Photoinduced Deaminative Coupling of Alkylpyridium Salts with Terminal Arylalkynes

Article abstract of DOI:10.1021/acs.joc.0c01928

A novel and simple Z-alkene synthesis by the photocatalyzed coupling reactions of alkylpyridium salts, which were prepared from primary amines, with terminal aryl alkynes at room temperature is reported here. A wide range of primary amines, which contain different functional groups, were tolerated under these conditions. The mild reaction conditions, broad substrate scope, functional group tolerance, and operational simplicity make this deaminative coupling reaction a valuable method in organic syntheses.

Full text of DOI:10.1021/acs.joc.0c01928

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Note
Photoinduced Deaminative Coupling of Alkylpyridium Salts with
Terminal Arylalkynes
Shu-Zhen Lai, Yu-Ming Yang, Hai Xu, Zhen-Yu Tang,* and Zhuangzhu Luo*
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ABSTRACT: A novel and simple Z-alkene synthesis by the
photocatalyzed coupling reactions of alkylpyridium salts, which
were prepared from primary amines, with terminal aryl alkynes at
room temperature is reported here. A wide range of primary
amines, which contain different functional groups, were tolerated
under these conditions. The mild reaction conditions, broad
substrate scope, functional group tolerance, and operational
simplicity make this deaminative coupling reaction a valuable
method in organic syntheses.
Scheme 1. Hydroalkylation of Alkynes with Alkyl
Electrophiles
rimary amines are widely available in drugs, natural
P
products, and synthetic chemicals.1 However, cross-
coupling of primary amines is limited in employing the only
electronically activated or strain-activated amine derivatives
until recently.2 The inactivated alkyl amines are less applied in
synthetic field owing to the inert C(sp3)−N bonds.3 Bench-
stable alkylpyridium salts (Katritzky salts), which were
prepared by condensation of alkyl amines with commercially
available triphenyl pyrylium salts,4 emerged as convenient
radical precursors by single electron reduction (SER) and have
attracted broad attention. In 2017, Watson published the first
example of an unactivated amine derivative in a deaminative
cross-coupling reaction.2a Afterward, many elegant studies have
been carried out in this area.5 For example, Watson6 and
Glorius7 reported that alkyl radicals were generated from
Katritzky salts via SER in the presence of nickel or a
photocatalyst. In addition, Aggarwal employed Katritzky salts
as alkylation regents by irradiation of electron−donor−
acceptor (EDA) complexes between the salts and Hantzsch
esters.8
Alkenes have been applied as fundamental building blocks in
synthetic chemistry, material and life science.9 Recently, many
strategies had been developed for syntheses of alkenes by
coupling readily available alkynes with alkyl electrophiles
(Scheme 1).10 In 2015, Hu reported the iron-catalyzed
reductive coupling of terminal alkynes with alkyl halides for
the selective synthesis of Z-olefins.10a In 2019, a nickel-
catalyzed deaminative hydroalkylation of internal alkynes was
described by Liu.11 Watson published a nickel-catalyzed
deaminative alkyl-vinyl coupling of alkyl pyridium salts to
form E-olefins.6c Inspired by these advances and based on our
previous work,12 we expected that alkyl radicals derived from
Katritzky salts could add to terminal alkynes through visible-
light photoredox catalysis. Herein, we report that the
photoinduced deaminative coupling reaction of Katritzky
salts with terminal arylalkynes, which leads to the unique
physiologically active Z-olefins.13
Our studies commenced with the model reaction of N-
cyclohexyl Katritzky pyridinium salt 1a and 1-chloro-
ethynylbenzene 2a (Table 1). The previous results reported
that DIPEA and catalyst fac-Ir(ppy)3 play an important role in
(E)- to (Z)- isomerization,14 which was also confirmed by our
Received: August 9, 2020
https://dx.doi.org/10.1021/acs.joc.0c01928
© XXXX American Chemical Society
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A

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Note
a
Table 1. Optimization of Reaction Conditions
Scheme 2. Substrate Scope with Respect to the
Alkylpyridium Salts
a
Entry
Solvent
Base
PC
Yield % (Z/E)
1
2
3
4
5
6
7
8
DMA
THF
DMF
DMSO
DCE
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
Et3N
DABCO
DBU
TMEDA
K2CO3
None
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(dtppy)(ppy)2PF6
Ru(bpy)3Cl2·6H2O
none
Ir(ppy)3
Ir(ppy)3
37 (84:16)
37 (78:22)
35 (83:17)
30 (83:17)
34 (82:18)
27 (85:15)
30 (78:22)
16 (83:17)
30 (84:16)
21 (83:17)
0
CH3CN
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
9
10
11
12
13
14
15
16
17
18
19
20
21
0
29 (81:19)
25 (78:22)
21 (72:28)
0
51 (95:5)
38 (72:28)
68 (95:5)
38 (86:14)
59 (87:13)
b
c
cd
,
none
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
cd
,
cde
,
,
cdf
,
,
a
Conditions: 1a (0.2 mmol), 2a (0.1 mmol), DIPEA (7 equiv), and
Ir(ppy)3 (1 mol %) in DMA (1 mL) were irradiated by blue LEDs for
1
16 h under Ar. Isolated yields. The Z/E ratio was determined by H
b
c
d
e
f
NMR. No light. DIPEA (50 equiv). 1a (3 equiv). 6 h. 11 h.
a
Conditions: 1 (0.3 mmol), 2a (0.1 mmol), and Ir(ppy)3 (1 mol %)
in a mixture of DIPEA/DMA (0.85 mL/1 mL) were irradiated by
blue LEDs for 16 h under Ar. Isolated yields of Z/E mixtures and the
Z/E ratio were determined by H NMR. Gram-scale reaction (1
mmol).
earlier research.12 Inspired by those results, we discovered that
simple mixing of 1a (0.2 mmol), 2a (0.1 mmol), DIPEA (7
equiv) and Ir(ppy)3 (1 mol %) in DMA irradiated by blue
LEDs for 16 h under argon afforded 37% (Z/E = 84:16)
coupling product 3a (entry 1). The initial results prompted us
to further improve both yield and Z/E selectivity. Different
solvents were screened under current conditions. Hydrophilic
solvents, such as DMF, DMA, and THF, resulted in better
yields than hydrophobic solvent (entries 2−6). When DIPEA
was replaced by Et3N, DABCO, and DBU, both yields and Z/E
ratios diminished (entries 7−9). No product was formed when
an inorganic base (K2CO3) was employed. Further photo-
catalysts screening proved fac-Ir(ppy)3 as the best catalyst.
Control experiments confirmed that light and a base were
necessary for this coupling reaction. Increasing the amount of
DIPEA to 50 equiv increased the yield (51%) and Z/E ratio
(95:5). Finally, increasing the amount of 1a to 3 equiv
produced the coupling product 3a with a 68% yield and Z/E
selectivity of 95:5 (entry 19). It is surprising to observe a 38%
yield without an iridium photocatalyst, which implied that the
EDA mechanism played some role in this transformation.
During our preliminary kinetic studies with reaction times of 6
and 11 h, the fac-Ir(ppy)3 dramatically improved both the yield
and selectivity (entries 20−21). Overall, the optimal
combination of base, solvent, and catalyst was the key for
this transformation.
b
1
salts, which were prepared from alkyl primary amines, were
subjected to the standard conditions and afforded the desired
products with good yields and excellent selectivities. When the
cyclic alkyl group is smaller, the yield improved (3a−3d).
Various aryl and heterocyclic groups were also well tolerated,
including pyran and piperidine (3i−3m). To our delight, alkyl
Katritzky salts with an unprotected alcohol also work well in
this coupling with moderate yields and high Z/E ratios (3n and
3o). Finally, primary, tertiary alkyl amines, and α-amino acid
derivatives pyridium salts were also tested and no products
were obtained. To demonstrate the robustness and scale-up
potential of our method, a gram-scale reaction of substrate 3a
(1 mmol) was checked and comparable results were observed
(50% vs 68%).
Subsequently, we sought to explore the scope of aryl alkynes
(Scheme 3). A wide range of alkynyl arenes with electron-
withdrawing or -donating functional groups including halogen,
trifluoromethyl, methoxy, and nitrile groups were all tolerated
under the standard conditions. Alkynyl arenes with ortho-
substitution generally have better selectivities and similar yields
with the meta- and para-substituted ones. Alkynyl heteroarene,
such as pyridine, could also form the product with a moderate
yield and a high Z/E ratio (4o). Alkyl alkyne (4p) and internal
aryl alkyne failed to afford the desired product under our
photocatalyzed conditions. A nickel-catalyzed deaminative
With the optimized reaction conditions in hand, the
alkylpyridium salt substrate scope was evaluated. As demon-
strated in Scheme 2, a range of cyclic and acyclic alkylpyridium
B
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Note
alkyl radical intermediate was involved in this transformation.
Isotopic labeling experiments were performed with the
addition of D2O in DMA or deuterated DMF as solvent. No
deuterated product was detected in either condition, which
implied that the hydrogen atom source could not be the trace
amount of water in solvent or solvent. In addition, the Z/E
isomerization of olefin product under the standard conditions
was explored. This result further confirmed Weaver’s14 and
Uchiyama’s15 reports that fac-Ir(ppy)3 promoted the isomer-
ization to the Z-isomer under visible light irradiation.
Scheme 3. Substrate Scope with Respect to Terminal
(Hetero) Arylalkynes
a
Based on the mechanic studies and the previous reports,16
a
plausible mechanism is proposed in Scheme 5. There are two
Scheme 5. Proposed Mechanism
a
Conditions: 1a (0.3 mmol), and 2 (0.1 mmol), Ir(ppy)3 (1 mol %)
in a mixture of DIPEA/DMA (0.85 mL/1 mL) were irradiated by
blue LEDs for 16 h under Ar. Isolated yields of Z/E mixtures and the
1
Z/E ratio were determined by H NMR.
hydroalkylation of alkylpyridinium salts with internal alkynes
was previously reported by Liu’s group.11
To understand the reaction mechanism, several control
experiments were conducted (Scheme 4). No desired product
was observed when radical scavenger 2,2,6,6-tetramethyl-1-
piperidinyloxy (TEMPO) was added into the reaction system.
Moreover, the reaction with a chiral Katritzky salt prepared
from (R)-cyclohexylethylamine resulted in the racemic product
3g under the standard conditions. These results proved that an
possible routes to form alkyl radical from alkyl pyridium salt 1.
Based on our UV/vis adsorption spectroscopy study between
alkyl pyridium salt 1 and DIPEA,5b there is a characteristic
bathchromic shift which indicates formation of EDA complex
A (see Supporting Information for UV/vis adsorption
spectrum). Photoinduced electron transfer (PET) and
fragmentation provided alkyl radical B. An alternative route
involves dihydropyridine radical B being formed from 1 via
single-electron transfer by photoexcited Ir(Ir*), which then
undergoes fragmentation to generate a reactive alkyl radical.
The alkyl radical was intercepted by aryl alkynes, generating
another radical intermediate, C. A hydrogen atom transfer
(HAT) from DIPEA to radical intermediate C delivers the
olefin product. Other hydrogen atom sources such as
Hantzsch’s ester, thiol, and silane were also tested, and none
of them produced the olefin product (see Supporting
Information for additive tests).6c,8,11 Finally, the Z-olefin is
formed from the isomerization effect of Ir(ppy)3 under the
standard conditions.
Scheme 4. Control Experiments
In conclusion, we have developed a convenient protocol for
the synthesis of Z-selective alkenes with readily available
primary amines and terminal aryl alkynes as starting materials.
The reaction occurs under mild conditions with high selectivity
and broad substrate scope. As it is complementary to the
current synthesis approach of Z-alkenes, it also expands the
utility of prevalent primary amines. Further efforts toward the
other photoinduced deaminative of Katritzky salts coupling
reaction are underway.
C
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Note
(m, 1H), 1.73−1.66 (m, 6H), 1.42−1.26 (m, 6H). 13C{H} NMR
(100 MHz, CDCl3) δ 140.7, 136.2, 133.6, 130.4, 129.3, 127.9, 126.3,
122.6, 38.2, 34.9, 28.5, 26.3. HRMS (EI) Calcd for C15H19Cl+ [M]+:
234.1170, found: 234.1171.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out in a liquid
scintillation vial under argon atmosphere. The vial was placed in 1 of
the 16 wells of the SynLED Parallel Photoreactor purchased from
Sigma-Aldrich (Z742680, 12W, 465−470 nm, 130−140 LM); the
distance between light source and bottom of the reaction vial is 1.5
cm. Reagents 2 used in this study are commercially available from
Energy Chemical and used without purification. Substrates 1 were
prepared as the reported procedures in the literatures.2a,4 All of the
reactions were monitored by thin layer chromatography (TLC). Flash
chromatography was performed using Dynamic Adsorbents Silica Gel
40−63 μm particle size. NMR spectra were recorded on a Bruker
(Z)-1-Chloro-2-(2-cyclododecylvinyl)benzene (3d). Colorless oil,
1
10.9 mg, 36% yield, Z/E = 98:2. Rf 0.8 (petroleum ether). H NMR
(400 MHz, CDCl3) δ 7.38−7.36 (m, 1H), 7.28−7.26 (m, 1H), 7.23−
7.16 (m, 2H), 6.44 (d, J = 11.3 Hz, 1H), 5.59 (t, J = 10.9 Hz, 1H),
2.62−2.51 (m, 1H), 1.55−1.47 (m, 2H), 1.35−1.13 (m, 18H), 1.11−
1.11 (m, 2H). 13C{H} NMR (100 MHz, CDCl3) δ 140.0, 136.6,
133.6, 130.6, 129.1, 127.9, 126.1, 125.5, 32.2, 30.4, 23.9, 23.7, 23.3,
22.8, 22.3. HRMS (EI) Calcd for C20H29Cl+ [M]+: 304.1952, found:
304.1951.
1
Avance 400 (400 MHz for H, 100 MHz for 13C) with CDCl3 as
(Z)-1-Chloro-2-(3-ethylpent-1-en-1-yl)benzene (3e). Colorless oil,
1
solvent. High-resolution mass spectra were obtained on the MAT
95XP (Thermo) mass spectrometer at Sun Yat-sen University Mass
Spectrometry Facilities and the GCT mass spectrometer at Institute
of Chemistry, Chinese Academy of Sciences.
14.7 mg, 71% yield, Z/E = 95:5. Rf 0.8 (petroleum ether). H NMR
(400 MHz, CDCl3) δ 7.40−7.18 (m, 4H), 6.56 (d, J = 11.6 Hz, 1H),
5.51 (t, J = 11.2 Hz, 1H), 2.31−2.23 (m, 1H), 1.50−1.41 (m, 2H),
1.32−1.23 (m, 2H), 0.95−0.85 (m, 6H). 13C{H} NMR (100 MHz,
CDCl3) δ 138.9, 136.5, 133.7, 130.5, 129.2, 127.8, 126.8, 126.1, 40.7,
28.0, 11.7. HRMS (EI-TOF) Calcd for C13H17Cl+ [M]+: 208.1019,
found: 208.1022.
General Procedure for the Synthesis of Pyridinium Salts 1.
Primary amine (1.2 equiv) was added to a suspension of 2,4,6-
triphenylpyrylium tetrafluoroborate (1.0 equiv) and EtOH (0.1 M) in
a round-bottomed flask equipped with a magnetic stirrer bar. The
reaction mixture was heated to 85−90 °C for 4 h and cooled to
ambient temperature. If precipitation occurred during this step, the
solid was collected by filtration and washed with EtOH and Et2O. In
case no precipitation occurred, Et2O was added to the reaction
mixture and the resulting suspension was stirred at room temperature
for at least 1 h to complete the precipitation process. If no
precipitation occurred at this point, the flask containing the reaction
mixture and Et2O was sealed and stored at −20 °C for 1−3 days (or
until precipitation occurred). The solid was collected by filtration and
washed with Et2O. If the salt still did not precipitate, it was subjected
to silica gel chromatography with acetone/DCM.
General Procedure for the Synthesis of Z-Alkenes. To a 3
mL vial, equipped with a magnetic stir bar, pyridium salt (0.3 mmol, 3
equiv), terminal (hetero) arylalkyne (0.1 mmol, 1 equiv), and
Ir(ppy)3 (1 mmol %) were added. DIPEA (50 equiv, 0.85 mL) and
DMA (1 mL) were added. The reaction mixture was degassed by
argon and placed in a SynLED Parallel Photoreactor. The vial was
stirred at room temperature under visible light irradiation for 16 h.
Upon completion, the mixture was quenched with water and extracted
three times with ethyl acetate. The combined organic extracts were
dried with Na2SO4 and concentrated in vacuo. The product was
further purified by flash chromatography to obtain the desired
product.
(Z)-1-Chloro-2-(2-cyclohexylvinyl)benzene (3a). Colorless oil,
15.0 mg, 68% yield, Z/E = 95:5. Gram Scale: 1a (3 mmol, 1.43
g),2a (1 mmol, 0.12 mL), 110.3 mg, 50% yield, Z/E = 95:5. Rf 0.8
(petroleum ether). This compound is known, and the data reported
here are consistent with the literature.12 1H NMR (400 MHz, CDCl3)
δ 7.38 (d, J = 7.6 Hz, 1H), 7.28−7.16 (m, 3H), 6.38 (d, J = 11.6 Hz,
1H), 5.61 (t, J = 10.9 Hz, 1H), 2.39−2.34 (m, 1H), 1.70−1.64 (m,
5H), 1.26−1.12 (m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ 140.0,
136.2, 133.5, 130.3, 129.3, 127.9, 126.3, 124.1, 37.0, 33.1, 25.9, 25.6.
HRMS (EI) Calcd for C14H17Cl+ [M]+: 220.1019, found: 220.1023.
1-Chloro-2-(2-cyclopentylvinyl)benzene (3b). Colorless oil, 14.8
(Z)-1-Chloro-2-(3-methyloct-1-en-1-yl)benzene (3f). Colorless oil,
1
14.5 mg, 62% yield, Z/E = 98:2. Rf 0.8 (petroleum ether). H NMR
(400 MHz, CDCl3) δ 7.37 (d, J = 7.4 Hz, 1H), 7.26−7.12 (m, 3H),
6.42 (d, J = 11.5 Hz, 1H), 5.56 (t, J = 11.0 Hz, 1H), 2.51−2.47 (m,
1H), 1.26−1.08 (m, 8H), 1.01 (d, J = 6.6 Hz, 3H), 0.83 (t, J = 7.2 Hz,
3H). 13C{H} NMR (100 MHz, CDCl3) δ 140.5, 136.4, 133.6, 130.5,
129.3, 127.9, 126.2, 124.9, 37.3, 32.2, 31.9, 26.9, 22.6, 21.1, 14.1.
HRMS (EI) Calcd for C15H21Cl+ [M]+: 236.1326, found: 236.1328.
(Z)-1-Chloro-2-(3-cyclohexylbut-1-en-1-yl)benzene (3g). Color-
less oil, 19.8 mg, 80% yield, Z/E = 98:2. Rf 0.8 (petroleum ether). 1H
NMR (400 MHz, CDCl3) δ 7.38 (d, J = 11.6 Hz, 1H), 7.29−7.17 (m,
3H), 6.46 (d, J = 11.6 Hz, 1H), 5.65 (t, J = 11.2 Hz, 1H), 2.34−2.28
(m, 1H), 1.79−1.62 (m, 5H), 1.29−1.10 (m, 4H), 1.02 (d, J = 6.7 Hz,
3H), 0.94−0.81 (m, 2H). 13C{H} NMR (100 MHz, CDCl3) δ 139.3,
136.5, 133.6, 130.5, 129.2, 127.8, 126.2, 125.2, 43.4, 37.6, 30.6, 30.4,
26.6 (2C), 18.1. HRMS (EI-TOF) Calcd for C16H21Cl+ [M]+:
248.1332, found: 248.1328.
(Z)-1-Chloro-2-(3-methyl-5-penylpent-1-en-1-yl)benzene (3h).
Colorless oil, 14.8 mg, 55% yield, Z/E = 98:2. Rf 0.8 (petroleum
1
ether). H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 7.5 Hz, 1H),
7.22−7.11 (m, 6H), 7.06 (d, J = 7.3 Hz, 2H), 6.51 (d, J = 11.5 Hz,
1H), 5.61 (t, J = 11.0 Hz, 1H), 2.66−2.53 (m, 2H), 2.50−2.42 (m,
1H), 1.70−1.57 (m, 2H), 1.08 (d, J = 6.6 Hz, 3H). 13C{H} NMR
(100 MHz, CDCl3) δ 142.5, 139.9, 136.2, 133.6, 130.4, 129.3, 128.4,
128.2, 128.0, 126.3, 125.6, 125.5, 39.3, 33.6, 31.8, 21.1. HRMS (EI)
Calcd for C18H19Cl+ [M]+: 270.1170, found: 270.1171.
2-(2-chlorostyryl)-2,3-dihydro-1H-indene (3i). White solid, 14.3
mg, 56% yield, Z/E = 91:9, mp 71−73 °C. Rf 0.7 (petroleum ether).
1H NMR (400 MHz, CDCl3) δ7.47−7.39 (m, 2H), 7.32−7.20 (m,
6H), 6.96 (d, J = 15.7 Hz, 0.09H), 6.61 (d, J = 11.4 Hz, 0.91H), 6.44
(dd, J = 15.8 Hz, J = 8.0 Hz, 0.09H), 6.01 (t, J = 10.8 Hz, 0.91H),
3.57−3.40 (m, 1H), 3.23−3.14 (m, 2H), 3.00−2.89 (m, 2H). 13C{H}
NMR (100 MHz, CDCl3) δ 142.9, 137.8, 135.9, 133.7, 130.4, 129.4,
128.2, 126.3, 125.9, 124.4, 40.2, 39.0. HRMS (EI) Calcd for
C17H15Cl+ [M]+: 254.0857, found: 254.0854.
1
mg, 72% yield, Z/E = 92:8. Rf 0.8 (petroleum ether). H NMR (400
(Z)-1-Chloro-2-(2-(4,4-difluorocyclohexyl)vinyl)benzene (3j). Col-
orless oil, 9.7 mg, 38% yield, Z/E = 97:3. Rf 0.8 (petroleum ether). 1H
NMR (400 MHz, CDCl3) δ 7.43−7.37 (m, 1H), 7.23 (br s, 3H), 6.47
(d, J = 11.5 Hz, 1H), 5.62 (t, J = 10.8 Hz, 1H), 2.44−2.36 (m, 1H),
2.17−2.00 (m, 2H), 1.78−1.48 (m, 6H). 13C{H} NMR (100 MHz,
CDCl3) δ 137.2 (d, J = 2.6 Hz), 135.9, 133.6, 130.1, 129.5, 128.3,
126.5, 126.2, 121.9 (d, J = 239.6 Hz), 35.0, 33.3, 33.0 (d, J = 2.6),
MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 0.09H), 7.38−7.29 (m, 2H),
7.24−7.10 (m, 2H), 6.75 (d, J = 15.7 Hz, 0.09H), 6.42 (d, J = 11.4
Hz, 1H), 6.19 (dd, J = 15.8 Hz, J = 7.8 Hz, 0.09H), 5.70 (t, J = 10.8
Hz, 1H), 2.80−2.63 (m, 1H), 1.83−1.79 (m, 2H), 1.73−1.65 (m,
2H), 1.62−1.55 (m, 2H), 1.46−1.26 (m, 2H). 13C{H} NMR (100
MHz, CDCl3) δ 139.5, 138.6, 136.2, 135.9, 133.6, 132.5, 130.5, 129.6,
129.3, 127.9, 127.7, 126.7, 126.5, 126.2, 124.5, 124.1, 44.0, 38.9, 34.1,
33.2, 25.6, 25.3. HRMS (EI) Calcd for C13H15Cl+ [M]+: 206.0857,
found: 206.0854.
(Z)-1-Chloro-2-(2-cycloheptylvinyl)benzene (3c). Colorless oil,
11.7 mg, 50% yield, Z/E = 98:2. Rf 0.8 (petroleum ether). 1H
NMR (400 MHz, CDCl3) δ 7.38 (d, J = 7.9 Hz, 1H), 7.28−7.16 (m,
3H), 6.33 (d, J = 11.5 Hz, 1H), 5.74 (t, J = 11.0 Hz, 1H), 2.53−2.50
+
32.8, 29.2 (d, J = 9.5 Hz). HRMS (EI) Calcd for C14H15ClF2 [M]+:
256.0825, found: 256.0822.
(Z)-4-(2-Cyclorostyryl)-tetrahydropyran (3k). Colorless oil, 9.5
mg, 43% yield, Z/E = 96:4. Rf 0.8 (petroleum ether: ethyl acetate =
6:1); 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 6.6 Hz, 1H), 7.25−
7.18 (m, 3H), 6.45 (d, J = 11.5 Hz, 1H), 5.61 (t, J = 10.8 Hz, 1H),
3.95−3.91 (m, 2H), 3.39−3.32 (m, 2H), 2.60−2.54 (m, 1H), 1.58−
D
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Note
+
1.49 (m, 4H). 13C{H} NMR (100 MHz, CDCl3) δ 138.0, 135.9,
133.6, 130.2, 129.5, 128.3, 126.4, 125.6, 67.3, 34.3, 32.6. HRMS (EI)
Calcd for C13H15ClO+ [M]+: 222.0806, found: 222.0804.
32.7, 26.1, 25.9, 25.5. HRMS (EI) Calcd for C15H17F3 [M]+:
254.1277, found: 254.1276.
(Z)-1-(2-cyclohexylvinyl)-2-methoxybenzene (4d). Colorless oil,
9.7 mg, 45% yield, Z/E = 99:1. Rf 0.8 (petroleum ether). H NMR
1
(Z)-4-(2-Cyclorostyryl)-1-(methylsulfonyl)piperidine (3l). Color-
(400 MHz, CDCl3) δ 7.26−7.21 (m, 2H), 6.93 (t, J = 7.4 Hz, 1H),
6.88 (d, J = 8.1 Hz, 1H), 6.40 (d, J = 11.7 Hz, 1H), 5.54 (dd, J = 11.3
Hz, J = 10.6 Hz, 1H), 3.83 (s, 3H), 2.48−2.45 (m, 1H), 1.72−1.63
(m, 5H), 1.26−1.15 (m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ
157.0, 138.9, 129.8, 127.9, 126.9, 122.1, 120.1, 110.4, 55.4, 37.1, 33.3,
26.1, 25.7. HRMS (EI) Calcd for C15H20O+ [M]+: 216.1509, found:
216.1508.
1-(2-cyclohexylvinyl)-4-fluorobenzene (4e). Colorless oil, 10.2
mg, 50% yield, Z/E = 89:11. Rf 0.8 (petroleum ether). This
compound is known, and the data reported here are consistent with
the literature.10a 1H NMR (400 MHz, CDCl3) δ7.30−7.19 (m, 2H),
7.03−6.95 (m, 2H), 6.32−6.25 (m, 1H), 6.09 (dd, J = 16.0 Hz, J = 7.0
Hz, 0.11H), 5.46 (t, J = 10.9 Hz, 0.89H), 2.55−2.47 (m, 0.89H),
2.14−2.08 (m, 0.11H), 1.81−1.66 (m, 5H), 1.33−1.12 (m, 5H).
13C{H} NMR (100 MHz, CDCl3) δ 161.5 (d, J = 245.5 Hz), 138.9
(d, J = 1.0 Hz), 133.9 (d, J = 3.4 Hz), 130.1 (d, J = 7.8 Hz), 125.8,
115.0 (d, J = 21.3 Hz), 36.8, 33.2, 26.0, 25.7. HRMS (EI) Calcd for
C14H17F+ [M]+: 204.1314, found: 204.1312.
1-Chloro-4-(2-cyclohexylvinyl)benzene (4f). Colorless oil, 11.2
mg, 51% yield, Z/E = 87:13. Rf 0.8 (petroleum ether). This
compound is known, and the data reported here are consistent with
the literature.10a 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 8.4 Hz,
1.7H), 7.26−7.24 (m, 0.6H), 7.18 (d, J = 8.4 Hz, 1.7H), 6.31−6.24
(m, 1H), 6.15 (dd, J = 16.0 Hz, J = 6.8 Hz, 0.13H), 5.51 (dd, J = 11.3
Hz, J = 10.6 Hz, 0.87H), 2.54−2.47 (m, 0.87H), 2.13−2.09 (m,
0.13H), 1.73−1.69 (m, 5H), 1.29−1.15 (m, 5H). 13C{H} NMR (100
MHz, CDCl3) δ 139.6, 137.6, 136.6, 136.4, 132.2, 132.1, 129.9, 128.6,
128.3, 127.2, 126.1, 125.7, 41.2, 36.9, 33.2, 32.9, 26.2, 26.0, 25.9, 25.7.
HRMS (EI) Calcd for C14H17Cl+ [M]+: 220.1019, found: 220.1015.
1-Bromo-4-(2-cyclohexylvinyl)benzene (4g). Colorless oil, 14.5
mg, 55% yield, Z/E = 86:14. Rf 0.8 (petroleum ether). This
compound is known, and the data reported here are consistent with
the literature.10a 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.3 Hz,
1.68H), 7.40 (d, J = 8.3 Hz, 0.32H), 7.20 (d, J = 8.3 Hz, 0.32H), 7.11
(d, J = 8.3 Hz, 1.68H), 6.29−6.22 (m, 1H), 6.16 (dd, J = 15.9 Hz, J =
6.8 Hz, 0.14H), 5.55−5.48 (m, 0.86H), 2.54−2.46 (m, 0.86H), 2.12−
2.11 (m, 0.14H), 1.81−1.65 (m, 5H), 1.32−1.11 (m, 5H). 13C{H}
NMR (100 MHz, CDCl3) δ 139.7, 137.7, 137.0, 136.8, 131.5, 131.3,
130.2, 127.5, 126.2, 125.7, 120.3, 120.2, 41.2, 36.9, 33.1, 32.8, 26.1,
26.0, 25.9, 25.6. HRMS (EI) Calcd for C14H17Br+ [M]+: 264.0514,
266.0493, found: 264.0518, 266.0491.
less oil, 12.2 mg, 41% yield, Z/E = 99:1. Rf 0.8 (petroleum ether: ethyl
acetate = 2:1); H NMR (400 MHz, CDCl3) δ 7.41−7.37 (m, 1H),
1
7.25−7.17 (m, 3H), 6.49 (d, J = 11.5 Hz, 1H), 5.65−5.55 (m, 1H),
3.76 (d, J = 11.9 Hz, 2H), 2.74 (s, 3H), 2.64−2.57 (m, 2H), 2.46−
2.36 (m, 1H), 1.79−1.75 (m, 2H), 1.61−1.51 (m, 2H). 13C{H} NMR
(100 MHz, CDCl3) δ 136.8, 135.8, 133.6, 130.0, 129.6, 128.4, 126.6,
126.5, 45.6, 34.6, 34.5, 31.5. HRMS (EI-TOF) Calcd for
C14H18ClNO2S+ [M]+: 299.0747, found: 299.0750.
(Z)-Tert-butyl-4-(2-cyclorostyryl)piperidine-1-carboxylate (3m).
Colorless oil, 16.0 mg, 50% yield, Z/E = 95:5. Rf 0.7 (petroleum
ether: ethyl acetate = 6:1). 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J
= 6.7 Hz, 1H), 7.24−7.18 (m, 3H), 6.45 (d, J = 11.5 Hz, 1H), 5.62−
5.54 (m, 1H), 4.05 (br s, 2H), 2.66 (t, J = 12.2 Hz, 2H), 2.53−2.41
(m, 1H), 1.61 (s, 2H), 1.45 (s, 9H), 1.40−1.28 (m, 2H). 13C{H}
NMR (100 MHz, CDCl3) δ 154.8, 137.8, 135.9, 133.6, 130.1, 129.5,
128.3, 126.4, 125.7, 79.4, 35.3, 31.9, 28.5. HRMS (EI) Calcd for
+
C18H24ClNO2 [M]+: 321.1490, found: 321.1492.
(Z)-2-Benzyl-4-(2-chlorophenyl)but-3-en-1-ol (3n). Colorless oil,
11.4 mg, 42% yield, Z/E = 99:1. Rf 0.8 (petroleum ether: ethyl acetate
= 6:1). 1H NMR (400 MHz, CDCl3) δ 7.37−7.03 (m, 9H), 6.75 (d, J
= 7.2 Hz, 1H), 6.63 (d, J = 11.5 Hz, 1H), 5.62 (t, J = 11.0 Hz, 1H),
3.60 (dd, J = 10.6 Hz, J = 5.3 Hz, 1H), 3.51 (dd, J = 10.6 Hz, J = 7.7
Hz, 1H), 2.93−2.87 (m, 1H), 2.77 (dd, J = 13.4 Hz, J = 5.9 Hz, 1H),
2.62 (dd, J = 13.5 Hz, J = 8.2 Hz, 1H). 13C{H} NMR (100 MHz,
CDCl3) δ 139.4, 135.5, 134.2, 133.5, 130.3, 130.1, 129.2, 129.1, 128.4,
128.3, 126.3, 126.2, 65.8, 42.9, 37.9. HRMS (EI-TOF) Calcd for
C17H17ClO+ [M]+: 272.0968, found: 272.0963.
(Z)-4-(2-Cyclorostyryl)cyclohexan-1-ol (3o). Colorless oil, 9.9 mg,
42% yield, Z/E = 93:7. Rf 0.6 (petroleum ether: ethyl acetate = 2:1).
1H NMR (400 MHz, CDCl3) δ 7.38 (dd, J = 7.5 Hz, J = 1.3 Hz, 1H,
7.26−7.15 (m, 3H), 6.42 (d, J = 11.6 Hz, 1H), 5.73 (t, J = 10.9 Hz,
1H), 3.97 (s, 1H), 2.43 (dd, J = 11.4 Hz, J = 7.9 Hz, 1H), 1.81−1.70
(m, 2H), 1.69−1.60 (m, 2H), 1.56−1.48 (m, 2H), 1.35−1.23 (m,
2H). 13C{H} NMR (100 MHz, CDCl3) δ 138.8, 136.2, 133.6, 130.3,
129.4, 128.0, 126.3, 124.8, 66.3, 35.6, 31.7, 27.0. HRMS (EI-TOF)
Calcd for C14H17ClO+ [M]+: 236.0968, found: 236.0972.
(2-Cyclohexylvinyl)benzene (4a). Colorless oil, 9.7 mg, 52% yield,
Z/E = 81:19. Rf 0.8 (petroleum ether). This compound is known, and
the data reported here are consistent with the literature.12 1H NMR
(400 MHz, CDCl3) δ 7.38−7.16 (m, 5H), 6.36−6.29 (m, 1H), 6.18
(dd, J = 15.7 Hz, J = 6.8 Hz, 0.19H), 5.53−5.44 (m, 0.81H), 2.62−
2.54 (m, 0.081H), 2.14−2.10 (m, 0.19H), 1.82−1.65 (m, 5H), 1.33−
1.12 (m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ 139.0, 138.0,
137.9, 136.8, 128.6, 128.4, 128.2, 127.2, 126.8, 126.7, 126.4, 125.9,
41.2, 36.9, 33.3, 32.9, 26.2, 26.0, 25.7.
1-(2-cyclohexylvinyl)-4-(trifluoromethyl)benzene (4h). Colorless
oil, 9.7 mg, 38% yield, Z/E = 90:10. Rf 0.8 (petroleum ether). This
compound is known, and the data reported here are consistent with
the literature.12 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.1 Hz,
1.80H), 7.53 (d, J = 8.2 Hz, 0.2H), 7.42 (d, J = 8.2 Hz, 0.2H), 7.34
(d, J = 8.1 Hz, 1.8H), 6.39−6.29 (m, 1H), 5.64−5.56 (m, 1H), 2.56−
2.48 (m, 0.9H), 2.18−2.14 (m, 0.1H), 1.80−1.66 (m, 5H), 1.32−1.17
(m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ 141.6, 141.5, 141.0,
139.6, 128.8, 128.6, 128.2, 126.1, 126.0, 125.7, 125.4 (q, J = 7.2 Hz),
125.1 (q, J = 6.8 Hz), 123.0, 41.2, 37.0, 33.1, 32.8, 26.1, 26.0, 25.9,
1-(2-Cyclohexylvinyl)-2-fluorobenzene (4b). Colorless oil, 11.2
1
mg, 60% yield, Z/E = 92:8. Rf 0.8 (petroleum ether). H NMR (400
MHz, CDCl3) δ 7.46−7.41 (m, 0.09H), 7.28−7.19 (m, 2H), 7.11−
7.02 (m, 2H), 6.51 (d, J = 16.1 Hz, 0.09H), 6.31 (d, J = 11.6 Hz, 1H),
6.24 (dd, J = 16.1 Hz, J = 7.0 Hz, 0.09H), 5.61 (t, J = 10.9 Hz, 1H),
2.45−2.37 (m, 1H), 2.21−2.11 (m, 0.09H), 1.83−1.64 (m, 5H),
1.30−1.11 (m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ 160.2 (d, J =
246.5 Hz), 140.9, 130.4 (d, J = 3.6 Hz), 128.2 (d, J = 8.2 Hz), 125.6
(d, J = 14.7 Hz), 123.6 (d, J = 3.6 Hz), 119.3 (d, J = 3.5 Hz), 115.3
(d, J = 22.3 Hz). 37.4, 33.1, 26.0, 25.6. HRMS (EI) Calcd for
C14H17F+ [M]+: 204.1309, found: 204.1310.
+
25.6. HRMS (EI) Calcd for C15H17F3 [M]+: 254.1282, found:
254.1285.
(Z)-1-(2-cyclohexylvinyl)-4-cyanobenzene (4i). Colorless oil, 8.2
mg, 39% yield, Z/E = 99:1. Rf 0.8 (petroleum ether: ethyl acetate =
9:1). This compound is known, and the data reported here are
consistent with the literature.10a 1H NMR (400 MHz, CDCl3) δ7.61
(d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 6.30 (d, J = 11.8 Hz,
1H), 5.64 (t, J = 11.0 Hz, 1H), 2.52−2.47 (m, 1H), 1.75−1.69 (m,
5H), 1.29−1.17 (m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ 142.7,
142.0, 132.0, 129.1, 125.5, 119.0, 109.9, 37.1, 33.0, 25.9, 25.5. HRMS
(EI) Calcd for C15H17N+ [M]+: 211.1361, found: 211.1362.
1-(2-cyclohexylvinyl)-4-methylbenzene (4j). Colorless oil, 8.0 mg,
40% yield, Z/E = 84:16. Rf 0.8 (petroleum ether). This compound is
known, and the data reported here are consistent with the
literature.10c 1H NMR (400 MHz, CDCl3) δ 7.25−7.08 (m, 4H),
1-(2-Cyclohexylvinyl)-2-(trifloromethyl)benzene (4c). Colorless
1
oil, 16.8 mg, 66% yield, Z/E = 92:8. Rf 0.8 (petroleum ether). H
NMR (400 MHz, CDCl3) δ 7.66−7.58 (m, 1H), 7.51−7.47 (m, 1H),
7.36−7.28 (m, 2H), 6.71 (d, J = 14.2 Hz, 0.08H), 6.51 (d, J = 11.3
Hz, 1H), 6.14 (dd, J = 15.4 Hz, J = 7.1 Hz, 0.08H), 5.61 (t, J = 11.0
Hz, 1H), 2.22−2.20 (m, 1H), 1.84−1.62 (m, 5H), 1.25−1.15 (m,
5H). 13C{H} NMR (100 MHz, CDCl3) δ 141.0, 140.4, 136.9, 131.7,
131.3, 130.9, 128.5 (q, J = 29.5 Hz), 128.3, 127.1, 126.6, 126.4, 125.7
(q, J = 5.5 Hz), 125.6, 123.8, 123.5, 122.9, 120.2, 41.3, 37.0, 32.9,
E
https://dx.doi.org/10.1021/acs.joc.0c01928
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
6.33−6.25 (m, 1H), 6.12 (dd, J = 15.9 Hz, J = 6.9 Hz, 0.16H), 5.48−
5.40 (m, 0.84H), 2.62−2.50 (m, 0.84H), 2.35 (s, 3H), 2.12−2.08 (m,
0.16H), 1.82−1.65 (m, 5H), 1.33−1.11 (m, 5H). 13C{H} NMR (100
MHz, CDCl3) δ 138.4, 136.4, 136.1, 135.9, 135.3, 135.1, 129.2, 128.9,
128.5, 127.0, 126.7, 125.8, 41.2, 36.9, 33.3, 33.0, 26.2, 26.1(2C), 25.7,
AUTHOR INFORMATION
Corresponding Authors
■
Zhen-Yu Tang − School of Pharmaceutical Science (Shenzhen),
Sun Yat-sen University, Guangzhou 510275, China; College of
Chemistry and Chemical Engineering, Central South University,
Changsha 410083, China; orcid.org/0000-0002-3972-
5047; Email: tangzhenyu@mail.sysu.edu.cn
Zhuangzhu Luo − School of Material, Sun Yat-sen University,
Guangzhou 510275, China; Email: luozhzhu@
mail.sysu.edu.cn
+
21.2, 21.1. HRMS (EI) Calcd for C15H20 [M]+: 200.1565, found:
200.1566.
1-(tert-Butyl)-4-(2-cyclohexylvinyl)benzene (4k). Colorless oil,
12.9 mg, 50% yield, Z/E = 86:14. Rf 0.8 (petroleum ether). This
compound is known, and the data reported here are consistent with
the literature.10a 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 8.3 Hz,
1.7H), 7.32−7.29 (m, 0.6H), 7.21 (d, J = 8.3 Hz, 1.7H), 6.34−6.25
(m, 1H), 6.13 (dd, J = 16.0 Hz, J = 6.9 Hz, 0.14H), 5.49−5.40 (m,
0.86H), 2.63−2.61 (m, 1H), 1.75−1.71 (m, 5H), 1.33 (s, 9H), 1.30−
1.12 (m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ 149.8, 149.3,
138.4, 136.1, 135.3, 135.1, 128.4, 126.9, 126.6, 125.6, 125.4, 125.1,
41.2, 36.9, 34.5, 33.3, 33.1, 31.3, 26.2, 26.1, 26.0, 25.7. HRMS (EI)
Authors
Shu-Zhen Lai − College of Chemistry and Chemical Engineering,
Central South University, Changsha 410083, China
Yu-Ming Yang − School of Pharmaceutical Science (Shenzhen),
Sun Yat-sen University, Guangzhou 510275, China; College of
Chemistry and Chemical Engineering, Central South University,
Changsha 410083, China
Hai Xu − College of Chemistry and Chemical Engineering,
Central South University, Changsha 410083, China;
orcid.org/0000-0003-1610-9556
+
Calcd for C18H26 [M]+: 242.2035, found: 242.2034.
(Z)-1-(2-cyclohexylvinyl)-4-methoxybenzene (4l). Colorless oil,
8.2 mg, 38% yield, Z/E = 98:2. Rf 0.8 (petroleum ether). This
compound is known, and the data reported here are consistent with
the literature.10a 1H NMR (400 MHz, CDCl3) δ 7.20 (d, J = 8.6 Hz,
2H), 6.87 (d, J = 8.7 Hz, 2H), 6.24 (d, J = 11.7 Hz, 1H), 5.40 (dd, J =
11.4 Hz, J = 10.2 Hz, 1H), 3.82 (s, 3H), 2.61−2.53 (m, 1H), 1.74−
1.65 (m, 5H), 1.31−1.15 (m, 5H). 13C{H} NMR (100 MHz, CDCl3)
δ 158.2, 137.6, 130.6, 129.8, 126.3, 113.6, 55.3, 36.9, 33.3, 26.1, 25.8.
HRMS (EI) Calcd for C15H20O+ [M]+: 216.1514, found: 216.1517.
1-(2-Cyclohexylvinyl)-3-fluorobenzene (4m). Colorless oil, 11.8
mg, 58% yield, Z/E = 82:18. Rf 0.8 (petroleum ether). 1H NMR (400
MHz, CDCl3) δ 7.30−7.21 (m, 1H), 7.10−6.85 (m, 3H), 6.33−6.25
(m, 1H), 6.18 (dd, J = 16.0 Hz, J = 6.8 Hz, 0.18H), 5.52 (dd, J = 11.3
Hz, J = 10.6 Hz, 0.82H), 2.58−2.50 (m, 0.82H), 2.14−2.12 (m,
0.18H), 1.82−1.65 (m, 5H), 1.34−1.13 (m, 5H). 13C{H} NMR (100
MHz, CDCl3) δ 163.2 (d, J = 244.7 Hz), 162.8 (d, J = 244.9 Hz),
140.5 (d, J = 7.7 Hz), 140.2 (d, J = 7.7 Hz), 140.1, 138.3, 129.8 (d, J =
8.5 Hz), 129.6 (d, J = 8.4 Hz), 126.3 (d, J = 2.5 Hz), 125.8 (d, J = 2.2
Hz), 124.3 (d, J = 2.7 Hz), 121.8 (d, J = 2.6 Hz), 115.3 (d, J = 21.3
Hz), 113.6, 113.3 (d, J = 21.1 Hz), 112.3 (d, J = 21.6 Hz), 41.1, 36.9,
33.1, 32.8, 26.1, 26.0, 25.6. HRMS (EI) Calcd for C14H17F+ [M]+:
204.1309, found: 204.1307.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01928
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support was provided by the National Natural
Science Foundation of China 21302231, Hunan Provincial
Natural Science Foundation of China 14JJ3021, Ph.D.
Programs Foundation of Ministry of Education of China
20130162120032.
REFERENCES
■
1-(2-Cyclohexylvinyl)-3,5-difluorobenzene (4n). Colorless oil,
11.5 mg, 52% yield, Z/E = 81:19. Rf 0.8 (petroleum ether). 1H
NMR (400 MHz, CDCl3) δ 6.84−6.74 (m, 2H), 6.70−6.64 (m, 1H),
6.24−6.19 (m, 1H), 6.18−6.16 (m, 0.2H), 5.56 (t, J = 11.0 Hz, 0.8H),
2.54−2.46 (m, 0.8H), 2.14−2.12 (m, 0.2H), 1.78−1.69 (m, 5H),
1.34−1.12 (m, 5H). 13C{H} NMR (100 MHz, CDCl3) δ 163.3 (d, J =
247.1 Hz), 163.2 (d, J = 247.0 Hz), 162.9 (d, J = 247.2 Hz), 162.8 (d,
J = 247.3 Hz), 141.6, 141.1, 139.6, 125.6 (t, J = 2.7 Hz), 125.1 (t, J =
2.4 Hz), 111.3 (d, J = 25.0 Hz), 111.3 (d, J = 11.7 Hz), 108.5 (d, J =
11.8 Hz), 108.5 (d, J = 25.2 Hz), 101.8 (t, J = 25.8 Hz), 101.8 (t, J =
25.5 Hz), 100.0, 41.0, 37.0, 33.0, 32.7, 26.1, 25.9, 25.5. HRMS (EI)
(1) (a) Ruiz-Castillo, P.; Buchwald, S. L. Applications of palladium-
catalyzed C−N cross-coupling reactions. Chem. Rev. 2016, 116,
12564−12649. (b) Liu, W.; Luo, X.; Bao, Y.; Liu, Y. P.; Ning, G.-H.;
Abdelwahab, I.; Li, L.; Nai, C. T.; Hu, Z. G.; Zhao, D.; Liu, B.; Quek,
S. Y.; Loh, K. P. A Two-Dimensional Conjugated Aromatic Polymer
via C−C Coupling Reaction. Nat. Chem. 2017, 9, 563−570.
(c) McGrath, N. A.; Brichacek, M.; Njardarson, J. T. A Graphical
Journey of Innovative Organic Architectures That Have Improved
Our Lives. J. Chem. Educ. 2010, 87, 1348−1349.
(2) (a) Basch, C. H.; Liao, J.; Xu, J.; Piane, J. J.; Watson, M. P.
Harnessing Alkyl Amines as Electrophiles for Nickel-Catalyzed Cross
Couplings via C−N Bond Activation. J. Am. Chem. Soc. 2017, 139,
5313−5316. (b) Blakey, S. B.; MacMillan, D. W. C. The First Suzuki
Cross-Couplings of Aryltrimethylammonium Salts. J. Am. Chem. Soc.
2003, 125, 6046−6047. (c) Moragas, T.; Gaydou, M.; Martin, R.
Nickel-Catalyzed Carboxylation of Benzylic C-N Bonds with CO2.
Angew. Chem. 2016, 128, 5137−5141. (d) Li, M.-B.; Wang, Y.; Tian,
S.-K. Regioselective and Stereospecific Cross-Coupling of Primary
Allylic Amines with Boronic Acids and Boronates through Palladium
Catalyzed C-N Bond Cleavage. Angew. Chem., Int. Ed. 2012, 51,
2968−2971. (e) Maity, P.; Shacklady-McAtee, D. M.; Yap, G. P.;
Sirianni, E. R.; Watson, M. P. Nickel-Catalyzed Cross Couplings of
Benzylic Ammonium Salts and Boronic Acids: Stereospecific
Formation of Diarylethanes via C−N Bond Activation. J. Am. Chem.
Soc. 2013, 135, 280−285.
+
Calcd for C14H16F2 [M]+: 222.1215, found: 222.1213.
(Z)-3-(2-cyclohexylvinyl)pyridine (4o). Colorless oil, 9.0 mg, 48%
yield, Z/E = 98:2. Rf 0.8 (petroleum ether: ethyl acetate = 6:1). This
compound is known, and the data reported here are consistent with
the literature.12 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 8.47 (d,
J = 4.4 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.33−7.30 (m, 1H), 6.25
(d, J = 11.7 Hz, 1H), 5.66 (t, J = 11.0 Hz, 1H), 2.51−2.43 (m, 1H),
1.73−1.65 (m, 5H), 1.33−1.15 (m, 5H). 13C{H} NMR (100 MHz,
CDCl3) δ 149.5, 147.3, 141.4, 135.8, 133.7, 123.2, 123.1, 37.1, 33.1,
25.9, 25.6. HRMS (EI) Calcd for C13H17N+ [M]+: 187.1361, found:
187.1362.
ASSOCIATED CONTENT
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sı
* Supporting Information
(3) (a) Bapat, J. B.; Blade, R. J.; Boulton, A. J.; Epsztajn, J.; Katritzky,
A. R.; Lewis, J.; Molina-Buendia, P.; Nie, P.-L.; Ramsden, C. A.
Pyridines as Leaving Groups in Synthetic Transformations:
Nucleophilic Displacements of Amino Groups, and Novel Prepara-
tions of Nitriles and Isocyanates. Tetrahedron Lett. 1976, 17, 2691−
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01928.
1H and 13C NMR spectra for all products (PDF)
F
https://dx.doi.org/10.1021/acs.joc.0c01928
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
2694. (b) Katritzky, A. R.; De Ville, G.; Patel, R. C. Carbon-alkylation
of Simple Nitronate Anions by N-substituted Pyridiniums. Tetrahe-
dron 1981, 37, 25−30.
Hydroxyphthalimide Esters with Terminal Arylalkynes. Org. Lett.
2019, 21, 2269−2272.
(13) (a) Dugave, C.; Demange, L. Cis−Trans Isomerization of
Organic Molecules and Biomolecules: Implications and Applications.
(4) Katritzky, A. R.; Marson, M. Pyrylium Mediated Trans-
formations of Primary Amino Groups into Other Functional Groups.
Angew. Chem., Int. Ed. Engl. 1984, 23, 420−429.
́
Chem. Rev. 2003, 103, 2475−2532. (b) Alvarez, R.; Vaz, B.;
́
Gronemeyer, H.; de Lera, A. R. Functions, Therapeutic Applications,
and Synthesis of Retinoids and Carotenoids. Chem. Rev. 2014, 114,
1−125.
(14) Singh, K.; Staig, S. J.; Weaver, J. D. Facile Synthesis of Z-
Alkenes via Uphill Catalysis. J. Am. Chem. Soc. 2014, 136, 5275−5278.
(15) Yang, Z. K.; Xu, N. X.; Wang, C.; Uchiyama, M. Photoinduced
C(sp3)−N Bond Cleavage Leading to the Stereoselective Syntheses of
Alkenes. Chem. - Eur. J. 2019, 25, 5433−5439.
(16) (a) Ociepa, M.; Turkowska, J.; Gryko, D. Redox-Activated
Amines in C(sp3)−C(sp) and C(sp3)-C(sp2) Bond Formation
Enabled by Metal-Free Photoredox Catalysis. ACS Catal. 2018, 8,
11362−11367. (b) Zhang, M.-M.; Liu, F. Visible-Light-Mediated
Allylation of Alkyl Radicals with Allylic Sulfones via a Deaminative
Strategy. Org. Chem. Front. 2018, 5, 3443−3446. (c) Jiang, X.; Zhang,
M.-M.; Xiong, W.; Lu, L.-Q.; Xiao, W.-J. Deaminative (Carbonylative)
Alkyl-Heck-type Reactions Enabled by Photocatalytic C-N Bond
Activation. Angew. Chem., Int. Ed. 2019, 58, 2402−2406. (d) Zhu, Z.-
F.; Zhang, M.-M.; Liu, F. Radical Alkylation of Isocyanides with
Amino Acid-/Peptide-Derived Katritzky salts via Photoredox
Catalysis. Org. Biomol. Chem. 2019, 17, 1531−1534. (e) Wang, X.;
Kuang, Y.; Ye, S.; Wu, J. Photoredox-Catalyzed Synthesis of Sulfones
through Deaminative Insertion of Sulfur Dioxide. Chem. Commun.
2019, 55, 14962−14964.
̈
(5) (a) Rossler, S. L.; Jelier, B. J.; Magnier, E.; Dagousset, G.;
Carreira, E. M.; Togni, A. Pyridinium Salts as Redox-Active
Functional Group Transfer Reagents. Angew. Chem., Int. Ed. 2020,
59, 9264−9280. (b) Wu, J.; He, L.; Noble, A.; Aggarwal, V. K.
Photoinduced Deaminative Borylation of Alkylamines. J. Am. Chem.
Soc. 2018, 140, 10700−10704. (c) He, F.-S.; Ye, S.; Wu, J. Recent
Advances in Pyridinium Salts as Radical Reservoirs in Organic
Synthesis. ACS Catal. 2019, 9, 8943−8960. (d) Sandfort, F.; Strieth-
Kalthoff, F.; Klauck, F. J. R.; James, M. J.; Glorius, F. Deaminative
Borylation of Aliphatic Amines Enabled by Visible Light Excitation of
an Electron Donor−Acceptor Complex. Chem. - Eur. J. 2018, 24,
17210−17214. (e) Hu, J.; Wang, G.; Li, S.; Shi, Z. Selective C−N
Borylation of Alkyl Amines Promoted by Lewis Base. Angew. Chem.,
Int. Ed. 2018, 57, 15227−15231. (f) Yue, H.; Zhu, C.; Shen, L.; Geng,
Q.; Hock, K. J.; Yuan, T.; Cavallo, L.; Rueping, M. Nickel-Catalyzed
C−N Bond Activation: Activated Primary Amines as Alkylating
Reagents in Reductive Cross-Coupling. Chem. Sci. 2019, 10, 4430−
4435. (g) Yang, M.; Cao, T.; Xu, T.; Liao, S. Visible-Light-Induced
Deaminative Thioesterification of Amino Acid Derived Katritzky Salts
via Electron Donor−Acceptor Complex Formation. Org. Lett. 2019,
21, 8673−8678.
(6) (a) Plunkett, S.; Basch, C. H.; Santana, S. O.; Watson, M. P.
Harnessing Alkylpyridinium Salts as Electrophiles in Deaminative
Alkyl−Alkyl Cross-Couplings. J. Am. Chem. Soc. 2019, 141, 2257−
2262. (b) Liao, J.; Basch, C. H.; Hoerrner, M. E.; Talley, M. R.;
Boscoe, B. P.; Tucker, J. W.; Garnsey, M. R.; Watson, M. P.
Deaminative Reductive Cross-Electrophile Couplings of Alkylpyr-
idinium Salts and Aryl Bromides. Org. Lett. 2019, 21, 2941−2946.
(c) Baker, K. P.; Baca, D. L.; Plunkett, S.; Daneker, M. E.; Watson, M.
P. Engaging Alkenes and Alkynes in Deaminative Alkyl−Alkyl and
Alkyl−Vinyl Cross-Couplings of Alkylpyridinium Salts. Org. Lett.
2019, 21, 9738−9741.
(7) Klauck, F. J. R.; James, M. J.; Glorius, F. Deaminative Strategy
for the Visible-Light-Mediated Generation of Alkyl Radicals. Angew.
Chem., Int. Ed. 2017, 56, 12336−12339.
(8) Wu, J.; Grant, P. S.; Li, X.; Noble, A.; Aggarwal, V. K. Catalyst-
Free Deaminative Functionalizations of Primary Amines by Photo-
induced Single-Electron Transfer. Angew. Chem., Int. Ed. 2019, 58,
5697−5701.
(9) (a) Sancheti, S. P.; Urvashi; Shah, M. P.; Patil, N. T. Ternary
Catalysis: A Stepping Stone Towards Multicatalysis. ACS Catal. 2020,
10, 3462−3489. (b) Ye, Y.; Chen, H.; Yao, K.; Gong, H. Iron-
Catalyzed Reductive Vinylation of Tertiary Alkyl Oxalates with
Activated Vinyl Halides. Org. Lett. 2020, 22, 2070−2075.
(10) (a) Cheung, C. W.; Zhurkin, F. E.; Hu, X. Z-Selective Olefin
Synthesis via Iron-Catalyzed Reductive Coupling of Alkyl Halides
with Terminal Arylalkynes. J. Am. Chem. Soc. 2015, 137, 4932−4935.
(b) Li, Y.; Ge, L.; Qian, B.; Babu, K. R.; Bao, H. Hydroalkylation of
Terminal Aryl Alkynes with Alkyl Diacyl Peroxides. Tetrahedron Lett.
2016, 57, 5677−5680. (c) Ouyang, X.-H.; Song, R.-J.; Liu, B.; Li, J.-H.
Metal-Free Oxidative Decarbonylative Hydroalkylation of Alkynes
with Secondary and Tertiary Alkyl Aldehydes. Adv. Synth. Catal. 2016,
358, 1903−1909. (d) Till, N. A.; Smith, R. T.; MacMillan, D. W. C.
Decarboxylative Hydroalkylation of Alkynes. J. Am. Chem. Soc. 2018,
140, 5701−5705. (e) Deng, H.-P.; Fan, X.-Z.; Chen, Z.-H.; Xu, Q.-H.;
Wu, J. Photo-Induced Nickel-Catalyzed Chemo- and Regioselective
Hydroalkylation of Internal Alkynes with Ether and Amide a-Hetero
C(sp3)-H Bonds. J. Am. Chem. Soc. 2017, 139, 13579−13584.
(11) Zhu, Z.-F.; Tu, J.-L.; Liu, F. Ni-Catalyzed deaminative
hydroalkylation of internal alkynes. Chem. Commun. 2019, 55,
11478−11481.
(12) Dai, G.-L.; Lai, S.-Z.; Luo, Z.; Tang, Z.-Y. Selective Syntheses of
Z-Alkenes via Photocatalyzed Decarboxylative Coupling of N-
G
https://dx.doi.org/10.1021/acs.joc.0c01928
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