Nickel-catalyzed asymmetric hydrovinylation using lewis acid activation

Article abstract of DOI:10.1002/ejoc.200900248

A broad range of commercially available Lewis acids were investigated for their ability to activate and regulate nickel catalysts for asymmetric hydrovinylation processes using styrene as model substrate and ligand (R _a,S_c,S_c

Full text of DOI:10.1002/ejoc.200900248

FULL PAPER
DOI: 10.1002/ejoc.200900248
Nickel-Catalyzed Asymmetric Hydrovinylation Using Lewis Acid Activation
Nicolas Lassauque,[a] Giancarlo Franciò,[a] and Walter Leitner*[a,b]
Keywords: Enantioselective catalysis / Olefin dimerisation / Nickel / Indium / Anion effects / C-C coupling
A broad range of commercially available Lewis acids were
investigated for their ability to activate and regulate nickel
catalysts for asymmetric hydrovinylation processes using sty-
rene as model substrate and ligand (Ra,SC,SC)-5 as bench-
mark system. The colour change during the activation step
associated with the halide abstraction furnishes helpful indi-
cations to adapt the activation conditions to the pre-catalyst/
Lewis acid system. In general, metal halide Lewis acids led
to higher activities and enantioselectivities than the corre-
sponding triflates. In particular, the use of InI3 as co-catalyst
resulted in the same chemo- and enantioselectivity and even
higher activity than the benchmark system based on
NaBArF. Moreover, InI3 is safe to handle and cheap, thus pro-
viding a simple and practical protocol for an efficient hydro-
vinylation reaction.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
The catalytic cycle of the nickel-catalyzed hydrovinyl-
ation occurs via cationic intermediates,[2] and the active spe-
cies is typically generated from a neutral nickel halide pre-
cursor with a suitable co-catalyst. This activation step can
be achieved by replacing the halide ligand with a weakly
coordinating anion (WCA) (Scheme 2a). Silver salts,[8] ionic
liquids,[9] and in particular NaBArF[10] have been used suc-
cessfully for this purpose. Since the pioneering work of
Introduction
Asymmetric hydrovinylation is a powerful synthetic strat-
egy to generate C–C bonds in a highly enantioselective and
perfectly atom-efficient way (Scheme 1).[1] Formally, it com-
prises the addition of a vinylic C–H bond to another ole-
finic double bond, and highly selective catalytic systems for
intermolecular,[1,2] and intramolecular[3,4] (cycloisomeri-
sation) transformations have been developed. Among vari-
ous transition metal complexes known to catalyze this reac-
tion in principle, nickel catalysts are often the system of
choice providing high activity combined with high chemo-,
regio- and enantioselectivity.[2] The chiral information is
introduced through chiral monodentate phosphorus li-
gands, whereby some of them bear an additional hemilabile
donor group. Recently, we showed that phosphoramidites
are extremely efficient chiral ligands for this transforma-
tion,[5] and they have gained increasing attention owing to
their large substrate scope.[6,7]
Wilke[1] and Bogdanovic,[11] it is well established that the
ˇ
nature of the WCA plays a decisive role in controlling the
activity, chemoselectivity and even enantioselectivity. Such
pronounced counterion effects on enantioselectivity are not
restricted to nickel catalysts in hydrovinylation reactions,
and other prominent examples include iridium-catalyzed
hydrogenation,[12] ruthenium-catalyzed cyclopropanation[13]
as well as acid-catalyzed hydroamination.[14]
Scheme 2. Activation processes using (a) a weakly coordinating
anion (WCA) and (b) a Lewis acid (LA).
Scheme 1. General asymmetric hydrovinylation reaction.
A second method for activation of nickel catalyst is the
use of Lewis acids (LA), which can abstract the halide li-
gand with formation of a corresponding adduct LAX– act-
ing as weakly coordinating anion in this case (Scheme 2b).
This approach was taken in the original standard protocol
developed by Wilke et al.[15] which comprised aluminium
[a] Institut für Technische und Makromolekulare Chemie, RWTH
Aachen University,
Worringer Weg 1, 52074 Aachen, Germany
Fax: +49-241-8022177
E-mail: leitner@itmc.rwth-aachen.de
[b] Max-Planck-Institut für Kohlenforschung,
45470 Mülheim an der Ruhr, Germany
Eur. J. Org. Chem. 2009, 3199–3202
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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N. Lassauque, G. Franciò, W. Leitner
FULL PAPER
Scheme 3. Benchmark hydrovinylation system.
sesquichloride as activator. BF3 has also been used in early
studies as activator in nickel-catalyzed hydrovinylation, but
it was speculated that the LA interacts with the substrate
Results and Discussion
The isolated complex [η3-(allyl)Ni{(Ra,SC,SC)-5}Cl] (6)
(styrene) or the ligand (PPh3).[16] In(OTf)3 has also been was used as hydrovinylation precatalyst[5a] for testing vari-
used successfully as activator in the palladium-catalyzed di- ous Lewis acids as alternative activators. The activation step
merisation of styrene with a Pd(OAc)2/PPh3 catalyst sys- was carried out at –40 °C by introducing a dichloromethane
tem.[17] This precatalyst does not contain halides, and it has solution of 6 in the presence of styrene (styrene/Ni = 1000)
also been speculated that the activation occurs by interac- in a Schlenk flask containing 1.1 equiv. of the Lewis acid.
tion with the substrate or formation of a Pd–In complex.
After 5 min, the hydrovinylation was started at the same
Given the large structural variety offered by LA acti- temperature by saturating the solution with ethylene and
vators and thus the strong regulating effect of the resulting then maintaining an ethylene atmosphere (1 bar) over the
counterion, it seems surprising that no more efforts have reaction mixture. After stirring for a given reaction time
been made to systematically exploit this activation method. (see Table 1), the reaction was quenched by adding an ex-
In the present study, we have investigated a broad range of cess of aqueous ammonia solution. Following the standard
Lewis acids for their ability to activate and regulate nickel workup procedure, conversion and enantioselectivity were
catalysts for asymmetric hydrovinylation processes using determined by GC analysis (Experimental Section). Under
styrene as model substrate and ligand (Ra,Sc,Sc)-5 as bench- these conditions, the benchmark activation procedure using
mark system (Scheme 3).
NaBArF for halide exchange led to full conversion of 1
Table 1. Hydrovinylation of styrene using catalyst 6 activated by metal halides.[a]
Entry Activator Activation temperature Color change Reaction temperature Reaction time Conversion TOF[b] Selectivity (3)
ee
[%]
[°C]
[°C]
[h]
[%]
[h–1]
[%]
1
2
3
4
5
6
7
8
9
11
10
12
13
14
15
16
17
18
19
20
21
Y(OTf)3
Bi(OTf)3
Yb(OTf)3
La(OTf)3
In(OTf)3
Gd(OTf)3
Zn(OTf)
Sc(OTf)3
InI3
InBr3
BiBr3
BiI3
LaI3
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–70
0
no
yes
no
yes
no
no
no
no
yes
yes
yes
no
yes
yes
yes
no
yes
no
yes
yes
yes
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–70
–70
–70
–70
–70
–70
–70
–70
1
1
1
1
1
1
1
1
0.5
0.5
0.5
0.5
0.5
2
2
2
2
2
–
31
5
24
7
Ͻ1
–
–
94
98
90
–
18
82
41
Ͻ1
24
3
–
–
310
50
240
70
–
–
97
99
90
99
–
–
–
99
99
99
–
99
99
99
–
99
99
99
99
99
70 (S)
n.d.[c]
64 (S)
n.d.[c]
–
–
–
70 (S)
66 (S)
68 (S)
–
66 (S)
92 (S)
88 (S)
–
67 (S)
n.d.[c]
91 (S)
85 (S)
87 (S)
–
1880
1960
1800
360
410
205
–
120
15
85
200
80
InI3
InBr3
InCl3
BiBr3
0
–70
–70
–70
0
LaI3
ZnCl2
GaCl3
GaI3
2
2
2
17
40
16
0
[a] For reaction conditions and analytic methods see Experimental Section. [b] Turnover frequency for conversion of 1. [c] Not calculated
due to low conversion.
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Eur. J. Org. Chem. 2009, 3199–3202

Nickel-Catalyzed Asymmetric Hydrovinylation
with a selectivity to 3 of 99% and an ee of 70% for the (S) efficient activator such as NaBArF (6 + NaBArF, blue
enantiomer.
trace) and InI3 (6 + InI3, orange trace). The resulting new
Initially, the performance of various metal triflates as spectra are largely identical with two maxima of absorbance
Lewis acids was screened. Representative results are re- around 370 and 477 nm, thus confirming that the mode of
ported in Table 1 (Entries 1–8). No conversion was ob- activation by the Lewis acids is halide abstraction to form
served when the triflates of Y, Gd, Zn and Sc were used. In a cationic species with a weakly coordinating anion as indi-
contrast, the triflates of Yb, In, La and Bi were able to cated in Scheme 2b. In contrast, only minor changes to the
activate 6 to some extent. In particular, conversions of 24% UV/Vis spectrum of the catalyst precursor were observed in
and 31% were obtained with La(OTf)3 and Bi(OTf)3, the presence of LaI3 (6 + LaI3, green trace) corresponding
respectively, corresponding to a TOF of up to 310 h–1. The to inefficient catalyst formation.[19] The reduced signal in-
desired product 3 was formed with high selectivity (90– tensity in this experiment was due to partial decomposition
99%), and enantioselectivity ranged between 64 and 70%. of complex 6 and formation of metal black.
A slight colour change from pale yellow to yellow-orange
was observed during the activation step with Bi(OTf)3,
Yb(OTf)3, La(OTf)3 and In(OTf)3 as the Lewis acids,
whereas no colour variation was detected with the triflates
that did not lead to activation (Table 1).
A substantial increase of the catalytic activity was ob-
served with simple halides as compared to the correspond-
ing triflates as Lewis acids (Entries 9–13). In particular,
InI3, InBr3 and BiBr3 were very efficient in the activation
of 6 resulting in conversions, chemo- and enantioselectivi-
ties very similar to those of the benchmark 6/NaBArF sys-
tem under identical conditions. Almost full conversion, per-
fect selectivity towards 3 and enantioselectivities ranging
Figure 2. UV/Vis spectra of 6 (black trace), 6 + LaI3 (green trace),
from 66 to 70% were achieved. The slightly higher enantio-
6 + InI3 (orange trace) and 6 + NaBArF (blue trace). Conditions:
selectivity achieved with InI3 (70%) with respect to InBr3
1
(5 mL, 43.46 mmol); 6 (30 mg, 0.044 mmol) and activator
(66%) may be related to the larger charge delocalization
and hence the weaker coordination ability of the resulting
anion [InI3Cl]– in comparison with [InBr3Cl]–. BiI3 showed
no activity, most likely owing to its very poor solubility in
CH2Cl2.
Again, the activation step was accompanied by a distinct
colour change for the effective Lewis acids. By using InI3
and InBr3 the colour of the solution turned from pale yel-
low to deep red. This colour change is less pronounced in
the case of BiBr3 and hardly noticeable for LaI3. Represen-
tative snapshots of the catalyst solutions taken immediately
after the activation are shown in Figure 1. The picture of a
solution of catalyst 6 activated with NaBArF is included
for comparison.
(0.049 mmol) are dissolved in CH2Cl2 (15 mL) at room tempera-
ture.
The colour change was used as a qualitative indicator
for the formation of an active species during the further
optimisation of the reaction conditions. Even at a reaction
temperature of –70 °C (Entries 14–21), a number of metal
halides induced significant activation, and very high to ex-
cellent chemo- and enantioselectivities were achieved. In
certain cases, it was necessary to warm the reaction mixture
to 0 °C for 5 min during the activation step, as no colour
change was observed at –70 °C. By far the best results in
terms of activity and selectivity were observed with InI3
(Table 1, Entry 14) where the activation and reaction can
both be performed at –70 °C. Most significantly, the results
obtained with this activator led to identical selectivities and
significant higher conversion as compared to the use of Na-
BArF under identical conditions (6/NaBArF, –70 °C: 63%
conversion, Ͼ99% 3, 93% ee).
Conclusion
Figure 1. Dichloromethane solutions of 6 in the presence of styrene
(a) and upon addition of different Lewis acids (b, c) and NaBArF
(d).
We evaluated a wide range of Lewis acids for their ability
to activate the nickel precursor 6 in the highly chemo- and
enantioselective hydrovinylation of styrene. The observation
The visual observation of the colour change was corre- of the colour change associated with the halide abstraction
lated with a change of the absorption properties by re- during the activation step proved to be a helpful tool to
cording the UV/Vis spectra of the precatalyst after the acti- adapt the activation conditions to the precatalyst/Lewis
vation.[18,19] Selected examples are shown in Figure 2. A acid system. In general, metal halides gave rise to more
strong redshift of the absorbance bands of the catalyst pre- active and enantioselective catalytic systems than the corre-
cursor 6 (black trace) was observed upon addition of an sponding triflates. Among these activators, InI3 appears to
Eur. J. Org. Chem. 2009, 3199–3202
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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N. Lassauque, G. Franciò, W. Leitner
FULL PAPER
be the candidate of choice since it leads to the same chemo-
and enantioselectivity and even higher activity than the
benchmark system based on NaBArF. In contrast to the
activation with silver salts,[8] no filtration is needed before
starting the reaction. Moreover, InI3 is safe to handle, com-
mercially available and relatively cheap, thus providing a
simple and practical protocol for efficient hydrovinylation
reaction.
[1] P. W. Jolly, G. Wilke, in Applied Homogeneous Catalysis with
Organometallic Compounds (Eds.: B. Cornils, W. A. Herrm-
ann), VCH, New York, 1996, vol. 2, p. 1024–1048.
[2] T. V. RajanBabu, Chem. Rev. 2003, 103, 2854–2860.
[3] B. M. Trost, Acc. Chem. Res. 1990, 23, 34–42.
[4] a) C. Böing, G. Franciò, W. Leitner, Chem. Commun. 2005,
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W. Leitner, Adv. Synth. Catal. 2008, 350, 1073–1080.
[5] a) G. Franciò, F. Faraone, W. Leitner, J. Am. Chem. Soc. 2002,
124, 736–737; b) M. Hölscher, G. Franciò, W. Leitner, Organo-
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Experimental Section
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General: All manipulations were carried out under argon by using
classical Schlenk-tube techniques. NaBArF,[20] phosphoramidite
(Ra,SC,SC)-5,[21] [η3-(allyl)NiCl]2,[22] and [η3-(allyl)Ni{(Ra,SC,SC)-
5}Cl] (6)[5a] were prepared according to literature procedures. UV/
Vis spectra were recorded with an Avantes Ava-light DHS. All
Lewis acids were provided by Aldrich except for InI3 (Acros Or-
ganics) and ZnCl2 (Fluka). All Lewis acids were dried under vac-
uum at 100 °C for 1 h before use.
[7] W.-J. Shi, Q. Zhang, J.-H. Xie, S.-F. Zhu, G.-H. Hou, Q.-L.
Zhou, J. Am. Chem. Soc. 2006, 128, 2780–2781.
[8] M. Nandi, J. Jin, T. V. RajanBabu, J. Am. Chem. Soc. 1999,
121, 9899–9900.
[9] A. Bösmann, G. Franciò, E. Janssen, M. Solinas, W. Leitner,
P. Wasserscheid, Angew. Chem. Int. Ed. 2001, 40, 2697–2699.
[10] N. Nomura, J. Jin, H. Park, T. V. RajanBabu, J. Am. Chem.
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[11] B. Bogdanovicˇ, Adv. Organomet. Chem. 1979, 17, 105.
[12] S. Kainz, A. Brinkmann, W. Leitner, A. Pfaltz, J. Am. Chem.
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[13] C. Bonaccorsi, A. Mezzetti, Organometallics 2005, 24, 4953–
4960.
[14] L. L. Anderson, J. Arnold, R. G. Bergman, J. Am. Chem. Soc.
2005, 127, 14542–14543.
[15] G. Wilke, J. Monkiewicz, H. Kuhn, US-Pat. 4912274, 1990.
[16] N. Kawata, K. Maruya, T. Mizoroki, A. Ozaki, Bull. Chem.
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[17] a) T. Tsuchimoto, S. Kamiyana, R. Negoro, E. Shirakawa, Y.
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[18] Due to the limited working temperature of the UV cell, the
UV/Vis spectra were recorded at room temperature, leading in
some cases to catalyst decomposition.
[19] A correlation between the colour change of the catalyst solu-
tion during the activation step and the catalyst activity has
been observed for other catalytic systems; see for instance: C. J.
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Int. Ed. 2009, 48, 956–959 and references cited therein.
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[22] M. Brookhart, E. Hauptman, WO Patent, 98/22424, 1998.
Received: March 8, 2009
General Procedure for the Hydrovinylation Reaction Using InI3 as
the Lewis Acid Activator at –70 °C: A solution of complex 6
(8.08 mg, 0.012 mmol) and styrene 1 (1.4 mL, 12.1 mmol) in
CH2Cl2 (3 mL) was precooled and added via syringe to a Schlenk
flask containing InI3 (6.54 mg, 0.0132 mmol) at –70 °C. The re-
sulting mixture was stirred under argon at –70 °C for 5 min, and
then the gas was exchanged for ethylene by bubbling it through the
solution for 5 s. The Schlenk flask was kept under ethylene at ambi-
ent pressure during the reaction. After 2 h, the reaction was
quenched with a solution of NH3 (20% w/w, 1 mL). Ethylbenzene
(1.6 mL, 12.1 mmol) was added as internal standard for the GC
analysis, and the solution was warmed up to room temperature.
The organic phase was separated, dried with sodium sulfate and
filtered through a pad of silica. Conversion and selectivity were
determined by GC on a CP-Sil PONA CB column (50 °C, 8 °C/
min, 270 °C); retention times [min]: ethylbenzene 14.90; styrene 1
15.75; 3-phenyl-1-butene 3: 19.50; 2-phenyl-1-butene (E)-4: 20.50;
2-phenyl-1-butene (Z)-4: 22.80. The enantioselectivity was deter-
mined by GC on an Ivadex 7 IVA column (60 °C, 1 °C/min, 80 °C,
20 °C/min, 180 °C), retention times [min]: (R)-3-phenyl-1-butene:
15.48; (S)-3-phenyl-1-butene: 15.70.
Acknowledgments
We are grateful to Mrs. H. Eschmann for the GC measurements
and to the Deutsche Forschungsgemeinschaft for financial support
(project CALAPAI, FR2487/1-1).
Published Online: May 14, 2009
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Eur. J. Org. Chem. 2009, 3199–3202