Introduction of (2-CF3)phenyl group via nickel-catalyzed C-CL bond activation and arylation

Article abstract of DOI:10.1002/zaac.201400609

A simple and mild catalytic arylation via C-Cl bond activation is described. The phenyl group containing a 2-trifluoromethyl group was introduced into the aromatic imine molecules through C,C-coupling reaction between chloroarenes and the organozinc reage

Full text of DOI:10.1002/zaac.201400609

Journal of Inorganic and General Chemistry
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Zeitschrift für anorganische und allgemeine Chemie
DOI: 10.1002/zaac.201400609
Introduction of (2-CF3)Phenyl Group via Nickel-catalyzed C–Cl Bond
Activation and Arylation
Zheng Peng,[a] Hongjian Sun,[a] Aiqin Du,[a] and Xiaoyan Li*[a]
Keywords: C–Cl activation; Nickel; Trifluoromethyl; Organozinc reagent; C,C-coupling; Chlorinated benzalimine
Abstract. A simple and mild catalytic arylation via C–Cl bond acti-
bis(2-(trifluoromethyl)phenyl)zinc, with tetrakis(trimethylphosphine)-
vation is described. The phenyl group containing a 2-trifluoromethyl nickel(0) complex as an effective catalyst. Under catalytic conditions
group was introduced into the aromatic imine molecules through C,C- chlorinated benzalimines were quantitatively converted into the ex-
coupling reaction between chloroarenes and the organozinc reagent,
pected benzalimines with trifluoromethyl group(s).
was also explored through the reaction of organometallic rea-
gent with CF3-containing reactant.[26]
1 Introduction
Although chloroarenes have been widely used in chemical
industry, medicine, pesticide, leatherworking, and many other
fields, their bioaccumulation, toxicity, carcinogenicity, and sta-
bility lead to globally environmental problems.[1] For this
reason, several methods have been developed to activate C–Cl
bonds in order to transform chloroarenes into useful, environ-
mentally-friendly substances.[2] In general, the reaction condi-
tions of traditional methods are harsh and the scope is very
narrow. In contrast, the use of transition metal complexes as
catalysts in this process is a useful exploration, such as the
Suzuki,[3] Kumada,[4] and Negishi coupling.[5] Some palla-
dium,[3–9] rhodium,[10–11] iron,[12–14] cobalt,[15–17] and
nickel,[18,19] complexes have been applied in the catalytic acti-
vation of C–Cl bonds.
We studied cyclometalation reaction involving C–Cl bond
activation at a central nickel(II) atom with an aldazine nitrogen
atom as an anchoring group to obtain the ortho-chelated
nickel(II) complexes with a [C–Ni–Cl] fragment [Equa-
tion (1)].[27]
In this paper, we extend our work from C–Cl bond acti-
vation to arylation of chloroarenes catalyzed by nickel(0) com-
plex with CF3-containing organozinc reagent to prepare novel
CF3-containing aromatic compounds.
Organic fluorides have many unique excellent properties,
such as excellent thermal stability, chemical inertness, unusual
surface property, low dielectric constant, and high transparency
as well as low refractive index. Therefore, they have been
widely used in many fields.[20] In some cases, the introduction
2 Results and Discussion
According to the mechanism of C–Cl bond functionalization
of trifluoromethyl group(s) into an organic molecule plays a and C,C-coupling reaction, the key step is the C–Cl bond acti-
decisive role for its property because the electronic structure vation. We realized the C–Cl bond activation of the chlorinated
and reactivity of trifluoromethyl group are different from those imine with Ni(PMe3)4.[27] As a continuation of our work in
of other substituents.[21] The molecular moieties with CF3-con- the field of C–Cl bond activation, the expected C,C-coupling
taining group(s) have been introduced to fine-tune biochemical reaction via C–Cl arylation with CF3-containing organozinc
properties in the design of drug molecules, agricultural chemi- reagent was explored. Several novel CF3-containing aromatic
cals, and other functional materials.[22] In recent years, the re- compounds were synthesized.
port on trifluoromethylation was disclosed.[23] In addition to
At the beginning of the research, (2,6-dichlorobenzylidene)-
direct trifluoromethylation,[24,25] indirect trifluoromethylation aniline (1a) was selected as a model substrate to optimize the
catalytic reaction conditions [Equation (2)]. The experimental
results on the optimization of the reaction conditions are listed
in Table 1. Entry 6 is the control experiment. Entries 1–5 indi-
cate that the most suitable solvent is toluene among the five
tested reaction media. With the increasing of the reaction tem-
perature from 30 °C to 100 °C, 80 °C is the optimized reaction
temperature (entries 7–9). Five equivalents of organozinc rea-
gent are more appropriate because the yield did not increase
* Prof. Dr. X. Li
Fax: +86-531-88564464
E-Mail: xli63@sdu.edu.cn
[a] School of Chemistry and Chemical Engineering
Key Laboratory of Special Functional Aggregated Materials
Ministry of Education
Shandong University
Shanda Nanlu 27
250199 Jinan, PR China
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838
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Table 1. Optimization of the catalytic reaction conditions.
Entry
Catalyst /mol%
Zn reagents
Solvent
T /°C
Time /h
Yield /%
1
2
3
4
5
6
7
8
10%
10%
10%
10%
10%
none
10%
10%
10%
10%
10%
10%
2.0%
0.5%
2.0%
2.0%
2.0%
2.0 eq
2.0 eq
2.0 eq
2.0 eq
2.0 eq
2.0 eq
2.0 eq
2.0 eq
2.0 eq
3.0 eq
5.0 eq
6.0 eq
5.0 eq
5.0 eq
5.0 eq
5.0 eq
5.0 eq
THF
60
60
60
60
60
60
30
80
100
80
80
80
80
80
80
80
80
24
24
24
24
24
24
24
24
24
24
24
24
24
24
5
54
56
trace
49
47
trace
45
69
63
79
88
88
89
trace
60
toluene
MeCN
dioxane
DMSO
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
9
10
11
12
13
14
15
16
17
15
30
93
93
with more organozinc reagent (entries 10–12). When the load- arylation products have less steric hindrance effect. Therefore,
ing of the catalyst was changed, it was found that 2.0 mol% they have only one single signal in the 19F NMR spectra. En-
of Ni(PMe3)4 are sufficient for the desired yields (entries 10– tries 7 and 8 indicated that the para-(C–Cl) bonds of the
14). Entries 15–17 verified that this catalytic reaction had fin- imines could also be activated and it is not indispensable that
ished within 15 h. According to the experimental results in the imine group plays a role as a directing group in this pro-
Table 1, the optimized catalytic reaction conditions can be cess. In comparison with the result of entry 5, the result of
summarized as follows: (2,6-dichlorobenzylidene)aniline entry 9 shows that the low yield might be caused by the steric
(1.0 equiv.), bis(2-(trifluoromethyl)phenyl)zinc (5.0 equiv.), effect of the isopropyl groups.
Ni(PMe3)4 (2.0 mol%), 1.5 mL toluene, 80 °C, 15 h.
The molecular structure of compound 2b was confirmed by
X-ray single crystal diffraction. A view of the structure of 2b
is shown in Figure 1. This structure shows a trans-configura-
tion with regard to the imine double bond in the crystal state.
After optimization of the catalytic reaction conditions, more
substrates of the chlorinated benzalimines were selected to ex-
plore the scope of this catalytic system under the optimized
reaction conditions [Equation (3)] (Table 2). The substrates in
Table 2 were prepared from the reaction of 2,4-dichlorobenz-
aldehyde, 2,6-dichlorobenzaldehyde, or 2-chlorobenzaldehyde
with aniline, 4-methylaniline, benzylaniline, 2,6-diisopropyl-
aniline, and 1-naphthylamine. In general, the conjugated aro-
matic imines as substrates have higher yields than those of the
unconjugated aromatic imines. Additionally, the reaction could
proceed for both mono-chlorinated and di-chlorinated phenyl
imines. With di-chlorinated phenyl imine as a substrate, no
mono-(C–Cl) bond arylation product could be isolated. How-
ever, based on the results in Table 2, it is difficult to find more
regularity of this nickel(0)-catalyzed C–Cl bond arylation.
All of the products (1b–8b) were characterized by NMR and
HRMS spectra. It should be noted that two single signals in
the 19F NMR spectra of 1b–4b were observed with different
integral intensities in the ratio of 1:1.34 to 1:1.73. This may
be caused by the trans- and cis-isomers of the imines. This
result could be attributed to the stronger steric hindrance effect
of the di-arylation products. Compounds 5b and 6b as mono- Figure 1. Molecular structure of 2b.
Z. Anorg. Allg. Chem. 2015, 838–841
839
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a)
Table 2. Ni-catalyzed arylation of chlorinated benzalimines
.
Unexpectedly, the two phenyl rings (C1–C7 and C15–C20)
with the ortho-trifluoromethylphenyl groups are not in the con-
b)
Entry
Substrate
Product
Yield /%
A/B
jugated phenyl-imine plane [N1=C14–(C8–C13)]. Two ortho-
trifluoromethyl groups orientate toward to the same direction
concerning the (C8–C13) phenyl ring. This structure might be
resulted from the packing effect in the crystal state. Owing to
the methylene group (C22) of the benzyl group, the conjuga-
tion of the (C23–C28) phenyl ring with the [N1=C14–(C8–
C13)] group is excluded.
1
93/88
50/46
1a
1b
3 Conclusions
2
A simple and efficient catalysis for C–Cl bond activation
and arylation is described. Trifluoromethyl group(s) were in-
troduced into the aromatic imine molecules through the C,C-
coupling reaction between chloroarenes and organozinc rea-
gent, bis(2-(trifluoromethyl)phenyl)zinc. Nickel(0) complex,
tetrakis(trimethylphosphine)nickel(0), is a good catalyst for
this process. Nine chlorinated benzalimines were transformed
to the expected benzalimines with trifluoromethyl group(s).
We believe that this catalytic system can be expanded to more
related substrates.
2a
2b
3
67/63
68/64
3a
3b
4 Experimental Section
4
5
4.1 General Procedures
All experiments for C,C-coupling reaction were performed using stan-
dard Schlenk techniques in an atmosphere of nitrogen. 1H and 19F
NMR spectra were recorded with a 300 MHz Bruker NMR instrument.
Mass spectra were recorded with an Agilent Q-TOF 6510 mass spec-
trometer. Melting points were measured in capillaries and were uncor-
rected. X-ray crystallography was performed with a Bruker Smart 1000
diffractometer.
4a
4b
98/93
90/86
5a
5b
4.2 Materials and Methods
6
7
Na2SO4 was obtained from commercial source and used as received.
Acetonitrile, DME, DMF, and DMSO were dried by refluxing over
CaH2. Toluene, pentane, THF, and diethyl ether were dried with so-
dium and used after distillation. Ni(PMe3)4 was synthesized according
to the method by Klein.[28] (C7H4F3)2Zn was prepared from
C7H4F3MgBr and ZnCl2 in THF. C7H4F3MgBr was synthesized by
C7H4F3Br and Mg in THF. Imines were prepared by corresponding
aldehyde and amines in small amount of ethanol, and recrystallized
from diethyl ether, pentane or THF. All imines are light yellow crys-
tals. The yields of imines are from 40% to 70%.
6a
6b
67/56
7a
8a
7b
8
9
58/50
4.3 General Experimental Procedure of Catalytic Study
(C7H4F3)2Zn (1.0 mmol) was injected to a solution of an aryl halide
(0.2 mmol) and Ni(PMe3)4 (0.004 mmol) in toluene (1.5 mL). The
mixture was stirred at 80 °C for 15 h. The reaction mixture was dried
under reduced pressure. The residue was extracted by pentane and
diethyl ether. The crude product was re-crystallized in pentane or di-
ethyl ether.
8b
c)
11/
9a
9b
4.4 Analytical Data for the Products
a) Reaction conditions: 1.0 equiv. imine, 5.0 equiv. bis(2-(trifluoromethyl)phenyl)-
zinc, 2 mol% Ni(PMe3)4, toluene, 80 °C, 15 h, N2. b) Yield A based on in situ 19
NMR spectra; yield B is the isolated yield. c) No isolated yield was determined.
F
N-((2,2ЈЈ-Bis(trifluoromethyl)-(1,1Ј:3Ј,1ЈЈ-terphenyl)-2Ј-yl)methyl-
ene)aniline (1b): Yield: 88%. M.p.: 92–93 °C. 1H NMR (CDCl3,
Z. Anorg. Allg. Chem. 2015, 838–841
840
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ARTICLE
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300 MHz, ppm): δ = 7.90–7.88 (m, 1 H), 7.77–7.72 (m, 2 H), 7.58– Crystallographic data (excluding structure factors) for the structure in
7.40 (m, 6 H), 7.36–7.31 (m, 3 H), 7.12–7.0 (m, 2 H), 7.02–6.96 (m,
1 H), 6.33–6.30 (m, 2 H). 19F NMR (CDCl3, 282 MHz, ppm):
δ = –58.38 (s), 58.80 (s) (1.00 : 1.43). HRMS (EI): m/z calculated for
C27H17F6N: 469.4203; found: 470.1319.
this paper have been deposited with the Cambridge Crystallographic
Data Centre, CCDC, 12 Union Road, Cambridge CB21EZ, UK.
Copies of the data can be obtained free of charge on quoting the de-
pository number CCDC-968364 (2) (Fax: +44-1223-336-033; E-Mail:
deposit@ccdc.cam.ac.uk, http://www.ccdc.cam.ac.uk).
N-((2,2ЈЈ-Bbis(trifluoromethyl)-(1,1Ј:3Ј,1ЈЈ-terphenyl)-2Ј-yl)meth-
1
ylene)-1-phenylmethanamine (2b): Yield: 46%. M.p.: 85–86 °C. H
NMR (CDCl3, 300 MHz, ppm): δ = 7.90–7.87 (m, 1 H), 7.69–7.62
(m, 2 H), 7.58–7.32 (m, 7 H), 7.26–7.24 (m, 2 H), 7.12–7.08 (m, 3
H), 6.64–6.62 (m, 2 H), 4.19–4.17 (m, 2 H). 19F NMR (CDCl3,
282 MHz, ppm): δ = –58.38 (s), 58.90 (s) (1.00 : 1.73). HRMS (EI):
m/z calculated for C28H19F6N: 483.4468; found: 484.1505.
Acknowledgements
We gratefully acknowledge the financial support by NSF China No.
21172132 and the support from Prof. Dr. Dieter Fenske and Dr. Olaf
Fuhr (Karlsruhe Nano-Micro Facility) on the determination of the
crystal structure.
N-((2,2ЈЈ-Bis(trifluoromethyl)-(1,1Ј:3Ј,1ЈЈ-terphenyl)-2Ј-yl)meth-
1
ylene)-4-methylaniline (3b): Yield: 63%. M.p.: 97–98 °C. H NMR
(CDCl3, 300 MHz, ppm): δ = 7.90–7.88 (m, 1 H), 7.75–7.70 (m, 2 H),
7.57–7.39 (m, 6 H), 7.35–7.24 (m, 3 H), 6.91–6.88 (m, 2 H), 6.26–
6.24 (m, 2 H), 2.20 (s, 3 H). 19F NMR (CDCl3, 282 MHz, ppm): δ =
–58.37 (s), 58.80 (s) (1.00 : 1.36). HRMS (EI): m/z calculated for
C28H19F6N: 483.5071; found: 484.1491.
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Received: December 22, 2014
Published Online: February 25, 2015
Z. Anorg. Allg. Chem. 2015, 838–841
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