Tetrabutylammonium Bifluoride as an Efficient Activating Agent for Copper-Catalyzed Vinylsilane Cross-Coupling Reactions

Article abstract of DOI:10.1055/s-0036-1588504

Vinylsilanes are versatile and efficient nucleophiles in cross-coupling reactions. Herein is described the use of tetrabutylammonium bifluoride as a mild, cheap and scalable activating agent in several copper-catalyzed vinylsilane cross-couplings.

Full text of DOI:10.1055/s-0036-1588504

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L. Cornelissen et al.
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Tetrabutylammonium Bifluoride as an Efficient Activating Agent
for Copper-Catalyzed Vinylsilane Cross-Coupling Reactions
Loïc Cornelissen
Audric Nagy
[Cu(MeCN)4]PF6 (5 mol%)
TBAHF2 (2.5 equiv)
R
Si(OEt)3
R
Br
Tom Leyssens
MeCN
E-, Z-, and 1,1'-alkenes
44–96% yield
14 examples
Olivier Riant*
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4-
8
5
2
6-
4
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R : allyl and alkynyl electrophiles
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
scalable
olivier.riant@uclouvain.be
Published as part of the Cluster Silicon in Synthesis and Catalysis
Received: 08.05.2017
Accepted after revision: 22.06.2017
Published online: 25.08.2017
[Cu(MeCN)4]PF6 (5 mol%)
TBAHF2 (2.5 equiv)
R
Si(OEt)3
R
Br
DOI: 10.1055/s-0036-1588504; Art ID: st-2017-b0337-c
MeCN
E-, Z-, and 1,1'-alkenes
high compatibility
scalable
Abstract Vinylsilanes are versatile and efficient nucleophiles in cross-
coupling reactions. Herein is described the use of tetrabutylammonium
bifluoride as a mild, cheap and scalable activating agent in several cop-
per-catalyzed vinylsilane cross-couplings.
Scheme 1 TBAHF2 as a mild and efficient activating agent in copper-
catalyzed transformations
Key words vinylsilane, copper, cross-coupling, activating agent, catal-
ysis
large number of different activating agents,10 and showed
TBAHF2 as the most efficient. Both one equivalent (Table 1,
entry 1) and two equivalents (Table 1, entry 2) were not
sufficient to fully promote the desired reaction. It was
found that 2.5 equivalents were appropriate, resulting in an
excellent 94% yield (Table 1, entry 3). This result is similar to
the one obtained with TBAT (Table 1, entry 4), albeit with-
out any of its drawbacks.7 The need of five equivalents of
fluoride per silicon atom suggests that the reaction goes
through a penta- or hexa-coordinated silicate intermedi-
ate.11 A smooth transmetalation with copper(I) and then an
addition onto the electrophile leads to the formation of the
desired cross-coupling product. Surprisingly, the formation
of ethanol after fluorination of the triethoxysilane with
TBAHF2was not a problem and only traces of the proto-
desilylated compound were observed.12
With optimal conditions in hand, we evaluated the
functional-group compatibility (Scheme 2). In light of this,
various vinylsiloxanes and several brominated electrophiles
were used in this cross-coupling reaction.
The first few examples were obtained by using β-(E)-
vinylsilanes.13 Nitrogen-containing enyne 2b could be syn-
thesized in excellent yield. Once again, the results were as
good as previously described with TBAT as an activating
agent.7 Allylic bromides as electrophiles were perfectly tol-
erated, as shown with phthalimide 2c and no isomerization
of the 1,4-diene was observed. The presence of a leaving
Organosilicon compounds are ubiquitous building
blocks in organic chemistry.1 Their readily availability, low
cost, and low toxicity led to the early development of many
efficient transition-metal-catalyzed cross-coupling reac-
tions.2 Copper-catalyzed transformations started to arise
recently.3 Both aryl- and vinylsilanes are now efficiently
used as nucleophiles, whereas aryl, alkyl, and allyl halides
can be employed as electrophiles.4
Over the past few years, our group developed efficient
copper-catalyzed vinylsilane cross-coupling reactions. Vari-
ous cis-, trans-, and 1,1′-disubstituted vinylsiloxanes could
be efficiently coupled with allyl5 and benzyl6 bromides, as
well as bromoalkynes.7 The use of tetrabutylammonium di-
fluorotriphenylsilicate (TBAT) as an activating agent in
these reactions was the main limitation as it brought sever-
al drawbacks such as relatively high cost and poor atom-
economy.
Herein is described the use of commercially available
tetrabutylammonium bifluoride (TBAHF2)
8
as a mild,
cheap, and scalable activating agent for the copper-
catalyzed cross-coupling of vinylsilanes with brominated
electrophiles (Scheme 1).9
We started our experiment using model vinylsilane 1a
as a nucleophile and phenylethynyl bromide as an electro-
phile (Table 1). The formation of 2a was studied using a
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C

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L. Cornelissen et al.
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Table 1 Initial Experiments
[Cu(MeCN)4]PF6 (5 mol%)
TBAHF2 (2.5 equiv)
R
Si(OEt)3
R
Br
O
MeCN
40 °C, 16 h
Si(OEt)3
(1.5 equiv)
[Cu(MeCN)4]PF6 (5 mol%)
N
activating agent
O
MeCN
40 °C, 16 h
E-alkenes
O
1a
Br
Ts
N
Ph
(1.5 equiv)
N
Ph
O
O
2b (96%)
(with TBAT: 92%)
2c (82%)
N
O
2a
Cl
Ph
O
Yield (%)a
2d (76%)
Entry
Activating agent (equiv)
2e (44%)
O
OEt
1
2
3
4
TBAHF2 (1)
32
81
94
95
nBu
TBAHF2 (2)
Ph
O
TBAHF2 (2.5)
TBA(Ph3SiF2) (2.5)
2f (80%)
2g (65%)
a Determined by 1H NMR spectroscopy vs. CHBr3 as an internal standard.
O
O
1,1′-Disubstituted vinylsilanes15 were synthesized and
employed as a mixture of α/β isomers, providing their cor-
responding cross-coupling products in moderate yields
with the same ratio of isomers. This is the result of the high
hindrance of such nucleophiles, lowering their reactivity. It
should, however, be noted that ester 2i and more specially
aldehyde 2j remained untouched during the reaction. Com-
pound 2k bearing an acidic hydrogen could also be synthe-
sized.
2h (80%)
1,1'-disubstituted alkenes
O
O
Ph
Ph
O
2j (67%)
82:18
α : β
2i (65%)
85:15
α : β
O
MeO2C
CO2Me
Ph
β-(Z)-Vinylsilanes16 could be efficiently synthesized and
engaged in this cross-coupling reaction as well. Full reten-
tion of stereochemistry was observed in all cases. 1,4-Diene
2l could be synthesized in almost quantitative yield. Very
challenging acrylic ester 2m could also be isolated in excel-
lent yield, no matter its instability and promptness to po-
lymerize.
2k (54%)
95:5
α : β
Z-alkenes
O
OEt
Ph
This cross-coupling reaction could easily be scaled-up to
gram quantities (Scheme 3). An important decrease of the
initial temperature was required because of the exother-
micity of the reaction. The preparation of enyne 2a was
2m (89%)
2l (95%)
Scheme 2 Evaluation of the functional group compatibility; isolated
yields are given in parentheses
O
Si(OEt)3
[Cu(MeCN)4]PF6 (5 mol%)
N
group on the nucleophilic precursor was allowed, as shown
with chlorine-containing 2d. Moderate yield was observed
with benzyl-protected 2e, although the deprotected alcohol
was not observed. Acrylic compound 2f could be easily syn-
thesized, no matter its instability. Once again, no isomeri-
zation of the desired product was observed, emphasizing
the very mild nature of this reaction. Complex enyne–ene
structures, present in several natural products,14 could be
obtained in good yields, as shown by 2g and 2h.
TBAHF2 (2.5 equiv)
O
MeCN
0 to 40 °C, 16 h
1a
Br
(1.5 equiv)
O
N
2a (2.43 g, 93%)
O
Scheme 3 Gram-scale synthesis of enyne 2a
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C

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L. Cornelissen et al.
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carried out on several grams of the starting silane 1a with-
out any loss in isolated yield, emphasizing the user-friendly
character of this method.
In conclusion, an efficient, mild, cheap, and scalable
copper-catalyzed vinylsilane cross-coupling reaction was
presented. This methodology uses TBAHF2 as an activating
agent and allows the synthesis of many challenging trans-,
cis-, and 1,1′-disubstituted alkenes.
(7) Cornelissen, L.; Lefrancq, M.; Riant, O. Org. Lett. 2014, 16, 3024.
(8) TBAHF2 was easily synthesized in large scale from TBA(HSO4)
and KHF2 according to: Landini, D.; Molinari, H.; Pensa, M.;
Rampoldi, A. Synthesis 1988, 953; TBAHF2was used as a 25 wt%
solution in MeCN and could be stored in the fridge for extended
periods.
(9) Vinylsilane Cross-Couplings: Typical Procedure
To a mixture of (E)-2-[4-(triethoxysilyl)but-3-enyl]isoindoline-
1,3-dione (1a, 0.20 mmol, 1.0 equiv) and (bromoethynyl)ben-
zene (0.30 mmol, 1.5 equiv) in an oven-dried vial was added
TBAHF2 (0.5 mmol, 2.5 equiv, 25 wt% solution in MeCN).
Cu[MeCN]4PF6 (0.01 mmol, 0.05 equiv) was added, and the
resulting mixture was stirred at 40 °C in an oil bath for 16 h. The
solution was diluted with Et2O (5 mL), filtered through a short
pad of silica and eluted with Et2O (25 mL). The solution was
evaporated under reduced pressure to afford the crude product.
The crude product (94% NMR yield using CHBr3 as an internal
standard) could be purified by flash chromatography using 20%
EtOAc in PE to afford 2a as a pale orange solid. Rf = 0.68 (95%
CH2Cl2 in PE). IR (thin film): 1771, 1497, 1394, 1364, 1340,
Acknowledgment
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 catholique de Louvain
are gratefully acknowledged.
Supporting Information
1219, 1055, 959, 870, 754, 719, 689 cm–1 1H NMR (300 MHz,
.
Supporting information for this article is available online at
CDCl3): δ = 7.85 (dd, J = 5.4, 3.1 Hz, 2 H), 7.71 (dd, J = 5.4, 3.1 Hz,
2 H), 7.45–7.35 (m, 2 H), 7.34–7.22 (m, 3 H), 6.19 (dt, J = 15.4,
7.2 Hz, 1 H), 5.77 (d, J = 15.8 Hz, 1 H), 3.80 (t, J = 7.1 Hz, 2 H),
2.68–2.49 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 168.16,
139.56, 133.94, 131.96, 131.42, 128.20 (br), 128.01, 123.25,
112.51, 88.85, 87.56, 36.95, 32.21. ESI-HRMS: m/z calcd for
https://doi.org/10.1055/s-0036-1588504.
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References and Notes
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C