Highly efficient nickel(II) chloride/bis(tricyclohexylphosphine)nickel(II) chloride-cocatalyzed hydrodefluorination of fluoroarenes and trifluorotoluenes with superhydride

Article abstract of DOI:10.1002/adsc.201100783

A simple and highly efficient approach for the hydrodefluorination of both fluoroarenes and trifluorotoluenes in the presence of lithium triethylborohydride using a catalytic amount of nickel(II) chloride (NiCl ₂, 2 mol%) combined with a catalytic amount of bis(tricyclohexylphosphine)nickel(II) chloride [NiCl₂(PCy ₃)₂, 2 mol%] as cocatalyst has been developed. Copyright

Full text of DOI:10.1002/adsc.201100783

COMMUNICATIONS
DOI: 10.1002/adsc.201100783
Highly Efficient Nickel(II) Chloride/Bis(tricyclohexylphosphine)-
nickel(II) Chloride-Cocatalyzed Hydrodefluorination of
Fluoroarenes and Trifluorotoluenes with Superhydride
a
a
a,
Wenwen Zhao, Jingjing Wu, and Song Cao *
a
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology,
Shanghai 200237, Peopleꢀs Republic of China
Fax : (+86)-21-6425-2603; phone: (+86)-21-6425-2945; e-mail: scao@ecust.edu.cn
Received: October 8, 2011; Published online: February 23, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100783.
Abstract: A simple and highly efficient approach
for the hydrodefluorination of both fluoroarenes
and trifluorotoluenes in the presence of lithium tri-
NiCl2 or
(5 mol%).
a
6]
catalytic amount of NiCl ACHTUNGTRENNUNG( PCy )
2 3 2
[
Recently, the application of a combination of two
different catalysts as two-component activation
system has gained much attention and has been suc-
ACHTUNGTRENNUNGe thylborohydride using a catalytic amount of nick-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
el(II) chloride (NiCl , 2 mol%) combined with a
2
[
7]
catalytic amount of bis(tricyclohexylphosphine)-
cessfully employed in organic synthesis. This power-
ful cooperative catalysis strategy can improve the re-
action significantly both in terms of rate, yield and se-
lectivity. For example, in 1998, Anderson developed a
novel cocatalyzed cyanation reaction involving Pd(0)
catalysts, he indicated that substoichiometric quanti-
ties of copper or zinc species dramatically improve
both conversion rate and efficiency of Pd(0)-catalyzed
nickel(II) chloride [NiCl ACHTNUGTRNEUNG( PCy ) , 2 mol%] as coca-
2 3 2
talyst has been developed.
Keywords: cocatalysts; fluorides; hydrodefluorina-
tion; lithium triethylborohydride; nickel catalysts;
reduction
[
8]
cyanation reactions. MacMillan merged two differ-
ent types of catalysts, photoredox catalyst
Ru(bpy) Cl and an imidazolidinone organocatalyst,
a
AHCTUNGTRENNUNG
3
2
The activation of carbon-fluorine bonds by transition to accomplish the enantioselective intermolecular a-
metal complexes remains a great challenge for the alkylation of aldehydes and a series of enantioen-
chemical community because the CÀF bond is one of riched a-alkylated aldehydes was synthesized effi-
[
9]
the most inert and strong functionalities found in or- ciently. In this communication, we reported a practi-
[1]
ganic molecules. Reduction of the CÀF bond into a cal and highly efficient approach for the catalytic hy-
CÀH bond (hydrodefluorination or HDF) is an impor- drodefluorination of both CÀF bonds of fluoroarenes
tant and simplest approach for the modification of or- and trifluorotoluenes by combining two catalysts,
[
2]
ganofluorine compounds. Nowadays, a lot of effi- NiCl and NiCl ACHTUGNTRNEUNG( PCy ) in one pot, in the presence of
2
2 3 2
cient transition metal catalysts have been developed lithium triethylborohydride (Scheme 1).
[3]
for HDF. Among these transition metal catalysts,
According to our previous studies, both fluoarenes
Ni-containing catalysts have exhibited high activity and a,a,a-trifluorotoluene derivatives could be re-
[
4]
for the activation of fluorinated organic compounds.
duced with LiEt BH in the presence of approximately
3
In our previous works, we described an unexpected half-stoichiometric amount of NiCl (40 mol%) and
2
hydrodefluorination of the CÀF bonds of CF deriva- afforded the corresponding arenes and toluenes in ex-
2
tives using LiAlH at room temperature without any
4
additional metal catalyst or in the presence of catalyt-
[
5]
ic amount of ZnCl2. More recently, we have devel-
oped a novel and highly efficient approach for the
HDF of fluoroarenes and a,a,a-trifluorotoluene de-
rivatives with superhydride (LiEt BH) in the presence
of an approximately half-stoichiometric amount of trifluorotoluenes with LiEt BH in the presence of 2 mol%
3
Scheme 1. Hydrodefluorination of fluoroarenes and a,a,a-
3
NiCl and 2 mol% NiCl
A
H
U
G
R
N
U
G
2
2
574
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 574 – 578

Highly Efficient Nickel(II) Chloride/Bis(tricyclohexylphosphine)nickel(II) Chloride-Cocatalyzed
[a,b]
Table 1. NiCl or NiCl ACTHUNGTRNEGNU( PCy ) as the sole catalyst for hydrodefluorination of 1a and 1b.
2 3 2
2
[c]
Entry
Substrate
Product A
Product B
Catalyst
Yield [%] of A/B
1
2
40 mol% NiCl2
2 mol% NiCl2
22/78
90/10
1a
2a
2a
3a
3a
3
2 mol% NiCl2
56/44
4
5
6
1a
1a
1b
2a
2a
2a
3a
3a
3a
5 mol% NiCl
2 mol% NiCl
2 mol% NiCl
A
T
N
R
N
U
G
85/15
94/6
37/63
2
3
2
2
2
AHCTUNGTRENNUG( PCy )
2 3
A
H
U
G
R
N
U
G
2
[a]
[b]
[c]
Reaction conditions: LiEt BH (4–12 equiv.), reflux in THF for 6–20 h.
3
[6]
The effect of amount of NiCl on the hydrodefluorination of fluorobenzene by LiEt BH was reported previously.
2
3
Yields were based on GC analysis.
Table 2. NiCl or NiCl
ligand.
A
H
U
G
R
N
U
G
2
2
3
2
3
[a]
[b]
Entry
Substrate
Product A
Product B
Catalysts
Yield [%] of A/B
1
5 mol% NiCl +10 mol% PCy
93/7
2
3
2
3
4
1a
1a
1a
2a
2a
2a
3a
3a
3a
10 mol% NiCl +10 mol% PCy
87/13
96/4
94/6
2
3
1 mol%NiCl ACHTUNGTERNN(NUG PCy ) +2 mol% PCy
2 3 2 3
5 mol% NiCl ACHTUNGTERNN(NUG PCy ) +5 mol% PCy
2 3 2 3
[
[
a]
b]
Reaction conditions: LiEt BH (4 equiv.), reflux in THF for 6 h.
Yields were based on GC analysis.
3
cellent yields, whereas 5 mol% NiCl ACHTUNGNRTEUNG( PCy ) , exhibit- for the HDF of both fluoroarenes and a,a,a-trifluoro-
2 3 2
ed specific activity for the HDF of fluoroarenes, but toluene derivatives in the presence of LiEt BH
3
left the CÀF bonds in a,a,a-trifluorotoluenes un- (Table 3, entries 5 and 6). Attempts to decrease the
[
6]
touched.
amount of cocatalysts, NiCl or NiCl ACHTUNGTRNNEUG( PCy ) , to less
2 2 3 2
In order to obtain a more highly efficient catalyst than 2 mol% led to lower conversion of the CÀF
system, in this paper, two types of catalysts have been bonds to CÀH bonds (entries 3 and 4).
mixed to improve conversion rate and efficiency of the
Recently, cobalt salts catalysts have received more
metal-catalyzed hydrodefluorination of both fluoarenes attention. Compared to the expensive palladium and
and a,a,a-trifluorotoluene derivatives. Initially, NiCl2 toxic nickel catalysts, cobalt catalysts are simple, inex-
or NiCl ACHTUNGTRENNUNG( PCy ) as the sole catalyst for hydrodefluori- pensive, and environmentally friendly and they can
2 3 2
nation of 1a and 1b was studied, respectively (Table 1). sometimes present a higher reactivity for some organ-
[
11]
However, a mixture of partially (product A) or com- ic reactions. Herein, we also performed a systemat-
pletely (product B) hydrodefluorinated products was ic study of hydrodefluorination of fluoroarenes and
obtained when a single Ni-based catalyst was used.
a,a,a-trifluorotoluene derivatives 1a–e using catalytic
(PCy ) as
It was reported that a phosphine ligand can be used amount of CoCl , CoBr or combined NiCl AHCUTNGTRENNUNG
2
2
2
3 2
to facilitate CÀF activation and act as a conduit that cocatalysts (Table 4). The results indicated that
[
10]
delivers fluoride to the metal. Therefore, we carried 2 mol% CoCl or 2 mol% CoBr in combination with
2
2
out the hydrodefluorination in the presence of some 2 mol% NiCl ACHTUNGTRENUNG( PCy ) exhibited good catalytic activity
2 3 2
additional phosphine ligand, PCy (Table 2). Unfortu- (entries 7 and 15). However, incomplete conversion
3
nately, no beneficial effects of added PCy were ob- of carbon-fluorine bonds was observed when they
3
served for the hydrodefluorination of 1a conducted in were applied to other substrates (entries 8 and 9).
this single catalyst approach.
It seems that the catalytic activity of CoCl2 or
(CoBr )/NiCl (PCy ) was inferior to that of
NiCl and NiCl ACHTUNGTRENNUNG( PCy ) to improve the catalytic activ- NiCl /NiCl ATHCNUTGERUNG(N PCy ) . To reach high conversion, the
2 3 2 2 2
Our next efforts focused on the combination of
A
H
U
G
R
N
N
ACHTUNGTRENNUNG
2
2
3 2
2
3 2
ity for hydrodefluorination. After a series of trials, we ratio of CoCl (CoBr ) to NiCl ACHTNUGTRNEUNG( PCy ) need to be in-
2
2
2 3 2
found that 2 mol% NiCl2 combined with 2 mol% creased slightly if the substrates are different (en-
NiCl (PCy ) as cocatalysts could be highly effective tries 10 and 11).
ACHTUNGTRENNUNG
2
3 2
Adv. Synth. Catal. 2012, 354, 574 – 578
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
575

Wenwen Zhao et al.
COMMUNICATIONS
[a]
Table 3. NiCl /NiCl ACHTNUGTRENN(NGU PCy ) cocatalyzed hydrodefluorination of 1a and 1b with LiEt BH.
2 3 2 3
2
[b]
Entry
Substrate
Product A
Product B
Catalysts
10 mol% NiCl +1 mol% NiCl
Yield [%] of A/B
1
A
H
U
T
E
N
N
7/93
2
2
2
3
4
5
1a
1a
1a
1a
2a
2a
2a
2a
3a
3a
3a
3a
5 mol% NiCl +1 mol% NiCl
A
T
N
T
E
N
N
(PCy )
22/78
80/20
77/23
0/100
2
2
3
2
2
2
2
1 mol% NiCl +2 mol% NiCl
A
H
U
G
R
N
U
G
2
2
3
2 mol% NiCl +1 mol% NiCl
A
H
U
G
R
N
U
G
2
2
3
2 mol% NiCl +2 mol% NiCl
A
H
U
G
R
N
U
G
2
2
3
6
2a
3a
2 mol% NiCl +2 mol% NiCl
A
H
U
G
E
N
N
0/100
2
2
[
[
a]
b]
Reaction conditions: LiEt BH (4–12 equiv.), reflux in THF for 4–20 h.
Yields were based on GC analysis.
3
[a]
Table 4. Survey of the CoCl /NiCl ACHTUNGTRENNU(NG PCy ) catalytic systems for the hydrodefluorination of 1a–e with LiEt BH.
2 3 2 3
2
[b]
Entry
1
Substrate
Product A
Product B
Catalysts
Yield[%] of A/B
[
[
c]
c]
–
–
2 mol% CoCl2
–
–
2
–
–
2 mol% CoCl2
3
4
1c
2a
5 mol% CoCl +10 mol% PCy
39/61
0/100
2
3
1a
5 mol% CoCl +2 mol% NiCl CAHTUNGTNRENUNG( PCy )
2 3 2
2
5
6
7
8
1a
1b
1a
1b
2a
2a
2a
2a
3a
3a
3a
3a
5 mol% CoCl +1 mol% NiCl
A
T
N
T
E
N
N
10/90
21/79
0/100
22/78
2
2
5 mol% CoCl +1 mol% NiCl
A
H
U
T
N
U
G
2
2
3
2
2
2
2 mol% CoCl +2 mol% NiCl
A
H
U
T
E
U
2
2
3
2 mol% CoCl +2 mol% NiCl
A
H
U
G
R
N
N
2
2
3
9
1c
1c
1c
3b
3b
3b
2 mol% CoCl +2 mol% NiCl
A
T
N
T
N
U
G
35/65
0/100
0/100
2
2
3
2
1
1
0
1
1c
10 mol% CoCl +2 mol% NiCl ACHTUNTGRENNUG( PCy )
2 2 3 2
5 mol% CoCl +2 mol% NiCl
2
2
[
[
c]
c]
12
13
14
15
1a
1b
1a
1b
–
–
2a
2a
–
–
3a
3a
2 mol% CoBr2
2 mol% CoBr2
–
–
2 mol% CoBr +2 mol% NiCl
A
H
U
G
R
N
U
G
8/92
0/100
2
2
3
2
2
2 mol% CoBr +2 mol% NiCl
A
H
U
G
R
N
U
G
2
2
[
[
[
a]
Reaction conditions: LiEt BH (4–14 equiv.), reflux in THF for 2–20 h.
Yields were based on GC analysis.
The mixture of partially or completely hydrodefluorinated products.
3
b]
c]
Based on the above observations, 2 mol% NiCl2 tives to evaluate the scope of the system in the
with additional 2 mol% NiCl (PCy ) could be identi- following studies (Table 5). Among the fluoroarenes
AHCTUNGTRENNUNG
2
3 2
fied as the best cocatalyst system for the hydrode- and substituted a,a,a-trifluorotoluenes tested, most of
fluorination of both fluoroarenes and a,a,a-trifluoro- them could be reduced efficiently to give the corre-
toluenes. Thus, this novel cocatalyzed hydrodefluori- sponding hydrocarbon products in high to excellent
nation was applied to a wide range of structurally di- yields. Both the aromatic CÀF bonds and benzylic CÀ
verse fluoroarenes and a,a,a-trifluorotoluene deriva- F bonds were converted to CÀH bonds with high effi-
576
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 574 – 578

Highly Efficient Nickel(II) Chloride/Bis(tricyclohexylphosphine)nickel(II) Chloride-Cocatalyzed
Table 5. NiCl /NiCl (PCy ) cocatalyzed hydrodefluorination due to the fact that a,a,a-trifluorotoluenes are one of
A
H
U
G
R
N
N
2
2
3 2
of a,a,a-trifluorotoluenes and fluoroarenes (1a–o) with
the most inert organofluorine compounds.
In summary, combination of NiCl2 and
NiCl (PCy ) as the cocatalysts has been successfully
employed in the hydrodefluorination of fluoroarenes
and trifluorotoluenes with lithium triethylborohy-
dride. The addition of a catalytic amount of NiCl2
[a]
LiEt BH.
3
a
[b]
2
ACHTUNGTRENNUNG
3 2
Entry Substrate
1
Product
Yield [%]
100
AHCTUNGTNERN(GU PCy ) (2 mol%) would greatly improve the catalytic
3 2
2
3
4
3a
100
100
100
activity of NiCl and the amount of NiCl would be
2 2
significantly reduced from 30-40 mol% to 2 mol%.
This cooperative catalysis protocol will have broad
potential utility in the activation of carbon-fluorine
bonds.
3b
Experimental Section
All chemicals were of analytical grade and obtained from
commercial suppliers and used without further purification.
All catalysts used in the reactions were anhydrous. Anhy-
drous THF was distilled from sodium-benzophenone.
5
6
7
3b
3b
3b
100
100
100
LiEt BH (1.0M in tetrahydrofuran) was purchased from J &
3
K Chemical Limited. All reactions were carried out under
an argon atmosphere with dry solvents. Gas chromatography
(
GC) was recorded on an HP 6890 Plus GC instrument and
gas chromatography-mass spectra (GC-MS) were recorded
on an HP 5973 MSD with 6890 GC. The GC and GC-MS
were calibrated by authentic standards.
[
[
[
c]
c]
c]
8
9
93
91
92
General Procedure for NiCl and NiCl
A
H
U
G
R
N
U
G
2
2
Cocatalyzed Hydrodefluorination
1
1
0
1
3d
3d
NiCl2 (0.01 mmol, 1 mg) and NiCl2
ACHTUNGTNERNU(GN PCy ) (0.01 mmol,
3 2
6
mg) were added to a substrate (1a–o, 0.5 mmol) in dry
[
c]
90
THF (2 mL) and LiEt BH (2–7.5 mmol, 1M in THF) was
3
added dropwise to the solution with a syringe at room tem-
perature under argon atmosphere. The reaction solution
turned black. The mixture was then heated to reflux and left
to stir while being periodically monitored by GC and GC/
MS. The yields of the products were based on GC analysis
12
13
14
3b
3a
80
77
70
(
Table 5).
Acknowledgements
15
76
We are grateful for financial supports from the National Nat-
ural Science Foundation of China (Grant No. 21072057), the
National Basic Research Program of China (973 Program,
2010CB126101), the Key Project in the National Science &
Technology Pillar Program of China in the twelfth five-year
plan period (2011BAE06B05), and the Shanghai Leading
Academic Discipline Project (B507).
[
a]
Reaction conditions: LiEt BH (4–14 equiv.), 2 mol%
3
NiCl +2 mol% NiCl ACHTUNGTRNEGNU( PCy ) , reflux in THF for 2–20 h.
2
2 3 2
[
[
b]
Yields were based on GC analysis.
Isolated yields.
c]
ciency (entries 1–12). It is noteworthy that the CÀF
References
bonds in a trifluoromethyl group are less reactive
than the CÀF bonds in fluoroarenes and only moder-
[
1] a) D. OꢀHagan, Chem. Soc. Rev. 2008, 37, 308–319;
b) H. Amii, K. Uneyama, Chem. Rev. 2009, 109, 2119–
2183; c) A. D. Sun, J. A. Love, Org. Lett. 2011, 13,
2750–2753; d) T.-T. Zheng, H.-J. Sun, Y. Chen, X.-Y.
ate yields of corresponding hydrocarbons were ob-
tained under the LiEt BH/2 mol% NiCl /2 mol%
3
2
NiCl ACHTUNGTRENNUNG( PCy ) system (entries 13–15). This might be
2 3 2
Adv. Synth. Catal. 2012, 354, 574 – 578
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
577

Wenwen Zhao et al.
COMMUNICATIONS
Li, S. Dꢂrr, U. Radius, K. Harms, Organometallics
N. Y. Adonin, V. N. Parmon, Tetrahedron Lett. 2010, 51,
2265–2268; d) A. Nova, M. Reinhold, R. N. Perutz,
S. A. Macgregor, J. E. McGrady, Organometallics 2010,
29, 1824–1831.
2
009, 28, 5771–5776.
[
2] a) J. L. Kiplinger, T. G. Richmond, C. E. Osterberg,
Chem. Rev. 1994, 94, 373–431; b) H. Torrens, Coord.
Chem. Rev. 2005, 249, 1957–1985; c) G. Meier, T.
Braun, Angew. Chem. 2009, 121, 1575–1577; Angew.
Chem. Int. Ed. 2009, 48, 1546–1548; d) C. Douvris,
O. V. Ozerov, Science 2008, 321, 1188–1190; e) C.
Douvris, C. M. Nagaraja, C. Chen, B. M. Foxman, O. V.
Ozerov, J. Am. Chem. Soc. 2010, 132, 4946–4953; f) M.
Klahn, C. Fischer, A. Spannenberg, U. Rosenthal, I.
Krossing, Tetrahedron Lett. 2007, 48, 8900–8903.
[5] a) J.-J. Wu, J.-H. Cheng, J. Zhang, L. Shen, X.-H. Qian,
S. Cao, Tetrahedron 2011, 67, 285–288; b) J.-H. Cheng,
J.-J. Wu, S. Cao, Tetrahedron Lett. 2011, 52, 3481–3484.
6] J.-J. Wu, S. Cao, ChemCatChem 2011, 3, 1582–1586.
7] a) E. A. R. Dustin, C. D. Benoit, H. Dane, A. S. Karl,
Nature Chem. 2010, 2, 766–771; b) S. Hwang, Y. Lee,
P. H. Lee, S. Shin, Tetrahedron Lett. 2009, 50, 2305–
[
[
2
308; c) X. Zhang, H. Huang, X. Guo, X. Guan, L.
[
3] a) M. Aizenberg, D. Milstein, J. Am. Chem. Soc. 1995,
Yang, W. Hu, Angew. Chem. 2008, 120, 6749–6751;
Angew. Chem. Int. Ed. 2008, 47, 6647–6649; d) M. Shi,
H. Qian, Appl. Organomet. Chem. 2006, 20, 771–774;
e) Y.-M. Shen, W.-L. Duan, M. Shi, Adv. Synth. Catal.
1
17, 8674–8675; b) B. M. Kraft, W. D. Jones, J. Am.
Chem. Soc. 2002, 124, 8681–8689; c) W. D. Jones,
Dalton Trans. 2003, 3991–3995; d) E. Clot, C. Mꢃgret,
B. M. Kraft, O. Eisenstein, W. D. Jones, J. Am. Chem.
Soc. 2004, 126, 5647–5653; e) T. Braun, D. Noveski, M.
Ahijado, F. Wehmeier, Dalton Trans. 2007, 3820–3825;
f) M. Teltewskoi, J. A. Panetier, S. A. Macgregor, T.
Braun, Angew. Chem. 2010, 122, 4039–4043; Angew.
Chem. Int. Ed. 2010, 49, 3947–3951; g) S. P. Reade,
M. F. Mahon, M. K. Whittlesey, J. Am. Chem. Soc.
2
003, 345, 337–340.
[
[
8] B. A. Anderson, E. C. Bell, F. O. Ginah, N. K. Harn,
L. M. Pagh, J. P. Wepsiec, J. Org. Chem. 1998, 63, 8224–
8
228.
9] D. A. Nicewicz, D. W. C. MacMillan, Science 2008, 322,
7–80.
10] J. Goodman, S. A. Macgregor, Coord. Chem. Rev. 2010,
54, 1295–1306.
7
[
[
2
009, 131, 1847–1861; h) K. Fuchibe, Y. Ohshima, K.
2
Mitomi, T. Akiyama, Org. Lett. 2007, 9, 1497–1499.
11] a) T. J. Korn, M. A. Schade, S. Wirth, P. Knochel, Org.
Lett. 2006, 8, 725–728; b) C. Gosmini, A. Moncomble,
Isr. J. Chem. 2010, 50, 568–576.
[
4] a) T. Braun, R. N. Perutz, Chem. Commun. 2002, 2749–
2
757; b) K. Sꢃbastien, R. Schneider, Y. Fort, Adv.
Synth. Catal. 2003, 345, 341–344; c) S. A. Prikhod’ko,
578
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 574 – 578