NiCl2(PCy3)2-catalyzed hydrodefluorination of fluoroarenes with LiAl(O-t-Bu)3H

Article abstract of DOI:10.1016/j.jfluchem.2012.12.002

A highly efficient and practical approach to the hydrodefluorination of CF bond in fluoroarenes in the presence of 5 mol% NiCl₂(PCy ₃)₂ with lithium tri-t-butoxyaluminium hydride (LiAl(O-t-Bu)₃H) under mild conditions has been developed.

Full text of DOI:10.1016/j.jfluchem.2012.12.002

Journal of Fluorine Chemistry 146 (2013) 76–79
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
NiCl (PCy ) -catalyzed hydrodefluorination of fluoroarenes with LiAl(O-t-Bu) H
2
3 2
3
a
b
a
a,
Juan Xiao , Jingjing Wu , Wenwen Zhao , Song Cao *
a
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A highly efficient and practical approach to the hydrodefluorination of C–F bond in fluoroarenes in the
presence of 5 mol% NiCl (PCy with lithium tri-t-butoxyaluminium hydride (LiAl(O-t-Bu) H) under
mild conditions has been developed.
Received 6 November 2012
Received in revised form 3 December 2012
Accepted 7 December 2012
Available online 19 December 2012
2
3
)
2
3
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
Hydrodefluorination
Nickel-based catalyst
Lithium tri-t-butoxyaluminium hydride
Fluoroarenes
1
. Introduction
mild reducing agent, lithium tri-t-butoxyaluminium hydride
LiAl(O-t-Bu) H) (Scheme 1).
In recent years, our group has devoted much effort to the
(
3
Most organofluorine compounds are chemically inert due to the
great strength of the C–F bond. As a consequence, the activation of
C–F bonds still remains a crucial challenge to organic chemists [1].
Hydrodefluorination (HDF) is considered as one of the simplest and
most efficient approaches for the modification of organic fluorides
hydrodefluorination of different types of C–F bonds under various
reaction conditions [4–6]. Generally, lithium aluminum hydride
4
(LiAlH ) is still by far the most common hydride reducing agent
used for the HDF of the fluorinated compounds with a transition
metal [7]. However, lithium aluminum hydride is a highly
flammable solid and may ignite in moist air, furthermore, its
powder is extremely corrosive to skin and eyes. Therefore, it is not
[
2]. Nowadays, catalytic hydrodefluorination of C–F bonds using
transition metal complexes as catalysts has attracted increasing
interest in fluorine and organometallic chemistry. Up to now, many
examples of Rh, Zr, Nb, Fe, Ru, Ti and Ni catalysts have been
reported [3]. Among these transition metal catalysts, Ni-based
catalysts have exhibited high activity for the activation of
fluorinated organic compounds.
a safe reducing agent with regards to storage and handling. Lithium
1
3
triethylborohydride (LiEt BH, Superhydride , 1 M in THF) is a
powerful and selective reducing agent which is far superior to
lithium aluminum hydride in many organic reactions [8]. The main
In our previous work, we have developed a novel and highly
efficient approach for the hydrodefluorination of fluoroarenes and
advantage of LiEt
successfully used it as reducing agent for hydrodefluorinating a
variety of fluoroarenes and -trifluorotoluenes in the presence
of NiCl or NiCl (PCy . Although lithium triethylborohydride
exhibited extraordinary reactivity for the HDF of fluoroarenes and
-trifluorotoluenes in the presence of Ni-based catalysts, the
BH in solid state reacts violently and exothermically with
3 4
BH is that it is safer than LiAlH . Previously, we
a
,
a
,a
-trifluorotoluenes derivatives with superhydride (LiEt
3
BH) in
a,a,a
the presence of 40 mol% NiCl or 5 mol% NiCl (PCy (PCy
2
2
3
)
2
3
=
2
2
3 2
)
tricyclohexylphosphine), respectively [4]. More recently, we
further disclosed a simple and facile method for the hydrode-
a,a,a
LiEt
3
fluorination of both fluoroarenes and
the presence of LiEt BH using a catalytic amount of 2 mol% NiCl
combined with 2 mol% NiCl (PCy as cocatalyst [5]. In continua-
a
,a
,a
-trifluorotoluenes in
3
2
water releasing flammable hydrogen gas and the pyrophoric
triethylborane vapor which can ignite spontaneously. Therefore,
2
3 2
)
tion of our research on the hydrodefluorination reaction, we herein
report a novel and practical approach for the hydrodefluorination
3
LiEt BH is often packaged and sold under argon in seal bottles in
THF, and should be stored in THF at low temperature (À20 8C).
of fluoroarenes catalyzed by 5 mol% NiCl
2
(PCy
3
)
2
with a safe and
From the storage, handling and transportation point of view, the
3
LiEt BH is not a good reducing agent. Thus, it is highly desirable to
find other alternative reducing agent for the hydrodefluorination
of C–F bonds.
Lithium tri-t-butoxyaluminium hydride is a mild and stable
hydride reducing agent which is often used to reduce ketones and
*
Corresponding author. Tel.: +86 21 64253452; fax: +86 21 64252603.
E-mail address: scao@ecust.edu.cn (S. Cao).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.12.002

J. Xiao et al. / Journal of Fluorine Chemistry 146 (2013) 76–79
77
Scheme 1. Hydrodefluorination of fluoroarenes and
a,a,a-trifluorotoluenes with
LiAl(O-t-Bu) H in the presence of 5 mol% NiCl (PCy ) .
3
2
3 2
aldehydes [9]. Lithium tri-t-butoxyaluminum hydride is a much
less reactive reducing agent than lithium aluminum hydride due to
steric hindrance. In addition, the powder LiAl(O-t-Bu)
commercially available, which can be stored under 2–8 8C and is
more convenient to handle than LiAlH and LiEt BH. Furthermore,
H is much cheaper than LiEt BH. Thus, we tried to use
H as reducing agent for the hydrodefluorination in
3
H is
4
3
LiAl(O-t-Bu)
LiAl(O-t-Bu)
3
3
3
the following investigation.
2
. Results and discussion
Scheme 2. Plausible mechanism for the hydrodefluorination of fluoroarenes with
Generally, hydrodefluorination of C–F bonds can be accom-
3 2 3 2
LiAl(O-t-Bu) H and NiCl (PCy ) .
plished using hydride reducing agent as a source of H in the
presence of different transition metal catalysts [10]. For our initial
studies, the hydrodefluorination of fluorobenzene with LiAl(O-t-
of the fluoroarenes (entries 1–14) could be reduced efficiently in
the presence of 5 mol% NiCl (PCy with LiAl(O-t-Bu) H to give
the corresponding arenes in high to excellent yields. In the case of
-trifluorotoluenes, except for (trifluoromethyl)benzene 1o
(entry 15), the reduction reaction did not proceed to completion
and mixture of partially, completely hydrodefluorinated
Bu)
3
H in THF at reflux temperature under argon was used as a
2
3
)
2
3
model reaction to examine the catalytic activity of various
transition-metal halide catalysts (Table 1). Among various types
a,a,a
of metal halides, NiCl
benzene in excellent yields (entries 9, 10 and 11). It indicated that
Ni-based catalyst and LiAl(O-t-Bu) H could constitute efficient
catalytic system for the hydrodefluorination. Next, we used nickel
2
(20–40 mol%) could give the product
a
products and starting materials was detected (entries 16–19).
These results suggested that C–F bonds of fluoroarenes are
3
(
II) complexes such as Ni(acac)
2
and NiCl
2
(PCy
3
)
2
as catalyst
(PCy
activated in preference to C–F bonds of
under the LiAl(O-t-Bu) H/NiCl (PCy system.
We suggested a plausible mechanism for the hydrodefluorina-
tion of fluoroarenes with LiAl(O-t-Bu) H/NiCl (PCy system in
Scheme 2. Initially, NiCl (PCy was reduced by LiAl(O-t-Bu) H to
form the electron-rich Ni(0) complex 3, which further underwent
oxidative addition by the aryl fluoride to afford aryl nickel species
4. Subsequently, this intermediate reacted with another molecule
a,a,a-trifluorotoluenes
(entries 12–14). Much to our delight, 5 mol% of NiCl
2
3
)
2
3
2
3 2
)
exhibited excellent catalytic activity and could carry out the HDF
smoothly within 3.5 h in the presence of 4 equiv. of LiAl(O-t-Bu)
entry 13). However, when NaH, NaBH and Bu SnH were used as
reducing agent in the presence of 5 mol% NiCl (PCy , the
3
H
3
2
3 2
)
(
4
3
2
3
)
2
3
2
3
)
2
reactions could not proceed efficiently and gave the mixture of
starting material and reduced product, the yield of expected
hydrodefluorinated product was very low.
3
of LiAl(O-t-Bu) H. The abstraction of the fluorine atom from 4
To survey the generality and scope of the novel LiAl(O-t-Bu)
3
H/
catalytic system, a broad variety of fluoroarenes and
-trifluorotoluenes were examined under the optimized
provided 5 and LiF. Finally, reductive elimination from nickel-
hydride complex 6 furnished the desired arene and the catalytic
cycle was closed by the regeneration of the active catalytic species
Ni (0).
NiCl
2
(PCy
3
)
2
a
,
a
,
a
reaction conditions (Table 2). Among the substrates tested, most
Table 1
a
3
Transition-metal catalyzed HDF of fluorobenzene with LiAl(O-t-Bu) H.
b
Entry
Catalyst
None
Mol (%)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
–
40
40
40
40
40
40
40
40
30
20
5
6
0
0
CuCl
CeCl
LaCl
AlCl
MnCl
FeCl
ZnCl
2
6
3
6
0
3
6
0
3
6
4.5
0
2
6
3
6
0
2
6
0
NiCl
NiCl
NiCl
2
1.5
6
100
97
87
76
100
82
10
11
12
13
14
2
2
6
Ni(acac)
2
6
NiCl
NiCl
2
(PCy
(PCy
3
)
)
2
2
5
3.5
6
2
3
3
a
Reaction condition: LiAl(O-t-Bu)
3
H (4 equiv.), metal halides, THF, reflux.
b
Yields were based on GC analysis.

7
8
J. Xiao et al. / Journal of Fluorine Chemistry 146 (2013) 76–79
Table 2
NiCl (PCy
a
2
3
)
2
3
catalyzed hydrodefluorination of 1a-s with LiAl(O-t-Bu) H.
b
Entry
Substrate
Product
6 6
C H 2a
Yield (%)
100
1
2
C
6
H
5
F 1a
2a
100
3
94
4
5
6
93
97
89
2d
7
8
2a
2d
100
98
9
2a
2c
75
90
1
0
1
1
2
2a
2a
94
95
1
1
1
3
4
2a
2a
84
73
1
5
6
2b
2b
80
63
1
1
7
54
1
1
8
9
33
53
2b
a
Reaction conditions: LiAl(O-t-Bu)
3
2 3 2
H (4–16 equiv.), NiCl (PCy ) (5 mol%), THF, reflux, 3.5–14 h.
b
Yields were based on GC analysis.

J. Xiao et al. / Journal of Fluorine Chemistry 146 (2013) 76–79
79
[
2] (a) D. O’Hagan, Chem. Soc. Rev. 37 (2008) 308–319;
In conclusion, a novel and highly efficient approach for the
hydrodefluorination of fluoarenes with a cheap, easy to handle
(b) T.F. Beltran, M. Feliz, R. Llusar, J.A. Mata, V.S. Safont, Organometallics 30
2011) 290–297;
(
reducing agent, LiAl(O-t-Bu)
NiCl (PCy under mild conditions has been developed. Under
this new catalytic system, C–F bonds of fluoroarenes are more
easily reduced than C–F bonds of -trifluorotoluenes.
3
H
in the presence of 5 mol%
(c) R.P. Hughes, Eur. J. Inorg. Chem. 31 (2009) 4591–4606;
d) P. Fischer, K. G o¨ tz, A. Eichhorn, U. Radius, Organometallics 31 (2012) 1374–
383;
e) G.A. Selivanova, A.V. Reshetov, I.V. Beregovaya, N.V. Vasil’eva, I.Y. Bagryans-
kaya, V.D. Shteingarts, J. Fluorine Chem. 137 (2012) 64–72;
(
1
(
2
3 2
)
a,a,a
(
(
(
(
f) W.X. Gu, O.V. Ozerov, Inorg. Chem. 50 (2011) 2726–2728;
g) T.F. Beltr a´ n, M. Feliz, R. Llusar, J.A. Mata, V.S. Safont, Organometallics 30
2011) 290–297;
3
. Experimental
h) J.H. Zhan, H.B. Lv, Y. Yu, J.L. Zhang, Adv. Synth. Catal. 354 (2012) 1529–1541;
All reactions were carried out under an argon atmosphere with
dry solvents under anhydrous conditions. General procedure for
the NiCl (PCy -catalyzed hydrodefluorination: NiCl (PCy
0.025 mmol) was added to a substrate (1a-s, 0.5 mmol) in dry
THF (4–10 mL) and then LiAl(O-t-Bu) H (2–8 mmol,) was added to
this solution slowly under argon atmosphere. The mixtures were
heated to reflux and left to stir while being periodically monitored
by GC and GC/MS. The yields of products were based on GC.
(i) Y. Sawama, Y. Yabe, M. Shigetsura, T. Yamada, S. Nagata, Y. Fujiwara,
T. Maegawa, Y. Monguchi, H. Sajiki, Adv. Synth. Catal. 354 (2012) 777–782;
(
j) D. Breyer, T. Braun, P. Kl a¨ ring, Organometallics 31 (2012) 1417–1424;
k) N. L u¨ hmann, H. Hirao, S. Shaik, T. M u¨ ller, Organometallics 30 (2011) 4087–4096;
(l) B.M. Kraft, R.J. Lachicotte, W.D. Jones, J. Am. Chem. Soc. 122 (2000) 8559–8560;
m) B.M.Kraft, R.J. Lachicotte,W.D. Jones,J. Am. Chem. Soc.123(2001)10973–10979.
3] (a) M. Aizenberg, D. Milstein, J. Am. Chem. Soc. 117 (1995) 8674–8675;
b) D. Noveski, T. Braun, M. Schulte, B. Neumann, H.G. Stammler, Dalton Trans. 21
(2003) 4075–4083;
2
3
)
2
2
3 2
)
(
(
(
3
[
(
(
(
c) D. Breyer, T. Braun, A. Penner, Dalton Trans. 39 (2010) 7513–7520;
d) J. Vela, J.M. Smith, Y. Yu, N.A. Ketterer, C.J. Flaschenriem, R.J. Lachicotte,
P.L. Holland, J. Am. Chem. Soc. 127 (2005) 7857–7870;
Acknowledgments
(e) M.F. K u¨ hnel, D. Lentz, Angew. Chem. Int. Ed. 49 (2010) 2933–2936;
(
f) S.A. Prikhod’ko, N.Yu. Adonin, D.E. Babushkin, V.N. Parmon, Mendeleev Com-
mun. 18 (2008) 211–212;
g) L.M. Guard, A.E. Ledger, S.P. Reade, C.E. Ellul, M.F. Mahon, M.K. Whittlesey,
J. Org. Chem. 696 (2011) 780–786;
We are grateful for financial supports from the National Natural
Science Foundation of China (Grant Nos. 21072057, 21272070), the
Key Project in the National Science & Technology Pillar Program of
China in the twelfth five-year plan period (2011BAE06B05), the
National Basic Research Program of China (973 Program,
(
(h) M.F. Kuehnel, T. Schlo
¨
der, S. Riedel, B. Nieto-Ortega, F.J. Ram ı´ rez,
J.T.L. Navarrete, J. Casado, D. Lentz, Angew. Chem. Int. Ed. 51 (2012) 2218–2220;
(i) J.A. Panetier, S.A. Macgregor, M.K. Whittlesey, Angew. Chem. Int. Ed. 50 (2011)
2783–2786;
2
010CB126101), and the National High Technology Research
and Development Program of China (863 Program,
011AA10A204).
(j) M.F. Kuehnel, P. Holstein, M. Kliche, J. Kr u¨ ger, S. Matthies, D. Nitsch, J. Schutt,
M. Sparenberg, D. Lentz, Chem. Eur. J. 18 (2012) 10701–10714;
(k) S. Kuhl, R. Schneider, Y. Fort, Adv. Synth. Catal. 345 (2003) 341–344;
l) R.J. Young Jr., V.V. Grushin, Organometallics 18 (1999) 294–296.
2
(
[
[
[
4] J.J. Wu, S. Cao, ChemCatChem 3 (2011) 1582–1586.
5] W.W. Zhao, J.J. Wu, S. Cao, Adv. Synth. Catal. 354 (2012) 574–578.
6] (a) J.J. Wu, J.H. Cheng, J. Zhang, L. Shen, X.H. Qian, S. Cao, Tetrahedron 67 (2011)
Appendix A. Supplementary data
2
85–288;
b) J.H. Cheng, J.J. Wu, S. Cao, Tetrahedron Lett. 52 (2011) 3481–3484.
7] (a) K. Fuchibe, Y. Ohshima, K. Mitomi, T. Akiyama, J. Fluorine Chem. 128 (2007)
158–1167;
(b) K. Fuchibe, K. Mitomi, R. Suzuki, T. Akiyama, Chem. Asian J. 3 (2008) 261–271;
(
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.jfluchem.2012.
[
1
12.002.
(c) H. Schirok, H. Paulsen, W. Kroh, G. Chen, P. Gao, Org. Process Res. Dev. 14
2010) 168–173.
(
References
[8] (a) H.C. Brown, S. Krishnamurthy, J. Am. Chem. Soc. 95 (1973) 1669–1671;
b) P.V.N. Reddy, Synlett 10 (2007) 1627–1628.
9] (a) R.V. Hoffman, N. Maslouh, F. Cervantes-Lee, J. Org. Chem. 67 (2002) 1045–
056;
(
[
[
1] (a) H. Amii, K. Uneyama, Chem. Rev. 109 (2009) 2119–2183;
1
(
(
b) T. Braun, F. Wehmeier, Eur. J. Inorg. Chem. 5 (2011) 613–625;
c) E. Clot, O. Elsenstein, N. Jasim, S.A. Macgregor, J.E. Mcgrady, R.N. Perutz,
(
(
(
(
(
b) H. Yang, L.S. Liebeskind, Org. Lett. 9 (2007) 2993–2995;
c) L.M. Mikkelsen, C.M. Jensen, B. Høj, P. Blakskjær, T. Skrydstrup, Tetrahedron 59
2003) 10541–10549;
d) F.A. Davis, P.M. Gaspari, B.M. Nolt, P.J. Xu, J. Org. Chem. 73 (2008) 9619–9626;
e) X.L. Wang, W.F. Huang, X.S. Lei, B.G. Wei, G.Q. Lin, Tetrahedron 67 (2011)
Accounts Chem. Res. 44 (2011) 333–348;
d) T. Schaub, P. Fischer, T. Meins, U. Radius, Eur. J. Inorg. Chem. 20 (2011) 3122–
126;
(
3
(e) E. Jiao, F. Xia, H. Zhu, Comput. Theor. Chem. 965 (2011) 92–100;
(f) X.F. Xu, H.J. Sun, Y.J. Shi, J. Jia, X.Y. Li, Dalton Trans. 40 (2011) 7866–7872;
(g) A. Kethe, A.F. Tracy, D.A. Klumpp, Org. Biomol. Chem. 9 (2011) 4545–4549;
(h) O. Allemann, S. Duttwyler, P. Romanato, K.K. Baldridge, J.S. Siegel, Science 332
(2011) 574–577.
4919–4923.
[
10] (a) F. Alonso, I.P. Beletskaya, M. Yus, Chem. Rev. 102 (2002) 4009–4091;
(
(
b) H. Lv, J.H. Zhan, Y.B. Cai, Y. Yu, B.W. Wang, J.L. Zhang, J. Am. Chem. Soc. 134
2012) 16216–16227.