within brackets.
palladium cross-coupling reactions because of the sensitivity of
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Notes and references
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Scheme 4 Benzylation of
stereochemistry.
a b-(Z)-vinylsilane with full retention of
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Scheme 5 Recyclability of the activating agent TBAT.
the halides. In both cases, no isomerization into an (E)-alkene
occurred and full retention of stereochemistry was observed.
In order to tackle the problem of cost linked to the use of
TBAT as an activating agent, efficient recycling was required.
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phenylsilane could be recovered by chromatographic separa-
tion (Scheme 5). As shown in the literature, treatment of the
latter with hydrogen fluoride in ethanol,15 followed by crystal-
lization with tetrabutylammonium fluoride (TBAF)16 allows an
efficient recyclability of the fluorinating agent.
An efficient copper-catalyzed Hiyama-type reaction was
described. Allylbenzenes were synthesized from vinylsilanes
in good yields by using benzylic bromides. A broad range of
electrophiles were functionalized in high yields. No isomeriza-
tion of the resulting alkene into a styrene was observed,
even when using electron-poor benzyl bromides. cis, trans and
1,10-Disubstituted alkenes were obtained, with full retention of
stereochemistry. Various sensitive moieties were tolerated,
including halides, esters and nitriles. Finally, it was shown that
TBAT (tetrabutylammonium difluorotriphenylsilicate) could be
employed as a recyclable activating agent. Further studies
concerning other copper-catalyzed cross-coupling reactions
are in progress and will be reported in due time.
´
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14 In this work, conversion, means the specific transformation of
the vinylsilane into the desired product (and not the amount of
starting material consumed). By analysis of the crude 1H NMR, a
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signals allowed us to quickly quantify the conversion of the vinyl-
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Financial support from the Fonds de la Recherche Scientifique
`
(FRS-FNRS), the Fonds pour la formation a la Recherche dans
´
l’Industrie et dans l’Agriculture (FRIA), and the Universite catholique
15 C. Eaborn, J. Chem. Soc., 1952, 2846.
de Louvain is gratefully acknowledged.
16 C. J. Handy, Y.-F. Lam and P. DeShong, J. Org. Chem., 2000, 65, 3542.
8020 | Chem. Commun., 2014, 50, 8018--8020
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