Ni-Catalyzed Dimerization and Hydroperfluoroarylation of 1,3-Dienes

Article abstract of DOI:10.1021/acs.joc.8b01266

A nickel-catalyzed three-component coupling reaction between perfluoroarenes and two molecules of a 1,3-diene in the presence of an alkyl Grignard reagent, which acted as a hydride source, provided 3-perfluoroarylated-1,7-octadienes via 1,3-diene dimeriza

Full text of DOI:10.1021/acs.joc.8b01266

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Article
Ni-catalyzed Dimerization and Hydroperfluoroarylation of 1,3-Dienes
Takanori Iwasaki, Xin Min, Asuka Fukuoka, Longzhi Zhu, Renhua Qiu,
Tao Yang, Masahiro Ehara, Arumugam Sudalai, and Nobuaki Kambe
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01266 • Publication Date (Web): 12 Jun 2018
Downloaded from http://pubs.acs.org on June 12, 2018
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Niꢀcatalyzed Dimerization and
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Hydroperfluoroarylation of 1,3ꢀDienes
Takanori Iwasaki,*,† Xin Min,† Asuka Fukuoka,† Longzhi Zhu,†,‡ Renhua Qiu,*,†,‡ Tao Yang,§,¶, ǁ
Masahiro Ehara,§,¶ Arumugam Sudalai,†, ʃ and Nobuaki Kambe*,†
†Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita,
Osaka 565ꢀ0871, Japan
‡State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and
Chemical Engineering, Hunan University, Changsha, 410082, China
§Department of Theoretical and Computational Molecular Science, Institute for Molecular
Science, 38 NishigoꢀNaka, Myodaiji, Okazaki, Aichi 444ꢀ8585, Japan
¶Elements Strategy Initiative for Catalysts and Batteries (ESICB), Kyoto University, Katsura,
Kyoto 615ꢀ8510, Japan
ǁFachbereich Chemie, PhilippsꢀUniversität Marburg, HansꢀMeerweinꢀStrasse, Marburg 35032,
Germany
ʃChemical Engineering & Process Development Division, CSIRꢀNational Chemical Laboratory,
Dr. Homi Bhabha Road, Pune, Maharashtra, 411008, India
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ABSTRACT
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A nickelꢀcatalyzed threeꢀcomponent coupling reaction between perfluoroarenes and two
molecules of a 1,3ꢀdiene in the presence of an alkyl Grignard reagent, which acted as a hydride
source, provided 3ꢀperfluoroarylatedꢀ1,7ꢀoctadienes via 1,3ꢀdiene dimerization and subsequent
perfluoroarylation upon C–F bond cleavage. The reaction proceeded smoothly in a regioselective
manner by simply combining of NiCl2 and PPh3 as a catalyst and tolerated various functional
groups on the perfluoroarenes. When substituted perfluoroarenes were employed, the reaction
selectively occurred at the paraꢀposition. Mechanistic studies revealed that an anionic Ni
complex, generated upon the reaction of Ni(0) with two molecules of a 1,3ꢀdiene and an alkyl
Grignard reagent, played an important role in the C–C bond forming step with perfluoroarenes.
The C–F bond cleavage was found to be a relatively fast step in the catalytic cycle.
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INTRODUCTION
Perfluorinated arenes have received much attention in medicinal and material science due to
their characteristic properties such as high metabolic stability, low LUMO energies, and unique
intermolecular interactions with aromatic rings and polar bonds.1 For the synthesis of more
complex fluoroarenes, the functionalization of easily accessible perfluoroarenes provides reliable
routes.2 Among the C–C bond forming reactions available to introduce a perfluoroaryl group into
organic molecules,3 the SNAr reaction with carbanions represents a useful method owing to the
facile accessibility of perfluoroarenes in comparison to monoꢀ or partially fluorinated arenes
(Scheme 1a).4 Transitionꢀmetalꢀcatalyzed crossꢀcoupling reactions also provide promising
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methods for the arylation,5 alkenylation,6 alkynylation,7 and methylation8 of
perfluoro(hetero)arenes via C–F bond cleavage (Scheme 1a).9 Multicomponent coupling
reactions10 are useful approaches since they allow the concomitant construction of more than one
chemical bonds. In this context, we recently reported a Niꢀcatalyzed fourꢀcomponent coupling
reaction of perfluoroarenes with two molecules of 1,3ꢀbutadiene and aryl Grignard reagents to
produce 1,6ꢀoctadienes bearing aryl and perfluoroaryl groups at the 8ꢀ and 3ꢀposition,
respectively (Scheme 1b).11 When a Cu catalyst was employed along with EtMgCl, the
hydroarylation of 1,3ꢀdienes with perfluoroarenes occurred to give allylperfluoroarenes as
mixtures of regioisomers: in this case, EtMgCl acted as a hydride source (Scheme 1c).12 These
successful results prompted us to examine the use of alkyl Grignard reagents instead of aryl
Grignard reagents in the Niꢀcatalyzed reaction of perfluoroarenes with 1,3ꢀbutadiene. It was
found that bisꢀterminal octadienes (1,7ꢀoctadienes) bearing a perfluoroaryl group at the 3ꢀ
position were formed under mild conditions (Scheme 1d). This umpolung telomerization13
enabled the dimerization and functionalization of 1,3ꢀbutadiene by perfluoroarenes owing to an
electrophilic carbon and hydride deriving from Grignard reagents.
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Scheme 1. C–C bond formation of perfluoroarenes via C–F bond cleavage.
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RESULTS AND DISCUSSION
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We initiated our study on this threeꢀcomponent coupling reaction using perfluorobenzene (1a),
1,3ꢀbutadiene, and different alkyl Grignard reagents (Table 1). When 1a was treated with 1.2
equiv of nꢀBuMgCl (2a) and 3 equiv of 1,3ꢀbutadiene in the presence of 10 mol % of NiCl2 and
20 mol % of PPh3 at room temperature for 30 min, 3ꢀpentafluorophenylꢀ1,7ꢀoctadiene (3a) was
obtained in 80% yield (Table 1, entry 1). Reducing the amount of PPh3 to 10 mol % improved
the efficiency of the reaction affording a nearly quantitative yield of 3a, while no reaction
occurred in the absence of PPh3, suggesting a crucial role of PPh3 in the catalytic reaction
(entries 2 and 3). Under the same conditions, other group 10 metals, such as Pd and Pt, and first
row transition metals did not lead to the formation of 3a.14 Among the ligands tested, PPh3 gave
the best results, while electronꢀrich and electronꢀdeficient phosphine ligands resulted in
somewhat lower yields (entries 4 and 5). Trialkylphosphines, such as PCy3 (entry 6) and P(nꢀ
Bu)3 were not effective.14 Furthermore, the catalyst loading could be reduced to 5 mol % without
significant loss of efficiency (entry 7). When iꢀBuMgCl (2b) was used, 3a was obtained in a
comparable yield (entry 8). Acyclic and cyclic secondary alkyl Grignard reagents (2c and 2d)
also promoted the reaction, albeit less efficiently (entries 9 and 10). When cyclopropyl Grignard
reagent was employed, 3a was not obtained, resulting in a low conversion of 1a (34% conv.).
The use of tꢀBuMgCl (2e) afforded only the direct coupling product 4ae in 11% yield, and 82%
of unreacted 1a was recovered (entry 11). MeMgCl, which has no βꢀhydrogens, did not afford
3a; conversely, a fourꢀcomponent coupling reaction took place to give 3ꢀpentafluorophenylꢀ1,6ꢀ
nonadiene 5af in 50% yield (Scheme 2, see also Scheme 6 for mechanistic discussion).
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Table 1. Nickelꢀcatalyzed threeꢀcomponent coupling reaction of 1a with 1,3ꢀbutadiene in the
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presence of alkyl Grignard reagents.a
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entry
1
cat. (mol %)
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
NiCl2 (10)
NiCl2 (5)
NiCl2 (5)
NiCl2 (5)
NiCl2 (5)
NiCl2 (5)
ligand (mol %)
PPh3 (20)
PPh3 (10)
none
RMgCl 2
3a (%)b
80
nꢀBuMgCl (2a)
nꢀBuMgCl (2a)
nꢀBuMgCl (2a)
nꢀBuMgCl (2a)
nꢀBuMgCl (2a)
nꢀBuMgCl (2a)
nꢀBuMgCl (2a)
iꢀBuMgCl (2b)
sꢀBuMgCl (2c)
CyMgCl (2d)
tꢀBuMgCl (2e)
2
99
3
n.d.
37
4
P(pꢀtol)3 (10)
P(pꢀFC6H4)3 (10)
PCy3 (10)
PPh3 (5)
5
70
6
5
7c
8d
9d
10d
11d
92(74)
81
PPh3 (5)
PPh3 (5)
50
PPh3 (5)
49
PPh3 (5)
n.d.e
aReaction conditions: A mixture of 1a (1.0 mmol), RMgCl (2) (1.2 mmol), 1,3ꢀbutadiene (3
b
mmol), and catalyst in THF was stirred at 30 °C for 30 min. GC yield. Yield is in parentheses.
cAt 30 °C for 40 min. dAt 30 °C for 14ꢀ16 h. eC6F5–tꢀBu (4ae) was solely obtained in 11% yield.
Cy = cyclohexyl.
Scheme 2. Reaction of 1a with MeMgCl in the presence of 1,3ꢀbutadiene.
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Under the optimized conditions shown in entry 7 (Table 1), 4% of disubstitution product 6a
was detected by GC analysis. Therefore, in order to selectively obtain 6a, the reaction was
conducted using excess amounts of Grignard reagent and 1,3ꢀbutadiene. When 1a was treated
with 2.4 equiv of nꢀBuMgCl (2a) and 10 equiv of 1,3ꢀbutadiene in the presence of 20 mol % of
catalyst, the disubstitution pathway predominated to afford 1,2,4,5ꢀtetrafluoroꢀ3,6ꢀbis(1,7ꢀ
octadienꢀ3ꢀyl)benzene (6a) in 66% yield with exclusive paraꢀselectivity along with 3% of 3a
(Scheme 3).
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Scheme 3. Disubstitution reaction of 1a.
Next, the scope of the reaction was investigated across a range of perfluoroarenes (Scheme 4).
The reaction of pentafluorotoluene (1b) and pentafluorobiphenyl (1c) predominantly occurred at
the paraꢀposition to give 3b and 3c in 65% and 62% yields with a 94% and 96% paraꢀposition
selectivity, respectively. The structure of product 3c was irrefutably determined by Xꢀray
crystallography.14,15 Functional groups including ether (1d), acetal (1e and 1f), thioether (1g),
amino (1h), and silyl (1i) groups remained intact affording the corresponding products 3d-i in
moderate to good yields with an excellent paraꢀselectivity, except for 1d and 1e. Similar poor
paraꢀposition selectivities were also observed in previous studies when 1d and 1e were used,11,12
and could be explained by electronic effects, i.e., the present reaction occurred preferentially at
the more electronꢀdeficient position (vide infra). Ester, amide, and phosphine groups, which
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might possibly serve as directing groups for orthoꢀsubstitution, also gave predominantly the
corresponding paraꢀsubstituted products 3j, 3k, and 3l in good yields. Aryl tosylates are widely
employed as useful substrates in Niꢀcatalyzed coupling reactions; however, the presence of
tosylate moiety as in 1m afforded 3m in a moderate yield under the present reaction conditions.
A thiophene moiety was well tolerated, and 3n was obtained in 74% yield. However, the
presence of a pyridine substituent largely affected the reaction, directing the substitution at the
orthoꢀposition that predominated to give 4oa in 72% yield, probably due to the coordination
ability of the pyridine moiety towards the Grignard reagent. Perfluorobiphenyl (1p) and
perfluoronaphthalene (1q) selectively reacted at the 4ꢀ and 2ꢀposition, respectively, furnishing
the desired products in slightly lower yields. The position selectivity of 1r was low giving rise to
a ca 2:1 mixture of the threeꢀcomponent coupling products. The reaction of highly electronꢀ
deficient perfluorotoluene (1s) resulted in a 15% yield, which could be increased to 31% yield
upon slow addition of iꢀBuMgCl.
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Scheme 4. Niꢀcatalyzed threeꢀcomponent coupling reaction of perfluoroarenes, 1,3ꢀbutadiene,
and alkyl Grignard reagents.
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Reaction conditions: NiCl2 (5 mol %), PPh3 (5 mol %), perfluoroarene 1 (1 mmol), nꢀBuMgCl
(1.2 mmol), and 1,3ꢀbutadiene (3 mmol) in THF (3 mL) at 30 °C for 2 h. GC yields are given in
parenthesis. Positionꢀselectivities were determined by GC and NMR (see the experimental
section for details) and are shown in percent. a10 mol % of NiCl2 and PPh3 were used. b1.5 mmol
c
d
of nꢀBuMgCl was used. 72% of directꢀcoupling product 4oa was formed. iꢀBuMgCl (1.5
9
mmol) was slowly added.
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When isoprene was employed instead of 1,3ꢀbutadiene, the corresponding threeꢀcomponent
coupling product 7 was obtained as a mixture of four regioisomers along with 12% of cyclized
product 8 (Scheme 5).14 In contrast to isoprene, 1,3ꢀpentadiene, an analogue of mono substituted
1,3ꢀbutadiene, did not give threeꢀcomponent coupling products.
Scheme 5. Reaction of isoprene with 1a and 2a.
In order to determine the origin of the observed positionꢀselectivities on the perfluoroarenes,
we performed density functional theory (DFT) calculations. The structure of perfluoroarenes 1bꢀ
d, 1g, and 1i were optimized with Gaussian 0916 at the B3LYP17/6ꢀ31+G(d) level of theory,
followed by frequency calculations at the same level of theory. The natural bond orbital (NBO)18
analysis of these optimized structures was conducted at the B3LYP/6ꢀ311++G(d,p) level of
theory. Figure 1 shows the results of the NBO population analysis of perfluoroarenes 1b-d, 1g,
and 1i along with the Hammett constants for these substituents. In all cases, orthoꢀcarbon is the
most electronꢀdeficient but could not react due to steric effects. The atomic charge difference
between the metaꢀ and paraꢀpositions of pentafluoroanisole 1d is 0.004, which is much smaller
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than those of pentafluorotoluene 1b (0.012) and pentafluorobiphenyl 1c (0.018). In the case of
perfluoroarenes bearing an SMe (1g) and TMS (1i) group, the paraꢀposition was found to be
much more electroꢀpositive than the metaꢀposition. These results are in good agreement with the
observed high paraꢀselectivity mentioned above.
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Figure 1. Atomic charges by NBO population analysis of 1b-d, 1g, and 1i and Hammett
constants of these substituents. The atomic charge values for orthoꢀ and metaꢀpositions are the
average of two equivalent carbons.
To reveal substituent effects, we conducted competitive reactions of perfluorobenzene (1a) and
substituted perfluoroarenes to reveal the effect of substituents (Table 2). When a 1:1 mixture of
1a and 1b (R = Me) was reacted with 1,3ꢀbutadiene and nꢀBuMgCl under the optimized
conditions, 3a and 3b were formed in 40:1 ratio, indicating that pꢀmethyl group largely retarded
the reaction. A similar competitive reaction of 1a with 1c (R = Ph) resulted in formation of 3a
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and 3c in 2.1:1 ratio. Hammett constant σp of Me, Ph, and F substituents is –0.17, +0.02, and
+0.06, respectively. These results indicate that the present reaction prefers electronꢀdeficient
perfluoroarenes rather than electronꢀrich ones, suggesting the SNAr mechanism.
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Table 2. Competitive reaction of perfluoroarenes.
R
3a (mmol)a
0.80
3b or 3c (mmol)a
3a/3b or 3c
σp
Me (1b)
Ph (1c)
–0.17
+0.02
0.02
0.27
40
0.56
2.1
aDetermined by GC. σp of F is +0.06.
Subsequently, we conducted kinetic studies using 1a as model substrate. Initially, we
attempted to determine the rate law using a conventional Schlenk technique; however, the
reaction was too fast to trace. Since a time course within 1 min is required to determine the initial
rates, for these kinetic studies, we employed a flow reactor19 in the presence of Ni(acac)2 (Figure
2).14,20 The kinetic study results suggested that the reaction obeyed an almost zerothꢀorder
kinetics with respect to 1,3ꢀbutadiene, whereas the concentrations of nꢀBuMgCl and catalyst
exerted significant effects on the rates.14 The rate law for the present catalytic reaction can be
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expressed as d[3a]/dt = k[Ni(acac)2/PPh3]0.64[1a]0.25[nꢀBuMgCl]0.65[1,3ꢀbutadiene]–0.03. The
relatively small rate order of 0.25 for 1a might suggest that the reaction of a perfluoroarene with
an anionic bis(πꢀallyl)nickel complex14 is a fast process, and thus it is not the rateꢀdetermining
step. This is in striking contrast with the fourꢀcomponent coupling reaction between a
perfluoroarene, aryl Grignard reagent, and two molecules of 1,3ꢀbutadiene catalyzed by a Ni
catalyst, where the reaction of a Ni intermediate with the perfluoroarene is the rateꢀdetermining
step.11
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Figure 2. A flow reactor used for kinetic studies and the standard conditions.
A proposed catalytic cycle is shown in Scheme 6. Initially, a Ni(II) salt is reduced by a
Grignard reagent to form Ni(0) species A, which then undergoes an oxidative dimerization with
1,3ꢀbutadiene to form bis(πꢀallyl)nickel complex B. As reported by Wilke and coꢀworkers,21
triphenylphosphine coordinates with complex B to form complex F as a resting state of the
present reaction. Complexation of B with an alkyl Grignard reagent leads to the formation of
anionic complex C,14,22ꢀ24 which selectively reacts with perfluoroarene 1 at the γꢀcarbon of the σꢀ
allyl group. Reductive elimination of the alkyl and allyl groups of Ni in complex D most likely
generates alkylperfluoroarylation product 5; however, this is a slow process, and the more facile
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βꢀhydrogen elimination proceeds selectively25 giving rise to threeꢀcomponent coupling product 3
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via hydride complex E.26 When Grignard reagents carrying no βꢀhydrogens are employed, the
reductive elimination of complex D occurs to form alkylperfluoroarylation product 5 as shown in
Scheme 2.27 When the reductive elimination is slow, the insertion of the terminal C–C double
bond into the allyl or alkyl C–Ni bond proceeds to give cyclic compound 8, as in the case of
isoprene (Scheme 5).14,28
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Scheme 6. Proposed catalytic cycle.
Finally, we investigated derivatization of the hydroperfluoroarylated products (Scheme 7). The
gramꢀscale synthesis of 3a using 5 mol % of catalyst afforded 5.65 g of product after simple
vacuum distillation. Ringꢀclosing metathesis between both terminal alkene moieties of 3a
afforded cyclized compound 9 in the presence of first generation Grubbs’ catalyst in CH2Cl2.
Epoxidation of 3a and 9 afforded the corresponding epoxides 10 and 11 in 69 and 88% yields,
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respectively. Furthermore, the treatment of 3a with HB(pin) provided diborylated product 12 in
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49% yield.29
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Scheme 7. Synthetic manipulation of 3a.
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CONCLUSIONS
In conclusion, we developed a Niꢀcatalyzed threeꢀcomponent coupling reaction for the
preparation of synthetically useful 1,7ꢀdienes bearing a perfluoroaryl moiety at the 3ꢀposition via
C–F bond cleavage of easily accessible perfluoroarenes. Mechanistic studies revealed that the
reaction involved an anionic Ni complex as key intermediate, and the C–F bond cleavage of
perfluoroarenes was a relatively fast step in the catalytic cycle. In this reaction, an alkyl Grignard
reagent acted not only as a hydride source but also as activator of the Ni intermediates by
forming anionic Ni complexes. This activation of the catalytic intermediates enabled the facile
cleavage of the aromatic C–F bonds without the assistance of an electronꢀwithdrawing or
directing group.
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EXPERIMENTAL SECTION
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Nuclear magnetic resonance (1H NMR, 13C NMR, 19F NMR, and 31P NMR) spectra were
recorded at 400 MHz (1H NMR), 100 MHz (13C NMR), 376 MHz (19F NMR), and 162 MHz (31P
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NMR) in 5 mm NMR tubes. All H NMR chemical shifts were reported in ppm relative to an
internal reference tetramethylsilane at δ 0.00. All 13C NMR chemical shifts were reported in ppm
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relative to the carbon of chloroformꢀd1 as δ 77.00. F NMR and P NMR chemical shifts were
reported in ppm relative to external references of α,α,αꢀtrifluorotoluene as δ –63.90 and 85%
H3PO4 aq. as δ 0.00, respectively. Infrared spectra were recorded using ATR. HPLC separations
were performed on a recycling preparative HPLC equipped with Shodex K2001 and 2002
columns (GPC) using CHCl3 as an eluent. GC analyses were performed with a GL Sciences
InertCap 5 capillary column (I.D. 0.25 mm, Length 30 m, df 0.25 ꢀm) using an internal standard.
Conventional and high resolution mass spectra were recorded with a doubleꢀfocusing magnetic
sector mass instrument or with a timeꢀofꢀflight mass instrument. Melting points were measured
using a glass capillary. Single crystallographic analysis was made on a diffractometer with a 2ꢀD
area detector using graphiteꢀmonochromated CuꢀKα radiation (λ = 1.54187 Å).
All manipulations involving airꢀ and moistureꢀsensitive compounds were carried out by the
standard Schlenk techniques under a nitrogen atmosphere. Dehydrated THF was purified by
SPS30 prior to use. Perfluoroarenes 1e, 1g-i, 1k, 1m, and 1r were prepared according to the
literature.11 CyMgCl was prepared by a standard procedure from the corresponding
chlorocyclohexane and Mg. Other THF solutions of Grignard reagents were purchased and used
after titration using I2. NiCl2 (Wako), 1,3ꢀbutadiene (TCI), PPh3 (Kishida), and all other
commercially available reagents were used as received.
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Synthesis of Substrates
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2,3,4,5,6ꢀPentafluoroꢀ1,1’ꢀbiphenyl (1c).31 A mixture of hexafluorobenzene (2.79 g, 15 mmol)
and PhMgBr (22.5 mmol. 0.82 M in THF) in THF (15 mL) was stirred at 60 °C for 67 h. The
resulting mixture was carefully quenched by H2O. The product was extracted by Et2O, dried over
Na2SO4, concentrated, and purified by silica gel column chromatography (pentane as an eluent)
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to give 1c as a white solid (1.32 g, 5.4 mmol, 36%). H NMR (400 MHz, CDCl3): δ 7.41ꢀ7.51
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(m, 5H); F NMR (376 MHz, CDCl3): δ –143.1 (dd, J = 22.5, 7.9 Hz, 2F), –155.7 (t, J = 21.0
Hz, 1F), –162.0ꢀ–162.2 (m, 2F).
2ꢀ(Pentafluorophenyl)ꢀ1,3ꢀdioxolane (1f).32 A mixture of pentafluorobenzaldehyde (1.96 g,
10.0 mmol), ethylene glycol (14.0 mL, 250 mmol), and pyridinium pꢀtoluenesulfonate (PPTS)
(0.25 g, 1.0 mmol) in benzene (70 mL) was stirred at 80 °C for 20 h. The resulting mixture was
washed with K2CO3 aq. and brine, dried over Na2SO4, and concentrated to give 1f as white
1
powder (2.40 g, 9.99 mmol, 99% yield). H NMR (400 MHz, CDCl3): δ 6.20 (s, 1H), 4.03ꢀ4.23
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(m, 4H); C{1H} NMR (100 MHz, CDCl3): δ 66.0, 96.4, 140.5, 143.0, 146.8; F NMR (376
MHz, CDCl3): δ –143.6ꢀ–143.7 (m, 2F), –152.3ꢀ–152.4 (tt, J = 20.5, 2.6 Hz, 1F), –161.7ꢀ–161.8
(m, 2F).
Pentafluorophenyl pivalate (1j).33 N,N’ꢀDicyclohexylcarbodiimide (DCC) (2.34 g, 11.3 mmol)
was added to a stirred solution of pivalic acid (1.04 g, 10.2 mmol) and pentafluorophenol (2.32
g, 12.6 mmol) in 1,4ꢀdioxane (40 mL) under dry nitrogen atmosphere. Stirring was continued for
12 h, by which time a colorless precipitate had formed. The mixture was filtered, evaporated, and
purified by silica gel column chromatography (EtOAc/hexane = 5/95) to yield the product as a
1
colorless oil (2.08 g, 7.8 mmol, 76%). H NMR (400 MHz, CDCl3): δ 1.40 (s, 9H); 19F NMR
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(376 MHz, CDCl3): δ –153.4 (d, J = 21.4 Hz, 2F), –158.4 (d, J = 21.6 Hz, 1F), –162.4ꢀ–162.6
(m, 2F).
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2ꢀPentafluorophenylꢀ5ꢀmethylthiophene (1n). The compound 1n was prepared by a similar
procedure reported by Tilley.34 A solution of 2ꢀmethylthiophene (0.98 g, 10 mmol) in THF (20
mL) was added nꢀBuLi (1.55 M in hexane, 6.45 mL, 10 mmol) at –78 °C and then stirred at 0 °C
for 1 h. The resulting solution was slowly cannulated into a solution of hexafluorobenzene (2.79
g, 15 mmol) in THF (20 mL) held in a dryꢀice/ethanol bath cooling. The cooling bath was
removed, and the stirring was continued for 8 h at rt. The reaction was carefully quenched by
slow addition of water. The product was extracted by CH2Cl2, dried over Na2SO4, and purified
by silica gel column chromatography (hexane as an eluent) to give 1n as a white solid (1.21 g,
4.6 mmol, 46%).1H NMR (400 MHz, CDCl3): δ 7.32 (d, J = 3.6 Hz, 1H), 6.83ꢀ6.82 (m, 1H),
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2.55 (s, 3H); F NMR (376 MHz, CDCl3): δ –140.3 (dd, J = 22.6, 7.1 Hz, 2F), –156.8 (t, J =
21.2 Hz, 1F), –162.2ꢀ–162.4 (m, 2F). These data matched with previously reported data for this
compound.35
General procedure for Ni-catalyzed three-component coupling of perfluorobenzene, n-
BuMgCl, and 1,3-butadiene (Table 1). An ovenꢀdried test tube was charged with catalyst,
ligand, and stirring bar and closed with a septum cap in a glove box. Undecane (50 ꢀL) as an
internal standard and THF (2.3 mL) were added at ambient temperature via a syringe and then
the mixture was cooled with dryꢀice/ethanol bath. Into this solution were added 1,3ꢀbutadiene
(67 mL as gas, 3.0 mmol), nꢀBuMgCl (2a) (1.74 M in THF, 0.69 mL, 1.2 mmol), and
perfluorobenzene (1a) (116 ꢀL, 1.0 mmol) in this order. The reaction mixture was stirred at 30
ºC. After 0.5 h, the reaction mixture was diluted with Et2O, carefully quenched by 1N HCl aq.,
and analyzed by GC.
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General procedure for Ni-catalyzed three-component coupling of perfluoroarenes, n-
BuMgCl, and 1,3-butadiene (Scheme 4). An ovenꢀdried test tube was charged with NiCl2 (7
mg, 0.05 mmol), PPh3 (13 mg, 0.05 mmol), and stirring bar and closed with a septum cap in a
glove box. THF (2.3 mL) was added at ambient temperature via a syringe and then the mixture
was cooled with dryꢀice/ethanol bath. Into this solution were added 1,3ꢀbutadiene (67 mL as gas,
3.0 mmol), nꢀBuMgCl (2a) (1.55 M in THF, 0.77 mL, 1.2 mmol), and perfluoroarene 1 (1.0
mmol) in this order. The reaction mixture was stirred at 30 ºC. After 2 h, the reaction mixture
was diluted with Et2O and carefully quenched by 1N HCl aq. The products were extracted by
Et2O for three times, dried over Na2SO4, concentrated, filtered through a short pad of silica gel
(hexane or Et2O as an eluent), and purified by GPC (CHCl3 as an eluent) to give the desired
product.
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1,2,3,4,5ꢀPentafluoroꢀ6ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)benzene (3a). The representative general
procedure was followed using hexafluorobenzene (116 ꢁL, 1.010 mmol) and butylmagnesium
chloride (in THF, 1.85 M, 0.65 mL, 1.2 mmol). Purification by GPC gave the desired product as
a colorless oil (203.4 mg, 74%); IR (neat): 1521, 1499, 1118, 977, 919, 652 cm–1; 1H NMR (400
MHz, CDCl3): δ 6.07ꢀ5.98 (m, 1H), 5.81ꢀ5.71 (m, 1H), 5.13ꢀ5.09 (m, 2H), 5.02ꢀ4.94 (m, 2H),
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3.72 (q, J = 8.0 Hz, 1H), 2.06 (q, J = 7.2 Hz, 2H), 1.88ꢀ1.72 (m, 2H), 1.47ꢀ1.21 (m, 2H); C
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1
NMR (100 MHz, CDCl3): δ 144.9 (dm, JCꢀF = 245.1 Hz, oꢀ), 139.6 (dm, JCꢀF = 250.8 Hz, pꢀ),
1
137.6 (dm, JCꢀF = 251.3 Hz, mꢀ), 117.2 (m, ipsoꢀ), 38.1, 137.7, 116.5, 114.9, 40.0, 33.3, 32.7,
26.9; 19F NMR (376 MHz, CDCl3): δ –142.2 (dd, J = 22.6, 7.1 Hz, 2F), –157.4 (t, J = 21.1 Hz,
1F), –162.3 (ddd, J = 22.6, 21.1, 7.1 Hz, 2F); HRMS (EI+) m/z [M]+ Calcd for C14H13F5:
276.0937; Found 276.0936.
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Procedure for largeꢀscale synthesis of 3a. To a 1000 mL threeꢀneck flask equipped with a
magnetic stirring bar was added NiCl2 (324.0 mg, 2.5 mmol), PPh3 (656.0 mg, 2.5 mmol), and
THF (200 mL). The mixture was cooled with a dry ice/ethanol bath and were added 1,3ꢀ
btuadiene (3350 mL as gas, 150 mmol) followed by adding nꢀbutylmagnesium chloride (50 mL,
1.1 M in THF, 55 mmol) and hexafluorobenzene (9.41g, 50 mmol) in this order. After stirring at
30 °C for 1 h, the reaction was quenched by 1 N HCl aq. (200 mL), and extracted by Et2O (200
mL x 3). The mixture was dried by Na2SO4 and concentrated by rotary evaporator to obtain a
yellow oil. The desired product was obtained as a colorless oil (5.65 g, 41%) by vacuum
distillation (at 0.6 kPa, bp = 100–103 °C).
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1,2,4,5ꢀTetrafluoroꢀ3ꢀmethylꢀ6ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)benzene (3b). The representative general
procedure was followed using 2,3,4,5,6ꢀpentafluorotoluene (180.0 mg, 0.989 mmol) and
butylmagnesium chloride (in THF, 1.95 M, 0.77 mL, 1.5 mmol). Purification by GPC gave 3b as
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a mixture of two isomers in p:m or o = 94:6 ratio (determined by GC and F NMR, but the
substitution pattern of the minor isomer could not be identified) as a colorless oil (175.6 mg,
65%): 1H NMR (400 MHz, CDCl3): δ 6.10–6.01 (m, 1H), 5.80–5.71 (m, 1H), 5.12–4.92 (m, 4H),
3.74 (q, J = 8.0 Hz, 1H), 2.23 (s, 3H), 2.06 (dt, J = 7.6, 7.4 Hz, 2H), 1.80 (q, J = 8.0 Hz, 2H),
1
1.47–1.22 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 145.1 (dm, JCꢀF = 224.0 Hz), 144.4
(dm, 1JCꢀF = 244.0 Hz), 138.4, 138.3, 116.0, 114.7, 40.2, 33.4, 32.8, 27.0, 7.4 (m) (carbon signals
from two ipso carbons of the perfluoroaryl ring were not observed); 19F NMR (376 MHz,
CDCl3): δ –144.4 (m, 4F); HRMS (EI+) m/z [M]+ Calcd for C15H16F4: 272.1188; Found
272.1190.
2,3,5,6ꢀTetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)ꢀ1,1'ꢀbiphenyl (3c). The representative general
procedure was followed using 2,3,4,5,6ꢀpentafluoroꢀ1,1'ꢀbiphenyl (245.0 mg, 1.00 mmol) and
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butylmagnesium chloride (in THF, 1.55 M, 0.77 mL, 1.2 mmol). Purification by GPC gave 3c as
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a mixture of two isomers in p:m or o = 96:4 ratio (determined by GC and F NMR, but the
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substitution pattern of the minor isomer could not be identified) as a white powder (208.0 mg,
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62%): m.p. = 51–54 ºC; H NMR (400 MHz, CDCl3): δ 7.50–7.42 (m, 5H), 6.13–6.08 (m, 1H),
5.82–5.76 (m, 1H), 5.19–4.95 (m, 4H), 3.82 (q, J = 7.6 Hz, 1H), 2.09 (q, J = 6.8 Hz, 2H), 1.86
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(dt, J = 8.0, 7.6 Hz, 2H), 1.53–1.42 (m, 1H), 1.40–1.31 (m, 1H); C{1H} NMR (100 MHz,
CDCl3): δ 144.9 (dm, 1JCꢀF = 237.4 Hz), 143.8 (dm, 1JCꢀF = 240.3 Hz), 138.3, 138.0, 130.1 (t, 4JCꢀF
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= 1.9 Hz), 128.9, 128.5, 121.3 (m), 118.3 (m), 116.4, 40.5, 33.4, 32.7 (d, JCꢀF = 1.9 Hz), 27.0
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(carbon signals from two ipso carbons of the perfluoroaryl ring were not observed); F NMR
(376 MHz, CDCl3): δ –143.1 (dd, J = 22.4, 12.2 Hz, 2F), –144.6 (dd, J = 22.4, 12.2 Hz, 2F);
HRMS (EI+) m/z [M]+ Calcd for C20H18F4: 334.1345; Found 334.1341. Single crystals of 3c
suitable for Xꢀray crystallography were obtained by recrystallization from Et2O. Xꢀray data for
3c (CCDC 1836311): The structure was solved by direct method (SIR2008)36. The structure was
refined on F2 by fullꢀmatrix leastꢀsquares method using SHELXLꢀ9737. The nonꢀhydrogen atoms
were refined anisotropically. Hydrogen atoms were refined using riding model. C1 and C4
carbons of octaꢀ1,7ꢀdiene moiety and hydrogens on C5 and C3 were refined as disorder model
(0.643(17):0.367(17) ratio). C20H18F4, T = 123(1) K, M = 334.36, colorless, monoclinic, P2/c
(#13), a = 13.0228(4) Å, b = 5.7000(2) Å, c = 22.0772(8) Å,
β = 95.7060(19)°, V = 1630.66(10)
Å3, Z = 4, Dcalcd = 1.362 g/cm3, Rint = 0.0862, R1 = 0.1007, wR2 = 0.2756 for I > 2σ(I), R1 =
0.1354, wR2 = 0.3210 for all data.
1,2,4,5ꢀTetrafluoroꢀ3ꢀmethoxyꢀ6ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)benzene (3d). The representative general
procedure was followed using 2,3,4,5,6ꢀpentafluoroanisole (199.0 mg, 1.005 mmol) and
butylmagnesium chloride (in THF, 1.85 M, 0.65 mL, 1.2 mmol). Purification by GPC gave 3d as
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a mixture of three isomers in p:m:o = 60:36:4 ratio (determined by F NMR) as a colorless oil
(200.6 mg, 70%): 1H NMR (400 MHz, CDCl3): δ 6.08–6.00 (m, 1H), 5.80–5.71 (m, 1H), 5.12–
4.93 (m, 4H), 4.05 (t, J = 1.8 Hz, 1.8H), 3.97 (s, 1.0H), 4.05 (t, J = 1.2 Hz, 0.2H), 3.70 (q, J = 7.6
Hz, 1H), 2.06 (dt, J = 7.2, 6.8 Hz, 2H), 1.83–1.79 (m, 2H), 1.45–1.37 (m, 1H), 1.31–1.26 (m,
1H); 13C{1H} NMR (100 MHz, CDCl3): δ 145.0 (dm, 1JCꢀF = 230.8 Hz), 141.0 (dm, 1JCꢀF = 228.8
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Hz), 138.3, 138.2, 116.0, 114.8, 62.4 (t, JCꢀF = 2.8 Hz), 62.1 (t, JCꢀF = 3.8 Hz), 39.9, 33.3, 32.8
(m), 26.9 (carbon signals from two ipso carbons of the perfluoroaryl ring were not observed); 19F
NMR (376 MHz, CDCl3): δ –136.6 (d, J = 7.9 Hz, 0.6F), –142.3 (dd, J = 22.6, 7.1 Hz, 0.08F), –
143.6 (d, J = 22.2 Hz, 0.6F), –144.0 (dd, J = 21.6, 8.1 Hz, 2F), –152.9 (d, J = 20.7 Hz, 0.6F), –
156.2 (dd, J = 20.3, 8.6 Hz, 0.08F), –158.2 (dd, J = 21.8, 8.6 Hz, 2F), –159.0 (t, J = 20.9 Hz,
0.08F), –163.6 (t, J = 21.6 Hz, 0.08F), –164.0 (m, 0.6F); HRMS (EI+) m/z [M]+ Calcd for
C15H16F4O: 288.1137; Found 288.1135.
1,2,4,5ꢀTetrafluoroꢀ3ꢀ(methoxymethoxy)ꢀ6ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)benzene
(3e).
The
representative general procedure was followed using 1,2,3,4,5ꢀpentafluoroꢀ6ꢀ(methoxymethoxy)
benzene (225.8 mg, 0.990 mmol) and butylmagnesium chloride (in THF, 1.41 M, 0.85 mL, 1.2
mmol). Purification by GPC gave 3e as a mixture of three isomers in p:m:o = 63:32:5 ratio
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(determined by F NMR) as a colorless oil (171.8 mg, 55%): H NMR (400 MHz, CDCl3): δ
6.06–6.01 (m, 1H), 5.80–5.73 (m, 1H), 5.18–4.93 (m, 6H), 3.70 (q, J = 7.6 Hz, 1H), 3.60 (d, J =
2.8 Hz, 3H), 2.09–2.03 (m, 2H), 1.84–1.76 (m, 2H), 1.44–1.39 (m, 1H), 1.31–1.25 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 144.9 (dm, 1JCꢀF = 247.9 Hz), 141.8 (dm, 1JCꢀF = 245.1 Hz),
138.3, 138.2, 138.1, 116.2, 116.1, 114.8 (d, 2JCꢀF = 2.8 Hz), 99.2 (t, 4JCꢀF = 3.9 Hz), 99.1 (t, 3JCꢀF
=
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3.4 Hz), 57.3 (d, JCꢀF = 3.4 Hz), 40.1 (d, JCꢀF = 1.9 Hz), 39.9, 33.3 (d, JCꢀF = 2.8 Hz), 32.7 (d,
3JCꢀF = 1.9 Hz), 26.9; 19F NMR (376 MHz, CDCl3): δ –135.6 (d, J = 8.6 Hz, 0.5F), –141.2 (dd, J
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= 21.4, 7.9 Hz, 0.08F), –142.1 (d, J = 22.6 Hz, 0.5F), –143.8 (dd, J = 21.8, 9.0 Hz, 2F), –151.5
(d, J = 21.1 Hz, 0.5F), –154.8 (dd, J = 20.9, 8.8 Hz, 0.08F), –156.8 (dd, J = 21.8, 9.0 Hz, 2F), –
158.8 (t, J = 20.9 Hz, 0.08F), –162.6 (t, J = 21.6 Hz, 0.08F), –163.9 (m, 0.5F); HRMS (EI+) m/z
[M]+ Calcd for C16H18F4O2: 318.1243; Found 318.1249.
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2ꢀ(2,3,5,6ꢀTetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)phenyl)ꢀ1,3ꢀdioxolane (3f). The representative
general procedure was followed using 2ꢀ(perfluorophenyl)ꢀ1,3ꢀdioxolane (242.5 mg, 1.010
mmol) and butylmagnesium chloride (in THF, 1.41 M, 0.85 mL, 1.2 mmol). Purification by GPC
gave 3f (pꢀonly) as a colorless oil (254.7 mg, 76%): 1H NMR (400 MHz, CDCl3): δ 6.22 (s, 1H),
6.06–5.99 (m, 1H), 5.79–5.72 (m, 1H), 5.12–5.08 (m, 2H), 5.02–4.93 (m, 2H), 4.23–4.20 (m,
2H), 4.06–4.03 (m, 2H), 3.76 (q, J = 7.6 Hz, 1H), 2.05 (dt, J = 7.2, 7.0 Hz, 2H), 1.84–1.77 (m,
2H), 1.44–1.37 (m, 1H), 1.31–1.23 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 145.1 (dm, 1JCꢀ
F = 245.0 Hz), 144.6 (dm, 1JCꢀF = 248.9 Hz), 138.2, 137.6, 123.5 (t, 3JCꢀF = 16.7 Hz), 116.5, 114.9,
2
4
3
114.7 (t, JCꢀF = 12.9 Hz), 96.7 (m), 66.0, 40.4 (d, JCꢀF = 1.9 Hz), 33.3, 32.6 (d, JCꢀF =1.9 Hz),
19
26.9; F NMR (376 MHz, CDCl3): δ –142.9 (dd, J = 21.2, 12.6 Hz, 2F), –145.1 (dd, J = 21.4,
12.8 Hz, 2F); HRMS (CI+) m/z [M+H]+ Calcd for C17H19F4O2: 331.1321; Found 331.1308.
2,3,5,6ꢀTetrafluoroꢀ1ꢀmethylthioꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)benzene (3g). The representative
general procedure was followed using methyl perfluorophenyl sulfide (215.8 mg, 1.008 mmol)
and butylmagnesium chloride (in THF, 1.41 M, 0.85 mL, 1.2 mmol). Purification by GPC gave
3g as a mixture of two isomers in p:m or o = 98:2 ratio (determined by GC and 19F NMR, but the
substitution pattern of the minor isomer could not be identified) as a colorless oil (213.6 mg,
70%): 1H NMR (400 MHz, CDCl3): δ 6.07–6.00 (m, 1H), 5.80–5.73 (m, 1H), 5.14–5.08 (m, 2H),
5.02–4.93 (m, 2H), 3.76 (q, J = 7.6 Hz, 1H), 2.50 (s, 3H), 2.06 (dt, J = 7.4, 6.8 Hz, 2H), 1.87–
1.81 (m, 2H), 1.46–1.38 (m, 1H), 1.32–1.26 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 146.6
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(dm, 1JCꢀF = 244.1 Hz), 144.7 (dm, 1JCꢀF = 246.0 Hz), 138.2, 137.8, 116.5, 114.8, 40.5, 33.3, 32.7,
26.9, 17.70 (carbon signals from two ipso carbons of the perfluoroaryl ring were not observed);
19F NMR (376 MHz, CDCl3): δ –135.4 (dd, J = 23.3, 11.7 Hz, 2F), –142.4 (dd, J = 23.7, 12.0
Hz, 2F); HRMS (EI+) m/z [M]+ Calcd for C15H16F4S: 304.0909; Found 304.0916.
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2,3,5,6ꢀTetrafluoroꢀN,Nꢀdimethylꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)aniline (3h). The representative
general procedure was followed using 2,3,4,5,6ꢀpentafluoroꢀN,Nꢀdimethylaniline (211.8 mg,
1.003 mmol) and butylmagnesium chloride (in THF, 1.95 M, 0.62 mL, 1.2 mmol). Purification
by GPC gave 3h as a mixture of two isomers in p:m = 88:12 ratio (determined by 19F NMR) as a
colorless oil (149.5 mg, 50%): 1H NMR (400 MHz, CDCl3): δ 6.07–6.02 (m, 1H), 5.80–5.74 (m,
1H), 5.11–4.92 (m, 4H), 3.67 (q, J = 8.0 Hz, 1H), 2.92 (t, J = 2.2 Hz, 5.2H), 2.86 (t, J = 1.6 Hz,
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0.8H), 2.06 (dt, J = 7.2, 7.0 Hz, 2H), 1.78 (dt, J = 8.0, 7.8 Hz, 2H), 1.44–1.25 (m, 2H); C{1H}
1
1
NMR (100 MHz, CDCl3): δ 145.1 (dm, JCꢀF = 242.2 Hz), 142.6 (dm, JCꢀF = 249.8 Hz), 138.6,
138.4, 115.7, 114.7, 43.4, 39.9, 33.4, 32.9, 27.0 (carbon signals from two ipso carbons of the
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perfluoroaryl ring were not observed); F NMR (376 MHz, CDCl3): δ –127.9 (d, J = 7.1 Hz,
0.14F), –143.5 (d, J = 22.9 Hz, 0.13F), –144.9 (dd, J = 20.3, 8.6 Hz, 2F), –145.6 (d, J = 21.1 Hz,
0.14F), –151.5ꢀ–151.6 (m, 2F), –165.0 (m, 0.13F); HRMS (EI+) m/z [M]+ Calcd for C16H19F4N:
301.1454; Found 301.1456.
Trimethyl(2,3,5,6ꢀtetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)phenyl)silane (3i). The representative
general procedure was followed using trimethyl(perfluorophenyl)silane (241.8 mg, 1.006 mmol)
and butylmagnesium chloride (in THF, 1.41 M, 0.85 mL, 1.2 mmol). Purification by GPC gave
3i as a mixture of two isomers in p:m or o = 96:4 ratio (determined by GC and 19F NMR, but the
substitution pattern of the minor isomer could not be identified) as a colorless oil (175.9 mg,
53%): 1H NMR (400 MHz, CDCl3): δ 6.09–6.02 (m, 1H), 5.80–5.72 (m, 1H), 5.14–5.07 (m, 2H),
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5.02–4.94 (m, 2H), 3.76 (q, J = 7.6 Hz, 1H), 2.06 (q, J = 7.2 Hz, 2H), 1.82 (dt, J = 8.4, 7.4 Hz,
2H), 1.48–1.37 (m, 1H), 1.35–1.25 (m, 1H), 0.38 (t, J = 1.4 Hz, 9H); 13C{1H} NMR (100 MHz,
CDCl3): δ 149.5 (dm, 1JCꢀF = 240.3 Hz), 145.0 (dm, 1JCꢀF = 246.0 Hz), 138.4, 138.1, 123.7 (t, 2JCꢀF
= 16.6 Hz), 116.3, 114.8, 40.7, 33.4, 32.7 (t, 3JCꢀF = 2.4 Hz), 27.0, 0.0 (t, 4JCꢀF = 2.9 Hz) (a carbon
signal from ipso carbon of the perfluoroaryl ring was not observed); 19F NMR (376 MHz,
CDCl3): δ –128.7 (dd, J = 23.8, 9.4 Hz, 2F), –143.1 (dd, J = 23.9, 9.4 Hz, 2F); HRMS (EI+) m/z
[M]+ Calcd for C17H22F4Si: 330.1427; Found 330.1432.
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2,3,5,6ꢀTetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)phenyl pivalate (3j). The representative general
procedure was followed using perfluorophenyl pivalate (267.1 mg, 0.996 mmol) and
butylmagnesium chloride (in THF, 1.55 M, 0.77 mL, 1.2 mmol). Purification by GPC gave 3j as
a mixture of three isomers in p:m:o = 80:15:5 ratio (determined by GC and 19F NMR) as a
1
yellow oil (273.4 mg, 69%): H NMR (400 MHz, CDCl3): δ 6.08–6.00 (m, 1H), 5.80–5.71 (m,
1H), 5.14–4.94 (m, 4H), 3.74 (q, J = 7.8 Hz, 1H), 2.07 (dt, J = 7.4, 7.2 Hz, 2H), 1.87–1.76 (m,
13
2H), 1.39 (s, 9H), 1.35–1.23 (m, 2H); C{1H} NMR (100 MHz, CDCl3): δ 174.7, 144.7 (dm,
1
2
1JCꢀF = 244.1 Hz), 140.7 (dm, JCꢀF = 247.0 Hz), 138.2, 137.8, 119.3 (t, JCꢀF =16.6 Hz), 116.5,
114.9, 45.2, 40.2, 39.4, 33.3, 32.7, 26.9 (a carbon signal from ipso carbon of the perfluoroaryl
ring was not observed); 19F NMR (376 MHz, CDCl3): δ –143.2 (dd, J = 22.2, 8.6 Hz, 2F), –154.5
(dd, J =21.8, 8.6 Hz, 2F); HRMS (CI+) m/z [M+H]+ Calcd for C19H23F4O2: 359.1634; Found
359.1635.
N,NꢀDiethylꢀ2,3,5,6ꢀtetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)benzamide (3k). The representative
general procedure was followed using N,Nꢀdiethylꢀ2,3,4,5,6ꢀpentafluorobenzamide (268.6 mg,
1.005 mmol) and butylmagnesium chloride (in THF, 1.95 M, 0.62 mL, 1.2 mmol). Purification
by GPC gave 3k as a mixture of two isomers in p:m or o = 97:3 ratio (determined by GC and 19F
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NMR, but the substitution pattern of the minor isomer could not be identified) as a colorless oil
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6
1
(210 mg, 59%): H NMR (400 MHz, CDCl3): δ 6.08–6.01 (m, 1H), 5.80–5.72 (m, 1H), 5.17–
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5.09 (m, 2H), 5.02–4.94 (m, 2H), 3.77 (q, J = 7.6 Hz, 1H), 3.59 (q, J = 7.4 Hz, 2H), 3.24 (dt, J =
7.4 Hz, 2H), 2.07 (q, J = 7.2 Hz, 2H), 1.90–1.76 (m, 2H), 1.50–1.30 (m, 2H), 1.27 (t, J = 7.4 Hz,
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3H), 1.14 (t, J = 7.4 Hz, 3H); C{1H} NMR (100 MHz, CDCl3): δ 158.7, 144.5 (dm, JCꢀF
=
1
2
243.1 Hz), 142.2 (dm, JCꢀF = 246.9 Hz), 138.0, 137.4, 123.3 (t, JCꢀF = 16.7 Hz), 116.7, 114.8,
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114.6 (t, JCꢀF = 21.9 Hz), 43.1, 40.5, 39.5, 33.2, 32.5, 26.8, 13.9, 12.6; F NMR (376 MHz,
CDCl3): δ –141.1 (dd, J = 22.7, 12.6 Hz, 1F), –141.4 (dd, J = 23.1, 13.0 Hz, 1F), –142.6ꢀ–142.8
(m, 2F); HRMS (EI+) m/z [M]+ Calcd for C19H23F4NO: 357.1716; Found 357.1715;
Diphenyl(2,3,5,6ꢀtetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)phenyl)phosphane (3l). The representative
general procedure was followed using (perfluorophenyl)diphenylphosphane (351.5 mg, 0.998
mmol) and butylmagnesium chloride (in THF, 1.85 M, 0.65 mL, 1.2 mmol). Purification by GPC
1
gave 3l (pꢀonly) as a white powder (293.3 mg, 66%): m.p. = 38–41 °C; H NMR (400 MHz,
CDCl3): δ 7.44–7.42 (m, 4H), 7.36–7.35 (m, 6H), 6.10–6.01 (m, 1H), 5.79–5.73 (m, 1H), 5.16–
5.09 (m, 2H), 5.02–4.94 (m, 2H), 3.76 (q, J = 7.8 Hz, 1H), 2.06 (dt, J = 7.2, 7.0 Hz, 2H), 1.89–
1.74 (m, 2H), 1.50–1.39 (m, 1H), 1.35–1.26 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.0
(dm, 1JCꢀF = 243.1 Hz), 144.7 (dm, JCꢀF = 247.0 Hz), 138.2, 137.6, 133.8 (d, J = 10.5 Hz), 133.0
1
2
(d, J = 21.0Hz) 129.1, 128.6 (d, J = 6.7 Hz), 124.9 (t, JCꢀF = 16.7 Hz), 116.8, 114.9, 113.5 (m),
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40.8, 33.3, 32.6, 26.9; F NMR (376 MHz, CDCl3): δ –128.6ꢀ–128.8 (m, 2F), –141.6 (dd, J =
22.7, 12.6 Hz, 2F); 31P NMR (162 MHz, CDCl3): δ –24.6 (t, J = 37.2 Hz); HRMS (EI+) m/z [M]+
Calcd for C26H23F4P: 442.1474; Found 442.1465.
2,3,5,6ꢀTetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)phenyl
4ꢀmethylbenzenesulfonate
(3m).
The
representative general procedure was followed using 4ꢀmethylbenzenesulfonate (338.3 mg, 1.000
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mmol) and butylmagnesium chloride (in THF, 1.41 M, 0.85 mL, 1.2 mmol). Purification by GPC
gave 3m as a mixture of two isomers in p:m or o = 88:12 ratio (determined by GC and 19F NMR,
but the substitution pattern of the minor isomer could not be identified) as a yellow oil (190.6
mg, 44%): 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H),
6.06–5.97 (m, 1H), 5.80–5.71 (m, 1H), 5.15–5.10 (m, 2H), 5.02–4.94 (m, 2H), 3.73 (q, J = 7.4
Hz, 1H), 2.50 (s, 3H), 2.09–2.04 (m, 2H), 1.85–1.75 (m, 2H), 1.46–1.39 (m, 1H), 1.31–1.25 (m,
1H); 13C{1H} NMR (100 MHz, CDCl3): δ 144.7 (dm, 1JCꢀF = 242.2 Hz), 141.6 (dm, 1JCꢀF = 252.7
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Hz), 146.4, 138.1, 137.3, 132.0, 130.0, 128.5, 121.2 (t, JCꢀF = 16.7 Hz), 116.9, 114.9, 40.4 (d,
4
3JCꢀF = 1.9 Hz), 33.2, 32.6 (t, JCꢀF = 1.9 Hz), 26.9, 21.8 (a carbon signal from ipso carbon of the
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perfluoroaryl ring was not observed); F NMR (376 MHz, CDCl3): δ –141.7 (dd, J = 20.9, 8.1
Hz, 2F), –151.6 (m, 2F); HRMS (CI+) m/z [M+H]+ Calcd for C21H21F4O3S: 429.1148; Found
429.1142.
2ꢀMethylꢀ5ꢀ(2,3,5,6ꢀtetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)phenyl)thiophene
(3n).
The
representative general procedure was followed using 2ꢀmethylꢀ5ꢀ(perfluorophenyl)thiophene
(264.9 mg, 1.003 mmol) and butylmagnesium chloride (in THF, 1.55 M, 0.77 mL, 1.2 mmol).
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Purification by GPC gave 3n (pꢀonly) as a colorless oil (256.9 mg, 72%): H NMR (400 MHz,
CDCl3): δ 7.37 (d, J = 3.6 Hz, 1H), 6.82 (d, J = 2.8 Hz, 1H), 6.12–6.03 (m, 1H), 5.81–5.74 (m,
1H), 5.16–4.96 (m, 4H), 3.77 (q, J = 7.6 Hz, 1H), 2.54 (s, 3H), 2.07 (q, J = 7.2 Hz, 2H), 1.84 (dt,
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J = 8.4, 7.6 Hz, 2H), 1.50–1.39 (m, 1H), 1.37–1.26 (m, 1H); C{1H} NMR (100 MHz, CDCl3):
1
1
3
δ 145.1 (dm, JCꢀF = 236.5 Hz), 143.5 (dm, JCꢀF = 247.9 Hz), 142.8 (t, JCꢀF = 3.9 Hz), 138.3,
4
2
138.0, 130.1 (t, JCꢀF = 5.7 Hz), 125.6, 125.4 (m), 120.0 (t, JCꢀF = 16.7 Hz), 116.3, 114.8, 112.6
19
(t, 2JCꢀF = 14.7 Hz), 40.3, 33.4, 32.7, 27.0, 15.1; F NMR (376 MHz, CDCl3): δ –141.3 (dd, J =
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23.9, 11.7 Hz, 2F), –143.4 (dd, J = 21.4, 11.7 Hz, 2F); HRMS (EI+) m/z [M]+ Calcd for
C19H18F4S: 354.1065; Found 354.1064.
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2ꢀ(2,3,5,6ꢀTetrafluoroꢀ4ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)phenyl)pyridine (3o). When nꢀBuMgCl was used
under the standard conditions, 4oa was yielded in 72% yield along with 4% of 3o. The
representative general procedure was followed using 2ꢀ(perfluorophenyl)pyridine (246.8 mg,
1.007 mmol) and 10 mol % of catalyst components, and iꢀBuMgCl (in THF, 1.55 M, 0.97 mL,
1.5 mmol) was added slowly. Purification by GPC gave 3o (pꢀonly) as a colorless oil (64 mg,
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19%) along with a crossꢀcoupling compound 4ob (111 mg, 39%): H NMR (400 MHz, CDCl3):
δ 8.77 (d, J = 8.0 Hz, 1H), 7.86–7.81 (m, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.39–7.36 (m, 1H), 6.14–
6.05 (m, 1H), 5.81–5.75 (m, 1H), 5.17–5.11 (m, 2H), 5.03–4.95 (m, 2H), 3.82 (q, J = 7.6 Hz,
1H), 2.11–2.04 (m, 2H), 1.86 (dt, J = 7.8, 8.0 Hz, 2H), 1.46–1.40 (m, 1H), 1.36–1.25 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 150.0, 138.3, 137.8, 136.6, 125.9, 123.5, 116.5, 114.9,
40.4, 33.4, 32.7, 26.9; 19F NMR (376 MHz, CDCl3): δ –142.7 (dd, J = 21.8, 12.4 Hz, 2F), –144.6
(dd, J = 22.4, 12.2 Hz, 2F); HRMS (DART) m/z [M+H]+ Calcd for C19H18F4N 336.1375; Found
336.1378.
2ꢀ(2ꢀButylꢀ3,4,5,6ꢀtetrafluorophenyl)pyridine (4oa). 1H NMR (400 MHz, CDCl3): δ 8.75–8.73
(m, 1H), 7.83–7.79 (m, 1H), 7.38–7.34 (m, 2H), 2.57–2.52 (m, 2H), 1.39–1.31 (m, 2H), 1.21–
1.11 (m, 2H), 0.76–0.71 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.8, 145.9 (dm, 1JCꢀF
=
1
1
1
240.3 Hz), 145.0 (dm, JCꢀF = 245.1 Hz), 140.3 (dm, JCꢀF = 251.7 Hz), 138.6 (dm, JCꢀF = 237.4
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Hz), 136.5, 125.7, 123.1, 31.9, 25.2, 22.3, 13.5; F NMR (376 MHz, CDCl3): δ –142.4 (dd, J =
22.4, 12.2 Hz, 1F), –143.3 (dd, J = 20.9, 12.2 Hz, 1F), –156.5–156.6 (m, 1F), –159.7 (dt, J =
21.3, 5.8 Hz, 1F); HRMS (DART) m/z [M]+ Calcd for C15H13F4N 283.0984; Found 283.1004.
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2,2',3,3',4,5,5',6,6'ꢀNonafluoroꢀ4'ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)ꢀ1,1'ꢀbiphenyl (3p). The representative
general procedure was followed using decafluorobiphenyl (336.0 mg, 1.006 mmol) and
butylmagnesium chloride (in THF, 1.81 M, 0.66 mL, 1.2 mmol). Purification by GPC gave 3p
(pꢀonly) as a colorless oil (165 mg, 39%) along with a disubstituted compound 6p (colorless oil,
46.5 mg, 9%): 1H NMR (400 MHz, CDCl3): δ 6.14–6.05 (m, 1H), 5.82–5.75 (m, 1H), 5.21–5.15
(m, 2H), 5.04–4.96 (m, 2H), 3.85 (q, J = 8.0 Hz, 1H), 2.10 (dt, J = 7.4, 6.8 Hz, 2H), 1.92–1.84
(m, 2H), 1.53–1.43 (m, 1H), 1.40–1.31 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 144.8 (dm,
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1JCꢀF = 237.4 Hz), 144.7 (dm, JCꢀF = 231.7 Hz), 144.6 (dm, JCꢀF = 247.0 Hz), 144.1 (dm, JCꢀF
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234.6 Hz), 142.3 (dm, JCꢀF = 243.1 Hz), 138.2, 137.3, 125.1 (t, JCꢀF = 16.2 Hz), 117.1, 115.0,
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103.9 (m), 102.6 (m), 40.8, 33.3, 32.6, 27.0; F NMR (376 MHz, CDCl3): δ –137.3 (m, 2F), –
138.8 (m, 2F), –141.4 (dd, J = 21.2, 11.8 Hz, 2F), –150.6 (m, 1F), –160.7 (m, 2F); HRMS (EI+)
m/z [M]+ Calcd for C20H13F9: 424.0874; Found 424.0867.
1
4,4'ꢀBis(octaꢀ1,7ꢀdienꢀ3ꢀyl)ꢀ2,2',3,3',5,5',6,6'ꢀoctafluoroꢀ1,1'ꢀbiphenyl (6p). H NMR (400
MHz, CDCl3): δ 6.14–6.05 (m, 2H), 5.84–5.74 (m, 2H), 5.21–4.96 (m, 8H), 3.83 (q, J = 7.6 Hz,
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2H), 2.10 (dt, J = 7.2, 6.8 Hz, 4H), 1.91–1.83 (m, 4H), 1.52–1.31 (m, 4H); C{1H} NMR (100
MHz, CDCl3): δ 138.2, 137.4, 117.0, 115.0, 40.8, 33.3, 32.6, 27.0; 19F NMR (376 MHz, CDCl3):
δ –138.8–138.9 (m, 4F), –141.8–142.0 (m, 4F); HRMS (DART) m/z [M+H]+ Calcd for C28H27F8
515.1985; Found 515.1989.
1,2,3,4,5,6,8ꢀHeptafluoroꢀ7ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)naphthalene (3q). The representative general
procedure was followed using perfluoronaphthalene (271.0 mg, 0.996 mmol) and butylꢀ
magnesium chloride (in THF, 1.41 M, 0.85 mL, 1.2 mmol). Purification by GPC gave 3q as a
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mixture of two isomers in 7:8 = 90:10 ratio (determined by GC and F NMR) as a colorless oil
(149.4 mg, 41%) along with a crossꢀcoupling compound 4qa (white powder, 19.8 mg, 6%): 1H
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NMR (400 MHz, CDCl3): δ 6.17–6.08 (m, 1H), 5.80–5.72 (m, 1H), 5.18–5.12 (m, 2H), 5.02–
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4.93 (m, 2H), 3.93 (q, J = 7.6 Hz, 1H), 2.08 (dt, J = 7.6, 6.8 Hz, 2H), 1.94–1.86 (m, 2H), 1.50–
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1.41 (m, 1H), 1.35–1.25 (m, 1H); C{1H} NMR (100 MHz, CDCl3): δ 149.9 (dm, JCꢀF = 235.5
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Hz), 146.7 (dm, JCꢀF = 246.9 Hz), 141.3 (dm, JCꢀF = 232.7 Hz), 141.0 (dm, JCꢀF = 245.1 Hz),
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140.7 (dm, JCꢀF = 247.9 Hz), 139.3 (dm, JCꢀF = 253.6 Hz), 138.6 (dm, JCꢀF = 225.2 Hz), 138.2,
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137.7, 116.9, 114.9, 110.2 (m), 107.9 (m), 40.4, 33.3, 32.6 (t, JCꢀF = 1.9 Hz), 27.0 (a carbon
signal from ipso carbon of the perfluoroaryl ring was not observed); 19F NMR (376 MHz,
CDCl3): δ –120.8 (dd, J = 70.3, 17.5 Hz, 1F), –136.4 (d, J = 15.0, 1F), –144.3–144.6 (m, 1F), –
146.4–146.6 (m, 1F), –148.9–149.1 (m, 1F), –154.4–154.5 (m, 1F), –156.1 (m, 1F); HRMS
(EI+) m/z [M]+ Calcd for C18H13F7: 362.0905; Found 362.0906
2ꢀButylꢀ1,3,4,5,6,7,8ꢀheptafluoronaphthalene (4qa). 1H NMR (400 MHz, CDCl3): δ 2.86 (t, J =
7.8 Hz, 2H), 1.68–1.61 (m, 2H), 1.50–1.37 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100
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1
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MHz, CDCl3): δ 150.2 (dm, JCꢀF = 252.6 Hz), 146.9 (dm, JCꢀF = 253.8 Hz), 141.1 (dm, JCꢀF
=
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268.9 Hz), 140.3 (dm, JCꢀF = 270.8 Hz), 139.1 (dm, JCꢀF = 268.8 Hz), 138.5 (dm, JCꢀF = 319.4
Hz), 110.0 (m), 107.8 (m), 31.4, 22.7, 22.4, 13.7; 19F NMR (376 MHz, CDCl3): δ –123.0 (dd, J =
68.1, 18.8 Hz, 1F), –138.7 (d, J = 17.7, 1F), –144.8–145.1 (m, 1F), –146.6–146.8 (m, 1F), –
149.7–149.9 (m, 1F), –155.1–155.2 (m, 1F), –156.5 (m, 1F); HRMS (DART) m/z [M+H]+ Calcd
for C14H10F7 311.0671; Found 311.0683.
1,2,4ꢀTrifluoroꢀ3ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)dibenzo[b,e][1,4]dioxine (3r). The representative general
procedure was followed using 1,2,3,4ꢀtetrafluorodibenzo[b,e][1,4]dioxine (257.0 mg, 1.003
mmol) and butylmagnesium chloride (in THF, 1.41 M, 0.85 mL, 1.2 mmol). Purification by GPC
gave 3r as a mixture of two isomers in 3:4 = 66:34 ratio (determined by 19F NMR) as a colorless
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oil (216.7 mg, 62%): H NMR (400 MHz, CDCl3): δ 6.97–6.93 (m, 4H), 6.08–6.01 (m, 1H),
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5.80–5.73 (m, 1H), 5.08–4.93 (m, 4H), 3.78 (q, J = 8.0 Hz, 0.35H), 3.67 (q, J = 8.0 Hz, 0.7H),
2.07–2.04 (m, 2H), 1.85–1.76 (m, 2H), 1.43–1.40 (m, 1H), 1.33–1.26 (m, 1H); 13C{1H} NMR
(100 MHz, CDCl3): δ 145.0 (dm, 1JCꢀF = 227.0 Hz), 144.5 (dm, 1JCꢀF = 230.8 Hz), 143.9 (dm, 1JCꢀ
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F = 247.9 Hz), 140.9, 140.6 (d, JCꢀF = 2.8 Hz), 140.2, 138.5, 138.4 (d, JCꢀF = 1.9 Hz), 132.1,
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132.0, 131.9 (d, JCꢀF = 1.9 Hz), 128.5, 128.4, 125.0, 124.8, 124.7 (d, JCꢀF = 1.9 Hz), 116.8 (d,
3JCꢀF = 3.8 Hz), 116.5 (d, JCꢀF = 3.8 Hz), 115.9, 115.7, 114.7 (d, JCꢀF = 3.8 Hz), 39.8, 39.5, 33.3
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(d, JCꢀF = 5.7 Hz), 32.7 (d, JCꢀF = 1.9 Hz), 32.5 (d, 3JCꢀF = 1.9 Hz), 27.0; F NMR (376 MHz,
CDCl3): δ –142.3 (d, J = 9.4 Hz, 1F), –144.7 (d, J = 22.2 Hz, 0.5F), –145.3 (d, J = 22.6 Hz, 1F),
–158.1 (d, J = 21.0 Hz, 0.5F), –163.4 (dd, J = 21.6, 9.2 Hz, 1F), –165.8 (t, J = 21.8 Hz, 0.5F);
HRMS (EI+) m/z [M]+ Calcd for C20H17F3O2: 346.1181; Found 346.1182.
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1,2,4,5ꢀTetrafluoroꢀ3ꢀ(octaꢀ1,7ꢀdienꢀ3ꢀyl)ꢀ6ꢀ(trifluoromethyl)benzene (3s). The representative
general procedure was followed using octafluorotoluene (236.4 mg, 1.001 mmol) and isoꢀ
butylmagnesium chloride (in THF, 1.72 M, 0.87 mL, 1.5 mmol). Purification by GPC gave 3s (pꢀ
only) as a yellow oil (102.9 mg, 31%): 1H NMR (400 MHz, CDCl3): δ 6.08–5.99 (m, 1H), 5.79–
5.71 (m, 1H), 5.17–5.13 (m, 2H), 5.03–4.94 (m, 2H), 3.81 (q, J = 7.8 Hz, 1H), 2.08 (dt, J = 7.4,
6.8 Hz, 2H), 1.90–1.79 (m, 2H), 1.47–1.41 (m, 1H), 1.32–1.26 (m, 1H); C{1H} NMR (100
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MHz, CDCl3): δ 144.9 (dm, 1JCꢀF = 240.3 Hz), 144.1 (dm, JCꢀF = 239.3 Hz), 138.0, 136.8, 127.2
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(t, JCꢀF = 16.2 Hz), 117.4, 115.1, 40.7, 33.2, 32.5, 26.9 (carbon signals of an ipso carbon of
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perfluoroaryl ring and the CF3 group were not observed); F NMR (376 MHz, CDCl3): δ –56.2
(t, J = 21.2 Hz, 3F), –140.3–140.5 (m, 2F), –140.8–141.0 (m, 2F); HRMS (EI+) m/z [M]+ Calcd
for C15H13F7: 326.0905; Found 326.0902.
(E)ꢀ1,2,3,4,5ꢀPentafluoroꢀ6ꢀ(nonaꢀ1,6ꢀdienꢀ3ꢀyl)benzene (5af). The representative general
procedure was followed using hexafluorobenzene (116 ꢁL, 1.010 mmol) and methylmagnesium
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