Full text of DOI:10.1021/acs.joc.8b00412

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Reactivity of 1,2,3- and 1,2,4-trifluorobenzenes
in Palladium-catalyzed direct arylation
Xinzhe Shi, Shuxin Mao, Jean-François Soulé, and Henri Doucet
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00412 • Publication Date (Web): 14 Mar 2018
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The Journal of Organic Chemistry
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Reactivity of 1,2,3- and 1,2,4-trifluorobenzenes in
Palladium-catalyzed direct arylation
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Xinzhe Shi, Shuxin Mao, JeanꢀFrançois Soulé,* Henri Doucet*
Univ Rennes, CNRS, ISCRꢀUMR 6226, Fꢀ35000 Rennes, France.
jean-francois.soule@univ-rennes1.fr; henri.doucet@univ-rennes1.fr
Graphical abstract
Abstract: The higher reactivity of C4ꢀH bond as compared to C5ꢀH bond of 1,2,3ꢀtrifluorobenzene in palladiumꢀcatalyzed
direct arylation allows the selective synthesis of 4ꢀarylꢀ1,2,3ꢀtrifluorobenzenes in moderate to high yields. In most cases,
phosphineꢀfree Pd(OAc)2 catalyst and inexpensive KOAc base were employed. Then, from these 4ꢀarylꢀ1,2,3ꢀ
trifluorobenzenes, the palladiumꢀcatalyzed CꢀH bond functionalization of the C6ꢀposition allows the synthesis of the
corresponding 4,6ꢀdiarylated 1,2,3ꢀtrifluorobenzenes. We also applied these reaction conditions to the regioselective direct
C3ꢀarylation of 1,2,4ꢀtrifluorobenzene.
Introduction
Several bioactive compounds contain a (poly)fluorobiphenyl motif, such as Diflunisal which exhibits analgesic and antiꢀ
inflamatory activity. Therefore, the discovery of simple, but general routes to (poly)fluorobiphenyls has potential for
medicinal chemistry. The Pdꢀcatalyzed direct arylation of a wide variety of (hetero)aromatics, via a C–H bond activation
step, has brought a synthesis revolution in the preparation of bi(hetero)aryls in recent years. Such couplings are very
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attractive, compared to the more classical Pdꢀcatalysed reactions such as Stille, Suzuki or Negishi couplings as they do not
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1
require the preliminary synthesis of organometallic derivatives. Several examples of metalꢀcatalyzed arylations via a CꢀH
2
3
bond activation of polyfluorobenzenes with aryl halides have been reported. Fagnou et al. and a few other groups have
4ꢀ6
already reported examples of Pdꢀcatalyzed direct arylations of tetraꢀand pentaꢀfluorobenzenes. They observed that the CꢀH
bonds flanked by two fluoro substituents such as in pentafluorobenzene, 1,2,4,5ꢀtetrafluorobenzene or even 1,3,5ꢀ
4aꢀg
trifluorobenzene, could be easily arylated with aryl halides.
In contrast, to our knowledge, a single example of metalꢀ
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catalyzed direct arylation of 1,2,3ꢀtrifluorobenzene has been reported (Scheme 1, top). For this reaction, Larrosa et al.
employed [Ru(tꢀBuCN) ][BF ] as the catalyst and (NMe )(4ꢀFC H CO ) (0.35 equiv.), (NMe )OPiv (0.4 equiv.),
6
4 2
4
6
4
2
4
(
NMe )(OC(CF ) ) (2.5 equiv) as additives. The coupling product was obtained as a mixture of two regioisomers (C4:C5
4 3 3
77:23) in 29 % yield. To our knowledge, the regioselective metalꢀcatalyzed direct arylation of 1,2,3ꢀtrifluorobromobenzene
has not yet been described (Scheme 1, bottom).
Previous work7
H
H
Me
F
H
F
[Ru(t-BuCN) ][BF ] 4 mol%
6
4 2
F
F
F
F
F
Me
Me
10 equiv.
(NMe )(4-FC H CO ) (0.35 equiv.),
4
6
4
2
22%
+
(
NMe )OPiv (0.4 equiv.),
4
+
Me
(
4 3 3
NMe )(OC(CF ) ) (2.5 equiv),
tBuCN (3 equiv.), 115 °C, 16 h
F
Br
F
Me
7%
Me
This work
H
H
F
H
R
F
H
Pd(OAc) 2 mol%
F
2
F
1
.5 equiv.
KOPiv (2 equiv.),
DMA, 150 °C, 16 h
F
F
+
Br
PdCl(C
KOPiv (2 equiv.), DMA,
50 °C, 16 h
3 5
H )(dppb) 2 mol%,
ArBr
R
1
R'
R
F
F
F
Scheme 1. Metalꢀcatalyzed arylations of 1,2,3ꢀtrifluorobenzene
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As the discovery of an effective method, for the arylation of such trifluorobenzene derivatives, especially using easily
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available catalyst and base is highly desirable, the reactivity and regioselectivity for direct arylation using 1,2,3ꢀ
trifluorobromobenzene in the presence of palladium catalysts needed to be investigated. Here, we report (i) on the
regioselectivity of the palladiumꢀcatalyzed direct arylation of 1,2,3ꢀtrifluorobenzene using a low loading of a phosphineꢀfree
palladium catalyst; (ii) on the scope of the reaction; (iii) on the subsequent reactivity of these 4ꢀarylꢀ1,2,3ꢀtrifluorobenzenes
in Pdꢀcatalysed CꢀH bond functionalization; and (iv) on the reactivity in direct arylation of 1,2,4ꢀtrifluorobenzene using a
phosphineꢀfree catalyst.
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The free energy of activation for direct arylation in the presence of palladiumꢀcatalysts via Concerted Metalation
8
,9,
Deprotonation (CMD) pathway for several poly(fluoro)benzenes has been calculated by Gorelsky (Figure 1). CꢀH bonds
flanked by two fluoroꢀsubstituents such as in pentafluorobenzene, 1,3,5ꢀtrifluorobenzene or even 1,3ꢀdifluorobenzene are
ꢀ1
generally very reactive, as their energy of activation is quite low (<26 kcal mol ). Conversely, for 1,2,3ꢀtrifluorobenzene, the
ꢀ1
energy of activation of the CꢀH bonds adjacent to one fluorine atom is higher (28.8 kcal mol ), and the other CꢀH bond has
ꢀ1
an energy of activation of 31.7 kcal mol . Therefore, due to the lower energy of activation of the CꢀH bonds adjacent to one
fluorine atoms of 1,2,3ꢀtrifluorobenzene, for reactions which proceed via a Pdꢀcatalyzed CMD mechanism, we expected to be
able to control the regioselectivity of their functionalization using Pdꢀcatalysis instead of Ruꢀcatalysis.
F
F
H
F
F
H
F
F
H
21.9
24.5
F
F
F
H
F
F
F
29.0 H
32.4 H
H
H 28.8
25.4
H
H 31.7
H
F
‡
−1
Figure 1. Free energy of activation (ꢁG
, kcal mol ) for direct arylation via the CMD pathway involving an
298K
8
acetate ligand with the [Pd(C H )(PMe )(OAc)] catalyst.
6
5
3
Results and discussion
4
ꢀBromopropiophenone (1 equiv.) and 1,2,3ꢀtrifluorobenzene (1.5 equiv.) were employed as model substrates for our study
(
Table 1). We initially examined the influence of the nature of the base on the aryl bromide conversion and on the
regioselectivity of the reaction using 2 mol% Pd(OAc) catalyst and DMA as the solvent. We had previously observed that
2
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this catalyst precursor associated to this solvent promoted the coupling of several polyfluorobenzenes with aryl bromides in
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high yields. Cs CO , K CO or NaOAc bases, led to high conversions of 4ꢀbromopropiophenone, but the desired product
2
3
2
3
1a was only obtained in trace amount (Table 1, entries 1ꢀ3). The use of the acetate salts, KOAc or CsOAc, afforded 1a in
higher yields; however, the yields remained moderate, even when an higher catalyst loading (5 mol%) or a palladiumꢀ
diphosphine catalyst were used (Table 1, entries 4ꢀ7). PivOK was found to be the most effective base for this reaction, as 1a
was obtained in 41% yield (Table 1, entry 8). The good performance of pivalate as base/ligand is consistent with a CMD
0
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pathway. Finally, the use of 3 equiv. of 1,2,3ꢀtrifluorobenzene in the presence of 2 mol% Pd(OAc) catalyst and PivOK as
2
base in DMA afforded 1a in 54% yield (Table 1, entry 11). In all cases, the 4,6ꢀdiarylated 1,2,3ꢀtrifluorobenzene 1b was
produced in very low yields (<10%) and C5ꢀarylated 1,2,3ꢀtrifluorobenzene was not detected.
Table 1: Influence of the reaction conditions on the Pdꢀcatalyzed C4ꢀarylation
of 1,2,3ꢀtrifluorobenzene with 4ꢀbromopropiophenone
Entry Catalyst (mol%)
Solvent Base
Conv. Ratio 1a:1b Yield
(%)
in 1a
%)
(
1
2
3
4
5
6
7
8
9
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
2
2
2
(2)
(2)
(2)
(2)
(5)
(2)
DMA
DMA
DMA
DMA
DMA
DMA
Cs CO 100 0:0
0
2
3
K CO 100 100:0
<5
<5
31
21
14
24
41
8
2
3
NaOAc 100 100:0
KOAc 100 93:7
KOAc 88
CsOAc 50
100:0
98:2
PdCl(C
H
)(dppb) (2) DMA
KOAc 100 100:0
KOPiv 100 91:9
KOAc 100 100:0
KOAc 100 93:7
KOPiv 100 95:5
3
5
Pd(OAc)
Pd(OAc)
Pd(OAc)
(2)
(2)
(2)
(2)
DMA
DMF
DMA
DMA
2
2
2
2
a
1
0
37
54
a
11 Pd(OAc)
Conditions: 4ꢀBromopropiophenone (1 equiv.), 1,2,3ꢀtrifluorobenzene (1.5 equiv.), base
a
(
2 equiv.), 16 h, 150 °C, conversion of 4ꢀbromopropiophenone, isolated yields. 3 equiv.
of 1,2,3ꢀtrifluorobenzene.
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The Journal of Organic Chemistry
1
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3
Then, 1,2,3ꢀtrifluorobenzene was coupled with a set of (hetero)aryl bromides in the presence of 2 mol% Pd(OAc)2,
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9
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5
5
5
5
5
6
KOPiv as the base in DMA (Scheme 2). Very regioselective C4ꢀarylations and quite good yields in 2ꢀ7 were obtained using
aryl bromides bearing nitro, cyano, formyl, acetyl, ester or trifluoromethyl paraꢀsubstitutents. In all cases, a regioselective
arylation at the CꢀH adjacent to a CꢀF bond was observed, and low amounts of diarylated 1,2,3ꢀtrifluorobenzene were
1
observed by GC/MS and H NMR analysis of the crude mixtures. Similar yields were obtained for the coupling of the
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electronꢀrich aryl bromides, 4ꢀbromotoluene and 4ꢀbromoanisole with 1,2,3ꢀtrifluorobenzene to give 8 and 9 in 48% and 64%
yield, respectively. Nitroꢀ, nitrileꢀ, formylꢀ, acetylꢀ and esterꢀsubstituents at metaꢀposition on the aryl bromides were also
tolerated giving access to 10ꢀ14 in 40ꢀ67% yield. Reactions with the more hindered substrates, 2ꢀbromobenzonitrile and 1ꢀ
bromonaphthalene were also successful. The use of the Nꢀcontaining heterocycles, 3ꢀbromopyridine and 3ꢀbromoquinoline
afforded the desired C4ꢀarylated trifluorobenzene derivatives 17 and 18 in 64% and 72% yields, respectively. In all cases, no
formation of the C5ꢀarylated 1,2,3ꢀtrifluorobenzenes was detected by GC/MS analysis of the crude mixture. It should be
noted that in a few cases such as for the preparation of 3, 4 and 15, the use of KOAc as base led to higher yields than with
PivOK, due to cleaner reactions.
H
F
H
R
F
3
F
equiv.
+
Pd(OAc)2 2 mol%
F
KOPiv (2 equiv.),
DMA, 150 °C, 16 h
F
F
Br
R
R
Yield (%)
37, 34*
51, 57*
41, 52*
52
53
55
48
64
F
4'-NO2
4'-CN
4'-CHO
4'-COMe
2
3
4
5
6
7
8
9
F
F
F
1
6 56%
4
4
4
4
3
3
3
3
3
2
'-CO Et
'-CF3
'-Me
'-MeO
'-NO2
'-CN
'-CHO
'-COMe 13 54
N
2
F
F
10 60
17 64%
11 67, 57**
12 40
N
F
'-CO Me 14 60
'-CN
2
F
F
15 54, 68**
18 72%
*
: KOAc (2 equiv.), 1,2,3-trifluorobenzene (1.5 equiv.)
**: KOAc (2 equiv.), 1,2,3-trifluorobenzene (3 equiv.)
Scheme 2. Scope of the C4ꢀarylation of 1,2,3ꢀtrifluorobenzene
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The one pot synthesis of 4,6ꢀdiarylated 1,2,3ꢀtrifluorobenzene from 1,2,3ꢀtrifluorobenzene was then examined (Scheme 3).
As seen in the table 1 and in the scheme 2, the 4,6ꢀdiarylation of this trifluorobenzene derivative using only one equiv. of aryl
bromide is generally observed in trace amount, revealing that the second arylation is much slower than the first one. The use
of an excess of the electronꢀrich aryl bromides, 4ꢀbromotoluene and 4ꢀbromoanisole (3 equiv.) in the presence of 2 mol%
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
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2
2
3
3
3
3
3
3
3
3
3
3
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4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Pd(OAc) catalyst afforded the desired product 19 and 20 in 63% and 31% yields, respectively. Lower yields in 21 and 22
2
were obtained from 2ꢀbromobenzonitrile and 1ꢀbromonaphthalene. In all cases, no arylation at the C5ꢀposition of 1,2,3ꢀ
trifluorobenzene was detected.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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8
9
0
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0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
R
R
H
F
F
H
F
F
F
F
Pd(OAc) 2 mol%
R
Yield (%)
19 63
4-MeO 20 31
2-CN 21 16
2
4-Me
KOPiv (3 equiv.),
DMA, 150 °C, 16 h
+
Br
R
3
equiv.
F
F
F
2
2 23%
Scheme 3. Scope of the one pot 4,6ꢀdiarylation of 1,2,3ꢀtrifluorobenzene
Then, the reactivity for C6ꢀarylation, via a CꢀH bond activation of the trifluorobenzene moiety of some of the previously
obtained C4ꢀarylated trifluorobenzene derivatives was evaluated (Scheme 4). The reaction of 9 with 4ꢀbromobenzonitrile
using 5 mol% PdCl(C H )(dppb) catalyst and KOPiv as base afforded 23 in 48% yield; whereas the use of Pd(OAc) catalyst
3
5
2
led to a low yield. From 8 and 4ꢀbromobenzonitrile, under the same conditions, the desired product 24 was obtained in 51%
yield. Conversely, the reaction of 3 and 4ꢀbromotoluene was quite sluggish affording 24 in <10% yield revealing that 1,2,3ꢀ
trifluorobenzene derivatives bearing an electronꢀdeficient benzene unit at C4ꢀposition are poorly reactive for C6ꢀarylation.
Therfore, for the preparation of nonꢀsymmetrically substituted 4,6ꢀdiarylꢀ1,2,3ꢀtrifluorobenzenes, the most electronꢀrich arene
should be introduced in the first step.
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The Journal of Organic Chemistry
R
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
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3
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3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
R
F
H
PdCl(C H )(dppb)
3
5
F
R'
5
mol%
F
F
3, 8 or 9
KOPiv (2 equiv.),
DMA, 150 °C, 16 h
F
R'
F
R
Yield (%)
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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6
7
8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
MeO CN 23 48
Me
CN
Me
CN 24 51
Me 24 <10
NO2
Br
R'
25 37
1
.5 equiv.
Scheme 4. Scope of the C6ꢀarylation of 1,2,3ꢀtrifluoroꢀ4ꢀarylꢀbenzenes
The reactivity of two 1,2,3ꢀtrifluorobenzene derivatives bearing a functional group at C4ꢀposition was also studied (Scheme
5
). For the coupling reactions with 1ꢀmethoxyꢀ2,3,4ꢀtrifluorobenzene, both C5 and C6 positions might have been arylated
(
Scheme 5, top). However, with both 2ꢀbromobenzonitrile and 3ꢀbromopyridine, only the CꢀH bond adjacent to one fluorine
atom was arylated to give 26 and 27 in 61% and 48% yields, respectively. This is certainly due to the higher acidity of this
position. Conversely, the reaction of 2,3,4ꢀtrifluoroaniline, under the same reaction conditions, gave no coupling product;
12
whereas, the use of the thermally more stable catalyst PdCl(C H )(dppb) associated to KOAc as base led exclusively to the
3
5
amination product 28 in low yield (Scheme 5, bottom). This amination product 28 could be obtained in a higher yield of 62%
using Cs CO as base.
2
3
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MeO
NC
MeO
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
F
F
H
Pd(OAc) 2 mol%
2
F
F
26 61%
F
F
KOPiv (2 equiv.), MeO
DMA, 150 °C, 16 h
1.5 equiv.
N
+
F
Br
or
Br
N
F
F
27 48%
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NC
H N
H N
NC
2
2
F
F
H
PdCl(C H )(dppb)
F
F
3
5
Not detected
F
F
2
mol%
CN
1.5 equiv.
KOAc (2 equiv.),
DMA, 150 °C, 16 h
+
NH
Br
F
NC
*
: 2 equiv. of
F
F
Cs CO as base
28 24% 62%*
2
3
Scheme 5. Reactivity of 1ꢀmethoxyꢀ2,3,4ꢀtrifluorobenzene and 2,3,4ꢀtrifluoroaniline
9
Very few results concerning the Pdꢀcatalyzed direct C3ꢀarylation of 1,2,4ꢀtrifluorobenzene, especially using aryl halides as
9c
9c
aryl source, have been reported so far. A single example was reported by Cazin et al. in 2014. They described that from
this trifluorobenzene derivative and 4ꢀbromotoluene, using a dual metal system involving Cu(Cl)(NHC) and
Pd(Cl)(cinnamyl)(NHC) as catalyst, the C3ꢀarylated trifluorobenzene could be obtained in good yield. As our “ligandꢀfree”
catalytic system was quite efficient for the regioselective C4ꢀarylation of 1,2,3ꢀtrifluorobenzene, we also investigated its
efficiency for the arylation of 1,2,4ꢀtrifluorobenzene (Scheme 6). In all cases, we observed a highly regioselective arylation
at C3ꢀposition of 1,2,4ꢀtrifluorobenzene, as no other regioisomers could be detected by GC/MS analysis of the crude
mixtures. Both electronꢀdonating and electronꢀwithdrawing sustituents on the aryl bromide were tolerated affording the
desired products 29ꢀ34 in 53ꢀ70% yields. From 3ꢀbromopyridine and 3ꢀbromoquinoline, the expected products 35 and 36
were also regioselectively obtained in good yields. For most of these reactions, the formation of sideꢀproducts in low yields
arising from the arylꢀbromides homoꢀcoupling and from the diarylation of 1,2,4ꢀtrifluorobenzene was also observed by
GC/MS analysis of the crude mixtures.
8
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F
F
F
1
2
3
4
5
6
7
8
H
R
F
1
F
F
Pd(OAc)
2
2 mol%
.5 equiv.
R
-NO
-CN
Yield (%)
53, 66*
30 70
KOAc (2 equiv.),
DMA, 150 °C, 16 h
+
29
4
4
2
Br
4-CHO 31 56, 53*
-COMe 32 60
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
R
4
4
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-Me
-CN
33 61
34 59
F
F
N
N
F
F
F
F
35 72%
36 58%
*
: KOPiv (2 equiv.), 1,2,4-trifluorobenzene (2 equiv.)
Scheme 6. Scope of the C3ꢀarylation of 1,2,4ꢀtrifluorobenzene
In summary, the use of a Pdꢀcatalyst instead of a Ruꢀcatalyst for the direct arylation of 1,2,3ꢀtrifluorobenzene allowed its
regioselective functionalization at C4ꢀposition. We demonstrated that, using only 2 mol% of easily available Pd(OAc)2
catalyst precursor and KOAc or KOPiv as inexpensive bases, a wide variety of 4ꢀ(hetero)arylated 1,2,3ꢀtrifluorobenzenes can
be obtained with high regioselectivities and good yields. This strategy allowed the straightforward synthesis of C4ꢀarylated
1
,2,3ꢀtrifluorobenzenes in only one step from commercially available compounds. The access to a few symmetrical and nonꢀ
symmetrical 4,6ꢀdiarylꢀ1,2,3ꢀtrifluorobenzenes in moderate yields via successive CꢀH bond functionalizations is also
described. This “phosphineꢀfree” catalyst procedure was also successfully employed for the regioselective C3ꢀarylation of
1
,2,4ꢀtrifluorobenzene.
Experimental section
General procedure for palladium-catalyzed direct (di)arylations of trifluorobenzenes
The reaction of the aryl bromide, trifluorobenzene derivative and KOPiv or KOAc in the presence of Pd(OAc) or
2
12
PdCl(C H )(dppb) (see schemes) at 150 °C during 16 h in DMA (4 mL) under argon affords the coupling
3
5
products 1-36 after evaporation of the solvent and purification on silica gel. Eluent heptane:ethyl acetate 9:1 for
compounds 1-6, 10-15, 20, 21, 23-26, 28, 30-32, 34; heptane:ethyl acetate 4:1 for compounds 17, 18, 35, 36;
heptane:ethyl acetate 1:1 for compound 27; heptane for compounds 7-9, 16, 19, 22, 29, 33.
1
-(2',3',4'-Trifluoro-[1,1'-biphenyl]-4-yl)propan-1-one (1a)
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From 4-bromopropiophenone (0.213 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 1a was
2
obtained in 54% yield (0.142 g) as a white solid: mp 89-92 °C.
1
H NMR (400 MHz, CDCl ): δ 8.05 (d, J = 8.3 Hz, 2H), 7.60 (d, J = 8.3 Hz, 2H), 7.23-7.02 (m, 2H), 3.03 (q, J = 7.6
3
13
Hz, 2H), 1.25 (t, J = 7.6 Hz, 3H). C NMR (100 MHz, CDCl ): δ 200.2, 150.9 (ddd, J = 251.8, 10.0, 3.0 Hz), 148.8
3
(
ddd, J = 252.6, 10.7, 3.3 Hz), 140.2 (dt, J = 251.7, 15.5 Hz), 138.4, 136.4, 129.0 (d, J = 3.0 Hz), 128.3, 125.6 (dd,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
J = 10.5, 3.7 Hz), 123.8 (m), 112.5 (dd, J = 17.5, 4.0 Hz), 31.9, 8.23. Anal. Calcd for C H F O (264.25): C,
15
11 3
68.18; H, 4.20. Found: C, 67.98; H, 4.00.
1
4
,4''-Di(propionyl)-4',5',6'-trifluoro-1,1':3',1''-terphenyl (1b) was also isolated in low yield: H NMR (400 MHz,
CDCl ): δ 8.07 (d, J = 8.5 Hz, 4H), 7.64 (d, J = 8.5 Hz, 4H), 7.30 (td, J = 7.7, 2.3 Hz, 1H), 3.05 (q, J = 7.5 Hz, 4H),
3
1.26 (t, J = 7.5 Hz, 6H).
2,3,4-Trifluoro-4'-nitro-1,1'-biphenyl (2)
From 4-bromonitrobenzene (0.202 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 2 was obtained in
2
37% yield (0.093 g) as a yellow solid: mp 145-148 °C.
1
13
H NMR (400 MHz, CDCl ): δ 8.32 (d, J = 8.7 Hz, 2H), 7.68 (d, J = 8.7 Hz, 2H), 7.25-7.04 (m, 2H). C NMR (100
3
MHz, CDCl ): δ 151.4 (ddd, J = 253.1, 10.0, 3.1 Hz), 148.9 (ddd, J = 253.0, 10.0, 3.4 Hz), 147.6 (m), 140.5 (dt, J =
3
252.6, 15.5 Hz), 140.4, 129.7 (d, J = 3.1 Hz), 124.5 (dd, J = 10.5, 3.9 Hz), 123.9, 123.8 (m), 112.8 (dd, J = 17.6,
4
.0 Hz). Anal. Calcd for C H F NO (253.18): C, 56.93; H, 2.39; N, 5.53. Found: C, 56.98; H, 2.21; N, 5.78.
12
6
3
2
2',3',4'-Trifluoro-[1,1'-biphenyl]-4-carbonitrile (3)
From 4-bromobenzonitrile (0.182 g, 1 mmol), 1,2,3-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 3 was obtained in
2
57% yield (0.133 g) as a white solid: mp 132-135 °C.
1
13
H NMR (400 MHz, CDCl ): δ 7.75 (d, J = 8.3 Hz, 2H), 7.61 (d, J = 8.3 Hz, 2H), 7.22-7.03 (m, 2H). C NMR (100
3
MHz, CDCl ): δ 151.1 (ddd, J = 251.3, 10.1, 3.0 Hz), 148.8 (ddd, J = 252.6, 10.7, 3.3 Hz), 140.4 (dt, J = 252.4,
3
15.5 Hz), 138.6, 132.5, 129.5 (d, J = 3.1 Hz), 124.8 (dd, J = 10.4, 3.7 Hz), 123.8 (m), 118.4, 112.7 (dd, J = 17.5,
4
.1 Hz), 112.1. Anal. Calcd for C H F N (233.19): C, 66.96; H, 2.59; N, 6.01. Found: C, 66.70; H, 2.41; N, 6.12.
13
6 3
2',3',4'-Trifluoro-[1,1'-biphenyl]-4-carbaldehyde (4)
1
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From 4-bromobenzaldehyde (0.185 g, 1 mmol), 1,2,3-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 4 was
2
obtained in 52% yield (0.123 g) as a white solid: mp 153-156 °C.
1
H NMR (400 MHz, CDCl ): δ 10.08 (s, 1H), 7.97 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 7.23-7.04 (m, 2H).
3
13
C NMR (100 MHz, CDCl ): δ 191.7, 151.0 (ddd, J = 252.2, 10.3, 3.0 Hz), 148.9 (ddd, J = 252.9, 10.7, 3.3 Hz),
3
1
1
4
40.3 (dt, J = 252.1, 15.5 Hz), 140.0, 135.9, 130.0, 129.5 (d, J = 3.0 Hz), 125.5 (dd, J = 10.5, 3.7 Hz), 123.9 (m),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
12.5 (dd, J = 17.4, 4.1 Hz). Anal. Calcd for C H F O (236.19): C, 66.11; H, 2.99 66.30; H, 3.21.
13
7 3
1
,4''-Di(formyl)-4',5',6'-trifluoro-1,1':3',1''-terphenyl was also isolated in low yield in an impure form: H NMR
(
400 MHz, CDCl ): δ 10.07 (s, 2H), 7.98 (d, J = 8.2 Hz, 4H), 7.71 (d, J = 8.2 Hz, 4H), 7.32 (td, J = 7.7, 2.3 Hz, 1H).
3
1-(2',3',4'-Trifluoro-[1,1'-biphenyl]-4-yl)ethan-1-one (5)
From 4-bromoacetophenone (0.199 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 5 was
2
obtained in 52% yield (0.130 g) as a white solid: mp 69-72 °C.
1
H NMR (400 MHz, CDCl ): δ 8.05 (d, J = 8.3 Hz, 2H), 7.60 (d, J = 8.3 Hz, 2H), 7.23-7.04 (m, 2H), 2.65 (s, 3H).
3
13
C NMR (100 MHz, CDCl ): δ 197.5, 150.9 (ddd, J = 251.8, 10.0, 3.0 Hz), 148.8 (ddd, J = 252.6, 10.7, 3.3 Hz),
3
140.4 (dt, J = 251.8, 15.5 Hz), 138.7, 136.6, 129.0 (d, J = 3.0 Hz), 128.7, 125.6 (dd, J = 11.0, 3.7 Hz), 123.8 (m),
12.5 (dd, J = 17.4, 4.0 Hz), 26.7. Anal. Calcd for C H F O (250.22): C, 67.20; H, 3.63; found: C, 67.34; H, 3.80.
1
14
9 3
Ethyl 2',3',4'-trifluoro-[1,1'-biphenyl]-4-carboxylate (6)
From ethyl 4-bromobenzoate (0.229 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 6 was
2
obtained in 53% yield (0.148 g) as a white solid: mp 81-84 °C.
1
H NMR (400 MHz, CDCl ): δ 8.12 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.21-7.02 (m, 2H), 4.41 (q, J = 7.6
3
13
Hz, 2H), 1.42 (t, J = 7.6 Hz, 3H). C NMR (100 MHz, CDCl ): δ 166.2, 150.9 (ddd, J = 251.5, 10.2, 2.9 Hz), 148.9
3
(ddd, J = 252.5, 10.6, 3.4 Hz), 140.3 (dt, J = 251.7, 15.5 Hz), 130.2, 129.9, 128.8 (d, J = 3.0 Hz), 125.7 (dd, J =
10.5, 3.8 Hz), 123.9 (m), 112.4 (dd, J = 17.4, 4.0 Hz), 61.2, 14.3. Anal. Calcd for C H F O (280.25): C, 64.29;
15
11
3
2
H, 3.96; found: C, 64.07; H, 4.11.
13
2,3,4-Trifluoro-4'-(trifluoromethyl)-1,1'-biphenyl (7)
1
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From 4-bromobenzotrifluoride (0.225 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 7 was
2
obtained in 55% yield (0.152 g) as a white solid: mp 64-67 °C.
1
H NMR (400 MHz, CDCl ): δ 7.72 (d, J = 8.2 Hz, 2H), 7.61 (d, J = 8.2 Hz, 2H), 7.20-7.03 (m, 2H).
3
1
4
,4''-Di(trifluoromethyl)-4',5',6'-trifluoro-1,1':3',1''-terphenyl was also isolated in low yield: H NMR (400 MHz,
CDCl ): δ 7.81 (d, J = 8.3 Hz, 4H), 7.74 (d, J = 8.3 Hz, 4H), 7.37 (td, J = 7.7, 2.3 Hz, 1H).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
13
2,3,4-Trifluoro-4'-methyl-1,1'-biphenyl (8)
From 4-bromotoluene (0.171 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol) in the
presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 8 was obtained in 48%
2
yield (0.106 g) as a white oil.
1
H NMR (400 MHz, CDCl ): δ 7.41 (d, J = 7.8 Hz, 2H), 7.28 (d, J = 7.8 Hz, 2H), 7.18-6.97 (m, 2H), 2.44 (s, 3H).
3
14
2,3,4-Trifluoro-4'-methoxy-1,1'-biphenyl (9)
From 4-bromoanisole (0.187 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol) in the
presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 9 was obtained in 64%
2
yield (0.152 g) as a white solid: mp 73-76 °C.
1
H NMR (400 MHz, CDCl ): δ 7.43 (d, J = 8.0 Hz, 2H), 7.15-7.07 (m, 1H), 7.05-6.97 (m, 1H), 6.99 (d, J = 8.0 Hz,
3
2H), 3.86 (s, 3H).
2,3,4-Trifluoro-3'-nitro-1,1'-biphenyl (10)
From 3-bromonitrobenzene (0.202 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 10 was obtained
2
in 60% yield (0.152 g) as a yellow solid: mp 102-105 °C.
1
H NMR (400 MHz, CDCl ): δ 8.36 (s, 1H), 8.25 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.64 (t, J = 8.0 Hz,
3
13
1
H), 7.24-7.05 (m, 2H). C NMR (100 MHz, CDCl ): δ 151.1 (ddd, J = 252.5, 10.1, 3.0 Hz), 148.7 (ddd, J = 252.5,
3
10.7, 3.4 Hz), 148.5, 140.2 (dt, J = 252.5, 15.5 Hz), 135.6, 134.8 (d, J = 3.3 Hz), 129.7, 124.3 (dd, J = 10.5, 3.8
Hz), 123.9 (m), 123.7 (d, J = 2.7 Hz), 123.1, 112.7 (dd, J = 17.5, 4.1 Hz).Anal. Calcd for C H F NO (253.18): C,
12
6
3
2
56.93; H, 2.39; N, 5.53. Found: C, 56.74; H, 2.24; N, 5.47.
2',3',4'-Trifluoro-[1,1'-biphenyl]-3-carbonitrile (11)
1
2
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From 3-bromobenzonitrile (0.182 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 11 was obtained
2
in 67% yield (0.156 g) as a white solid: mp 92-95 °C.
1
H NMR (400 MHz, CDCl ): δ 7.78 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.58 (t, J = 7.8 Hz,
3
13
1H), 7.20-7.04 (m, 2H). C NMR (100 MHz, CDCl ): δ 151.0 (ddd, J = 252.3, 10.1, 3.0 Hz), 148.8 (ddd, J = 252.5,
3
1
0.7, 3.4 Hz), 140.1 (dt, J = 252.5, 15.5 Hz), 135.3, 133.1 (d, J = 3.0 Hz), 132.3 (d, J = 2.8 Hz), 131.7, 129.6,
24.4 (dd, J = 10.6, 3.7 Hz), 123.7 (m), 118.3, 113.1, 112.8 (dd, J = 17.5, 4.1 Hz). Anal. Calcd for C H F N
0
1
2
3
4
5
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7
8
9
0
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2
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13
6 3
(
233.19): C, 66.96; H, 2.59; N, 6.01. Found: C, 66.78; H, 2.69; N, 5.92.
1
3
7
1
,3''-Dicyano-4',5',6'-trifluoro-1,1':3',1''-terphenyl was also isolated in low yield: H NMR (400 MHz, CDCl ): δ
3
.90 (s, 2H), 7.85 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.67 (t, J = 7.8 Hz, 2H), 7.32 (td, J = 7.7, 2.3 Hz,
H).
2',3',4'-Trifluoro-[1,1'-biphenyl]-3-carbaldehyde (12)
From 3-bromobenzaldehyde (0.185 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 12 was
2
obtained in 40% yield (0.094 g) as a white solid: mp 69-72 °C.
1
H NMR (400 MHz, CDCl ): δ 10.08 (s, 1H), 8.00 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.64 (t,
3
13
J = 7.8 Hz, 1H), 7.25-7.14 (m, 1H), 7.13-7.04 (m, 1H). C NMR (100 MHz, CDCl ): δ 191.8, 151.0 (ddd, J = 252.3,
3
10.1, 3.0 Hz), 148.8 (ddd, J = 252.5, 10.6, 3.3 Hz), 140.4 (dt, J = 252.0, 15.5 Hz), 136.8, 135.1, 134.6 (d, J = 3.1
Hz), 129.8 (d, J = 2.5 Hz), 129.5, 129.4, 125.3 (dd, J = 10.7, 3.7 Hz), 123.8 (m), 112.5 (dd, J = 17.4, 4.1 Hz). Anal.
Calcd for C H F O (236.19): C, 66.11; H, 2.99. Found: C, 66.00; H, 2.87.
13
7 3
1-(2',3',4'-Trifluoro-[1,1'-biphenyl]-3-yl)ethan-1-one (13)
From 3-bromoacetophenone (0.199 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 13 was
2
obtained in 54% yield (0.135 g) as a white solid: mp 92-95 °C.
1
H NMR (400 MHz, CDCl ): δ 8.07 (s, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.56 (t, J = 7.8 Hz,
3
1
3
1
2
=
2
H), 7.24-7.13 (m, 1H), 7.13-7.01 (m, 1H), 2.65 (s, 3H). C NMR (100 MHz, CDCl ): δ 197.6, 150.7 (ddd, J =
3
51.3, 10.1, 3.0 Hz), 148.8 (ddd, J = 251.8, 10.5, 3.3 Hz), 140.1 (dt, J = 252.0, 15.5 Hz), 137.5, 134.6, 133.3 (d, J
3.1 Hz), 129.0, 128.6 (d, J = 2.5 Hz), 128.1, 125.7 (dd, J = 10.7, 3.9 Hz), 123.9 (m), 112.4 (dd, J = 17.3, 4.0 Hz),
6.7. Anal. Calcd for C H F O (250.22): C, 67.20; H, 3.63. Found: C, 67.40; H, 3.69.
14
9 3
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Methyl 2',3',4'-trifluoro-[1,1'-biphenyl]-3-carboxylate (14)
From methyl 3-bromobenzoate (0.215 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 14 was
2
obtained in 60% yield (0.160 g) as a yellow solid: mp 64-67 °C.
1
H NMR (400 MHz, CDCl ): δ 8.16 (s, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 7.8 Hz,
3
0
1
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9
0
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9
0
13
1
H), 7.23-7.14 (m, 1H), 7.12-7.03 (m, 1H), 3.95 (s, 3H). C NMR (100 MHz, CDCl ): δ 166.6, 150.7 (ddd, J =
3
251.0, 10.1, 3.0 Hz), 148.7 (ddd, J = 251.9, 10.5, 3.3 Hz), 140.1 (dt, J = 251.7, 15.5 Hz), 134.4, 133.2 (d, J = 3.1
Hz), 130.8, 129.9 (d, J = 2.3 Hz), 129.3, 128.8, 125.7 (dd, J = 10.7, 3.9 Hz), 123.9 (m), 112.4 (dd, J = 17.3, 4.0
Hz), 52.3. Anal. Calcd for C H F O (266.22): C, 63.16; H, 3.41. Found: C, 63.08; H, 3.34.
14
9
3
2
2',3',4'-Trifluoro-[1,1'-biphenyl]-2-carbonitrile (15)
From 2-bromobenzonitrile (0.182 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOAc (0.196 g, 2 mmol) in
the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 15 was obtained in
2
68% yield (0.158 g) as a yellow solid: mp 121-124 °C.
1
H NMR (400 MHz, CDCl ): δ 7.80 (d, J = 8.6 Hz, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.48 (d, J =
3
1
3
8
=
1
6
.2 Hz, 1H), 7.22-7.06 (m, 2H). C NMR (100 MHz, CDCl ): δ 151.5 (ddd, J = 252.6, 10.1, 3.0 Hz), 148.7 (ddd, J
3
252.3, 10.7, 3.5 Hz), 140.2 (dt, J = 252.9, 15.5 Hz), 137.5, 133.4, 132.8, 130.9 (d, J = 1.2 Hz), 128.9, 124.8 (m),
23.4 (dd, J = 12.3, 3.7 Hz), 117.6, 112.8, 112.5 (dd, J = 17.6, 4.0 Hz). Anal. Calcd for C H F N (233.19): C,
13
6 3
6.96; H, 2.59; N, 6.01. Found: C, 67.05; H, 2.75; N, 5.80.
1-(2,3,4-Trifluorophenyl)naphthalene (16)
From 1-bromonaphthalene (0.207 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 16 was obtained
2
in 56% yield (0.144 g) as a white solid: mp 63-66 °C.
1
H NMR (400 MHz, CDCl ): δ 7.95 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 1H), 7.60-7.46 (m, 3H), 7.44 (d, J = 7.8
3
13
Hz, 1H), 7.18-7.06 (m, 2H). C NMR (100 MHz, CDCl ): δ 150.8 (ddd, J = 250.1, 10.1, 2.9 Hz), 149.1 (ddd, J =
3
250.1, 10.0, 3.4 Hz), 140.1 (dt, J = 251.9, 15.5 Hz), 133.6, 131.9 (d, J = 1.8 Hz), 131.6, 129.1, 128.5, 127.9, 126.6,
125.7, 125.6 (m), 125.3, 125.2, 112.0 (dd, J = 17.3, 4.0 Hz). Anal. Calcd for C H F (258.24): C, 74.42; H, 3.51.
16
9 3
Found: C, 74.61; H, 3.34.
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-(2,3,4-Trifluorophenyl)pyridine (17)
The Journal of Organic Chemistry
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From 3-bromopyridine (0.158 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol) in
the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 17 was obtained in
2
64% yield (0.134 g) as a yellow solid: mp 94-97 °C.
1
H NMR (400 MHz, CDCl ): δ 8.77 (s, 1H), 8.68 (s, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.43 (bs, 1H), 7.21-7.04 (m, 2H).
3
13
C NMR (100 MHz, CDCl ): δ 151.0 (ddd, J = 251.8, 10.1, 2.9 Hz), 149.4 (bs), 148.8 (ddd, J = 251.5, 10.0, 3.6
0
1
2
3
4
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7
8
9
0
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9
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Hz), 140.5 (dt, J = 252.2, 15.5 Hz), 136.1, 130.1, 123.8 (m), 123.4 (bs), 112.6 (dd, J = 17.5, 4.0 Hz). Anal. Calcd
for C H F N (209.17): C, 63.16; H, 2.89; N, 6.70. Found: C, 63.27; H, 2.74; N, 6.57.
11
6 3
3-(2,3,4-Trifluorophenyl)quinoline (18)
From 3-bromoquinoline (0.208 g, 1 mmol), 1,2,3-trifluorobenzene (0.396 g, 3 mmol), KOPiv (0.280 g, 2 mmol) in
the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 18 was obtained in
2
72% yield (0.186 g) as a yellow solid: mp 158-161 °C.
1
H NMR (400 MHz, CDCl ): δ 9.04 (s, 1H), 8.28 (s, 1H), 8.15 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.77 (t, J
3
13
= 7.8 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.32-7.22 (m, 1H), 7.16-7.06 (m, 1H). C NMR (100 MHz, CDCl ): δ 151.0
3
(ddd, J = 250.8, 10.1, 2.9 Hz), 150.8 (m), 148.9 (ddd, J = 252.2, 10.5, 3.6 Hz), 140.3 (dt, J = 252.2, 15.5 Hz),
1
1
3
47.5, 135.6 (d, J = 3.2 Hz), 130.2, 129.3, 128.1, 127.5, 127.3, 127.0, 124.0 (m), 123.5 (dd, J = 11.0, 3.7 Hz),
12.7 (dd, J = 17.5, 4.0 Hz). Anal. Calcd for C H F N (259.23): C, 69.50; H, 3.11; N, 5.40. Found: C, 69.42; H,
15
8 3
.04; N, 5.24.
4',5',6'-Trifluoro-4,4''-dimethyl-1,1':3',1''-terphenyl (19)
From 4-bromotoluene (0.513 g, 3 mmol), 1,2,3-trifluorobenzene (0.132 g, 1 mmol), KOPiv (0.420 g, 3 mmol) in the
presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 19 was obtained in 63%
2
yield (0.196 g) as a white solid: mp 90-93 °C.
1
H NMR (400 MHz, CD Cl ): δ 7.43 (d, J = 8.0 Hz, 4H), 7.28 (d, J = 8.0 Hz, 4H), 7.23 (td, J = 7.7, 2.3 Hz, 1H), 2.40
2
2
13
(
s, 6H). C NMR (100 MHz, CD Cl ): δ 147.5 (ddd, J = 250.2, 10.6, 2.9 Hz), 140.4 (dt, J = 249.0, 16.3 Hz), 138.4,
2
2
1
31.1, 129.4, 128.7 (m), 126.3 (dd, J = 9.6, 5.5 Hz), 124.4 (m), 20.9. Anal. Calcd for C H F (312.34): C, 76.91;
20 15 3
H, 4.84. Found: C, 76.74; H, 5.04.
4',5',6'-Trifluoro-4,4''-dimethoxy-1,1':3',1''-terphenyl (20)
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From 4-bromoanisole (0.561 g, 3 mmol), 1,2,3-trifluorobenzene (0.132 g, 1 mmol), KOPiv (0.420 g, 3 mmol) in the
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presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 20 was obtained in 31%
2
yield (0.106 g) as a white solid: mp 131-134 °C.
1
H NMR (400 MHz, CDCl ): δ 7.47 (d, J = 8.5 Hz, 4H), 7.19 (td, J = 8.0, 2.2 Hz, 1H), 6.99 (d, J = 8.5 Hz, 4H), 3.86
3
13
(s, 6H). C NMR (100 MHz, CDCl ): δ 159.6, 147.2 (ddd, J = 250.4, 10.6, 2.9 Hz), 140.6 (dm, J = 250.0 Hz),
3
130.0 (m), 126.5, 125.8 (dd, J = 9.2, 5.8 Hz), 123.9 (m), 114.2, 55.4. Anal. Calcd for C H F O (344.33): C,
20 15 3 2
0
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7
8
9
0
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9
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5
6
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8
9
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2
3
4
5
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7
8
9
0
69.76; H, 4.39. Found: C, 69.58; H, 4.31.
2,2''-Dicyano-4',5',6'-trifluoro-1,1':3',1''-terphenyl (21)
From 2-bromobenzonitrile (0.546 g, 3 mmol), 1,2,3-trifluorobenzene (0.132 g, 1 mmol), KOPiv (0.420 g, 3 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 21 was obtained
2
in 16% yield (0.053 g) as a yellow solid: mp 192-195 °C.
1
H NMR (400 MHz, CDCl ): δ 7.81 (d, J = 8.3 Hz, 2H), 7.72 (t, J = 8.0 Hz, 2H), 7.59 (d, J = 8.3 Hz, 2H), 7.56 (t, J =
3
13
7.8 Hz, 2H), 7.29 (td, J = 7.7, 2.3 Hz, 1H). C NMR (100 MHz, CDCl ): δ 148.9 (ddd, J = 255.6, 10.8, 3.6 Hz),
3
140.5 (dt, J = 254.6, 15.7 Hz), 137.0, 133.4, 133.1, 131.1, 129.2, 126.3 (m), 123.2 (dd, J = 10.4, 6.4 Hz), 117.7,
1
12.8. Anal. Calcd for C H F N (334.30): C, 71.86; H, 2.71; N, 8.38. Found: C, 71.99; H, 2.59; N, 8.40.
20 9 3 2
1,1'-(4,5,6-Trifluoro-1,3-phenylene)dinaphthalene (22)
From 1-bromonaphthalene (0.621 g, 3 mmol), 1,2,3-trifluorobenzene (0.132 g, 1 mmol), KOPiv (0.420 g, 3 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 22 was obtained
2
in 23% yield (0.088 g) as a yellow solid: mp 182-185 °C.
1
H NMR (400 MHz, CDCl ): δ 7.94 (d, J = 8.0 Hz, 4H), 7.82-7.78 (m, 2H), 7.60-7.48 (m, 8H), 7.26 (td, J = 7.7, 2.3
3
13
Hz, 1H). C NMR (100 MHz, CDCl ): δ 148.5 (ddd, J = 250.9, 10.1, 2.9 Hz), 140.1 (dt, J = 253.9, 17.0 Hz), 133.6,
3
131.7 (m), 131.6, 129.1, 128.5, 128.1, 127.9, 126.7, 126.2, 125.3, 125.2. Anal. Calcd for C H F (384.40): C,
26
15 3
81.24; H, 3.93. Found: C, 81.40; H, 3.98.
4
',5',6'-Trifluoro-4''-methoxy-[1,1':3',1''-terphenyl]-4-carbonitrile (23)
From 4-bromobenzonitrile (0.273 g, 1.5 mmol), 2,3,4-trifluoro-4'-methoxy-1,1'-biphenyl 9 (0.238 g, 1 mmol), KOPiv
0.280 g, 2 mmol) in the presence of PdCl(C H )(dppb) (30.5 mg, 0.05 mmol) in DMA (4 mL) at 150 °C during 16
(
3
5
h, product 23 was obtained in 48% yield (0.163 g) as a white solid: mp 151-154 °C.
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The Journal of Organic Chemistry
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H NMR (400 MHz, CDCl ): δ 7.76 (d, J = 8.5 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H), 7.46 (d, J = 8.5 Hz, 2H), 7.23 (td, J
3
1
2
3
4
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7
8
9
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1
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1
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1
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1
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1
2
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5
5
5
5
5
5
6
13
=
7.8, 2.3 Hz, 1H), 7.00 (d, J = 8.5 Hz, 2H), 3.87 (s, 3H). C NMR (100 MHz, CDCl ): δ 159.9, 148.3 (ddd, J =
3
2
53.1, 10.6, 2.8 Hz), 147.4 (ddd, J = 252.7, 11.2, 2.7 Hz), 140.7 (dt, J = 251.7, 16.1 Hz), 138.7, 132.5, 130.0 (d, J
= 2.8 Hz), 129.5 (d, J = 2.9 Hz), 126.7 (dd, J = 11.0, 4.1 Hz), 125.8, 124.2 (dd, J = 11.3, 4.2 Hz), 124.1 (m), 118.5,
114.3, 112.1, 55.4. Anal. Calcd for C H F NO (339.32): C, 70.80; H, 3.56; N, 4.13. Found: C, 71.07; H, 3.39; N,
20
12 3
4.40.
0
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4
',5',6'-Trifluoro-4''-methyl-[1,1':3',1''-terphenyl]-4-carbonitrile (24)
From 4-bromobenzonitrile (0.273 g, 1.5 mmol), 2,3,4-trifluoro-4'-methyl-1,1'-biphenyl 8 (0.222 g, 1 mmol), KOPiv
0.280 g, 2 mmol) in the presence of PdCl(C H )(dppb) (30.5 mg, 0.05 mmol) in DMA (4 mL) at 150 °C during 16
(
3
5
h, product 24 was obtained in 51% yield (0.164 g) as a white solid: mp 167-170 °C.
1
H NMR (400 MHz, CDCl ): δ 7.76 (d, J = 8.5 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 7.27 (d, J
3
13
=
1
8.5 Hz, 2H), 7.24 (td, J = 7.8, 2.3 Hz, 1H), 2.42 (s, 3H). C NMR (100 MHz, CDCl ): δ 148.5 (ddd, J = 253.4,
3
0.6, 2.9 Hz), 147.6 (ddd, J = 253.0, 10.2, 2.9 Hz), 140.7 (dt, J = 251.9, 16.0 Hz), 138.7 (m), 132.5, 130.6, 129.5
(m), 128.6 (d, J = 2.7 Hz), 127.0 (dd, J = 11.0, 4.1 Hz), 124.3 (m), 118.5, 112.2, 21.2. Anal. Calcd for C H F N
20
12 3
(
323.32): C, 74.30; H, 3.74; N, 4.33. Found: C, 74.41; H, 3.78; N, 4.60.
4
',5',6'-Trifluoro-4-methyl-4''-nitro-1,1':3',1''-terphenyl (25)
From 4-bromonitrobenzene (0.303 g, 1.5 mmol), 2,3,4-trifluoro-4'-methyl-1,1'-biphenyl 8 (0.222 g, 1 mmol), KOPiv
0.280 g, 2 mmol) in the presence of PdCl(C H )(dppb) (30.5 mg, 0.05 mmol) in DMA (4 mL) at 150 °C during 16
(
3
5
h, product 25 was obtained in 37% yield (0.127 g) as a yellow solid: mp 150-153 °C.
1
H NMR (400 MHz, CD Cl ): δ 8.30 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 8.5 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 7.35-7.27
2
2
13
(
m, 3H), 2.40 (s, 3H). C NMR (100 MHz, CD Cl ): δ 148.6 (ddd, J = 253.9, 10.6, 2.9 Hz), 147.6, 147.5 (ddd, J =
2
2
2
52.3, 11.0, 2.9 Hz), 140.6 (dt, J = 250.9, 16.0 Hz), 140.5, 138.8, 130.6, 129.8 (d, J = 3.0 Hz), 129.5, 128.6 (d, J =
.2 Hz), 127.0 (dd, J = 11.0, 4.2 Hz), 124.6 (m), 124.0 (dd, J = 10.4, 4.4 Hz), 123.8, 20.9. Anal. Calcd for
2
C H F NO (343.31): C, 66.47; H, 3.52; N, 4.08. Found: C, 66.57; H, 3.41; N, 3.79.
19
12
3
2
2
',3',4'-Trifluoro-5'-methoxy-[1,1'-biphenyl]-2-carbonitrile (26)
From 2-bromobenzonitrile (0.182 g, 1 mmol), 1,2,3-trifluoro-4-methoxybenzene (0.243 g, 1.5 mmol), KOPiv (0.280
g, 2 mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 26
2
was obtained in 61% yield (0.160 g) as a white solid: mp 128-131 °C.
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H NMR (400 MHz, CDCl ): δ 7.80 (d, J = 8.6 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.50 (d, J =
3
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5
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5
5
5
6
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.2 Hz, 1H), 6.78 (td, J = 6.3, 2.4 Hz, 1H), 3.93 (s, 3H). C NMR (100 MHz, CDCl ): δ 144.8 (m), 142.8 (ddd, J =
3
2
45.5, 11.2, 1.7 Hz), 142.3 (ddd, J = 253.1, 11.7, 1.9 Hz), 141.2 (ddd, J = 251.3, 16.7, 13.0 Hz), 137.5, 133.5,
132.8, 131.0 (m), 128.9, 121.1 (dd, J = 12.7, 4.5 Hz), 117.7, 112.8, 108.5 (m), 57.1. Anal. Calcd for C H F NO
14
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(263.22): C, 63.88; H, 3.06; N, 5.32. Found: C, 64.11; H, 3.00; N, 5.07.
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3
-(2,3,4-Trifluoro-5-methoxyphenyl)pyridine (27)
From 3-bromopyridine (0.158 g, 1 mmol), 1,2,3-trifluoro-4-methoxybenzene (0.243 g, 1.5 mmol), KOPiv (0.280 g,
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 27 was
2
2
obtained in 48% yield (0.115 g) as a yellow solid: mp 142-145 °C.
1
H NMR (400 MHz, CDCl ): δ 8.77 (bs, 1H), 8.67 (bs, 1H), 7.84 (d, J = 7.3 Hz, 1H), 7.42 (bs, 1H), 6.75 (t, J = 6.3
3
13
Hz, 1H), 3.94 (s, 3H). C NMR (100 MHz, CDCl ): δ 149.3, 145.1 (dt, J = 8.2, 2.8 Hz), 143.1 (ddd, J = 245.5, 11.6
3
Hz), 141.7 (ddd, J = 252.5, 11.7, 2.7 Hz), 141.2 (ddd, J = 251.3, 17.0, 13.0 Hz), 136.3, 130.4, 123.5, 121.1 (d, J =
10.5, 2.9 Hz), 107.6, 57.1. Anal. Calcd for C H F NO (239.20): C, 60.26; H, 3.37; N, 5.86. Found: C, 60.07; H,
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3.24; N, 5.68.
2-((2,3,4-Trifluorophenyl)amino)benzonitrile (28)
From 2-bromobenzonitrile (0.182 g, 1 mmol), 2,3,4-trifluoroaniline (0.220 g, 1.5 mmol), KOAc (0.196 g, 2 mmol) in
the presence of PdCl(C H )(dppb) (12.2 mg, 0.02 mmol), in DMA (4 mL) at 150 °C during 16 h, product 28 was
3
5
obtained in 24% yield (0.059 g) as a yellow solid: mp 123-126 °C.
1
H NMR (400 MHz, CDCl ): δ 7.54 (dd, J = 8.2, 1.6 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.10-6.96 (m, 3H), 6.93 (d, J
3
13
=
7.1 Hz, 1H), 6.13 (s, 1H). C NMR (100 MHz, CDCl ): δ 148.0 (ddd, J = 248.0, 10.2, 2.5 Hz), 146.2, 145.2 (ddd,
3
J = 250.1, 11.1, 3.2 Hz), 140.6 (ddd, J = 252.6, 16.0, 13.9 Hz), 134.1, 133.2, 125.5 (dd, J = 9.4, 3.6), 120.5, 117.4
(ddd, J = 7.5, 3.7, 0.8 Hz), 117.0, 114.4, 111.8 (dd, J = 18.2, 4.1 Hz), 99.6. Anal. Calcd for C H F N (248.21): C,
13
7
3
2
62.91; H, 2.84; N, 11.29. Found: C, 62.99; H, 2.90; N, 11.47.
15
2
,3,6-Trifluoro-4'-nitro-1,1'-biphenyl (29)
From 4-bromonitrobenzene (0.202 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 29 was
2
obtained in 53% yield (0.134 g) as a white solid: mp 127-130 °C.
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H NMR (400 MHz, CDCl ): δ 8.34 (d, J = 8.7 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.30-7.17 (m, 1H), 7.06-6.94 (m,
3
1
2
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H). C NMR (100 MHz, CDCl ): δ 154.8 (ddd, J = 247.0, 4.5, 3.0 Hz), 147.9, 147.6 (dm, J = 252.2 Hz), 147.5
3
(
dm, J = 246.1 Hz), 135.0 (d, J = 1.9 Hz), 131.3 (t, J = 2.1 Hz), 123.6, 118.1 (dd, J = 20.2, 14.0 Hz), 117.3 (ddd, J
= 19.5, 10.0, 1.6 Hz), 111.4 (ddd, J = 25.0, 6.6, 4.2 Hz).
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2',3',6'-Trifluoro-[1,1'-biphenyl]-4-carbonitrile (30)
From 4-bromobenzonitrile (0.182 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 30 was obtained
2
in 70% yield (0.163 g) as a white solid: mp 143-146 °C.
1
H NMR (400 MHz, CDCl ): δ 7.76 (d, J = 8.3 Hz, 2H), 7.59 (d, J = 8.3 Hz, 2H), 7.27-7.16 (m, 1H), 7.04-6.94 (m,
3
13
1
2
1
H). C NMR (100 MHz, CDCl ): δ 154.8 (ddd, J = 246.8, 4.4, 2.9 Hz), 147.6 (dm, J = 252.2 Hz), 147.5 (dm, J =
3
46.1 Hz), 133.1 (d, J = 1.8 Hz), 132.2, 131.0 (t, J = 2.2 Hz), 118.4, 118.3 (dd, J = 20.1, 14.6 Hz), 117.1 (ddd, J =
9.5, 10.0, 1.5 Hz), 112.6, 111.4 (ddd, J = 25.1, 6.7, 4.3 Hz).
2',3',6'-Trifluoro-[1,1'-biphenyl]-4-carbaldehyde (31)
From 4-bromobenzaldehyde (0.185 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 31 was
2
obtained in 56% yield (0.132 g) as a white solid: mp 100-103 °C.
1
H NMR (400 MHz, CDCl ): δ 10.07 (s, 1H), 7.98 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.3 Hz, 2H), 7.24-7.11 (m, 1H),
3
13
7
.00-6.92 (m, 1H). C NMR (100 MHz, CDCl ): δ 191.7, 155.0 (ddd, J = 247.5, 4.4, 2.9 Hz), 147.6 (ddd, J = 251.8,
3
1
4.5, 7.1 Hz), 147.5 (ddd, J = 245.6, 13.5, 3.7 Hz), 136.2, 134.5 (d, J = 1.6 Hz), 130.9 (t, J = 2.1 Hz), 129.6, 119.0
(
dd, J = 20.2, 14.7 Hz), 116.8 (ddd, J = 19.4, 10.0, 1.3 Hz), 111.2 (ddd, J = 25.3, 6.7, 4.3 Hz). Anal. Calcd for
C H F O (236.19): C, 66.11; H, 2.99. Found: C, 66.00; H, 3.19.
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7 3
1-(2',3',6'-Trifluoro-[1,1'-biphenyl]-4-yl)ethan-1-one (32)
From 4-bromoacetophenone (0.199 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2
mmol) in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 32 was
2
obtained in 60% yield (0.150 g) as a white solid: mp 127-130 °C.
1
H NMR (400 MHz, CDCl ): δ 8.06 (d, J = 8.3 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H), 7.22-7.11 (m, 1H), 6.99-6.92 (m,
3
13
1
H), 2.65 (s, 3H). C NMR (100 MHz, CDCl ): δ 197.5, 155.1 (ddd, J = 246.1, 4.4, 2.9 Hz), 147.7 (ddd, J = 251.8,
3
1
4.5, 7.1 Hz), 147.6 (ddd, J = 245.6, 13.5, 3.7 Hz), 137.0, 133.1 (d, J = 1.6 Hz), 130.5 (t, J = 2.1 Hz), 128.3, 119.2
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dd, J = 20.3, 14.8 Hz), 116.5 (ddd, J = 19.4, 10.0, 1.3 Hz), 111.1 (ddd, J = 25.3, 6.7, 4.2 Hz), 26.7. Anal. Calcd for
C H F O (250.72): C, 67.20; H, 3.63. Found: C, 66.97; H, 3.47.
Page 20 of 23
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2,3,6-Trifluoro-4'-methyl-1,1'-biphenyl (33)
From 4-bromotoluene (0.171 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2 mmol) in
the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 33 was obtained in
2
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61% yield (0.135 g) as a white oil.
1
H NMR (400 MHz, CDCl ): δ 7.36 (d, J = 7.8 Hz, 2H), 7.29 (d, J = 7.8 Hz, 2H), 7.15-7.05 (m, 1H), 6.95-6.85 (m,
3
13
1
H), 2.42 (s, 3H). C NMR (100 MHz, CDCl ): δ 155.3 (ddd, J = 245.0, 4.6, 2.8 Hz), 147.8 (ddd, J = 249.6, 14.3,
3
7
.5 Hz), 147.6 (ddd, J = 244.5, 13.8, 3.7 Hz), 138.7, 130.0 (t, J = 2.0 Hz), 129.2, 125.3 (d, J = 2.0 Hz), 120.2 (dd, J
20.7, 15.1 Hz), 115.3 (ddd, J = 19.4, 10.0, 1.4 Hz), 110.8 (ddd, J = 25.5, 6.6, 4.2 Hz), 21.3.
=
2',3',6'-Trifluoro-[1,1'-biphenyl]-2-carbonitrile (34)
From 2-bromobenzonitrile (0.182 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2 mmol)
in the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 34 was obtained
2
in 59% yield (0.137 g) as a yellow oil.
1
H NMR (400 MHz, CDCl ): δ 7.78 (d, J = 8.3 Hz, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.57 (t, J = 7.9 Hz, 1H), 7.49 (d, J =
3
13
8
.3 Hz, 1H), 7.33-7.19 (m, 1H), 7.06-6.95 (m, 1H). C NMR (100 MHz, CDCl ): δ 155.0 (ddd, J = 246.7, 4.0, 2.8
3
Hz), 147.6 (ddd, J = 252.0, 14.2, 6.8 Hz), 147.4 (ddd, J = 246.2, 13.0, 3.7 Hz), 133.2, 132.7, 132.2 (d, J = 1.9 Hz),
131.6, 129.4, 117.8 (ddd, J = 19.3, 9.9, 1.4 Hz), 117.3, 116.9 (dd, J = 21.9, 16.0 Hz), 113.9, 111.3 (ddd, J = 24.6,
6
.6, 4.3 Hz). Anal. Calcd for C H F N (233.19): C, 66.96; H, 2.59; N, 6.01. Found: C, 66.88; H, 2.40; N, 5.68.
13
6 3
15
3-(2,3,6-Trifluorophenyl)pyridine (35)
From 3-bromopyridine (0.158 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2 mmol) in
the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 35 was obtained in
2
72% yield (0.150 g) as a white solid: mp 53-56 °C.
1
H NMR (400 MHz, CDCl ): δ 8.73 (bs, 1H), 8.66 (d, J = 3.7 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.42 (dd, J = 7.8,
3
13
4
.8 Hz, 1H), 7.25-7.12 (m, 1H), 7.02-6.93 (m, 1H). C NMR (100 MHz, CDCl ): δ 155.3 (ddd, J = 246.3, 4.6, 2.8
3
Hz), 150.6 (m), 149.7, 147.7 (ddd, J = 251.5, 14.6, 7.2 Hz), 147.5 (ddd, J = 245.5, 13.4, 3.7 Hz), 137.5 (t, J = 2.0
Hz), 124.8, 123.3; 116.9 (dd, J = 20.7, 15.1 Hz), 116.8 (ddd, J = 19.4, 10.1, 1.4 Hz), 111.2 (ddd, J = 25.1, 6.6, 4.2
Hz).
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3-(2,3,6-Trifluorophenyl)quinoline (36)
From 3-bromoquinoline (0.208 g, 1 mmol), 1,2,4-trifluorobenzene (0.198 g, 1.5 mmol), KOAc (0.196 g, 2 mmol) in
the presence of Pd(OAc) (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 °C during 16 h, product 36 was obtained in
2
58% yield (0.150 g) as a white solid: mp 109-112 °C.
1
H NMR (400 MHz, CDCl ): δ 9.00 (s, 1H), 8.30 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.77 (t, J
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=
7.8 Hz, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.25-7.17 (m, 1H), 7.05-6.97 (m, 1H). C NMR (100 MHz, CDCl ): δ 155.4
3
(
ddd, J = 246.1, 4.6, 3.8 Hz), 150.8 (m), 148.1 (ddd, J = 251.3, 14.6, 7.2 Hz), 147.7 (ddd, J = 245.5, 13.5, 3.7 Hz),
1
47.6, 137.5 (t, J = 2.0 Hz), 130.4, 129.4, 128.2, 127.5, 127.2, 121.9, 117.0 (dd, J = 20.5, 15.0 Hz), 116.7 (ddd, J
19.4, 10.1, 1.4 Hz), 111.3 (ddd, J = 25.0, 6.6, 4.2 Hz).
=
Acknowledgment We are grateful to the ANR for a grant to X. S. We thank CNRS and “Rennes Metropole” for
providing financial support.
1
13
1
Supporting Information Available H and C NMR spectra of new compounds and H NMR spectra of known
compounds. This material is available free of charge via the Internet at http://pubs.acs.org.
References
(
1) (a) Ackermann, L. Modern arylation methods, (Eds.: Wiley Online Library, 2009. (b) Skhiri, A.; Ben Salem, R.;
Soulé, J.ꢀF.; Doucet, H. Access to (hetero)arylated selenophenes via palladiumꢀcatalysed Stille, Negishi or Suzuki couplings
or C−H bond functionalization reaction ChemCatChem 2017, 9, 2895ꢀ2913.
(
2) For reviews on metalꢀcatalyzed C–H bond functionalization: (a) Alberico, D.; Scott, M. E.; Lautens, M. Aryl−aryl
bond formation by transitionꢀmetalꢀcatalyzed direct arylation Chem. Rev. 2007, 107, 174ꢀ238; (b) Satoh, T.; Miura, M.
Catalytic direct arylation of heteroaromatic compounds Chem. Lett. 2007, 36, 200ꢀ205. (c) Li, B.ꢀJ.; Yang, S.ꢀD.; Shi, Z.ꢀJ.
Recent advances in direct arylation via palladiumꢀcatalyzed aromatic C–H activation Synlett 2008, 949ꢀ957. (d) Ackermann,
L.; Vicente, R.; Kapdi, A. Transitionꢀmetalꢀcatalyzed direct arylation of (hetero)arenes by C–H bond cleavage Angew. Chem.
Int. Ed. 2009, 48, 9792ꢀ9826. (e) Chen, X.; Engle, K. M.; Wang, D.ꢀH.; Yu, J.ꢀQ. Palladium(II)ꢀcatalyzed C–H activation/C–
C crossꢀcoupling reactions: versatility and practicality Angew. Chem. Int. Ed. 2009, 48, 5094ꢀ5115. (f) Chiusoli, G. P.;
Catellani, M.; Costa, M.; Motti, E.; Della Ca, N.; Maestri, G. Catalytic C–C coupling through C–H arylation of arenes or
heteroarenes Coord. Chem. Rev. 2010, 254, 456ꢀ469. (g) Kuhl, N.; Hopkinson, M. N.; WencelꢀDelord, J.; Glorius, F. Beyond
directing groups: transitionꢀmetalꢀcatalyzed C–H activation of simple arenes Angew. Chem. Int. Ed. 2012, 51, 10236ꢀ10254.
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h) Rossi, R.; Bellina, F.; Lessi, M.; Manzini, C. Crossꢀcoupling of heteroarenes by C–H functionalization: recent progress
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towards direct arylation and heteroarylation reactions involving heteroarenes containing one heteroatom Adv. Synth. Catal.
2014, 356, 17ꢀ117. (i) Bheeter, C. B.; Chen, L.; Soulé, J.ꢀF.; Doucet, H. Regioselectivity in palladiumꢀcatalysed direct
arylation of 5ꢀmembered ring heteroaromatics Cat. Sci. Technol. 2016, 6, 2005ꢀ2049.
(
3) He, M.: Soulé, J.ꢀF.; Doucet, H. Synthesis of (poly)fluorobiphenyls through metalꢀcatalyzed C–H bond
activation/arylation of (poly)fluorobenzene derivatives ChemCatChem, 2014, 6, 1824ꢀ1859.
4) For palladiumꢀcatalyzed direct arylations of pentafluorobenzene: (a) Lafrance, M.; Rowley, C. N.; Woo, T. K.;
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(
Fagnou, K. Catalytic intermolecular direct arylation of perfluorobenzenes J. Am. Chem. Soc. 2006, 128, 8754ꢀ8756. (b)
Lafrance, M.; Shore, D.; Fagnou, K. Mild and general conditions for the crossꢀcoupling of aryl halides with
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