Cu(i)-Catalyzed addition-cycloisomerization difunctionalization reaction of 1,3-enyne-alkylidenecyclopropanes (ACPs)

Article abstract of DOI:10.1039/d0ob01692f

A copper(i)-catalyzed three-component addition-cycloisomerization difunctionalization reaction of 1,3-enyne-ACPs with Togni I reagent and TMSCN under mild reaction conditions has been developed, affording 3-trifluoroethylcyclopenta[b]naphthalene-4-carbonitrile derivatives. The reaction proceeded through a copper(i)-catalyzed 1,4-addition of conjugated 1,3-enynes via a radical relay process and aromatic cycloisomerization of allene-ACP intermediates.

Full text of DOI:10.1039/d0ob01692f

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DOI: 10.1039/D0OB01692F
Journal Name
Cu(I)-Catalyzed Addition-Cycloisomerization Difunctionalization
Reaction of 1,3-Enyne-Alkylidenecyclopropanes (ACPs)
Peng-Hua Li,a,b Yin Weia and Min Shia,b*
Received 00th Aug 2020,
Accepted 00th Aug 2020
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
copper(I)
catalyzed
three-component
addition-
As a long-standing research topic, the difunctionalization of
alkenes is a powerful and efficient transformation to increase the
complexity and potential applicability to a wide variety of organic
molecules.3 The conjugated 1,3-enynes, as a special kind of
structure, can generate the 1,2-addition or 1,4-addition allene
products through alternative insertion reactions of the C=C bond via
allenyl anionic or cationic intermediates in the presence of
organocatalysts4 or organometallic catalysts.5 Moreover, the
reactions with conjugated 1,3-enynes proceeding through a radical
pathway have unique advantages to produce substituted allenes,
which can not be formed by a normal allenyl anion reaction
process.6 For instance, in 2018, Liu and co-workers developed a
copper-catalyzed 1,2- or 1,4-difunctionalization of conjugated 1,3-
enynes through a radical relay process.6b The regioselective 1,2- and
1,4-addition could be controlled by bisoxazoline ligand and
phenthalene-type ligand to tri- or tetrasubstituted allenyl nitriles
with trifluoromethyl group, respectively (Scheme 1a). Meanwhile, it
is also an effective method for constructing cyano compounds that
are useful and transformable building blocks in the synthesis of
biologically active compounds, fluorescent materials, and drugs.7
cycloisomerization difunctionalization reaction of 1,3-enyne-ACPs
with Togni I reagent and TMSCN under mild reaction conditions
has
trifluoroethylcyclopenta[b]naphthalene-4-carbonitrile derivatives.
The reaction proceeded through a copper(I)-catalyzed 1,4-addition
been
developed,
affording
3-
of conjugated 1,3-enyne via
cycloisomerization of allene-ACP intermediate.
a radical relay and aromatic
Introduction
Although fluorine is widespread in nature, the fluorinated natural
products are rare. Furthermore, numerous studies show that the
physical and chemical properties (including the bioavailability, the
permeability of cell membrane, and the stability of cell metabolism)
of biologically active compounds can be obviously improved by
introducing fluorine atom or fluorine group (Figure 1).1 Thus far, the
development of novel and effective methods for the fluorination of
alkenes, arenes or alkanes has attracted a substantial amount of
attention from numerous scientists since it plays an important role
in constructing fluorine-containing pharmaceuticals, agrochemicals
and materials in recent years.2
a) Liu's work
HO
O
Cu(MeCN)4PF6 (5 mol%)
Ligand (6 mol%)
HO
O
R
H
CN
CF3
R
H
CF3
HN
or
R
O
S
H
H
F
F
Togni I / TMSCN
MeCN
NC
CF3
O
N
CF3
F
F
1,2-addition: bisoxazoline-type ligand, -15 o
1,4-addition: phenthalene-type ligand, r.t.
C
H
6
HO
O
F
HO
N
O
O
b) Previous work
S
OH
OH
R1
X
R1
Faslodex
Fludelone
Trifluridine
R1
S

1: 6 -electrocyclization
S
2: rearrangement
Fig. 1 Trifluoromethyl-containing drugs and biologically active compounds.
R2
R2
R2
X = C, N
Y = C, N, O, S
Y
X
Y
X
Y
c) This work
R1
R1
Cu-cat / Ligand
Togni I / TMSCN
R1
S

1: 6 -electrocyclization
S
2: rearrangement
a
State Key Laboratory of Organometallic Chemistry, Center for Excellence in
CN
CF3
CF3
NC
Molecular Synthesis, University of Chinese Academy of Sciences, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, China. mshi@mail.sioc.ac.cn.
Key Laboratory for Advanced Materials and Institute of Fine Chemicals,
School of Chemistry & Molecular Engineering, East China University of Science
Scheme 1 The reaction modes of 1,3-enynes and allene-type ACPs.
b
As
a
special family of cyclopropanes, highly strained
alkylidenecyclcoproanes (ACPs) are useful building blocks in organic
synthesis, while exhibiting excellent chemical reactivities in the
presence of transition-metal catalysts, Lewis acid and Brønsted acid
catalysts.8 A series of reports demonstrated that the allene-type
and Technology, 130 Meilong Road, Shanghai 200237, China.
†
Electronic Supplementary Information (ESI) available: Experimental
procedures, characterization data of new compounds, CCDC 1967399 and
2017000, See DOI: 10.1039/c000000x
This journal is © The Royal Society of Chemistry 2019
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ACP intermediates, generated from different substrates and
conditions, can undergo consecutive 6-electrocyclization and
vinylcyclopropane rearrangement to form more stable
aromatization heterocyclic products (Scheme 1b).9
Table 1 Optimization of the reaction conditions for the synthesis of 2a.
View Article Online
DOI: 10.1039/D0OB01692F
CF3
CF3
TMSCN (2.0 equiv)
catalyst (10 mol%)
ligand (15 mol%)
CF3
I
CN
CN
O
+
+
solvent, T, 6 h
On the basis of previous work, we wondered that the ACPs with
Togni I
(1.5 equiv)
conjugated
cyclopenta[b]naphthalene
1,3-enynes
could
derivatives
offer
difunctionalized
through the
2a
3a
1a
entrya
catalyst
ligand
solvent
T (oC)
yield
(%)
b
2a 3a
/
33/9
5/-
MeCN
MeCN
r.t.
r.t.
1
Cu(MeCN)4PF6
Cu(MeCN)4PF6
2,2'-bpy
-
difunctionalization of allene-ACP intermediates via allenyl radical
pathway (Scheme 1c). These cyclopenta[b]naphthalene derivatives,
bearing trifluoromethyl and cyano groups, have great potential to
serve as attachable fluorophores in pharmaceuticals, dyes and
liquid crystals.10 Herein, we wish to report our findings on the
2
r.t.
r.t.
27/8
12/5
MeCN
MeCN
3
Cu(MeCN)4BF4
CuI
2,2'-bpy
2,2'-bpy
4
5
CuBr
2,2'-bpy
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCM
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
40
40
40
40
r.t.
r.t.
r.t.
24/7
24/8
22/7
31/8
21/7
19/7
6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
4,4'-tBu-2,2'-bpy
4,4'-OMe-2,2'-bpy
1,10-Phen
neocuproine
2,9-iPr-1,10-Phen
2,2'-bpy
7
synthesis
of
3-trifluoroethylcyclopenta[b]naphthalene-4-
8
carbonitrile derivatives through a sequence of copper-catalyzed
difunctionalization of conjugated 1,3-enynes, consecutive 6-
electrocyclization and vinylcyclopropane rearrangement of allene-
type ACPs.
9
10
11
12
13
14
15
16
17
18
19
33c/11
27d/12
50/19
19e/9
11f/6
2,2'-bpy
DCE
2,2'-bpy
DCE
2,2'-bpy
DCE
Results and discussion
2,2'-bpy
DCE
2,2'-bpy
DCE
44g/16
(58h)/22
15/6
We initiated our studies employing a 1,3-enyne-ACP (1a), Togni I
reagent and trimethylsilyl cyanide (TMSCN) as the starting materials
to optimize the reaction conditions, and all of the results are
summarized in Table 1. When the reaction of 1a with Togni I
reagent and TMSCN was carried out in the presence of
Cu(MeCN)4PF6 (10 mol%), 2,2'-bipyridine (2,2'-bpy) (15 mol%) in
acetonitrile (MeCN) at room temperature for 6 h, we were pleased
to access the corresponding cyclopenta[b]naphthalene 2a in 33%
yield along with the byproduct 3a in 9% yield (Table 1, entry 1).
Notably, the reaction gave the trace amount of desired products in
the absence of ligands (Table 1, entry 2). The subsequent
investigation of various copper catalysts found that the use of
Cu(MeCN)4BF4, CuI and CuBr could not afford 2a or 3a in higher
yields (Table 1, entries 3-5). Therefore, the copper salt
Cu(MeCN)4PF6 was selected as the best catalyst, and other reaction
conditions were further screened. With respect to ligands, both the
substituted bipyridine-type ligands (Table 1, entries 6-7) and
phenanthroline-type ligands (Table 1, entries 8-10) could give the
target products, albeit in lower yields. Screening solvents revealed
that using dichloromethane (DCM) with better solubility gave the
desired product 2a in 33% yield along with 32% recovery of starting
material (Table 1, entry 11). The similar result in a lower yield with
the higher starting material recovery was obtained using 1,2-
dichloroethane (DCE) as solvent (Table 1, entry 12). Raising the
2,2'-bpy
DMF
2,2'-bpy
DMAc
DMSO
2,2'-bpy
4/-
[a]
Reaction conditions: 1a (0.1 mmol), Togni I (0.15 mmol), TMSCN (0.20 mmol),
catalyst (10 mol%), ligand (15 mol%) and solvent (1.0 mL) were used. 19F NMR
[b]
yield of 2a and 3a determined by CF3-DMAc (N,N-dimethyl trifluoroacetamide) as
[c]
[d]
an internal standard. 32% recovery of starting materials. 52% recovery of
starting materials.
[e]
[f]
Togni I (1.0 equiv) and TMSCN (1.5 equiv) were used.
Togni I (3.0 equiv) and TMSCN (4.5 equiv) were used. [g] Cu(MeCN)4PF6 (10 mol%),
[h]
Togni I (3.0 equiv) and TMSCN (4.5 equiv) were used in 3 portions. Isolated
yield of pure 2a after purification by flash chromatography.
Having determined the optimized reaction conditions, the scope
of this difunctionalization of 1,3-enyne-ACP substrates through a
copper-catalyzed radical strategy was investigated, and the results
are shown in Scheme 2. The most 1,3-enyne-ACP substrates could
undergo the reactions and give the corresponding products in
moderate yields, with the side products formed in about 10-20%
yields under the optimal conditions. First, using 4'-Cl substituted
1,3-enyne-ACP 1b, the pure product 2b was isolated in 59% yield,
along with the byproduct 3b in 22% yield. The structure of
byproduct 3b has been unambiguously confirmed by X-ray
diffraction (Figure 2, right).11 Similarly, for substrate with different
alkyl groups, aryl groups and halogen atom at the 4' or 3' positions
of the benzene ring, the reactions could proceed smoothly and give
the corresponding pure products 2c-2g in moderate yields ranging
from 48% to 66%. When the chlorine atom is at 5-position of the
benzene ring, the corresponding product 2h was obtained in 64%
yield. Then, the disubstituted 1,3-enyne-ACPs 1i and 1j, containing
fluorine and chlorine atoms or two chlorine atoms, could undergo
the difunctionalization to generate the corresponding products 2i
and 2j in 44% and 50% yields, respectively. It should be noted that
2j was obtained as a pair of rotamers in 1:1 ratio. When 4-Me
substituted 1,3-enyne-ACP 1k was used, the reaction proceeded to
afford an inseparable mixture of 2k and 3k in total 41% yield with a
1:4 ratio. Next, the monosubstituted ACP substrates were
investigated. For substrate 1l, an inseparable mixture of 2l and 3l
was generated in total 85% yield and a 4:1 ratio. Having different
substituents on the benzene ring (1m-1q), the mixture products
o
temperature to 40 C, the desired product 2a was formed in 50%
yield (Table 1, entry 13). When the amount of Togni I reagent and
TMSCN was decreased or increased in DCE, the yield of target
product 2a was both significantly reduced (Table 1, entries 14-15).
In addition, when copper salt, Togni I reagent and TMSCN were
added in portions in DCE, the moderate yield (44%) of 2a was
detected (Table 1, entry 16). The further exploration of solvent
demonstrated that using N,N-dimethylformamide (DMF) as solvent
could give isolated product 2a in 58% yield albeit along with the
byproduct 3a in 22% yield, which was better than other solvents
such as N,N-dimethylacetamide (DMAc) and dimethyl sulfoxide
(DMSO) (Table 1, entries 17-19).
2 | J. Name., 2020, 00, 1-5
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were obtained in 77−84% total yields with 2:1 to 6:1 ratio. For
substrates 1r and 1s, having chlorine atom on the 5- and 4-position
of benzene ring, the corresponding pure products 2r and 2s could
be isolated in 66% and 62% yields, respectively. The reaction of the
5-methoxy group substituted substrate 1t successfully provided the
desired product 2t in 64% isolated yield. Furthermore, the scale-up
experiment of 1,3-enyne-ACP 1t was conducted and gave 2t in 59%
isolated yield (471.0 mg), showing that the reaction has good
scalability (The full NMR spectroscopic data of 2t including DEPT,
COSY, HSQC and HMBC were exhibited in the Supporting
Information). For substrate 1u, containing the structure of 1,3-
benzodioxole, the reaction also proceeded smoothly to form the
product 2u in 55% yield. To further investigate the scope of this
reaction, the cyclohexene-substituted 1,3-enyne-ACP 1v, which has
the non-terminal olefin structure, was synthesized and investigated
under the standard conditions, an inseparable mixture of 2v and 3v
was obtained in total 40% yield and a 2:1 ratio. In addition, the
reaction of 1w did not provide the desired product 2w or the
corresponding allenyl nitrile product under the standard conditions,
presumably due to the higher stability of naphthalene moiety. The
structure of 2c had been unambiguously determined by X-ray
diffraction pattern (Figure 2, left).12 The related CIF data of 2c and
3b are provided in the Supplementary Information.
View Article Online
DOI: 10.1039/D0OB01692F
3b
2c
Fig. 2 X-ray crystal structure of 2c (left) and 3b (right).
On the basis of the previous literature and our own
experimental results,6,9 a plausible mechanistic pathway is
proposed in Scheme 3. Using copper(I) catalyst, the
trifluoromethyl radical can be generated from the Togni I
reagent along with the formation of copper(II) complex in the
first step. The addition of CF3 radical to the double bond of 1,3-
enyne 1 generates the propargylic radical intermediate A,
which undergoes isomerization to give the allenyl radical
intermediate B. By trapping the allenyl radical intermediate B
with copper(II) cyanide species, which is generated through
the ligand exchange process of the copper(II) complex with
TMSCN, the allenyl nitrile intermediate D is formed through
the reductive elimination of allenyl-Cu(III) species C. The 6-
electrocyclization13 of allene-ACP intermediate D can give the
vinylcyclopropane intermediate E, and the further
vinylcyclopropane rearrangement to form more stable
aromatic cyclopenta[b]naphthalene product 2. In addition, the
CF3
Cu(MeCN)4PF6 (10 mol%)
2,2'-bpy (15 mol%)
Togni I
(1.5 equiv)
CN
2'
2
R1
+
1
1'
3'
3
4
R2
TMSCN
(2.0 equiv)
R1
DMF, r.t., 6 h
6
R2
4'
5
1
2
CF3
CF3
CF3
CF3
CN
R
CN
CN
CN
vinylcyclopropane intermediate
intermediate F in the presence of copper catalyst. The
rearrangement of the intermediate generates an
intermediate through the cyclopropane ring-opening
E possibly produces an
R
R
b
2b
(R = Cl) (59%
)
F
Cl
(R = tBu) (55%b
b
)
2f
b
Cl
2c
2d
2e
(R = Cl) (57%
)
b
b
2i
2j
b
(R = F) (44% )
(R = Cl) (50%b, d.r. = 1:1)
2h
(64%
)
(R = Ph) (66%
(R = Me) (48%
)
2g
(R = Me) (59%
)
G
b
)
process. Finally, the intermediate G undergoes the elimination
to form alkene moiety under the action of 2,2'-bipyridine as
base; the next protonolysis of copper catalyst occurs to give
the side product 3. In addition, a cyano-catalyzed pathway is
also possible. The intermediate H, generated from
intermediate E under the interaction of cyano anion, can give
the product 2 or 3 through SN2 or E2 competitive reaction,
respectively (Scheme 3b).
CF3
CF3
CN
CF3
CF3
CN
CN
CN
2
2
1
H
1
3
3
H
6
R
R
Me
Me
6
4
4
5
5
c
d
2k 3k
+
(41% ) (1:4
)
CF3
c
d
CF3
CN
2l 3l
+
(R = H) (85% ) (4:1
c
)
d
2m 3m
+
(R = 6-F) (80% ) (4:1 )
c
d
2n 3n
+
(R = 3-Cl) (80% ) (4:1 )
CN
2o 3o
+
(R = 5-CF3) (77%c) (2:1d
)
H
H
c
d
2p 3p
+
(R = 5-F) (83% ) (6:1
)
c
d
2q 3q
+
(R = 4-Me) (84% ) (2:1
)
Cl
b
Cl
2r
b
2s
(62%
)
(66%
)
CF3
CF3
CN
F3
C
CF3
CF3
CN
CN
CN
CN
O
H
H
H
H
c
H
MeO
O
b
d
2w
(trace)
2v 3v
(64%b) (59%e
)
+
(40% ) (2:1
)
2u
2t
(55%
)
Scheme 2 Substrate scope of different 1,3-enyne-ACP substrates.a
[a]
[b]
All the reactions were carried on 0.1 mmol. Isolated yield of pure 2; ca. 20% yield
[c]
[d]
of 3 was isolated simultaneously. Total isolated yield of 2+3. The ratio of 2/3 was
determined from the crude 19F-NMR spectroscopy. [e] 2.50 mmol scale.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-5 | 3
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a)
triplet; ddd, double double doublet; dq, double quartet; t, triplet; q,
View Article Online
quartet; m, multiplet and brs, broad singlet.DTOhIe: 1c0o.1u0p3l9in/Dg0cOoBn0s1t6a9n2tFs
(J) for protons are reported in hertz (Hz). Infrared spectra were
recorded on a Perkin-Elmer PE-983 spectrometer with absorption in
cm-1. HRMS spectra were recorded by EI and measured on a HP-
5989 instrument. Melting points were determined on a digital
melting point apparatus and temperatures were uncorrected.
CF3
R2
R1
1
CF3
radical addition
R2
R1
A
LCuII
TMSCN
Togni I
CF3
LCuII(CN)
CF3
LCuI
NC
CF3
General protocol for the synthesis of 1,3-enyne-ACPs 1
R2
R1
B
(CN)CuIII
R
1,3-Enyne-ACPs
1 were prepared from the corresponding
R2
R1
D
C
substituted 2-halogen-aryl aldehyde or 2-halogen-aryl ketone
through a different order of Wittig reaction and Sonogashira cross-
coupling reaction. See Supplementary Information for the details.
1-(cyclopropylidene(phenyl)methyl)-2-(3-methylbut-3-en-1-yn-1-
yl)benzene (1a) A light yellow solid, m.p. 84-86 oC, 76% yield
(1.2365 g). 1H NMR (CDCl3, 400 MHz, TMS) δ 7.50 (d, J = 7.6 Hz, 1H),
7.43 (d, J = 8.0 Hz, 2H), 7.34-7.25 (m, 5H), 7.20 (t, J = 7.2 Hz, 1H),
5.08-5.06 (m, 1H), 5.01-4.96 (m, 1H), 1.64 (s, 3H), 1.61-1.54 (m, 2H),
1.26-1.21 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 143.0, 142.4, 134.0,
132.6, 130.1, 129.2, 128.1, 127.4, 127.1, 127.0, 126.5, 125.2, 123.0,
121.5, 94.3, 87.9, 23.1, 5.2, 2.3. IR (EtOH):  2998, 2969, 2911, 2207,
1613, 1539, 1511, 1388, 1283, 1111, 972, 838, 768 cm-1. HRMS (EI):
Calcd. for C21H18 requires 270.1411, found 270.1409.
1-((4-chlorophenyl)(cyclopropylidene)methyl)-2-(3-methylbut-3-
en-1-yn-1-yl)benzene (1b) Yellow oil, 68% yield (645.3 mg). 1H NMR
(CDCl3, 400 MHz, TMS) δ 7.50 (d, J = 8.0 Hz, 1H), 7.46-7.42 (m, 1H),
7.34-7.24 (m, 4H), 7.23-7.16 (m, 2H), 5.10 (s, 1H), 5.02 (s, 1H), 1.67
(s, 3H), 1.61-1.57 (m, 2H), 1.28-1.24 (m, 2H). 13C NMR (CDCl3, 100
MHz) δ145.4, 139.7, 133.7, 133.6, 130.2, 128.2, 128.1, 127.1, 126.9,
126.7, 126.6, 121.8, 121.6, 94.8, 87.1, 23.0, 5.2, 2.3. IR (EtOH): 
2977, 2938, 2911, 2203, 1774, 1593, 1494, 1294, 1159, 1006, 842,
756, 695 cm-1. HRMS (EI): Calcd. for C21H17Cl requires 304.1016,
found 304.1019.
6-electrocyclization
CF3
CN
CF3
CN
cycloisomerization
R2
R1
R2
2
R1
E
[Cu]
CF3
CF3
CN
CF3
[Cu]
[Cu]
CN
CN
- H+
base . H+
[Cu]
ring-opening
base
R2
R1
R2
R1
3
G
R2
R1
b)
F
CF3
CF3
NC
CN
2
3
H
SN2
CN
CN
E2
R2
R2
R1
R1
E
H
Scheme 3 Proposed Reaction Mechanism.
Conclusions
In
conclusion,
we
have
developed
a
novel
trifluoromethylcyanation reaction for the rapid construction of
cyclopenta[b]naphthalene derivatives in moderate yields from
1,3-enyne-ACPs through a copper(I)-catalyzed 1,4-addition of
1,3-enyne and aromatic cycloisomerization of allene-ACP
intermediate under mild reaction conditions. A plausible
mechanism for the generation of 2 and 3 has been proposed.
This reaction provides a practical method for the synthesis of
trifluoromethylated and cyanated cyclopenta[b]naphthalene
derivatives. Further investigations on expanding this synthetic
method are ongoing in our laboratory.
1-((4-(tert-butyl)phenyl)(cyclopropylidene)methyl)-2-(3-
methylbut-3-en-1-yn-1-yl)benzene (1c) Yellow oil, 77% yield (936.5
mg). 1H NMR (400 MHz, CDCl3, TMS): δ 7.49 (d, J = 7.2 Hz, 1H), 7.38
(d, J = 8.4 Hz, 2H), 7.34-7.25 (m, 5H), 5.06 (s, 1H), 4.96 (s, 1H), 1.62
(s, 3H), 1.59-1.54 (m, 2H), 1.31 (s, 9H), 1.25-1.20 (m, 2H). 13C NMR
(100 MHz, CDCl3): δ 149.4, 143.9, 137.5, 132.5, 130.2, 128.9, 127.9,
126.9, 126.8, 126.7, 125.0, 124.9, 123.0, 121.3, 93.9, 88.4, 34.5,
31.3, 23.1, 5.1, 2.1. IR (EtOH):  2969, 2903, 2864, 2197, 1781, 1600,
1508, 1451, 1247, 1019, 893, 781, 755 cm-1. HRMS (EI): Calcd. for
C25H26 requires 326.2033, found 326.2035.
Experimental section
General information
4-(cyclopropylidene(2-(3-methylbut-3-en-1-yn-1-
Unless otherwise noted, all solvents and other reagents were
commercially available and used without further purification. Thin
layer chromatography (TLC) employed glass 0.25 mm silica gel
plates (Huanghai GF254). Flash chromatography columns were
yl)phenyl)methyl)-1,1'-biphenyl (1d) Yellow oil, 66% yield (575.2
mg). 1H NMR (400 MHz, CDCl3, TMS): δ 7.59 (d, J = 7.2 Hz, 2H), 7.55-
7.49 (m, 5H), 7.42 (t, J = 7.2 Hz, 2H), 7.35-7.27 (m, 4H), 5.06 (s, 1H),
5.00 (s, 1H), 1.64 (s, 3H), 1.63-1.59 (m, 2H), 1.28-1.24 (m, 2H). 13C
NMR (100 MHz, CDCl3): δ 143.6, 141.0, 139.5, 139.2, 132.5, 130.2,
128.8, 128.7, 128.0, 127.4, 127.1, 126.94, 126.92, 126.86, 126.7,
126.1, 123.0, 121.4, 94.1, 88.2, 23.1, 5.2, 2.2. IR (EtOH):  3026,
2969, 2914, 2194, 1773, 1605, 1516, 1480, 1281, 1160, 1077, 1011,
901, 836, 757, 694 cm-1. HRMS (EI): Calcd. for C27H22 requires
346.1723, found 346.1722.
1
packed with 300–400 mesh silica gel. H, 13C and 19F NMR spectra
were recorded by using Brucker AC 400 (400 MHz) or Ascend 600
(600 MHz), Brucker AC 400 (100 MHz) or Ascend 600 (150 MHz) and
Brucker AC 400 (376 MHz) or Ascend 600 (564 MHz) for proton,
carbon and fluorine nuclei, respectively. Chemical shifts were
reported in parts per million (ppm) and based on the
tetramethylsilane peak at δ = 0.000 ppm for proton NMR and CHCl3
peak δ = 77.000 ppm (t) for carbon NMR. Signal patterns are
mentioned as s, singlet; d, doublet; dd, double doublet; dt, double
1-(cyclopropylidene(p-tolyl)methyl)-2-(3-methylbut-3-en-1-yn-1-
yl)benzene (1e) Yellow oil, 61% yield (483.2 mg). 1H NMR (400 MHz,
4 | J. Name., 2020, 00, 1-5
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CDCl3, TMS): δ 7.49 (d, J = 7.2 Hz, 1H), 7.33-7.24 (m, 5H), 7.10 (d, J = 2901, 2288, 1610, 1503, 1432, 1383, 1260, 1077, 1045, 899, 802,
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8.0 Hz, 2H), 5.08 (s, 1H), 5.01 (s, 1H), 2.32 (s, 3H), 1.66 (s, 3H), 1.57- 757 cm-1. HRMS (EI): Calcd. for C21H16Cl2 reDqOuIi:re10s.1303389./0D603O1B,0f1o6u9n2dF
1.52 (m, 2H), 1.24-1.20 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 144.0, 338.0629.
137.7, 136.2, 132.5, 130.1, 128.9, 128.7, 127.9, 126.99, 126.96, 1-(cyclopropylidene(phenyl)methyl)-4-methyl-2-(3-methylbut-3-
126.8, 124.8, 123.1, 121.2, 93.7, 88.3, 23.1, 21.1, 5.0, 2.2. IR (EtOH): en-1-yn-1-yl)benzene (1k) Yellow oil, 39% yield (248.6 mg). This
 2977, 2943, 2911, 2195, 1774, 1593, 1486, 1440, 1294, 1169, substrate is unstable at room temperature. 1H NMR (CDCl3, 400
1006, 838, 758, 727, 695 cm-1. HRMS (EI): Calcd. for C22H20 requires MHz, TMS) δ 7.43 (d, J = 8.0 Hz, 2H), 7.33 (s, 1H), 7.28 (t, J = 7.6 Hz,
284.1563, found 284.1565.
1-((3-chlorophenyl)(cyclopropylidene)methyl)-2-(3-methylbut-3-
2H), 7.20 (dd, J = 7.6, 4.4 Hz, 2H), 7.14 (dd, J = 8.0, 1.6 Hz, 1H), 5.07-
5.05 (m, 1H), 4.97 (q, J = 2.0 Hz, 1H), 2.36 (s, 3H), 1.64 (s, 3H), 1.57-
en-1-yn-1-yl)benzene (1f) Yellow oil, 68% yield (645.3 mg). 1H NMR 1.54 (m, 2H), 1.25-1.21 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 140.9,
(CDCl3, 400 MHz, TMS) δ 7.50 (d, J = 7.2 Hz, 1H), 7.49 (s, 1H), 7.33- 140.6, 136.5, 133.0, 130.1, 128.9, 128.3, 127.9, 127.0, 126.9, 126.4,
7.16 (m, 6H), 5.10 (s, 1H), 5.02 (s, 1H), 1.67 (s, 3H), 1.61-1.56 (m, 125.5, 122.8, 121.2, 93.6, 88.4, 23.1, 20.9, 5.1, 2.2. IR (EtOH): 
2H), 1.28-1.23 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 143.0, 142.4, 2969, 2899, 2866, 2212, 1751, 1573, 1495, 1370, 1262, 1161, 1103,
134.0, 132.6, 130.1, 129.2, 128.2, 128.1, 127.4, 127.1, 127.0, 126.8, 1045, 882, 760, 666 cm-1. HRMS (EI): Calcd. for C22H20 requires
126.5, 125.2, 123.0, 121.5, 94.3, 87.9, 23.1, 5.2, 2.3. IR (EtOH):  284.1560, found 284.1557.
2976, 2943, 2893, 2191, 1774, 1593, 1486, 1440, 1294, 1169, 1006, 1-(cyclopropylidenemethyl)-2-(3-methylbut-3-en-1-yn-1-
838, 758 cm-1. HRMS (EI): Calcd. for C21H17Cl requires 304.1018, yl)benzene (1l) Yellow oil, 84% yield (556.3 mg). 1H NMR (CDCl3,
found 304.1019.
400 MHz, TMS) δ 7.81 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H),
7.28 (s, 1H), 7.24 (t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 5.42 (s,
1-(cyclopropylidene(m-tolyl)methyl)-2-(3-methylbut-3-en-1-yn-1-
yl)benzene (1g) Yellow oil, 43% yield (345.3 mg). 1H NMR (CDCl3, 1H), 5.29-5.28 (m, 1H), 2.01 (s, 3H), 1.42-1.37 (m, 2H), 1.21-1.15 (m,
400 MHz, TMS) δ 7.49 (d, J = 7.2 Hz, 1H), 7.33 (s, 1H), 7.31-7.24 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 139.2, 132.2, 128.1, 126.8, 126.2,
4H), 7.10 (d, J = 8.0 Hz, 2H), 5.09-5.06 (m, 1H), 5.01 (s, 1H), 2.32 (s, 125.1, 121.6, 121.3, 116.0, 94.8, 86.9, 23.5, 4.2, 0.6. IR (EtOH): 
3H), 1.66 (s, 3H), 1.57-1.52 (m, 2H), 1.24-1.20 (m, 2H). 13C NMR 2977, 2932, 2896, 2202, 1613, 1490, 1435, 1278, 1158, 1079, 954,
(CDCl3, 100 MHz) δ 140.9, 140.6, 136.5, 133.0, 130.1, 128.9, 128.8, 854, 765 cm-1. HRMS (EI): Calcd. for C15H14 requires 194.1090, found
128.3, 127.9, 127.0, 126.9, 126.8, 126.4, 125.5, 122.8, 121.2, 93.6, 194.1086.
88.4, 23.1, 20.9, 5.1, 2.2. IR (EtOH):  2971, 2934, 2900, 2190, 1647, 2-(cyclopropylidenemethyl)-1-fluoro-3-(3-methylbut-3-en-1-yn-1-
1482, 1455, 1381, 1329, 1273, 1243, 1084, 1042, 883, 806, 671 cm-1. yl)benzene (1m) Yellow oil, 45% yield (278.2 mg). This substrate is
HRMS (EI): Calcd. for C22H20 requires 284.1565, found 284.1565.
unstable at room temperature. 1H NMR (CDCl3, 400 MHz, TMS) δ
4-chloro-2-(cyclopropylidene(phenyl)methyl)-1-(3-methylbut-3-en- 7.26-7.23 (m, 1H), 7.10 (td, J = 8.0, 5.2 Hz, 1H), 7.04 (t, J = 1.6 Hz,
1-yn-1-yl)benzene (1h) Yellow oil, 55% yield (343.1 mg). 1H NMR 1H), 7.00 (ddd, J = 9.6, 8.0, 1.2 Hz, 1H), 5.41 (q, J = 2.0 Hz, 1H), 5.33-
(400 MHz, CDCl3, TMS): δ 7.44-7.38 (m, 3H), 7.32-7.20 (m, 5H), 5.09- 5.31 (m, 1H), 2.00 (s, 3H), 1.41-1.37 (m, 2H), 1.33-1.28 (m, 2H). 13C
5.07 (m, 1H), 4.98 (q, J = 1.2 Hz, 1H), 1.63 (s, 3H), 1.61-1.55 (m, 2H), NMR (CDCl3, 100 MHz) δ 160.2 (d, J = 248.7 Hz), 132.2 (d, J = 5.9 Hz),
1.28-1.22 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 145.4, 139.7, 133.7, 128.2 (d, J = 3.3 Hz), 127.2 (d, J = 9.3 Hz), 127.1 (d, J = 15.1 Hz),
133.6, 130.2, 128.2, 128.1, 127.1, 126.9, 126.7, 126.6, 121.8, 121.6, 126.7, 123.8 (d, J = 6.2 Hz), 122.2, 116.0 (d, J = 22.9 Hz), 111.9 (d, J =
94.8, 87.1, 23.0, 5.2, 2.3. IR (EtOH):  2976, 2943, 2893, 2191, 1774, 1.9 Hz), 95.4, 86.6 (d, J = 4.7 Hz), 23.4, 6.2 (d, J = 8.3 Hz), 3.8 (d, J =
1599, 1517, 1484, 1294, 1157, 1006, 907, 838, 758, 695 cm-1. HRMS 2.7 Hz). 19F NMR (376 MHz, CDCl3): δ -112.4 ~ -112.5 (m). IR (EtOH):
(EI): Calcd. for C21H17Cl requires 304.1019, found 304.1022.
4-chloro-2-(cyclopropylidene(2-fluorophenyl)methyl)-1-(3-
 2973, 2928, 2871, 2190, 1737, 1647, 1500, 1422, 1388, 1257,
1101, 1061, 860, 758, 664 cm-1. HRMS (EI): Calcd. for C15H13F
methylbut-3-en-1-yn-1-yl)benzene (1i) Yellow oil, 44% yield (296.3 requires 212.0996, found 212.0991.
mg). 1H NMR (400 MHz, CDCl3, TMS): δ 7.37 (d, J = 8.4 Hz, 1H), 7.33 1-chloro-3-(cyclopropylidenemethyl)-2-(3-methylbut-3-en-1-yn-1-
(d, J = 2.4 Hz, 1H), 7.26-7.19 (m, 3H), 7.09-7.00 (m, 2H), 5.13-5.11 yl)benzene (1n) Yellow oil, 45% yield (278.2 mg). This substrate is
(m, 1H), 5.06 (s, 1H), 1.71 (s, 3H), 1.47-1.37 (m, 4H). 13C NMR (100 unstable at room temperature. 1H NMR (CDCl3, 400 MHz, TMS) δ
MHz, CDCl3): δ 160.2 (d, J = 247.8 Hz), 145.3, 133.9, 133.7, 131.5 (d, 7.72 (d, J = 8.0 Hz, 1H), 7.27-7.23 (m, 2H), 7.17 (t, J = 8.0 Hz, 1H),
J = 1.8 Hz), 130.4 (d, J = 3.8 Hz), 129.6, 128.4 (d, J = 8.2 Hz), 128.3 (d, 5.49 (q, J = 1.2 Hz, 1H), 5.36-5.34 (m, 1H), 2.05 (s, 3H), 1.45-1.41 (m,
J = 13.2 Hz), 127.0, 126.6, 123.7, 123.67 (d, J = 3.5 Hz), 121.8, 120.9, 2H), 1.26-1.21 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 141.3, 136.4,
115.9 (d, J = 22.3 Hz), 95.0, 86.8, 23.1, 4.9 (d, J = 4.5 Hz), 4.4. 19F 128.4, 128.0, 127.0, 126.8, 123.3, 122.4, 121.2, 116.1, 100.4, 83.7,
NMR (376 MHz, CDCl3): δ -112.6 ~ -112.7 (m). IR (EtOH):  2971, 23.3, 4.3, 0.9. IR (EtOH):  2971, 2924, 2885, 2145, 1647, 1482,
2916, 2882, 2196, 1769, 1665, 1600, 1517, 1437, 1264, 1077, 1006, 1455, 1381, 1329, 1273, 1084, 1042, 883, 671 cm-1. HRMS (EI):
907, 838, 768, 725, 695 cm-1. HRMS (EI): Calcd. for C21H16ClF Calcd. for C15H13Cl requires 228.0700, found 228.0701.
requires 322.0919, found 322.0925.
2-(cyclopropylidenemethyl)-1-(3-methylbut-3-en-1-yn-1-yl)-4-
4-chloro-2-((2-chlorophenyl)(cyclopropylidene)methyl)-1-(3-
(trifluoromethyl)benzene (1o) Yellow oil, 44% yield (287.2 mg). This
methylbut-3-en-1-yn-1-yl)benzene (1j) Yellow oil, 39% yield (248.6 substrate is unstable at room temperature. 1H NMR (CDCl3, 600
1
mg). H NMR (CDCl3, 400 MHz, TMS) δ 7.47-7.29 (m, 4H), 7.28-7.20 MHz, TMS) δ 8.06 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.4 Hz,
(m, 3H), 5.21-5.17 (m, 2H), 1.82 (s, 3H), 1.54-1.48 (m, 2H), 1.43-1.37 1H), 7.32-7.21 (m, 1H), 5.47 (s, 1H), 5.37-5.35 (m, 1H), 2.03 (s, 3H),
(m, 2H). 13C NMR (CDCl3, 100 MHz) δ 144.8, 139.7, 134.2, 133.5, 1.50-1.46 (m, 2H), 1.27-1.24 (m, 2H). 13C NMR (CDCl3, 150 MHz) δ
133.3, 132.0, 131.4, 129.8, 129.3, 128.2, 126.9, 126.8, 126.7, 126.3, 139.9, 132.7, 129.9 (q, J = 32.0 Hz), 128.6, 126.6, 124.7, 124.0 (q, J =
121.8, 120.7, 94.8, 87.3, 23.1, 5.0, 4.3. IR (EtOH):  2990, 2951, 270.4 Hz), 122.8, 122.7 (q, J = 3.9 Hz), 122.0 (q, J = 3.9 Hz), 115.3,
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97.0, 85.7, 23.3, 4.2, 0.8. 19F NMR (564 MHz, CDCl3): δ -63.0 (s). IR 5-(cyclopropylidenemethyl)-4-(3-methylbut-3-en-1-yn-1-
(EtOH):  2973, 2928, 2884, 2177, 1737, 1656, 1489, 1422, 1388, yl)benzo[d][1,3]dioxole (1u) White solid, m.p. 100-102 C, 73%
1257, 1101, 1061, 860, 758, 664 cm-1. HRMS (EI): Calcd. for C16H13F3 yield (462.3 mg). 1H NMR (CDCl3, 400 MHz, TMS) δ 7.30 (s, 1H),
View Article Online
o
DOI: 10.1039/D0OB01692F
requires 262.0691, found 262.0696.
7.26-7.13 (m, 1H), 6.86 (s, 1H), 5.95 (s, 2H), 5.39 (q, J = 1.2 Hz, 1H),
2-(cyclopropylidenemethyl)-4-fluoro-1-(3-methylbut-3-en-1-yn-1-
5.29-5.27 (m, 1H), 2.01 (s, 3H), 1.42-1.37 (m, 2H), 1.22-1.16 (m, 2H).
yl)benzene (1p) Yellow oil, 45% yield (278.2 mg). H NMR (CDCl3, 13C NMR (CDCl3, 100 MHz) δ 148.2, 146.1, 135.1, 127.0, 124.5, 121.3,
400 MHz, TMS) δ 7.50 (dd, J = 10.4, 2.8 Hz, 1H), 7.40 (dd, J = 8.8, 6.0 116.0, 114.8, 111.3, 105.0, 101.2, 93.8, 87.0, 23.6, 4.1, 0.6. IR
Hz, 1H), 7.28-7.19 (m, 1H), 6.85 (td, J = 8.4, 2.8 Hz, 1H), 5.42 (q, J = (EtOH):  2971, 2924, 2885, 2179, 1774, 1647, 1482, 1391, 1317,
1.2 Hz, 1H), 5.32-5.29 (m, 1H), 2.02 (s, 3H), 1.47-1.41 (m, 2H), 1.25- 1241, 1084, 1042, 883, 804, 747 cm-1. HRMS (EI): Calcd. for C16H14O2
1.19 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 162.5 (d, J = 246.3 Hz), requires 238.0988, found 238.0992.
1
141.7 (d, J = 8.3 Hz), 134.1 (d, J = 8.6 Hz), 128.0 (d, J = 1.0 Hz), 126.8, 1-(cyclohex-1-en-1-ylethynyl)-2-(cyclopropylidenemethyl)benzene
121.8, 117.5 (d, J = 3.0 Hz), 115.5 (d, J = 2.6 Hz), 113.8 (d, J = 22.6 (1v) Yellow oil, 42% yield (132.2 mg). 1H NMR (CDCl3, 400 MHz, TMS)
Hz), 111.7 (d, J = 22.9 Hz), 94.5 (d, J = 1.6 Hz), 86.0, 23.5, 4.2, 0.7. 19
F
δ 7.81 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.29 (s, 1H), 7.23 (t,
NMR (376 MHz, CDCl3): δ -111.3 ~ -111.4 (m). IR (EtOH):  2979, J = 7.6 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.27-6.20 (m, 1H), 2.29-2.24
2924, 2880, 2202, 1723, 1597, 1485, 1270, 1223, 1155, 985, 870, (m, 2H), 2.18-2.13 (m, 2H), 1.72-1.60 (m, 4H), 1.44-1.40 (m, 2H),
820, 749 cm-1. HRMS (EI): Calcd. for C15H13F requires 212.0996, 1.23-1.17 (m, 2H). 13C NMR (CDCl3, 100 MHz) δ 139.1, 134.9, 132.2,
found 212.0991.
127.7, 126.3, 126.0, 125.1, 121.9, 120.9, 116.3, 95.7, 85.3, 29.3,
1-(cyclopropylidenemethyl)-4-methyl-2-(3-methylbut-3-en-1-yn-1- 25.8, 22.3, 21.5, 4.2, 0.7. IR (EtOH):  2990, 2943, 2877, 2165, 1647,
o
yl)benzene (1q) Yellow solid, m.p. 90-92 C, 49% yield (403.9 mg). 1498, 1435, 1391, 1260, 1105, 1061, 749, 663 cm-1. HRMS (EI):
1H NMR (CDCl3, 400 MHz, TMS) δ 7.72 (d, J = 8.0 Hz, 1H), 7.34-7.18 Calcd. for C18H18 requires 234.1403, found 234.1402.
(m, 2H), 7.08 (d, J = 8.0 Hz, 1H), 5.41 (q, J = 1.2 Hz, 1H), 5.30-5.28 (m, 2-(cyclopropylidenemethyl)-1-(3-methylbut-3-en-1-yn-1-
1H), 2.30 (s, 3H), 2.02 (s, 3H), 1.43-1.38 (m, 2H), 1.22-1.16 (m, 2H). yl)naphthalene (1w) Yellow oil, 42% yield (256.6 mg). 1H NMR
13C NMR (CDCl3, 100 MHz) δ 136.7, 136.0, 132.7, 129.3, 127.0, (CDCl3, 400 MHz, TMS) δ 8.35 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.8 Hz,
125.13, 125.10, 121.6, 121.2, 116.0, 94.6, 87.1, 23.6, 20.9, 4.2, 0.7. 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.58-7.51 (m,
IR (EtOH):  2982, 2936, 2866, 2183, 1760, 1649, 1498, 1419, 1391, 2H), 7.48-7.43 (m, 1H), 5.55 (q, J = 1.2 Hz, 1H), 5.39-5.37 (m, 1H),
1260, 1061, 860, 758, 663 cm-1. HRMS (EI): Calcd. for C16H16 requires 2.14 (s, 3H), 1.55-1.51 (m, 2H), 1.29-1.24 (m, 2H). 13C NMR (CDCl3,
208.1247, found 208.1245.
100 MHz) δ 138.1, 133.7, 132.1, 128.1, 128.0, 127.5, 127.1, 126.8,
4-chloro-2-(cyclopropylidenemethyl)-1-(3-methylbut-3-en-1-yn-1-
126.4, 125.9, 123.3, 121.8, 117.9, 117.2, 100.8, 84.9, 23.7, 4.6, 0.9.
yl)benzene (1r) Yellow oil, 66% yield (514.3 mg). 1H NMR (CDCl3, IR (EtOH):  2988, 2928, 2884, 2177, 1737, 1656, 1489, 1422, 1383,
400 MHz, TMS) δ 7.77 (d, J = 2.0 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 1246, 1108, 1061, 860, 758, 664 cm-1. HRMS (EI): Calcd. for C19H16
7.24-7.15 (m, 1H), 7.11 (dd, J = 8.4, 2.0 Hz, 1H), 5.43 (s, 1H), 5.33- requires 244.1247, found 244.1242.
5.31 (m, 1H), 2.02 (s, 3H), 1.50-1.41 (m, 2H), 1.25-1.19 (m, 2H). 13C
NMR (CDCl3, 100 MHz) δ 140.8, 134.2, 133.5, 128.1, 126.7, 126.5, Experimental procedures for products 2
125.1, 122.1, 119.8, 115.2, 95.7, 85.9, 23.5, 4.3, 0.8. IR (EtOH): 
Under Ar atmosphere, in an oven dried 10 mL Schlenk tube
2988, 2936, 2884, 2197, 1746, 1645, 1489, 1440, 1419, 1391, 1260,
equipped with a magnetic stirring bar, Cu(MeCN)4PF6 (3.7 mg, 0.01
1103, 1061, 860, 758, 664 cm-1. HRMS (EI): Calcd. for C15H13Cl
mmol, 10 mol%) and 2,2'-bpy (2.3 mg, 0.015 mmol, 15 mol%) was
requires 228.0700, found 228.0707.
stirred in 0.5 mL DMF for 60 min at room temperature. Then, the
4-chloro-1-(cyclopropylidenemethyl)-2-(3-methylbut-3-en-1-yn-1-
solution of 1,3-enyne-ACP 1 (0.1 mmol), Togni I (49.5 mg, 0.15
yl)benzene (1s) Yellow oil, 32% yield (114.3 mg). 1H NMR (CDCl3,
mmol, 1.5 equiv), TMSCN (25.4 μL, 0.2 mmol, 2.0 equiv) in 0.5 mL
400 MHz, TMS) δ 7.84 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 2.0
DMF was added into the catalyst system. The reaction mixture was
Hz, 1H), 7.17 (d, J = 8.4 Hz, 1H), 5.49 (s, 1H), 5.39-5.37 (m, 1H), 2.08
stirred for another 6 h at room temperature. When the starting
(s, 3H), 1.55-1.49 (m, 2H), 1.31-1.26 (m, 2H). 13C NMR (CDCl3, 100
material 1 was completely consumed, the mixture was washed by
MHz) δ 140.8, 134.2, 133.5, 128.1, 126.7, 126.5, 125.1, 122.1, 119.8,
EA/H2O to remove DMF. Dried by Na2SO4, the residue was
115.2, 95.7, 85.9, 23.5, 4.3, 0.8. IR (EtOH):  3026, 2969, 2914, 2194,
evaporated under vacuum and purified by a silica gel column
1720, 1660, 1605, 1516, 1480, 1281, 1160, 1077, 1011, 901, 836,
chromatography (eluent: petroleum ether) to afford the desired
757, 694 cm-1. HRMS (EI): Calcd. for C15H13Cl requires 228.0700,
product 2 along with the formation of small amount of side product
found 228.0698.
3.
2-(cyclopropylidenemethyl)-4-methoxy-1-(3-methylbut-3-en-1-yn-
1-yl)benzene (1t) White solid, m.p. 96-98 C, 88% yield (944.6 mg).
1H NMR (CDCl3, 400 MHz, TMS) δ 7.37-7.31 (m, 2H), 7.28-7.20 (m,
3-methyl-9-phenyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
o
cyclopenta[b]naphthalene-4-carbonitrile (2a) A light yellow oil.
1
58% yield (21.2 mg). H NMR (CDCl3, 600 MHz, TMS) δ 8.31 (dt, J =
1H), 6.69 (dd, J = 8.4, 2.8 Hz, 1H), 5.38 (q, J = 1.2 Hz, 1H), 5.26-5.24
8.4, 1.2 Hz, 1H), 7.65-7.59 (m, 2H), 7.53-7.44 (m, 4H), 7.30 (t, J = 8.0
(m, 1H), 3.76 (s, 3H), 2.01 (s, 3H), 1.44-1.37 (m, 2H), 1.22-1.15 (m,
Hz, 2H), 3.06 (dq, J = 15.2, 11.2 Hz, 1H), 2.87-2.75 (m, 3H), 2.43 (dt, J
2H). 13C NMR (CDCl3, 100 MHz) δ 159.3, 140.7, 133.6, 127.0, 126.4,
= 13.2, 7.6 Hz, 1H), 2.07 (dt, J = 13.6, 7.6 Hz, 1H), 1.71 (s, 3H). 13C
120.9, 116.0, 114.0, 112.5, 110.0, 93.5, 86.9, 55.0, 23.5, 4.1, 0.6. IR
NMR (CDCl3, 150 MHz) δ 153.5, 140.9, 140.4, 137.6, 133.0, 131.7,
(EtOH):  2973, 2911, 2882, 2194, 1727, 1601, 1448, 1379, 1323,
129.3, 128.7, 128.4, 128.0, 127.6, 127.0, 126.6, 126.5 (q, J = 276.9
1270, 1088, 1046, 880, 804 cm-1. HRMS (EI): Calcd. for C16H16O
Hz), 125.0, 116.7, 103.6, 46.4, 42.0 (q, J = 26.7 Hz), 38.1, 29.2, 26.1.
requires 224.1205, found 224.1201.
6 | J. Name., 2020, 00, 1-5
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19F NMR (564 MHz, CDCl3) δ -59.9 (t, J = 11.8 Hz). IR (EtOH):  2959, 1485, 1372, 1260, 1087, 1042, 875, 768, 666 cm-1. HRMS (EI): Calcd.
View Article Online
DOI: 10.1039/D0OB01692F
2916, 2855, 2215, 1581, 1518, 1455, 1368, 1251, 1176, 1132, 1077, for C29H22NF3 requires 441.1704, found 441.1702.
1024, 959, 802, 766 cm-1. HRMS (EI): Calcd. for C23H18NF3 requires 3-methyl-9-(p-tolyl)-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
365.1392, found 365.1391.
9-(4-chlorophenyl)-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-
cyclopenta[b]naphthalene-4-carbonitrile (2e) A light yellow solid,
m.p. 136-138 oC, 48% yield (18.2 mg). 1H NMR (400 MHz, CDCl3,
1H-cyclopenta[b]naphthalene-4-carbonitrile (2b) A light yellow oil. TMS): δ 8.30 (d, J = 8.4 Hz, 1H), 7.71-7.56 (m, 2H), 7.48-7.41 (m, 1H),
1
59% yield (23.6 mg). H NMR (CDCl3, 400 MHz, TMS) δ 8.31 (dt, J = 7.33 (d, J = 8.0 Hz, 2H), 7.24-7.13 (m, 2H), 3.06 (dq, J = 15.2, 11.2 Hz,
8.4, 0.8 Hz, 1H), 7.64 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.58 (d, J = 8.4 1H), 2.90-2.70 (m, 3H), 2.47 (s, 3H), 2.42 (dt, J = 15.2, 7.6 Hz, 1H),
Hz, 1H), 7.54-7.43 (m, 3H), 7.28-7.23 (m, 2H), 3.04 (dq, J = 15.2, 11.2 2.07 (dt, J = 14.0, 7.2 Hz, 1H), 1.70 (s, 3H). 13C NMR (150 MHz,
Hz, 1H), 2.89-2.71 (m, 3H), 2.44 (dt, J = 13.6, 7.6 Hz, 1H), 2.08 (dt, J = CDCl3): δ 153.5, 141.1, 140.4, 137.8, 134.6, 133.0, 131.9, 129.34,
14.0, 7.2 Hz, 1H), 1.70 (s, 3H). 13C NMR (CDCl3, 100 MHz) δ 153.5, 129.29, 129.2, 129.1, 127.5, 126.9, 126.7, 126.5 (q, J = 277.2 Hz),
140.4, 139.5, 136.0, 134.2, 132.9, 131.5, 130.7, 130.6, 129.0, 128.9, 125.0, 116.7, 103.4, 46.4, 42.0 (q, J = 26.3 Hz), 38.1, 29.2, 26.0, 21.3.
127.7, 127.2, 126.4 (q, J = 277.1 Hz), 126.2, 125.1, 116.5, 104.0, 46.4, 19F NMR (564 MHz, CDCl3): δ -59.9 (t, J = 11.8 Hz). IR (EtOH):  2964,
42.0 (q, J = 26.7 Hz), 38.0, 29.2, 26.2. 19F NMR (376 MHz, CDCl3) δ - 2927, 2846, 2215, 1576, 1501, 1456, 1369, 1256, 1160, 1131, 1121,
59.9 (t, J = 11.3 Hz). IR (EtOH):  2981, 2920, 2882, 2218, 1592, 1502, 1078, 1059, 1022, 963, 916, 862, 832, 788 cm-1. HRMS (EI): Calcd.
1454, 1372, 1260, 1134, 1087, 1042, 875, 768, 666 cm-1. HRMS (EI): for C24H20NF3 requires 379.1548, found 379.1548.
Calcd. for C23H17ClNF3 requires 399.1000, found 399.1002.
9-(3-chlorophenyl)-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-
4-(4-chlorophenyl)-2-(4,4,4-trifluorobutan-2-yl)-3-vinyl-1-
1H-cyclopenta[b]naphthalene-4-carbonitrile (2f) A light yellow oil.
o
1
naphthonitrile (3b) A light yellow solid, m.p. 130-132 C, 22% yield 57% yield (23.5 mg). H NMR (CDCl3, 400 MHz, TMS) δ 8.23 (d, J =
1
(8.6 mg). H NMR (CDCl3, 400 MHz, TMS) δ 8.33 (d, J = 8.8 Hz, 1H), 8.4 Hz, 1H), 7.58-7.54 (m, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.46 (s, 1H),
7.66 (ddd, J = 8.4, 6.4, 1.6 Hz, 1H), 7.51-7.37 (m, 4H), 7.19-7.04 (m, 7.44-7.36 (m, 2H), 7.20-7.15 (m, 2H), 2.97 (dq, J = 15.2, 11.2 Hz, 1H),
2H), 6.54 (dd, J = 17.6, 12.0 Hz, 1H), 5.43 (dd, J = 11.2, 1.6 Hz, 1H), 2.81-2.65 (m, 3H), 2.42-2.30 (m, 1H), 2.01 (dt, J = 14.0, 7.6 Hz, 1H),
5.01 (dd, J = 17.6, 1.6 Hz, 1H), 4.05 (brs, 1H), 3.14-2.70 (m, 2H), 1.65 1.62 (s, 3H). 13C NMR (CDCl3, 100 MHz) δ 153.7, 141.8, 140.1, 136.9,
(d, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 150 MHz) δ 147.8, 142.9, 136.9, 133.3, 132.6, 131.3, 129.2, 129.1, 128.9, 128.8, 128.4, 128.3, 126.6,
136.3, 134.0, 133.7, 131.7, 131.4, 131.1, 128.6, 128.5, 127.4, 127.2, 126.4 (q, J = 277.4 Hz), 125.4, 116.2, 103.8, 46.5, 42.0 (q, J = 26.6
126.0 (q, J = 267.2 Hz), 124.8, 122.9, 117.7, 107.5, 39.0 (q, J = 27.6 Hz), 38.0, 29.3, 26.2. 19F NMR (376 MHz, CDCl3) δ -60.0 (t, J = 11.8
Hz), 30.0, 20.1. 19F NMR (564 MHz, CDCl3) δ -64.7 (t, J = 11.8 Hz). IR Hz). IR (EtOH):  2969, 2927, 2855, 2215, 1581, 1518, 1455, 1368,
(EtOH):  2987, 2937, 2898, 2218, 1613, 1490, 1451, 1406, 1260, 1263, 1176, 1123, 1077, 1024, 959, 827, 766 cm-1. HRMS (EI): Calcd.
1134, 1063, 938, 804, 757 cm-1. HRMS (EI): Calcd. for C23H17F3NCl for C23H17ClNF3 requires 399.1002, found 399.1007.
requires 399.1003, found 399.1002.
3-methyl-9-(m-tolyl)-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
9-(4-(tert-butyl)phenyl)-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-
cyclopenta[b]naphthalene-4-carbonitrile (2g) A light yellow oil.
1
dihydro-1H-cyclopenta[b]naphthalene-4-carbonitrile (2c) Light 59% yield (22.4 mg). H NMR (400 MHz, CDCl3, TMS): δ 8.30 (d, J =
yellow solid, m.p. 131-133 oC, 55% yield (23.2 mg). 1H NMR (400 8.4 Hz, 1H), 7.67-7.57 (m, 2H), 7.48-7.38 (m, 2H), 7.28 (d, J = 7.6 Hz,
MHz, CDCl3, TMS): δ 8.30 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 1H), 7.15-7.01 (m, 2H), 3.13-3.00 (m, 1H), 2.88-2.71 (m, 3H), 2.44 (s,
7.64-7.59 (m, 1H), 7.57-7.48 (m, 2H), 7.47-7.43 (m, 1H), 7.26-7.20 3H), 2.47-2.38 (m, 1H), 2.07 (dt, J = 13.6, 7.6 Hz, 1H), 1.70 (s, 3H).
(m, 2H), 3.07 (dq, J = 15.2, 11.2 Hz, 1H), 2.92-2.70 (m, 3H), 2.41 (dt, 13C NMR (100 MHz, CDCl3): δ 153.5, 141.1, 140.3, 138.3, 137.5,
J = 15.2, 7.6 Hz, 1H), 2.06 (dt, J = 14.0, 7.2 Hz, 1H), 1.70 (s, 3H), 1.41 132.9, 131.7, 129.8, 128.7, 128.5, 127.5, 126.9, 126.7, 126.5 (q, J =
(s, 9H). 13C NMR (100 MHz, CDCl3): δ 153.5, 150.9, 141.1, 140.4, 277.2 Hz), 126.3, 126.2, 124.9, 116.7, 103.4, 46.4, 42.0 (q, J = 26.6
134.5, 133.0, 131.9, 129.0, 128.9, 127.5, 126.8, 126.7, 126.5 (q, J = Hz), 38.1, 29.2, 26.0, 21.5. 19F NMR (376 MHz, CDCl3): δ -59.9 (t, J =
277.1 Hz), 125.5, 125.4, 125.0, 116.7, 103.3, 46.4, 42.0 (q, J = 26.5 11.8 Hz). IR (EtOH):  2977, 2940, 2851, 2215, 1603, 1493, 1438,
Hz), 38.1, 34.7, 31.4, 29.3, 26.0. 19F NMR (376 MHz, CDCl3): δ -59.9 1364, 1257, 1197, 1137, 1097, 1048, 896, 752 cm-1. HRMS (EI):
(t, J = 11.3 Hz). IR (EtOH):  2964, 2906, 2877, 2220, 1579, 1498, Calcd. for C24H20NF3 requires 379.1548, found 379.1545.
1370, 1262, 1131, 1103, 1045, 836, 760, 666 cm-1. HRMS (EI): Calcd. 7-chloro-3-methyl-9-phenyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-
for C27H26NF3 requires 421.2015, found 421.2017.
9-([1,1'-biphenyl]-4-yl)-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-
1H-cyclopenta[b]naphthalene-4-carbonitrile (2h) A light yellow oil.
64% yield (26.6 mg). 1H NMR (400 MHz, CDCl3, TMS): δ 8.28-8.20 (m,
dihydro-1H-cyclopenta[b]naphthalene-4-carbonitrile (2d) A light 1H), 7.61-7.43 (m, 5H), 7.30-7.26 (m, 2H), 3.02 (dq, J = 15.2, 11.2 Hz,
yellow solid, m.p. 139-140 oC, 66% yield (29.1 mg). 1H NMR (400 1H), 2.89-2.72 (m, 3H), 2.43 (dt, J = 14.4, 7.6 Hz, 1H), 2.07 (dt, J =
MHz, CDCl3, TMS): δ 8.32 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 14.0, 7.2 Hz, 1H), 1.70 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.7,
7.74-7.67 (m, 3H), 7.66-7.62 (m, 1H), 7.53-7.45 (m, 3H), 7.44-7.35 141.8, 140.1, 136.9, 133.3, 132.6, 131.3, 129.2, 129.1, 128.9, 128.8,
(m, 3H), 3.07 (dq, J = 15.2, 11.2 Hz, 1H), 2.98-2.70 (m, 3H), 2.45 (dt, 128.4, 128.3, 126.6, 126.4 (q, J = 277.4 Hz), 125.4, 116.2, 103.8, 46.5,
J = 14.8, 7.6 Hz, 1H), 2.10 (dt, J = 14.0, 7.2 Hz, 1H), 1.72 (s, 3H). 13C 42.0 (q, J = 26.6 Hz), 38.0, 29.3, 26.2. 19F NMR (376 MHz, CDCl3): δ -
NMR (100 MHz, CDCl3): δ 153.6, 140.9, 140.6, 140.5, 140.4, 136.5, 59.9 (t, J = 10.9 Hz). IR (EtOH):  2969, 2927, 2868, 2221, 1581, 1518,
133.0, 131.7, 129.8, 129.7, 128.9, 127.63, 127.61, 127.34, 127.29, 1442, 1368, 1263, 1189, 1123, 1077, 1024, 952, 800, 766 cm-1.
127.1, 127.0, 126.6, 126.5 (q, J = 277.4 Hz), 125.1, 116.7, 103.7, 46.5, HRMS (EI): Calcd. for C23H17ClF3N requires 399.1002, found
42.0 (q, J = 26.7 Hz), 38.1, 29.3, 26.1. 19F NMR (376 MHz, CDCl3): δ - 399.1007.
59.9 (t, J = 11.3 Hz). IR (EtOH):  2977, 2932, 2888, 2218, 1654, 1574, 7-chloro-9-(2-fluorophenyl)-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-
dihydro-1H-cyclopenta[b]naphthalene-4-carbonitrile (2i) A light
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1
yellow oil. 44% yield (18.4 mg). H NMR (400 MHz, CDCl3, TMS): δ (q, J = 26.2 Hz), 38.4, 29.2, 26.0. 19F NMR (376 MHz, CDCl3, 2l) δ -
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8.25 (d, J = 8.8 Hz, 1H), 7.59 (dd, J = 8.8, 2.0 Hz, 1H), 7.56-7.48 (m, 60.0 (t, J = 11.3 Hz). IR (EtOH):  2977, 2940,D2O8I5: 110, .21023195/,D106O0B30,11649923F,
2H), 7.34 (td, J = 7.6, 1.2 Hz, 1H), 7.31-7.27 (m, 1H), 7.26-7.23 (m, 1438, 1364, 1257, 1197, 1137, 1097, 1048, 896, 752 cm-1. HRMS (EI):
1H), 3.04 (dq, J = 15.2, 11.2 Hz, 1H), 2.91-2.68 (m, 3H), 2.46 (dt, J = Calcd. for C17H14F3N requires 289.1073, found 289.1078.
14.4, 8.0 Hz, 1H), 2.09 (dt, J = 14.0, 7.6 Hz, 1H), 1.71 (s, 3H). 13C 8-fluoro-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
NMR (150 MHz, CDCl3): δ 159.5 (d, J = 245.6 Hz), 153.7, 143.0, 133.7, cyclopenta[b]naphthalene-4-carbonitrile (2m) A light yellow oil.
133.6, 132.5, 131.3 (d, J = 3.8 Hz), 131.2, 130.8, 130.7, 128.6, 126.8, 80% total yield of 2m+3m (24.6 mg) (2m/3m = 4:1). 1H NMR (CDCl3,
126.4 (q, J = 277.2 Hz), 124.9, 124.6 (d, J = 3.9 Hz), 124.1 (d, J = 17.0 400 MHz, TMS, 2m) δ 8.16 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.55 (td, J
Hz), 116.4 (d, J = 21.3 Hz), 116.1, 104.6, 46.5, 42.0 (q, J = 26.6 Hz), = 8.0, 5.6 Hz, 1H), 7.25-7.20 (m, 1H), 3.19-3.08 (m, 2H), 3.00 (dq, J =
37.9, 29.1, 25.9. 19F NMR (376 MHz, CDCl3): δ -60.0 (t, J = 11.3 Hz, 15.2, 11.2 Hz, 1H), 2.77 (dq, J = 15.2, 11.2 Hz, 1H), 2.52 (dt, J = 13.2,
CF3), -113.6 ~ -113.7 (m, F). IR (EtOH):  2995, 2927, 2859, 2220, 7.6 Hz, 1H), 2.16 (dt, J = 13.6, 6.8 Hz, 1H), 1.66 (s, 3H). 13C NMR
1579, 1487, 1451, 1375, 1257, 1147, 1105, 956, 817, 760 cm-1. (CDCl3, 150 MHz, 2m) δ 158.7 (d, J = 251.1 Hz), 155.0, 142.5, 134.0
HRMS (EI): Calcd. for C23H16ClF4N requires 417.0902, found (d, J = 4.4 Hz), 127.7 (d, J = 8.5 Hz), 126.4 (q, J = 276.9 Hz), 123.1 (d,
417.0910.
J = 17.6 Hz), 121.0 (d, J = 5.5 Hz), 120.7 (d, J = 4.2 Hz), 116.1, 110.8
(d, J = 19.6 Hz), 104.3 (d, J = 3.8 Hz), 46.1 (d, J = 1.5 Hz), 42.0 (q, J =
7-chloro-9-(2-chlorophenyl)-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-
dihydro-1H-cyclopenta[b]naphthalene-4-carbonitrile (2j) Orange 26.7 Hz), 38.3, 29.4, 26.1. 19F NMR (376 MHz, CDCl3, 2m) δ -60.0 (t, J
oil. 50% yield (d.r. = 1:1) (21.7 mg). 1H NMR (600 MHz, CDCl3, TMS): = 11.8 Hz, CF3), -121.9 ~ -122.0 (m, F). IR (EtOH):  2966, 2937, 2853,
δ 8.25 (d, J = 8.8 Hz, 1H), 7.61-7.57 (m, 2H), 7.54-7.49 (m, 1H), 7.48- 2218, 1608, 1490, 1459, 1370, 1257, 1134, 1092, 1048, 906, 802,
7.44 (m, 2H), 7.39-7.32 (m, 4H), 7.29-7.26 (m, 1H), 7.25-7.20 (m, 3H), 755 cm-1. HRMS (EI): Calcd. for C17H13F4N requires 307.0979, found
3.07-2.95 (m, 2H), 2.88-2.63 (m, 6H), 2.52-2.41 (m, 2H), 2.29-2.20 307.0978.
(m, 1H), 2.13-2.07 (m, 1H), 1.72 (s, 3H), 1.69 (s, 3H). 13C NMR (150 5-chloro-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
MHz, CDCl3): δ 153.7, 152.5, 145.0, 144.9, 142.7, 142.6, 137.2, 137.1, cyclopenta[b]naphthalene-4-carbonitrile (2n) A light yellow oil.
1
135.6, 133.6, 133.5, 133.4, 133.3, 132.2, 131.5, 131.2, 131.1, 131.0, 80% total yield of 2n+3n (25.8 mg) (2n/3n = 4:1). H NMR (CDCl3,
130.8, 130.7, 130.2, 130.1, 128.9, 128.6, 127.4, 127.3, 126.8, 126.5 600 MHz, TMS, 2n) δ 7.88 (t, J = 1.6 Hz, 1H), 7.74 (dd, J = 8.0, 1.2 Hz,
(q, J = 277.8 Hz), 126.4 (q, J = 273.9 Hz), 124.8, 123.0, 119.8, 116.1, 1H), 7.63 (dd, J = 7.6, 1.2 Hz, 1H), 7.44-7.41 (m, 1H), 3.13-3.07 (m,
116.0, 104.43, 104.41, 46.5, 46.4, 42.5 (q, J = 26.8 Hz), 42.4 (q, J = 2H), 2.94-2.90 (m, 1H), 2.69-2.62 (m, 1H), 2.57-2.53 (m, 1H), 2.17-
26.2 Hz), 37.9, 37.8, 28.9, 28.8, 26.3, 26.2. 19F NMR (564 MHz, 2.13 (m, 1H), 1.70 (s, 3H). 13C NMR (CDCl3, 150 MHz, 2n) δ 157.6,
CDCl3): δ -60.0 (t, J = 11.3 Hz), -60.1 (t, J = 11.3 Hz). IR (EtOH):  143.0, 135.0, 130.7, 130.2, 129.2, 128.0, 127.6, 126.8, 126.5 (q, J =
2956, 2924, 2869, 2223, 1597, 1495, 1459, 1367, 1254, 1139, 1053, 270.6 Hz), 117.5, 103.1, 46.8, 40.8 (q, J = 26.4 Hz), 38.6, 28.7, 25.4.
954, 836, 742 cm-1. HRMS (EI): Calcd. for C23H16Cl2F3N requires 19F NMR (376 MHz, CDCl3, 2n) δ -60.0 (t, J = 11.3 Hz). IR (EtOH): 
433.0610, found 433.0615.
3,6-dimethyl-9-phenyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
2993, 2921, 2875, 2195, 1593, 1493, 1442, 1293, 1242, 1189, 1155,
1037, 905, 826, 767, 713 cm-1. HRMS (EI): Calcd. for C17H13F3NCl
cyclopenta[b]naphthalene-4-carbonitrile (2k) + 7-methyl-4-phenyl- requires 323.0689, found 323.0694.
2-(4,4,4-trifluorobutan-2-yl)-3-vinyl-1-naph thonitrile (3k) A light 3-methyl-3-(2,2,2-trifluoroethyl)-7-(trifluoromethyl)-2,3-dihydro-
yellow oil. 41% total yield of 2k+3k (15.5 mg) (2k/3k = 1:4). 1H NMR 1H-cyclopenta[b]naphthalene-4-carbonitrile (2o) A light yellow oil.
1
(400 MHz, CDCl3, TMS, 3k): δ 8.09 (s, 1H), 7.48-7.40 (m, 3H), 7.33 (d, 77% total yield of 2o+3o (27.5 mg) (2o/3o = 2:1). H NMR (CDCl3,
J = 8.8 Hz, 1H), 7.30-7.27 (m, 1H), 7.20-7.10 (m, 2H), 6.53 (dd, J = 400 MHz, TMS, 2o) δ 8.35 (d, J = 8.8 Hz, 1H), 8.13 (s, 1H), 7.98 (s,
17.2, 11.6 Hz, 1H), 5.37 (dd, J = 11.2, 1.6 Hz, 1H), 4.99 (d, J = 17.6 Hz, 1H), 7.81 (ddd, J = 13.2, 8.8, 1.6 Hz, 1H), 3.22-3.08 (m, 2H), 2.99 (dq,
1H), 4.05 (brs, 1H), 3.09-2.98 (m, 1H), 2.83-2.77 (m, 1H), 2.56 (s, 3H), J = 15.4, 11.2 Hz, 1H), 2.80 (dq, J = 15.4, 11.2 Hz, 1H), 2.54 (dt, J =
1.65 (d, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3, 2k+3k): δ 153.5, 13.6, 7.6 Hz, 1H), 2.18 (dt, J = 14.0, 7.6 Hz, 1H), 1.67 (s, 3H). 13C
147.7, 144.1, 140.8, 139.3, 138.8, 138.6, 137.8, 137.7, 134.2, 133.3, NMR (CDCl3, 100 MHz, 2o) δ 156.2, 143.7, 133.8, 131.6, 129.1 (q, J =
132.1, 132.0, 130.3, 129.9, 129.4, 129.2, 129.1, 128.6, 128.56, 32.7 Hz), 129.0, 126.3 (q, J = 276.8 Hz), 126.1, 125.7 (q, J = 4.4 Hz),
128.53, 128.4, 128.2, 128.1, 127.9, 127.5, 127.4, 126.7 (q, J = 275.2 123.9 (q, J = 270.7 Hz), 123.4 (q, J = 3.4 Hz), 115.8, 104.6, 46.2, 42.0
Hz), 126.4, 124.1, 123.7, 122.2, 118.1, 116.9, 102.8, 46.4, 42.0 (q, J = (q, J = 26.8 Hz), 38.2, 29.2, 26.2. 19F NMR (376 MHz, CDCl3, 2o) δ -
26.8 Hz), 39.0 (q, J = 27.4 Hz), 38.1, 29.7, 29.1, 26.0, 21.8, 21.7, 20.1. 60.0 (t, J = 11.8 Hz, -CH2CF3), -62.5 (s, ArCF3). IR (EtOH):  2974,
19F NMR (376 MHz, CDCl3, 2k+3k): δ -59.9 (t, J = 11.3 Hz), -64.7 (t, J 2924, 2888, 2218, 1613, 1461, 1375, 1346, 1299, 1257, 1124, 1069,
= 11.3 Hz). IR (EtOH):  2959, 2921, 2855, 2222, 1576, 1501, 1448, 917, 825, 781, 660 cm-1. HRMS (EI): Calcd. for C18H13F6N requires
1369, 1256, 1157, 1119, 1056, 1024, 959, 802, 766 cm-1. HRMS (EI): 357.0947, found 357.0951.
Calcd. for C24H20F3N requires 379.1548, found 379.1552.
7-fluoro-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
cyclopenta[b]naphthalene-4-carbonitrile (2p) A light yellow oil.
1
cyclopenta[b]naphthalene-4-carbonitrile (2l) A light yellow oil. 84% 83% total yield of 2p+3p (25.5 mg) (2p/3p = 6:1). H NMR (CDCl3,
total yield of 2l+3l (24.3 mg) (2l/3l = 4:1). 1H NMR (CDCl3, 400 MHz, 400 MHz, TMS, 2p) δ 8.23 (dd, J = 9.2, 5.2 Hz, 1H), 7.82 (s, 1H), 7.47-
TMS, 2l) δ 8.24 (d, J = 8.4 Hz, 1H), 7.90-7.82 (m, 2H), 7.65-7.55 (m, 7.37 (m, 2H), 3.17-3.06 (m, 2H), 2.99 (dq, J = 15.2, 11.2 Hz, 1H), 2.74
2H), 3.13-2.96 (m, 3H), 2.74 (dq, J = 15.2, 11.2 Hz, 1H), 2.50 (dt, J = (dq, J = 15.2, 11.2 Hz, 1H), 2.50 (dt, J = 13.6, 7.6 Hz, 1H), 2.15 (dt, J =
13.6, 7.6 Hz, 1H), 2.15 (dt, J = 14.0, 7.6 Hz, 1H), 1.66 (s, 3H). 13C 13.6, 7.2 Hz, 1H), 1.65 (s, 3H). 13C NMR (CDCl3, 150 MHz, 2p) δ 161.4
NMR (CDCl3, 150 MHz, 2l) δ 154.0, 141.9, 132.6, 128.4, 128.1, 127.8, (d, J = 248.3 Hz), 153.4, 143.3, 133.6 (d, J = 9.8 Hz), 129.4, 127.6 (d, J
127.4, 127.1, 126.4 (q, J = 276.9 Hz), 124.9, 116.4, 104.2, 46.0, 41.9 = 5.6 Hz), 127.4 (d, J = 9.6 Hz), 126.4 (q, J = 277.2 Hz), 118.0 (d, J =
8 | J. Name., 2020, 00, 1-5
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25.0 Hz), 116.2, 111.4 (d, J = 20.6 Hz), 104.4, 45.9, 41.9 (q, J = 26.8 2197, 1599, 1485, 1405, 1293, 1239, 1185, 1155, 1065, 934, 826,
View Article Online
-1
Hz), 38.3, 29.2, 26.1. 19F NMR (376 MHz, CDCl3, 2p) δ -60.0 (t, J = 797, 767, 713 cm . HRMS (EI): Calcd. for C18H16F3NO requires
DOI: 10.1039/D0OB01692F
10.9 Hz, CF3), -112.9 ~ -113.0 (m, F). IR (EtOH):  2979, 2928, 2854, 319.1179, found 319.1178.
2208, 1599, 1467, 1401, 1242, 1157, 1113, 1037, 909, 796, 713 cm-1. 9-methyl-9-(2,2,2-trifluoroethyl)-8,9-dihydro-7H-
HRMS (EI): Calcd. for C17H13F4N requires 307.0984, found 307.0990.
3,6-dimethyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
cyclopenta[6,7]naphtho[1,2-d][1,3]dioxole-10-carbonitrile (2u) A
white solid, m.p. 125-127 C, 55% yield (18.3 mg). H NMR (CDCl3,
o
1
cyclopenta[b]naphthalene-4-carbonitrile (2q) A light yellow oil. 400 MHz, TMS) δ 7.68 (s, 1H), 7.54 (s, 1H), 7.09 (s, 1H), 6.11 (s, 2H),
1
84% total yield of 2q+3q (25.5 mg) (2q/3q = 2:1). H NMR (CDCl3, 3.15-2.88 (m, 3H), 2.69 (dq, J = 15.2, 11.2 Hz, 1H), 2.46 (dt, J = 14.8,
400 MHz, TMS, 2q) δ 8.01 (s, 1H), 7.83 (s, 1H), 7.73 (d, J = 8.4 Hz, 7.6 Hz, 1H), 2.11 (dt, J = 14.0, 7.2 Hz, 1H), 1.63 (s, 3H). 13C NMR
1H), 7.38 (dd, J = 8.4, 1.6 Hz, 1H), 3.11-2.92 (m, 3H), 2.72 (dq, J = (CDCl3, 150 MHz) δ 151.6, 149.6, 148.6, 140.3, 130.6, 130.0, 127.5,
15.2, 11.2 Hz, 1H), 2.57 (s, 3H), 2.48 (dt, J = 13.6, 7.6 Hz, 1H), 2.13 126.5 (q, J = 277.0 Hz), 116.8, 103.9, 103.2, 101.8, 101.6, 45.9, 42.0
(dt, J = 13.6, 7.2 Hz, 1H), 1.65 (s, 3H). 13C NMR (CDCl3, 100 MHz, 2q) (q, J = 26.4 Hz), 38.5, 29.1, 26.1. 19F NMR (564 MHz, CDCl3) δ -60.0 (t,
δ 153.9, 140.8, 138.0, 132.9, 130.9, 129.3, 128.1, 127.9, 126.5 (q, J = J = 12.4 Hz). IR (EtOH):  2972, 2916, 2869, 2197, 1599, 1485, 1466,
277.1 Hz), 123.9, 116.7, 103.3, 46.0, 41.9 (q, J = 26.6 Hz), 38.4, 29.1, 1372, 1293, 1239, 1185, 1153, 1065, 934, 826, 797, 767, 713 cm-1.
26.0, 21.9. 19F NMR (376 MHz, CDCl3, 2q) δ -60.0 (t, J = 11.2 Hz). IR HRMS (EI): Calcd. for C18H14F3NO2 requires 333.0971, found
(EtOH):  2979, 2917, 2854, 2199, 1599, 1564, 1467, 1401, 1242, 333.0970.
1188, 1037, 909, 796, 710 cm-1. HRMS (EI): Calcd. for C18H16F3N 2-(trifluoromethyl)-2',3'-dihydrospiro[cyclohexane-1,1'-
requires 303.1235, found 303.1231.
7-chloro-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
cyclopenta[b]naphthalene]-9'-carbonitrile (2v) A light yellow oil.
40% total yield of 2v+3v (13.2 mg) (2v/3v = 2:1). H NMR (CDCl3,
1
cyclopenta[b]naphthalene-4-carbonitrile (2r) A light yellow oil. 400 MHz, TMS, 2v) δ 8.24 (d, J = 8.4 Hz, 1H), 7.85 (s, 1H), 7.82 (d, J =
1
66% yield (21.4 mg). H NMR (CDCl3, 400 MHz, TMS) δ 8.23 (s, 1H), 8.0 Hz, 1H), 7.62-7.51 (m, 2H), 3.46-3.37 (m, 1H), 3.15-3.02 (m, 2H),
7.86 (s, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H), 3.16- 2.55 (ddd, J = 14.4, 9.2, 6.0 Hz, 1H), 2.35 (td, J = 13.6, 4.0 Hz, 1H),
2.91 (m, 3H), 2.75 (dq, J = 15.6, 11.2 Hz, 1H), 2.51 (dt, J = 14.0, 7.6 2.17-2.08 (m, 2H), 2.00-1.87 (m, 2H), 1.81-1.76 (m, 1H), 1.66-1.58
Hz, 1H), 2.15 (dt, J = 13.6, 7.2 Hz, 1H), 1.65 (s, 3H). 13C NMR (CDCl3, (m, 3H). 13C NMR (CDCl3, 150 MHz, 2v) δ 154.5, 142.3, 132.7, 132.5,
100 MHz) δ 155.0, 142.4, 134.2, 133.3, 130.9, 129.5, 128.2, 128.1, 128.2, 128.0, 127.5, 127.4 (q, J = 276.8 Hz), 126.8, 124.8, 116.9,
126.3 (q, J = 277.2 Hz), 124.0, 116.0, 103.5, 46.1, 41.9 (q, J = 27.3 103.8, 50.7, 46.4 (q, J = 23.6 Hz), 38.5, 30.6, 29.3, 24.6, 23.4 (q, J =
Hz), 38.3, 29.2, 26.1. 19F NMR (376 MHz, CDCl3) δ -60.0 (t, J = 11.3 2.9 Hz), 22.4. 19F NMR (376 MHz, CDCl3, 2v) δ -65.8 (d, J = 9.4 Hz). IR
Hz). IR (EtOH):  2959, 2921, 2855, 2222, 1576, 1501, 1448, 1369, (EtOH):  2993, 2921, 2875, 2763, 2195, 1593, 1493, 1405, 1293,
1256, 1157, 1119, 1056, 1024, 959, 802, 766 cm-1. HRMS (EI): Calcd. 1242, 1216, 1155, 1065, 1006, 905, 826, 767, 713 cm-1. HRMS (EI):
for C17H13F3NCl requires 323.0689, found 323.0694.
Calcd. for C20H18F3N requires 329.1391, found 329.1396.
6-chloro-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
cyclopenta[b]naphthalene-4-carbonitrile (2s) A light yellow oil. Conflicts of interest
1
62% yield (20.0 mg). H NMR (CDCl3, 400 MHz, TMS) δ 8.23 (d, J =
There are no conflicts of interest to declare.
2.0 Hz, 1H), 7.86 (s, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.50 (dd, J = 8.8, 2.0
Hz, 1H), 3.14-3.06 (m, 2H), 2.98 (dq, J = 15.2, 11.2 Hz, 1H), 2.75 (dq,
J = 15.2, 11.2 Hz, 1H), 2.51 (dt, J = 13.2, 7.6 Hz, 1H), 2.15 (dt, J = 13.6,
7.2 Hz, 1H), 1.65 (s, 3H). 13C NMR (CDCl3, 100 MHz) δ 155.0, 142.4,
134.2, 133.3, 130.9, 129.5, 128.2, 128.1, 126.3 (q, J = 276.8 Hz),
124.0, 116.0, 103.5, 46.1, 41.9 (q, J = 26.7 Hz), 38.3, 29.2, 26.1. 19F
NMR (376 MHz, CDCl3) δ -60.0 (t, J = 11.3 Hz). IR (EtOH):  2993,
Acknowledgment
We are grateful for the financial support from the Strategic
Priority Research Program of the Chinese Academy of Sciences
(Grant No. XDB20000000), the National Natural Science
Foundation of China (21372250, 21121062, 21302203,
2928, 2875, 2208, 1604, 1493, 1467, 1293, 1242, 1189, 1113, 1037, 20732008, 21772037, 21772226, 21861132014 and 91956115)
932, 835, 796, 713 cm-1. HRMS (EI): Calcd. for C17H13F3NCl requires
323.0689, found 323.0688.
and the Fundamental Research Funds for the Central
Universities 222201717003.
7-methoxy-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-
cyclopenta[b]naphthalene-4-carbonitrile (2t) A white solid, m.p.
120-122 oC, 64% yield (0.1 mmol scale, 20.4 mg); 59% yield (2.50
mmol scale, 471.0 mg). 1H NMR (CDCl3, 400 MHz, TMS) δ 8.12 (d, J =
8.8 Hz, 1H, -C(4)H), 7.76 (s, 1H, -C(9)H), 7.27 (dd, J = 9.2, 2.4 Hz, 1H, -
C(5)H), 7.11 (d, J = 2.4 Hz, 1H, -C(7)H), 3.93 (s, 3H, -OC(18)H3), 3.16-
3.05 (m, 2H, -C(12)H2-), 2.99 (dq, J = 15.2, 11.6 Hz, 1H, -C(15)H2CF3),
2.70 (dq, J = 15.2, 11.2 Hz, 1H, -C(15)H2CF3), 2.47 (dt, J = 13.6, 7.6 Hz,
1H, -C(11)H2-), 2.19-2.05 (m, 1H, -C(11)H2-), 1.64 (s, 3H, -C(14)H3). 13C
NMR (CDCl3, 150 MHz) δ 158.5 (C6), 151.4 (C1), 142.4 (C10), 128.0
(C3), 127.1 (C9), 126.5 (q, J = 277.2 Hz, C16), 126.3 (C4), 120.3 (C5),
116.6 (C17), 106.2 (C7), 103.9 (C2), 55.4 (C18), 45.8 (C13), 42.0 (q, J
= 27.2 Hz, C15), 38.4 (C11), 29.3 (C12), 26.0 (C14). 19F NMR (376
MHz, CDCl3) δ -60.0 (t, J = 11.3 Hz). IR (EtOH):  2972, 2921, 2851,
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10 | J. Name., 2020, 00, 1-5
This journal is © The Royal Society of Chemistry 2020
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Page 11 of 11
Organic & Biomolecular Chemistry
Journal Name
COMMUNICATION
Cu(I)-Catalyzed Addition-Cycloisomerization Difunctionalization A novel synthesis of 3-trifluoroethylcyclopenta[b]naphthalene-4-
Reaction of 1,3-Enyne-Alkylidenecyclopropanes (ACPs)
carbonitrile derivatives from 1,3-enyne-ADCOPsI: 1v0ia.10C3Vu9ie(/IwD)-0AcOraticBtla0el1Oy6nz9lei2ndFe
1,4-addition of 1,3-enyne and aromatic cycloisomerization of
allene-ACP-type intermediate has been developed.
CF3
Cu(I)/ligand
Togni I/TMSCN
CN
2'
2
R1
1
1'
3'
3
4
R2
R1
22 examples
6
4'
up to 66% yield
R2
5
cyclopenta[b]naphthalene derivatives
cascade
1,4-addition of 1,3-enyne
cycloisomerization of allene-ACP
Peng-Hua Li, Yin Wei and Min Shi*
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-5 | 11
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