Highly regioselective cobalt-catalyzed [2+2+2] cycloaddition of fluorine-containing internal alkynes to construct various fluoroalkylated benzene derivatives

Article abstract of DOI:10.1016/j.jfluchem.2018.06.004

Novel cobalt-catalyzed [2+2+2] cycloaddition using fluorine-containing alkynes was described. Cyclotrimerization of fluorinated alkynes under the influence of CoCl₂(dppb) in acetonitrile at 80 °C for 3 h took place smoothly, affording the corre

Full text of DOI:10.1016/j.jfluchem.2018.06.004

Accepted Manuscript
Title: Highly regioselective cobalt-catalyzed [2+2+2]
cycloaddition of fluorine-containing internal alkynes to
construct various fluoroalkylated benzene derivatives
Authors: Tatsuya Kumon, Shigeyuki Yamada, Tomohiro
Agou, Toshio Kubota, Tsutomu Konno
PII:
S0022-1139(18)30191-X
DOI:
Reference:
https://doi.org/10.1016/j.jfluchem.2018.06.004
FLUOR 9182
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10-5-2018
12-6-2018
12-6-2018
Please cite this article as: Kumon T, Yamada S, Agou T, Kubota T, Konno T, Highly
regioselective cobalt-catalyzed [2+2+2] cycloaddition of fluorine-containing internal
alkynes to construct various fluoroalkylated benzene derivatives, Journal of Fluorine
Chemistry (2018), https://doi.org/10.1016/j.jfluchem.2018.06.004
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Highly regioselective cobalt-catalyzed [2+2+2] cycloaddition of fluorine-containing
internal alkynes to construct various fluoroalkylated benzene derivatives
Tatsuya Kumona, ShigeyukiYamadaa, TomohiroAgoub, Toshio Kubotab, and Tsutomu Konnoa,*
aFaculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology,
Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Tel: +81-75-724-7504; E-mail: konno@kit.ac.jp
b Department of Materials Science, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi 316-8511, Japan
Graphical abstract
Highlight
1. Cobalt-catalyzed [2+2+2] cycloaddition using fluorine-containing alkynes proceeded under mild reaction conditions.
2. The reaction can be performed at low catalyst loading.
3. High regioselection was observed in the trimerization of fluorine-containing alkynes.
4. Cycloaddition of fluorinated alkynes with non-fluorinated diynes proceeded very smoothly.
Abstract: Novel cobalt-catalyzed [2+2+2] cycloaddition using fluorine-containing alkynes was described.
Cyclotrimerization of fluorinated alkynes under the influence of CoCl2(dppb) in acetonitrile at 80 °C for 3 h took place
smoothly, affording the corresponding benzene derivatives in excellent yields with high regioselectivity.Additionally,
intermolecular cycloaddition of fluorinated alkynes with non-fluorinated diynes also proceeded in the presence of a catalytic
amount of CoCl2((S)-BINAP) and ZnI2 to give various bicyclic aromatic compounds in high yields.

Keyword: Fluorine-containing alkynes, cobalt catalysts, [2+2+2] cycloaddition, regioselective
1. Introduction
Benzene derivatives bearing a fluoroalkyl (Rf) group have been recognized as one of the most important
fluorinated frameworks because they are widely distributed in the skeleton of pharmaceuticals, agrochemicals, and
functional materials and have a unique physicochemical and biochemical property, such as significantly enhanced
lipophilicity, stability, and binding affinity [1]. Consequently, tremendous efforts have been devoted to the
development of novel synthetic approaches to various classes of fluoroalkylated benzene materials so far [2].
Transition metal-catalyzed [2+2+2] cycloaddition reactions using alkynes have been widely considered as one
of the most efficient and convenient protocols for the construction of various aromatic rings [3]. There have been
numerous studies on the reaction with non-fluorinated alkynes under the influence of various transition metals,
such as Ni [4], Rh [5], Au [6], Ru [7], Co [8], Ti [9], Ir [10], Fe [11], and Nb [12]. Despite of their potent utility, on
the other hand, very little attention has been paid to the [2+2+2] cycloaddition reactions of fluorine-containing
alkynes [13]. Although there have been reported several examples on the fluorinated version of [2+2+2]
cycloaddition reactions, they still have drawbacks, like the use of expensive catalysts, prolonged reaction times, or
poor atom efficiency. Accordingly, the development of more efficient and convenient cycloaddition reactions
using fluorine-containing alkynes remains highly desirable.
In this article, we describe a highly regioselective trimerization of CF3-alkynes in the presence of inexpensive
cobalt catalysts under mild reaction conditions (Scheme 1 (a)) [14]. In addition, it is also disclosed that the efficient
access to various mono-substituted fluoroalkylated bicyclic aromatic compounds via the cobalt-catalyzed [2+2+2]
cycloaddition reaction of fluoroalkylated alkynes with various diynes (Scheme 1 (b)).
Scheme 1. Cobalt-Catalyzed [2+2+2] Cycloaddition Reactions of Fluorine-ContainingAlkynes.
2. Results and discussion
An initial screening of the reaction conditions for the cobalt-catalyzed [2+2+2] cyclotrimerization was
performed using trifluoromethylated internal alkyne 1a. The results are summarized in Table 1.
Thus, treatment of 1a in the presence of 5 mol% of CoCl2 and 2.75 equiv. of zinc powder in acetonitrile at 80
°C for 3 h gave an inseparable mixture of isomeric trimerization products 2a and 3a in 60% combined yield

(2a:3a = 87:13) (Entry 1). While the use of cobalt catalyst coordinated with a monodentate ligand, such as PPh3,
did not drastically improve the yield or isomeric ratio of the reaction product (Entry 2), changing the ligand from a
monodentate to a bidentate ligand, e.g. 1,2-bis(diphenylphosphino)ethane (dppe), led to a significant increase in
the yield (Entry 3). It should be noted that the length of the carbon linker in the bidentate ligand significantly
affected the regioselectivity. Thus, cyclotrimerization in the presence of cobalt catalyst coordinated with
1,3-bis(diphenylphosphino)propane (dppp) or 1,4-bis(diphenylphosphino)butane (dppb) afforded the
corresponding benzene derivatives in excellent yields with high regioselectivity (Entries 4 and 5).
1,1’-Bis(diphenylphosphino)ferrocene (dppf) was also found to be a suitable ligand for the present trimerization
reaction (Entry 6); however, the use of (S)-2,2’-bis(diphenylphosphino)-1,1’-binaphthyl ((S)-BINAP) as ligand
decreased the yield of the desired cycloadducts (Entry 7). A decrease in the catalyst loading (3 mol%) also
afforded the trimerization products in high yield (Entry 8). However, further decreasing the catalyst loading to 1
mol% resulted in the sluggish formation of cycloadducts along with the recovery of unreacted 1a (Entry 9).
Additionally, 2a and 3a were not obtained in the absence of cobalt catalyst (Entry 10). Finally, the best yield was
obtained when the reaction was carried out using less amount of zinc powder (1.0 equiv.) (Entry 11).
Table 1
Initial screening of the cyclotrimerization conditions.
Entry
1
Ligand
None
2PPh3
dppe
X
5
5
5
5
5
5
5
3
1
0
3
Yielda/% of 2a+3a
Ratiob of 2a:3a
87:13
88:12
84:16
96:4
60
2
64
3
88
4
dppp
90
5
dppb
93
96:4
6
dppf
86
96:4
7
(S)-BINAP
dppb
64
92:8
8
95
96:4
9
dppb
73
96:4
10
11c
dppb
0
-
dppb
97 (95)
96:4
a Determinedby19FNMR.Valueinparentheses isof isolated yieldof2a+3a.
b Determinedby19FNMR.
c Thereactionwascarriedoutusing1.0 equiv. ofZn.

We next examined the substrate scope in the present cobalt-catalyzed [2+2+2] cyclotrimerization under the
optimized reaction conditions (Table 2).
Alkynes 1b, c, which have a phenyl or methoxy group at the para position on the benzene ring, participated
efficiently in the present cyclotrimerization to give the corresponding trimerization adducts in good to excellent
yields with an isomeric ratio of 95:5 (Entries 2 and 3). While meta substitution on the benzene ring of the substrate
did not affect significantly the outcome of the reaction (Entry 4), ortho substitution completely retarded the
formation of 2e, 3e (Entry 5). The introduction of a strongly electron-withdrawing group onto the benzene ring of
the substrate, e.g. 1f, also impeded the reaction to progress completely (Entry 7). In both cases, the addition of 30
mol% of zinc iodide caused a significant improvement of the chemical yields and the corresponding products
were obtained in 58% and 83% yields, respectively, with high regioselectivity (Entries 6 and 8). On the other
hand, alkynes 1g and 1h with a bulky dimethylphenylsilyl or n-nonafluorobutyl groups were found to be
unsuitable for the reaction and the starting materials were recovered quantitatively (Entries 9 and 10).
Table 2
Cobalt-catalyzed cyclotrimerization of various fluorine-containing alkynes.
Entry
1
Substrate
1a
Yielda/% of 2+3
97 (95)
92 (90)
74 (69)
95 (84)
trace
Ratiob of 2:3
96:4
2
1b
95:5
3
1c
95:5
4
1d
95:5
5
6d
1e
N.D.c
98:2e
N.D.c
1e
58 (56)
trace
7
1f
8d
9d
10d
1f
83 (70)
trace
96:4
1g
N.D.c
N.D.c
1h
trace
a Determinedby19FNMR.Values inparenthesesareof isolated yieldof2+3.
bDeterminedby19FNMR.
c Notdetermined.
d 30 mol%of ZnI2 wasused.

e Manyatropisomersof2eand3e weredetected.
With deep literature investigations, it was strictly limited an efficient intermolecular [2+2+2] cycloaddition
using a fluorinated alkyne and non-fluorinated diynes [13]. Very interestingly, present cobalt-catalytic system was
found to sufficiently applicable to the intermolecular [2+2+2] cycloaddition reaction, leading to fluoroalkylated
bicyclic compounds well. Table 3 describes the ligand screening for the optimal reaction conditions.
Thus, treatment of 1.2 equiv. of 1a and 1.0 equiv. of 4A in the presence of 3 mol% of CoCl2(dppb) and 1.0
equiv. of zinc powder in acetonitrile at 80 °C for 3 h gave only a trace amount of cycloadduct 5aA (Entry 1).
However, the yield of 5aA significantly improved when 10 mol% of zinc iodide was used as an additive (55% 19F
NMR yield, Entry 2). The cycloaddition also proceeded using cobalt catalyst with no ligand to give the
corresponding adduct 5aA in 57% yield (Entry 3). As shown in Entries 4–9, we carried out the reaction using
cobalt catalysts with various phosphine ligands. The best result was obtained when (S)-BINAP was used as a ligand and
the desired cycloadduct 5aA was obtained in 83% isolated yield (Entry 9).
Table 3
Ligand screening for the cycloaddition of CF3-alkyne 1a with diyne 4Aa.
Entry
Ligand
dppb
Yieldb/% of 5aA
1c
2
3
4
5
6
7
8
9
trace
55
dppb
None
57
2PPh3
2P(t-Bu)3
dppe
71
71
12
dppp
71
dppf
20
(S)-BINAP
88 (83)
a Reactionconditions:1a (1.2 equiv.), 4A (1.0equiv.).
b Determinedby19FNMR.Valueinparentheses isof isolated yieldof5aA.
c WithoutZnI2.
With the optimized reaction conditions in hand (Table 3, Entry 9), we next investigated the cycloaddition of
various fluorine-containing alkynes with diyne 4A. The results are summarized in Table 4.
1

Table 4
Cobalt-catalyzed cycloaddition of various fluorinated alkynes with various diynes.
R2
CoCl2((S)-BINAP) (3 mol%)
Zn (100 mol%)
ZnI2 (10 mol%)
R2
F3C
R1
Rf
R1
X
+
X
CH3CN, 80 °C, 3 h
R2
R2
5a
1 (1.2 equiv.)
4 (1.0 equiv.)
F3C
F3C
F3C
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
F3C
CO2Et
CO2Et
Cl
Cl
Ph
MeO
5aA : 88% (83%)
5bA : 88% (81%)
5cA : 85% (83%)
5dA : 85% (82%)
F3C
F3C
Cl
F9C4
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
F3C
CO2Et
CO2Et
PhMe2Si
EtO2C
Cl
5eA : 84% (80%)
5fA : 92% (83%)
5gA : 58%
: 74% (68%)b
5hA : quant. (88%)
F3C
F3C
F3C
CO2Bn
CO2Bn
F3C
CO2Et
CO2Et
OH
Cl
Cl
Cl
5aB : 81% (75%)
5iA : 48% (46%)
5aC : 56% (52%)
5aD : 0%
Ph
F3C
F3C
F3C
CO2Et
CO2Et
O
NTs
Cl
Cl
Ph
Cl
5aG : 11%
5aF : 85% (78%)
5aE : 70% (64%)
: 53% (43%)c
aDetermined by19FNMR.Values inparentheses areof isolated yieldof5.
b 2.4 equiv. of1g wasused.
c Thereactionwascarriedoutfor9husing3.6 equiv. of1a, 10 ml%of CoCl2((S)-BINAP), and30 mol%of ZnI2.
Various substituents on the benzene ring of the fluoroalkylated alkynes, such as electron-withdrawing (Ph, CO2Et) or
electron-donating groups (MeO) did not influence considerably the [2+2+2] cycloaddition, giving the corresponding
products 5bA, 5fA, and 5cA in excellent yields. Notably, the position of the substituent on the benzene ring did not affect the
reaction (5aA, 5dA, 5eA). Although the cycloaddition of fluorine-containing alkyne 1g having a bulky silyl group with
diyne 4A was somewhat sluggish, the isolated yield of the product 5gA could increase to 68% when the reaction was carried
out using 2.4 equiv. of 1g. The cycloaddition of alkyne 1h bearing a n-C4F9 substituent with diyne 4A proceeded efficiently
to afford the corresponding perfluorobutylated benzene derivative 5hA in excellent yield. On the other hand, the fluorinated
propargyl alcohol 1i was found to be less reactive, affording the desired product 5iA in moderate yield.
Subsequently, we examined the cobalt-catalyzed [2+2+2] cycloaddition using alkyne 1a with a variety of diynes (4B–G).
Thus, cycloaddition of 1a with dibenzyl dipropargylmalonate (4B) proceeded well to give the corresponding adduct (5aB) in
good yield (75% isolated yield). In sharp contrast, the reaction with 1,6-heptadiyne (4C) was less efficient, leading to the
formation of 5aC in only 52% isolated yield. Disappointingly, 1,7-octadiyne (4D) was an unsuitable substrate for this

cycloaddition. It should be noted that the [2+2+2] cycloaddition of 1a with dipropargyl ether (4E) or N,N-dipropargyl
tosylamide (4F) proceeded smoothly to give the corresponding heterocyclic aromatics 5aE or 5aF in 64% or 78% isolated
yields, respectively. The internal diyne 4G was less reactive in the present cycloaddition and corresponding 5aG was
obtained in only 11% yield. After several attempts to improve the reaction efficiency, cycloadduct 5aG could be isolated in
43% yield when the reaction was conducted with 3.6 equiv. of 1a in the presence of 10 mol% of CoCl2((S)-BINAP), 1.0
equiv. of zinc powder, and 30 mol% of zinc iodide for 9 h.
A possible reaction mechanism for the cobalt-catalyzed [2+2+2] cyclotrimerization of fluorinated alkynes or
cycloaddition with diynes is shown in Scheme 2 [15].
First, the cobalt(II) catalyst is reduced by zinc metal to generate the cobalt(I) species (LnCoI). This reduction
process is possibly accelerated by ZnI2 because the formation of a CoCl2•••ZnI2 complex might weaken a Co–Cl
bond [16]. In the case of the trimerization reaction, the generated Co(I) species interacts with two molecules of the
fluorinated alkyne through a strong π-back donation to form cobaltacyclopentadiene complex Int-1 [13(c),17, 18].
Subsequent [4+2] cycloaddition of Int-1 with another fluorinated alkyne furnishes cobaltanorbornadiene Int-2
,
which immediately undergoes reductive elimination to afford the desired tris(trifluoromethyl)benzene derivative
2
in a regioselective manner [13(c),(d)]. On the other hand, when a non-fluorinated diyne is employed, the generated
Co(I) species possibly interacts with the diyne much faster than with the fluorinated alkyne, resulting in the
formation of cobaltacyclopentadiene complex Int-1’. Then, a [4+2] cycloaddition with the fluorinated alkyne
proceeds to give cobaltanorbornadiene Int-2’, followed by the subsequent reductive elimination, affording the
corresponding cyclized product 5.
II
R2
ZnI2
Cl
Cl
Rf
CoCl2Ln
LnCo
ZnI2
R1
R1
Rf
Rf
R1
X
Zn
R1
1
ZnCl2
2
R2
5
Rf
2
Ln
Ln
CoIII
III
R2
Co Rf
Rf
R1
Rf
R1
LnCoI
R2
R2
X
R1
Int-2'
R2
R1
Int-2
Rf
R1
X
2Rf
[4+2]
Cycloaddition
[4+2]
Cycloaddition
R2
Ln
CoIII
III
Rf
Rf
R1
Ln Co
X
Oxidative coupling
R1
Int-1
Rf
R1
R2
Int-1'
Rf
R1
Scheme 2. Possible reaction mechanism.
3. Conclusion
In summary, we have developed a novel cobalt-catalyzed [2+2+2] cycloaddition using fluorinated alkynes,
which have comparative advantages, like reaction efficiency, regioselectivity, and low catalyst loading, rather than
the reported procedures. Trimerization of fluorinated alkynes took place smoothly in the presence of a catalytic

amount of CoCl2(dppb) and 1.0 equiv. of zinc metal, affording the corresponding cycloadducts in excellent yields
with high regioselectivity. Additionally, the intermolecular cycloaddition of fluorinated alkynes with
non-fluorinated diynes also proceeded smoothly in the presence of CoCl2((S)-BINAP), zinc metal, and ZnI2, to
provide various bicyclic aromatic compounds in high yields.
4. Experimental sections
4.1. General experimental procedures
Infrared spectra (IR) were obtained on liquid films on a NaCl plate with a JASCO FT/IR-4100 type A spectrometer and
all spectra are reported in wavenumber (cm–1). 1H and 13C NMR spectra were recorded with a Bruker AVANCE III 400
NMR spectrometer (1H: 400 MHz and 13C: 100 MHz) in chloroform-d (CDCl3) and the chemical shifts are reported in parts
per million (ppm) and are referenced to the residual proton of the NMR solvent. 19F NMR (376 MHz) spectra were recorded
with a Bruker AVANCE III 400 NMR spectrometer in CDCl3 with CFCl3 (δF = 0 ppm) as internal standard. The Bruker
AVANCE III 400 NMR spectrometer was used for determining the yield of the products with trifluoromethylbenzene
(CF3C6H5) or hexafluorobenzene (C6H6) as internal references. High-resolution mass spectra (HRMS) were recorded on a
JEOL JMS-700MS spectrometer using the fast atom bombardment (FAB) method.
4.1.1. Materials
All reactions were carried out using dried glassware with a magnetic stirrer bar and routinely monitored by 19F NMR
spectroscopy or thin-layer chromatography (TLC). All chemicals were of reagent grade and, if necessary, purified in the
usual manner prior to use. Column chromatography was carried out on silica gel (Wako gelⓇ60N, 38-100 μm) and TLC
analysis was performed on silica gel TLC plates (Merck, Silica gel 60F254).
4.2. Typical procedure for the cobalt-catalyzed cyclotrimerization of fluoroalkylated alkynes.
In a 30 mL two-necked round bottomed-flask, equipped with a magnetic stirring bar, were placed fluoroalkylated alkyne
(1a, 0.099 g, 0.48 mmol), zinc powder (0.033 g, 0.50 mmol), and CoCl2(dppb) (8.34 mg, 15 μmol) in acetonitrile (1.5 mL),
and the resulting mixture was stirred at 80 °C with an oil bath. After 3 h, the reaction mixture was subjected to flash column
chromatography using silica gel as stationary phase and CH2Cl2 as mobile phase. After removal of the solvent from the
eluent under reduced pressure, the residue was purified by column chromatography (hexane/AcOEt = 50:1) to give an
inseparable mixture of 3,5,6-tris(4-chlorophenyl)-1,2,4-tris(trifluoromethyl)benzene (2a) and
2,4,6-tris(4-chlorophenyl)-1,3,5-tris(trifluoromethyl)benzene (3a) in 95% combined yield (0.094 g, 0.15 mmol) as a white
solid.
4.3. X-Ray structural analysis of 2a•CH2Cl2.
A colorless prismic crystal of 2a•CH2Cl2 having approximate dimensions of 0.13×0.12×0.10 mm was mounted on a
glass fiber. All measurements for 2a•CH2Cl2 were made on a diffractometer with filtered MoKα radiation (λ= 0.71075 Å)
and a rotating anode generator using a VariMax with PILATUS/DW (Rigaku); Compound 2a•CH2Cl2. monoclinic, a =
16.7701(9) Å, b = 8.4760(4) Å, c = 21.2137(13) Å, α = 90°, β = 109.939(6)°, γ = 90°, V = 2834.6(3) Å3, T = 173(2) K, space
group P 21/c (no. 14), Z = 4, 5272 reflection measured, 3626 unique which were used in all calculations. The final R1 and
wR2 were 0.071 and 0.203 (I > 2σ(I)). All calculations were performed using the CrystalStructure crystallographic software

package. The structure was solved by direct methods and expanded using Fourier techniques. The structural model was
refined by a full-matrix least-squares method using SHELXL-2014/6 [19] . All calculations were performed using the
SHELXL program. Crystallographic data for this compound has been deposited with the Cambridge Crystallographic Data
Centre as supplementary data no. CCDC 1817768. Copy of the data can be obtained free of charge by applying to The
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK
(https://summary.ccdc.cam.ac.uk/structure-summary-form).
4.4. Typical procedure for the cobalt-catalyzed cycloaddition of fluoroalkylated alkynes with diynes.
In a nitrogen-filled glove box, a 30 mL two-necked round bottomed-flask, equipped with a magnetic stirring bar, was
charged with zinc iodide (0.016 g, 0.050 mmol). Subsequently the flask was taken out of the gloved box and zinc powder
(0.033 g, 0.50 mmol), fluorinated alkyne 1a (0.123 g, 0.60 mmol), diethyl dipropargylmalonate 4A (0.117 g, 0.50 mmol),
and acetonitrile (1.5 mL) were added to the mixture. The resulting mixture was stirred at 80 °C with an oil bath. After 3 h,
the reaction mixture was subjected to flash column chromatography using silica gel as stationary phase and CH2Cl2 as
mobile phase. After removal of solvent from the eluent under reduced pressure, the residue was purified by column
chromatography (hexane/AcOEt = 10/1) to give diethyl 6-(4-chlorophenyl)-
5-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate 5aA in 83% yield (0.181 g, 0.41 mmol) as colorless oil.
4.4.1. Diethyl 6-(3-chlorophenyl)-5-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate (5dA)
Yield: 82%; Colorless oil; 1H NMR: δ 1.27 (t, J = 7.1 Hz, 6H), 3.65 (s, 2H), 3.68 (s, 2H), 4.23 (q, J = 7.1 Hz, 4H), 7.12
(s, 1H), 7.18 (d, J = 7.3 Hz, 1H), 7.27–7.37 (m, 3H), 7.57 (s, 1H); 13C NMR: δ 14.1, 40.2, 40.4, 60.5, 62.1, 122.1 (q, J = 5.3),
124.2 (q, J = 273.75 Hz), 127.4 (d, J = 1.1 Hz), 127.5 (q, J = 29.6 Hz), 127.75, 127.80, 129.0, 129.2 (d, J = 1.26 Hz), 133.7,
139.0, 140.2, 141.7, 144.1, 171.3; 19F NMR: δ –56.90 (s, 3F); IR (neat): ν 1734, 1346, 1297, 1281, 1247, 1205, 1190, 1156,
1136, 1124, 1097, 1065 cm–1; HRMS (FAB): calcd for [M+H]+ C22H21ClF3O4: 441.1080, Found: 441.1096.
4.4.2. Diethyl 6-(2-chlorophenyl)-5-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate (5eA)
Yield: 80%; White solid; M.p. 73–75 °C; 1H NMR: δ 1.30 (td, J = 7.1, 2.0 Hz, 6H), 3.62–3.80 (m, 4H), 4.27 (quint, J =
7.1 Hz, 4H), 7.13 (s, 1H), 7.22–7.37 (m, 3H), 7.42–7.52 (m, 1H), 7.63 (s, 1H); 13C NMR: δ 14.1, 40.3, 40.4, 60.4, 62.0,
122.0 (q, J = 5.1 Hz), 124.1 (q, J = 273.9 Hz), 126.0, 127.6, 127.8 (q, J = 29.9 Hz), 129.2, 129.3, 131.3, 133.6, 137.2 (d, J =
2.0 Hz), 138.2, 140.4, 144.0, 171.2, 171.4; 19F NMR: δ –59.11 (s, 3F); IR (KBr): ν 1728, 1435, 1367, 1347, 1300, 1289,
1257, 1240, 1189, 1163, 1137, 1120, 1078, 1057, 768 cm–1; HRMS (FAB): calcd for [M+H]+ C22H21ClF3O4: 441.1080,
Found: 441.1073.
4.4.3. Diethyl 6-(4-ethoxycarbonylphenyl)-5-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate (5fA).
Yield: 83%; Colorless oil; 1H NMR: δ 1.27 (t, J = 7.2 Hz, 6H), 1.39 (t, J = 7.1 Hz, 3H), 3.64 (s, 2H), 3.68 (s, 2H), 4.23 (q,
J = 7.2 Hz, 4H), 4.39 (q, J = 7.1 Hz, 2H), 7.13 (s, 1H), 7.36 (d, J = 8.2 Hz, 2H), 7.57 (s, 1H), 8.05 (d, J = 8.2 Hz, 2H); 13C
NMR: δ 14.1, 14.4, 40.2, 40.4, 60.4, 61.1, 62.1, 122.1 (q, J = 5.2 Hz), 124.2 (q, J = 273.5 Hz), 127.4 (q, J = 30.5 Hz), 127.5,
129.0, 129.2, 129.8, 139.5, 140.2, 144.1, 144.6, 166.4, 171.2; 19F NMR: δ –56.84 (s, 3F); IR (neat): ν 2983, 1734, 1367,
1347, 1297, 1277, 1246, 1206, 1189, 1157, 1135, 1103, 1063, 1021, 738, 710 cm–1; HRMS (FAB): calcd for [M+H]+
C25H26F3O6: 479.1681, Found: 479.1682.

4.4.4. Diethyl 6-dimethylphenylsilyl-5-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate (5gA).
Yield: 68%; Colorless oil; 1H NMR: δ 0.60 (d, J = 1.2 Hz, 6H), 1.26 (t, J = 7.1 Hz, 6H), 3.57 (s, 2H), 3.63 (s, 2H), 4.21
(q, J = 7.1 Hz, 4H), 7.30–7.38 (m, 3H), 7.40 (s, 1H), 7.43–7.50 (m, 2H), 7.54 (s, 1H); 13C NMR: δ –0.7 (q, J = 2.8 Hz), 14.1,
40.5, 40.6, 60.2, 62.0, 122.4 (q, J = 5.4 Hz), 125.2 (q, J = 273.5 Hz), 127.8, 129.1, 133.1, 134.1, 134.4 (q, J = 30.9 Hz), 135.3
(d, J = 1.9 Hz), 138.7, 141.8, 143.2, 171.4; 19F NMR: δ –57.56 (s, 3F); IR (neat): ν 1735, 1333, 1297, 1254, 1232, 1190,
1162, 1147, 1119, 1095, 1069, 948, 818, 404 cm–1; HRMS (FAB): calcd for [M+H]+ C24H28F3O4Si: 465.1709, Found:
465.1694.
4.4.5. Diethyl 6-(4-chlorophenyl)-5-nonafluorobutyl-1H-indene-2,2(3H)-dicarboxylate (5hA).
Yield: 88%; Yellow oil; 1H NMR: δ 1.27 (t, J = 7.1 Hz, 6H), 3.64 (s, 2H), 3.69 (s, 2H), 4.24 (q, J = 7.1 Hz, 4H), 7.05 (s,
1H), 7.14 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 7.44 (s, 1H); 13C NMR: δ 14.0, 40.2, 40.4, 60.4, 62.1, 105.0–114.0
(m, 2C), 117.5 (qt, J = 288.3, 33.4 Hz), 117.0 (tt, J = 259.3, 34.1 Hz), 124.2 (t, J = 8.1 Hz), 125.3 (t, J = 22.2 Hz), 127.5,
128.6, 130.6, 133.4, 139.0, 140.4, 140.7, 144.3, 171.3; 19F NMR: δ –126.35 (t, J = 14.1 Hz, 2F), –121.06 (d, J = 8.24 Hz, 2F),
–103.03 (d, J = 14.1 Hz, 2F), –81.51 (t, J = 9.6 Hz, 3F); IR (neat): ν 1736, 1483, 1352, 1237, 1209, 1191, 1134, 1093, 1072,
1016, 841, 732 cm–1; HRMS (FAB): calcd for [M+H]+ C25H21ClF9O4: 591.0985, Found: 591.0989.
4.4.6. Diethyl 6-(1-hydroxycyclohexan-1-yl)-5-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate (5iA).
Yield: 46%; Colorless oil; 1H NMR: δ 1.25 (t, J = 7.1 Hz, 6H), 1.56–1.90 (m, 11H), 3.59 (s, 2H), 3.60 (s, 2H), 4.20 (q, J
= 7.1 Hz, 4H), 7.40 (s, 1H), 7.56 (s, 1H); 13C NMR: δ 14.1, 22.0, 25.5, 39.3 (d, J = 1.0 Hz), 40.2, 40.7, 60.5, 62.0, 74.6,
123.6, 124.0 (q, J = 7.67 Hz), 125.3 (q, J = 273.2 Hz), 126.4 (q, J = 30.7 Hz), 138.8, 144.0, 148.4, 171.4; 19F NMR: δ –53.35
(s, 3F); IR (neat): ν 3539, 2981, 2934, 2860, 1731, 1446, 1368, 1352, 1334, 1292, 1252, 1190, 1151, 1130, 1111, 1070, 1054,
990, 906, 734 cm–1; HRMS (FAB): calcd for [M+H]+ C22H28F3O5: 429.1889, Found: 429.1898.
4.4.7. Dibenzyl 6-(4-chlorophenyl)-5-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate (5aB).
Yield: 75%; Yellow oil; 1H NMR: δ 3.71 (s, 2H), 3.74 (s, 2H), 5.20 (s, 4H), 7.14 (s, 1H), 7.21–7.42 (m, 14H), 7.60 (s,
1H); 13C NMR: δ 40.3, 40.5, 60.7, 67.8, 122.2 (q, J = 5.59 Hz), 124.3 (q, J = 273.3 Hz), 127.6 (d, J = 30.0 Hz), 127.8, 128.0,
128.2, 128.6, 128.7, 130.5, 133.8, 135.3, 138.4, 139.4, 139.9, 143.9, 170.9; 19F NMR: δ –56.92 (s, 3F); IR (neat): ν 1735,
1485, 1347, 1298, 1281, 1234, 1206, 1184, 1156, 1134, 1104, 1091, 1061, 907, 734, 697 cm–1; HRMS (FAB): calcd for
[M+H]+ C32H25ClF3O4: 565.1393, Found: 565.1395.
4.4.8. 6-(4-Chlorophenyl)-5-trifluoromethyl-1H-indene (5aC).
Yield: 52%; Colorless oil; 1H NMR: δ 2.18 (quint, J = 7.4 Hz, 2H), 2.99 (t, J = 7.4 Hz, 2H), 3.0 (t, J = 7.4 Hz, 2H), 7.16
(s, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.61 (s, 1H); 13C NMR: δ 25.6, 32.7, 32.9, 122.1 (q, J = 4.9 Hz),
124.6 (q, J = 273.9 Hz), 126.6 (q, J = 29.7 Hz), 127.9, 128.0, 130.6, 133.6, 138.4, 139.0, 144.1, 148.3; 19F NMR: δ –56.65 (s,
3F); IR (neat): ν 2957, 1484, 1417, 1341, 1288, 1267, 1242, 1200, 1154, 1119, 1094, 1058, 1016, 889, 833 cm–1; HRMS
(FAB): calcd for [M+] C16H12ClF3: 296.0580, Found: 296.0585.
4.4.9. 5-(4-Chlorophenyl)-6-trifluoromethyl-1,3-dihydroisobenzofuran (5aE)
Yield: 64%; Colorless oil; 1H NMR: δ 5.13 (s, 2H), 5.16 (s, 2H), 7.14 (s, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4
Hz, 2H), 7.60 (s, 1H); 13C NMR: δ 73.3, 73.4, 119.1 (q, J = 5.5 Hz), 124.2 (q, J = 273.8 Hz), 124.7, 128.07 (q, J = 30.0 Hz),

128.13, 130.5 (d, J = 1.2 Hz), 134.0, 138.2, 139.2, 139.9, 143.1; 19F NMR: δ –57.00 (s, 3F); IR (neat): ν 1484, 1425, 1320,
1264, 1243, 1209, 1160, 1131, 1093, 1052, 1016, 885, 830, 591 cm–1; HRMS (FAB): calcd for [M+] C15H10ClF3O:
298.0372, Found: 298.0370.
4.4.10. Experimental procedure for the cobalt-catalyzed cycloaddition of the fluoroalkylated alkyne 1a with the diyne 4G.
In a nitrogen-filled glove box, a 30 mL two-necked round bottomed-flask, equipped with a magnetic stirring bar, was
charged with zinc iodide (0.048 g, 0.150 mmol). Subsequently the flask was taken out of the gloved box and zinc powder
(0.033 g, 0.50 mmol), fluorinated alkyne 1a (0.370 g, 1.8 mmol), diethyl dipropargylmalonate 4G (0.194 g, 0.50 mmol), and
acetonitrile (1.5 mL) were added to the mixture. The resulting mixture was stirred at 80 °C with an oil bath. After 9 h, the
reaction mixture was subjected to flash column chromatography using silica gel as stationary phase and CH2Cl2 as mobile
phase. After removal of solvent from the eluent under reduced pressure, the residue was purified by column chromatography
(hexane/AcOEt = 10/1) to give diethyl 5-(4-chlorophenyl)-4,7-diphenyl-6-trifluoromethyl-1H-indene-2,2(3H)-
dicarboxylate 5aG in 43% yield (0.128 g, 0.216 mmol) as white solid.
Diethyl 5-(4-chlorophenyl)-4,7-diphenyl-6-trifluoromethyl-1H-indene-2,2(3H)-dicarboxylate (5aG)
Yield: 43%; White solid; M.p. 233–234 °C; 1H NMR: δ 1.19 (t, J = 7.1 Hz, 6H), 3.32 (s, 2H), 3.39 (s, 2H), 4.15 (q, J =
7.1 Hz, 4H), 6.90–7.02 (m, 4H), 7.10 (d, J = 8.3 Hz, 2H), 7.12–7.24 (m, 3H), 7.31 (d, J = 8.3 Hz, 2H), 7.39 (t, J = 7.3 Hz,
1H), 7.46 (t, J = 7.2 Hz, 2H); 13C NMR: δ 14.1, 41.0, 41.2, 59.6, 62.0, 124.5 (q, J = 277.2), 126.6 (q, J = 27.5 Hz), 127.0,
127.3, 127.5, 128.1, 128.4, 129.5, 131.6 (d, J = 1.2 Hz), 132.8, 137.38, 137.41, 137.44, 138.3, 138.9 (d, J = 1.4 Hz), 139.18,
139.21, 140.7, 142.6, 171.3; 19F NMR: δ –48.19 (s, 3F); IR (KBr): ν 1731, 1443, 1348, 1329, 1298, 1280, 1243, 1215, 1189,
1151, 1124, 1098, 1016, 753, 703, 523 cm–1; HRMS (FAB): calcd for [M+H]+ C34H29ClF3O4: 593.1706, Found: 593.1704.
Acknowledgements
The authors gratefully acknowledge toTosoh Finechem Corp. for the gift of 2-bromo-3,3,3-trifluoropropene for the
preparing various CF3-alkynes.
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the reaction easier, that is, zinc iodide may also promote the reduction.
[17] The regioselective formation of Int-1 may be stemmed from an efficient decrease of LUMO energy level at the
sp-hybridized carbon adjacent to CF3, which is due to a strong electron-withdrawing character of a CF3 group. It was
reported that the formation of similar metalacyclopentadiene from CF3-alkyne and Ru-catalyst by Kawatsura and Itoh’s

group, see: Ref. 13(c).
[18] When alkynes with bulky substituents as R1 are used, the trimerization reaction does not proceed well. This might be
due to the suppression of formation of cobaltacyclopentadiene Int-1 by large steric repulsion between R1 substituents.
Since such steric repulsion does not exist in the case of using diyne, on the other hand, the reaction proceeds without
problem, even if a bulky perfluorobutylated alkyne etc. are used as substrates.
[19] (a) G. M. Sheldrick. SHELXS-2014, Program for Crystal Structure Solution, University of Göttingen, 2014;
(b) G. M. Sheldrick,Ashort history of SHELX,Acta Crystallogr., Sect.A, 64 (2008) 112122.