Copper porphyrin-catalyzed cross dehydrogenative coupling of alkanes with carboxylic acids: Esterification and decarboxylation dual pathway

Article abstract of DOI:10.1016/j.tet.2021.132377

A dual-functional copper porphyrin-catalyzed cross dehydrogenative coupling (CDC) of carboxylic acids with alkanes was reported firstly. The reaction gives allylic esters or alkylalkenes depending on the carboxylic acid substrates. Copper porphyrin catalyzed CDC method has the superiority of short reaction time, good functional group tolerance, base and solvent free, producing target products in an atom-economic manner.

Full text of DOI:10.1016/j.tet.2021.132377

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper porphyrin-catalyzed cross dehydrogenative coupling of
alkanes with carboxylic acids: Esterification and decarboxylation dual
pathway
,
Xiao-Yan Chen a, Shuang Yang a, Bao-Ping Ren a, Lei Shi b **, Dong-Zi Lin c, Hao Zhang a,
,
*
Hai-Yang Liu a
a Department of Chemistry, The Key Laboratory of Fuel Cell Technology of Guangdong Province, South China University of Technology, Guangzhou, 510641,
China
b Department of Chemistry, Guangdong University of Education, Guangzhou, 510303, China
c Department of Laboratory Medicine, Foshan Forth People's Hospital, Foshan, 528041, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A dual-functional copper porphyrin-catalyzed cross dehydrogenative coupling (CDC) of carboxylic acids
with alkanes was reported firstly. The reaction gives allylic esters or alkylalkenes depending on the
carboxylic acid substrates. Copper porphyrin catalyzed CDC method has the superiority of short reaction
time, good functional group tolerance, base and solvent free, producing target products in an atom-
economic manner.
Received 1 June 2021
Received in revised form
30 July 2021
Accepted 1 August 2021
Available online xxx
© 2021 Elsevier Ltd. All rights reserved.
Keywords:
Cross dehydrogenative coupling
Carboxylic acids
Alkanes
Porphyrin
Copper
1. Introduction
conditions. However, using alkanes as starting materials in CDC
reaction for the preparation of esters is scarce. In 2014, Pan's group
Direct functionalization of inert C(sp [3])-H bond is of consid-
erable challenge, owing to the high CeH bond dissociation energy
and low polarity of alkanes [1]. To date, remarkable advances have
been made on the formation of C-X (X ¼ C, N, O, S) bonds via cross
dehydrogenative coupling (CDC) involving CeH activation [2]. The
active investigation and application of CDC reaction are mainly
initiated from CeC bond formation [3]. In recent years, CeH func-
tionalization towards CeO bond construction of esters via CDC
method has attracted much attentions [4], due to the typical uses of
developed a Cu(OAc)2-catalyzed CDC reaction of cycloalkanes with
aromatic aldehydes, which involved four CeH bond activations and
gave cycloallyl esters directly [8]. Afterwards, the synthesis of allylic
esters via the oxidative dehydrogenative carboxylation of cyclo-
hexane using copper catalysts has been quickly developed [9].
Metalloporphyrins [10], as a class of bioinspired multifunctional
catalysts [11], have been successfully applied in many reactions
such as cyclopropanation [12], olefination [13], cycloaddition [14],
oxidation [15], carbene [16] and nitrene [17] CeH insertion re-
actions. Whereas the application of metalloporphyrin catalysts in
CDC reaction is a less explored topic. In 2013, Che reported the first
use of palladium porphyrin in CDC reaction between tertiary
amines and dimethyl malonate or diethyl phosphite under illumi-
nation [18]. In 2016, Guo applied copper porphyrin catalyst to the
homocoupling reaction of terminal alkynes [19]. Recently, we have
found copper [20] or iron-porphyrin [21] may be used in CDC re-
action of carboxylic acids and cyclic ethers, which provided esters
in high yields (Scheme 1, a). The CDC esterification of cyclohexene
and carboxylic acids could also be achieved with high TON by using
bioactive esters in nature [5]. The CDC reactions of a-C(sp [3])-H
bond adjoining to heteroatoms or unsaturated bonds with car-
boxylic acid [6] or its precursors [7] (benzyl alcohols, aldehydes,
alkylbenzenes and alkenes) have been achieved successfully, either
using copper, iron and MOFs catalyst or under metal-free
* Corresponding author.
** Corresponding author.
E-mail addresses: shil@gdei.edu.cn (L. Shi), chhyliu@scut.edu.cn (H.-Y. Liu).
https://doi.org/10.1016/j.tet.2021.132377
0040-4020/© 2021 Elsevier Ltd. All rights reserved.
Please cite this article as: X.-Y. Chen, S. Yang, B.-P. Ren et al., Copper porphyrin-catalyzed cross dehydrogenative coupling of alkanes with
carboxylic acids: Esterification and decarboxylation dual pathway, Tetrahedron, https://doi.org/10.1016/j.tet.2021.132377

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
Scheme 2. Molecular structure of metal porphyrin complexes.
tetrakis(phenyl)porphyrinato-copper(II) (CuTPP) showed the su-
preme catalysis reactivity, offering the allylic ester in 80 % yield
(Table 1, entry 1). Meanwhile, tetrakis(perfluorophenyl)
porphyrinato-copper(II) (CuF20TPP) provided higher yield than
tetrakis(ethoxycarbonyl)porphyrinato-copper(II) (CuTECP) (Table 1,
entries 2 and 3). It turns out that electron-donating groups on the
porphyrin rings are more favorable for this reaction. Contrary to our
expectation, the other tested tetrakis(phenyl)porphyrinato-metal
complexes (M-TPP) (M ¼ Mn, Fe, Co, Ni, Zn, Pd, Ag) were not
active (Table 1, entries 4e10), why these metal porphyrins did not
work for current reaction is unclear. The reaction could not yield
the target product without catalyst (Table 1, entry 11). Furthermore,
no significant improvements in the yield of cyclohex-2-en-1-yl
benzoate (3aa) when decreasing or increasing the loading
amounts of catalyst (Table 1, entries 12 and 13).
The influence of oxidant on this reaction was next investigated
as shown in Table 2, when oxidant DTBP was replaced by other
oxidants such as PhI(OAc)2, m-CPBA, DDQ, H2O2, Oxone and K2S2O8,
the coupling reaction of benzoic acid and cyclohexane could not
happen (Table 2, entries 1e6). A remarkable drop in yield of 3aa
was given by TBHP (Table 2, entry 7), perhaps owing to the strong
oxidation power of hydroxyl radical from TBHP is unfavorable for
the regeneration of CuTPP in the catalytic cycle. Significantly, the
yield of desired product was up to 93 % using 5.0 equivalent DTBP,
Scheme 1. Direct functionalization of C(sp [3])-H bonds.
copper-porphyrin catalyst [22] (Scheme 1, b). While acetals could
be obtained from copper-porphyrin catalyzed CDC reaction of
phenol derivatives and cyclic ethers [23] (Scheme 1, c). In all these
reactions, the C(sp [3])-H bonds of substrates are adjacent to the
ethereal oxygen atom or allyl group. We herein would like to report
the extension of C(sp [3])-H substrate to alkanes (Scheme 1, d).
Surprisingly, except for the normal ester products, alkylalkenes
could also be obtained when using cinnamic acid as substrates.
2. Results and discussion
We commenced our investigation via examining the reaction of
benzoic acid (1a) with cyclohexane (2a) utilizing DTBP as the
oxidant to determine the optimal reaction conditions (Table 1).
Initially, copper porphyrin catalysts substituted by different push-
or pull-electron groups (Scheme 2) were tested and
Table 2
Oxidant optimizationa.
Table 1
Catalyst optimizationa.
Entry
Oxidant
Yieldb(%)
1
2
3
4
5
6
7
8
PhI(OAc)2
m-CPBA
DDQ
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
22
Entry
Catalyst
Yieldb(%)
1
2
3
4
5
6
7
8
CuTPP
CuF20TPP
CuTECP
MnTPPCl
FeTPPCl
CoTPP
NiTPP
ZnTPP
PdTPP
AgTPP
e
80
75
70
H2O2
Oxone
K2S2O8
TBHP
DTBP
DTBP
DTBP
e
N.D.
trace
trace
N.D.
trace
N.D.
N.D.
N.D.
66c
47c
9
10
11
93d
69e
9
N.D.
10
11
12
13
a
Reaction conditions: benzoic acid (0.5 mmol), cyclohexane (1.0 mL), CuTPP
(1.0 mol%), oxidant (4.0 equiv.) at 120 ꢀC for 12 h.
CuTPP
CuTPP
b
Yields were determined by 1H NMR spectra using trimethylphenylsilane as an
78d
internal standard.
a
c
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mL), catalyst (1.0 mol%), DTBP (4.0
3.0 equiv. of DTBP was used.
5.0 equiv. of DTBP was used.
d
equiv.) at 120 ꢀC for 12 h.
b
e
Yields were determined by 1H NMR spectra using trimethylphenylsilane as an
6.0 equiv. of DTBP was used. DTBP ¼ di-tert-butyl peroxide. m-CPBA ¼ 3-
internal standard.
chloroperbenzoic acid. DDQ ¼ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. H2O2
(30 % in water). Oxone ¼ potassium peroxymonosulfate. TBHP ¼ tert-butyl hydro-
peroxide (5e6 M, in decane). N.D. ¼ not detected.
c
0.5 mol% of catalyst was used.
3.0 mol% of catalyst was used. N.D. ¼ not detected.
d
2

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
but it would decrease with higher or lower amounts of DTBP
(Table 2, entries 8e10). Besides, no product was detected entirely in
the absence of oxidant (Table 2, entry 11). Other elements such as
reaction time and temperature were studied to complete the re-
action optimization (Table S2).
moiety, providing moderated yield may be attributed to the sub-
stituents steric hindrance (3ta). Gratifyingly, this protocol was
compatible well with heteroaryl carboxylic acids and 1-naphthoic
acid (3ua-3va, 3xa). Besides, aliphatic carboxylic acids such as 3-
phenylpropionic acid could also furnish excellent yield of 3ya.
Possibly owing to the strong axial coordination between pyridyl or
amide group and CuTPP, the esterification reaction could not pro-
ceed smoothly (3wa, 3za).
Subsequently, the substrate scope of alkanes was also explored
and the results were summarized in Table 4. Under the optimum
reaction parameters, cyclopentane possessing bigger tension could
react with carboxylic acid and its derivatives smoothly, which
gained corresponding products in excellent yields (4a-4c). By
contrast, using cyclooctane as coupling partner, only a trace
quantity of the product was given (4d). Other cyclohexane de-
rivatives such as chlorocyclohexane and bromocyclohexane pro-
vided isomer mixture products in poor and trace yields, perhaps
due to the electron-withdrawing effect of chlorine and bromine
(4e-4f). Moreover, acyclic alkane was suitable to present trans-
formation as well. When n-hexane as the substrate was tested, we
found that the ratio of four regioselective isomers analyzed by GC-
MS was 48:22:21:8, respectively (4g). To our surprise, when indan
With the optimum reaction conditions in hand (Table 2, entry
8), the oxidative esterification of a vast array of structurally variable
carboxylic acids and cyclohexane (2a) was explored. As illustrated
in Table 3, benzoic acids with miscellaneous mono-substituted
groups were all applicable in the developed strategy, correspond-
ing coupled products were obtained in good to excellent yields.
Benzoic acids bearing electron-donating groups gave correspond-
ing products in 80%e93 % yields (3ba-3ha), regardless of the sub-
stituent (methoxy or methyl) positions (3ba-3fa). Otherwise,
carboxylic acids bearing various electron-withdrawing substituents
such as fluoro, chloro, bromo, iodo, trifluoromethoxy and cyano
group were perfectly tolerated (3ia-3pa). Nevertheless, the reac-
tion failed to form target product when p-nitrobenzoic acid was
used as substrate, which possibly due to the capture of radical by
nitro group [24] (3qa). 4-hydroxybenzoic acid and 2,4-
dihydroxybenzoic acid were also tested but both gave slightly low
yields (3ra-3sa). In the case of two methoxy groups on aromatic
Table 3
Substrate scope of carboxylic acidsa.
3

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
Table 4
Substrate scope of alkanesa.
was employed to couple with benzoic acid, a direct functionaliza-
tion on indan C(sp [3])-H bond delivered ester 4h, rather than
produce allylic ester by the oxidative CDC protocol. This result
suggests that the methodology has a great prospect in alkylation of
more complicated alkanes.
Concerning to the reaction sequence of bond formation for
oxidative dehydrogenative carboxylation of alkanes to generate
allylic esters, two possible reaction pathways are involved: (i) initial
the C(sp [3])-O bond formation between alkanes and carboxylic
acids, followed by dehydrogenation in the situ of cyclohexyl ben-
zoate; (ii) initial conversion of alkanes to olefins, followed by the
formation of allylic CeO bond. Consequently, a series of control
experiments were performed to verify the sequence of bond for-
mation in Scheme 3. Target product cyclohex-2-en-1-yl benzoate
(3aa) was not detected when cyclohexyl benzoate (7a) as the
substrate, suggesting that 7a is not the key intermediate in current
reaction (Scheme 3, A). Under the identical reaction conditions, the
CDC reaction of cyclohexene (8a) with benzoic acid could furnish a
high 1H NMR yield (91 %) of the expected product 3aa (Scheme 3,
B). Meanwhile, cyclohexane was also successfully converted to
cyclohexene (Scheme 3, C). This shows that cyclohexene may be
generated in process of the reaction between benzoic acid and
cyclohexane. Besides, the dehydrogenation of cyclohexane to
cyclohexene could not proceed without catalyst CuTPP or oxidant
In order to prove feasibility of this CDC strategy further, the
reactivity patterns of cinnamic acid derivatives and alkanes were
investigated under typical conditions (Table 5). Strikingly, the re-
action could not generate anticipated allylic esters, but the decar-
boxylative coupling alkenylation products (E-alkenes) in good to
moderate yields. Hence, several representative cinnamic acid sub-
strates were selected to react with cyclohexane, and all provided
good yields regardless electron-rich or electron-poor cinnamic
acids (6a-6c). Furthermore, diverse alkanes including cycloalkanes
and linear alkanes were studied likewise. Good yields were ob-
tained by coupling cinnamic acid with cyclopentane and cyclo-
octane respectively (6d-6e). In terms of n-hexane, a mixture of two
regioselective alkyl olefin products in a ratio of 63:37 was provided
(6f).
Table 5
Decarboxylative coupling of cinnamic acids with alkanesa.
4

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
Scheme 5. Study on kinetic isotope effect experiments.
Scheme 3. Control experiments to check the sequence of bond formation.
DTBP, indicating catalyst and oxidant are crucial for this trans-
formation (Scheme 3, D and E). According to these experimental
results, we can infer that during the CDC reaction of alkanes and
carboxylic acids, dehydrogenative olefination precedes ester CeO
bond formation, which is in consistent with literature results
recorded previously [9a].
Scheme 6. Plausible reaction mechanism.
reacts with benzoic acid (1a) to form
a key intermediate
In addition, radical trapping and kinetic isotope effect (KIE)
experiments were performed to elucidate the reaction mechanism
in detailed. The reaction was absolutely inhibited when adding
radical scavenger 2,2,6,6-tetramethylpiperidinooxy (TEMPO) or
butylated hydroxytoluene (BHT) to the reaction system. Besides,
TEMPO-cyclohexane or BHT-cyclohexane adduct could be detected
by ESI-MS respectively, manifesting the cyclohexane radical inter-
mediate is involved in this reaction (Scheme 4). In order to check
the possible rate-limiting step, an intermolecular competitive KIE
experiments were conducted (Scheme 5). A significant KH/KD value
was estimated 5.25, indicating that the cleavage of cyclohexane
C(sp [3])-H bond probably constitutes a rate-determing step among
the whole catalytic system.
[TPPCu(III)eO2CPh] (E) and deliver tert-butanol concurrently. Next,
the generated tert-butoxy radical abstracts a hydrogen atom from
cyclohexane (2a) to furnish a relatively instantaneous cyclohexyl
radical (B), followed by oxidative dehydrogenation to cyclohexene
(C) via hydrogen atom transfer (HAT) process. A third CeH
abstraction by a tert-butoxy radical occurs on the resulting cyclo-
hexene (C) to afford a cyclohexenyl radical species (D), which is
trapped by the TPPCu(III)-benzoate (E) immediately. The desired
esterification product allylic ester (3aa) is obtained by the classical
Kharasch-Sosnovsky reaction route [26] (Scheme 6, path I). On the
other hand, substrate cinnamic acid (5a) can also react with com-
plex A to produce intermediate G. Subsequently, addition of
cyclohexyl (B) to the a-position of the double bond in G gives in-
On the basis of above-obtained experimental results and
documented literature [9a,20], a plausible reaction mechanism for
esterification and decarboxylation of alkanes with carboxylic acids
is depicted in Scheme 6. The catalysis is initiated by the homolysis
of DTBP with the assistance of TPPCu(II), generating a tert-butoxy
radical and [TPPCu(III)-tBuO] (A) complex [25], which quickly
termediate H. The radical intermediate H undergoes oxidative
decarboxylation to afford product alkylalkene (6a) and releases
carbon dioxide (Scheme 6, path II). Finally, two paths regenerate
the efficient catalyst TPPCu(II) to finish the catalytic cycle.
3. Conclusion
In conclusion, we have developed an efficient and facile copper
porphyrin-catalyzed CDC esterification and decarboxylation dual
pathway for the coupling of carboxylic acids with alkanes. Various
carboxylic acid derivatives and alkanes were excellent substrates
for this transformation, delivering allylic ester or alkylalkene
products in high yields. The preliminary mechanistic experiments
revealed the key intermediate for two class products might be the
TPPCu(III)-benzoate or TPPCu(III)-cinnamate intermediate. The
mechanistic details of current reaction are still needed to be further
explored.
Scheme 4. Radical trapping experiments with TEMPO or BHT.
5

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
then the tube was sealed with Teflon screw cap tightly. This
resulting mixture was stirred at 120 ꢀC for 12 h in air at-
mosphere. After accomplishment, the reaction was cooled to
room temperature. No expected product allylic ester 3aa was
detected by TLC.
4. Experimental section
4.1. General information
All the reagents and chemicals employing in the experiments
were purchased from commercial suppliers and used without pu-
rification unless mentioned specially. The free-base tetraphe-
nylporphyrin (TPP) [27] and all metallporphyrins [20] were
synthesized from a modified method based on the literature. Re-
actions were monitored by Thin-layer chromatography (TLC) on
silica gel 60 F254 (0.25 mm) using UV light as visualizing agent.
Silica gel (300e400 mesh) was used for flash column chromatog-
raphy at atmospheric pressure and room temperature and the
eluent was a mixture of hexane and ethyl acetate. 1H, 13C or 19F NMR
spectra of all products were recorded in CDCl3 on Bruker AscendTM
500 (1H: 500 MHz and 13C: 126 MHz) or Bruker Advance 400 M
NMR (1H: 400 MHz, 13C: 101 MHz 19F: 471 MHz) spectrometers.
(ii) To a 25 mL Schlenk tube was charged with a magnetic stir
bar, CuTPP (3.4 mg, 0.005 mmol, 1.0 mol %), benzoic acid (1a,
61 mg, 0.5 mmol, 1.0 equiv.), cyclohexene (8a, 1.0 mL) and
DTBP (2.5 mmol, 475 mL, 5.0 equiv.) were added, and then the
tube was sealed with Teflon screw cap tightly. This resulting
mixture was stirred at 120 ꢀC for 12 h in air atmosphere. After
accomplishment, the reaction was cooled to room tempera-
ture. The solvent was removed under vacuum, and the res-
idue was purified by flash column chromatography on silica
gel with hexane/ethyl acetate as the eluent (10/1) to afford
the pure allylic ester 3aa.
(iii) To a 25 mL Schlenk tube was charged with a magnetic stir
bar, CuTPP (3.4 mg, 0.005 mmol, 1.0 mol %), cyclohexane (2a,
Chemical shifts were recorded in parts per million (ppm,
to tetramethylsilane (
d) relative
1.0 mL) and DTBP (2.5 mmol, 475 mL, 5.0 equiv.) were added,
d
¼ 0.0 ppm) or solvent peak (CDCl3 at
7.26 ppm for 1H NMR and CDCl3 at 77.16 ppm for 13C NMR) as the
internal standard. The following abbreviations were used:
(s ¼ single; d ¼ double (d); t ¼ triple; q ¼ quartet; dd ¼ doublet of
doublets; dt ¼ triplet of doublets; td ¼ doublet of triplets;
dq ¼ quartet of doublets; qd ¼ doublet of quartets; m ¼ multiplet;
High resolution mass (HR-MS) spectra were obtained using an
Agilent 6210 ESI mass spectrometer.
and then the tube was sealed with Teflon screw cap tightly.
This resulting mixture was stirred at 120 ꢀC for 12 h in air
atmosphere. After accomplishment, the reaction was cooled
to room temperature. No expected product allylic ester 3aa
was detected by TLC.
4.4.2. Free radical capture experiments
To a 25 mL Schlenk tube was charged with a magnetic stir bar,
CuTPP (3.4 mg, 0.005 mmol, 1.0 mol %), benzoic acid (1a, 61 mg,
0.5 mmol, 1.0 equiv.), cyclohexane (2a, 1.0 mL), DTBP (2.5 mmol,
4.2. General procedures for the synthesis of allylic esters via
oxidative esterification of carboxylic acids and alkanes: preparation
of 3aa as a representative example
475 mL, 5.0 equiv.) and 2,2,6,6-tetramethylpiperidinooxy (TEMPO,
469 mg, 6.0 equiv.) or butylated hydroxytoluene (BHT, 661 mg, 6.0
equiv.) were added, and then the tube was sealed with Teflon screw
cap tightly. This resulting mixture was stirred at 120 ꢀC for 12 h in
air atmosphere. After accomplishment, the reaction was cooled to
room temperature. No expected product allylic ester 3aa was
detected by TLC.
To a 25 mL Schlenk tube was charged with a magnetic stir bar,
CuTPP (3.4 mg, 0.005 mmol, 1.0 mol %), benzoic acid (1a, 61 mg,
0.5 mmol, 1.0 equiv.), cyclohexane (2a, 1.0 mL) and DTBP (2.5 mmol,
475 mL, 5.0 equiv.) were added, and then the tube was sealed with
Teflon screw cap tightly. This resulting mixture was stirred at 120 ꢀC
for 12 h in air atmosphere. After accomplishment, the reaction was
cooled to room temperature. The solvent was removed under
vacuum, and the residue was purified by flash column chroma-
tography on silica gel with hexane/ethyl acetate as the eluent (10/1)
to afford the pure allylic ester 3aa.
4.4.3. Intermolecular competitive kinetic isotopic effect experiments
To a 25 mL Schlenk tube was charged with a magnetic stir bar,
CuTPP (3.4 mg, 0.005 mmol, 1.0 mol %), benzoic acid (1a, 61 mg,
0.5 mmol, 1.0 equiv.), cyclohexane (2a, 0.5 mL), cyclohexane-d12
4.3. General procedures for the synthesis of alkylalkenes via
decarboxylative alkenylation of cinnamic acids with alkanes:
preparation of 6a as a representative example
(2a0, 0.5 mL) and DTBP (2.5 mmol, 475
mL, 5.0 equiv.) were added,
and then the tube was sealed with Teflon screw cap tightly. This
resulting mixture was stirred at 120 ꢀC for 12 h in air atmosphere.
After accomplishment, the reaction was cooled to room tempera-
ture. The solvent was removed under vacuum, and the residue was
purified by flash column chromatography on silica gel with hexane/
ethyl acetate as the eluent (10/1) to afford the pure allylic ester.
To a 25 mL Schlenk tube was charged with a magnetic stir bar,
CuTPP (3.4 mg, 0.005 mmol, 1.0 mol %), trans-cinnamic acid (5a,
74 mg, 0.5 mmol, 1.0 equiv.), cyclohexane (2a, 1.0 mL) and DTBP
(2.5 mmol, 475 mL, 5.0 equiv.) were added, and then the tube was
sealed with Teflon screw cap tightly. This resulting mixture was
stirred at 120 ꢀC for 12 h in air atmosphere. After accomplishment,
the reaction was cooled to room temperature. The solvent was
removed under vacuum, and the residue was purified by flash
column chromatography on silica gel with hexane/ethyl acetate as
the eluent (10/1) to afford the pure (E)-alkene 6a.
4.5. Characterization data of all compounds
4.5.1. Cyclohex-2-en-1-yl benzoate (3aa) [9d]
Colorless oil (93 mg, 92 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
8.06 (dd, J ¼ 8.4, 1.4 Hz, 2H),
7.58e7.49 (m, 1H), 7.48e7.37 (m, 2H), 6.06e5.94 (m, 1H), 5.84 (ddt,
J ¼ 10.0, 3.8, 2.0 Hz, 1H), 5.52 (dtq, J ¼ 5.3, 3.6, 1.7 Hz, 1H), 2.14 (dttd,
J ¼ 13.1, 5.6, 3.8, 1.9 Hz, 1H), 2.09e1.93 (m, 2H), 1.93e1.79 (m, 2H),
1.70 (dqt, J ¼ 13.8, 5.9, 3.4 Hz, 1H). 13C NMR (101 MHz, CDCl3)
4.4. Procedure for control experiments
4.4.1. To check the sequence of bond formation
d 166.3, 132.9, 132.8, 130.9, 129.7, 128.3, 125.8, 77.5, 77.2, 76.8, 68.7,
28.5, 25.0, 19.0.
(i) To a 25 mL Schlenk tube was charged with a magnetic stir
bar, CuTPP (3.4 mg, 0.005 mmol, 1.0 mol %), cyclohexyl
benzoate (7a, 102 mg, 0.5 mmol, 1.0 equiv.), benzene (1.0 mL)
4.5.2. Cyclohex-2-en-1-yl 2-methoxybenzoate (3ba) [9d]
Colorless oil (93 mg, 80 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
and DTBP (2.5 mmol, 475
mL, 5.0 equiv.) were added, and
v/v). 1H NMR (400 MHz, CDCl3)
d
7.76 (dd, J ¼ 7.9, 1.8 Hz, 1H),
6

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
7.46e7.38 (m, 1H), 7.00e6.89 (m, 2H), 6.03e5.90 (m, 1H), 5.83 (ddt,
J ¼ 10.0, 3.8, 2.0 Hz, 1H), 5.57e5.40 (m, 1H), 3.87 (s, 3H), 2.16e2.05
(m, 1H), 2.05e1.90 (m, 2H), 1.83 (ddtt, J ¼ 20.3, 10.1, 5.6, 2.7 Hz, 2H),
1.67 (dddt, J ¼ 13.5, 8.1, 5.6, 3.0 Hz, 1H). 13C NMR (101 MHz, CDCl3)
4.5.9. Cyclohex-2-en-1-yl 2-fluorobenzoate (3ia) [22]
Colorless oil (93 mg, 84 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
7.91 (td, J ¼ 7.6, 1.9 Hz, 1H),
7.54e7.41 (m, 1H), 7.22e7.03 (m, 2H), 6.08e5.92 (m, 1H), 5.90e5.76
(m, 1H), 5.58e5.44 (m, 1H), 2.18e2.07 (m, 1H), 2.07e1.88 (m, 3H),
1.82 (dddt, J ¼ 13.1, 9.5, 5.6, 3.1 Hz, 1H), 1.68 (ttd, J ¼ 11.4, 5.7, 3.6 Hz,
d
165.8, 159.2, 133.3, 132.7, 131.5, 125.9, 120.8, 120.1, 112.1, 77.5, 77.2,
76.8, 68.4, 56.0, 56.0, 28.4, 25.0, 19.0.
1H). 13C NMR (101 MHz, CDCl3)
d 164.1, 164.1, 163.4, 160.8, 134.3,
134.2, 133.2, 132.1, 125.5, 123.9, 123.9, 119.6, 119.5, 117.1, 116.9, 77.5,
4.5.3. Cyclohex-2-en-1-yl 3-methoxybenzoate (3ca) [22]
77.2, 76.8, 69.1, 28.5, 25.0, 18.9. 19F NMR (471 MHz, CDCl3)
Colorless oil (103 mg, 89 %). Hex/EA as the eluent (Hex/
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d
7.64 (d, J ¼ 7.6 Hz, 1H),
d
ꢁ109.62.
7.56 (s, 1H), 7.31 (t, J ¼ 7.9 Hz, 1H), 7.07 (dd, J ¼ 8.2, 2.7 Hz, 1H), 5.99
(dt, J ¼ 10.0, 3.8 Hz, 1H), 5.89e5.76 (m, 1H), 5.55e5.43 (m, 1H), 3.83
(s, 3H), 2.18e2.07 (m, 1H), 2.07e1.91 (m, 2H), 1.85 (dddd, J ¼ 24.9,
15.9, 10.3, 6.2 Hz, 2H), 1.69 (tt, J ¼ 10.3, 5.5 Hz, 1H). 13C NMR
4.5.10. Cyclohex-2-en-1-yl 4-fluorobenzoate (3ja) [22]
Colorless oil (96 mg, 87 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
8.05 (dd, J ¼ 8.6, 5.6 Hz, 2H), 7.07
(t, J ¼ 8.6 Hz, 2H), 6.07e5.90 (m, 1H), 5.89e5.74 (m, 1H), 5.56e5.39
(m, 1H), 2.17e2.07 (m, 1H), 2.06e1.92 (m, 2H), 1.90e1.76 (m, 2H),
1.68 (dtd, J ¼ 13.6, 8.8, 5.7 Hz, 1H). 13C NMR (101 MHz, CDCl3)
(101 MHz, CDCl3)
d 166.1, 159.6, 132.9, 132.2, 129.3, 125.8, 122.0,
119.2, 114.2, 77.5, 77.2, 76.8, 68.8, 55.4, 28.4, 25.0, 19.0.
d
166.9, 165.2, 164.4, 132.9, 132.1, 132.0, 127.1, 127.0, 125.6, 115.5,
4.5.4. Cyclohex-2-en-1-yl 4-methoxybenzoate (3da) [9d]
115.2, 77.4, 77.1, 76.8, 68.8, 28.4, 24.9, 18.9. 19F NMR (471 MHz,
CDCl3)
ꢁ106.08.
Colorless oil (105 mg, 90 %). Hex/EA as the eluent (Hex/
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d
8.00 (d, J ¼ 8.8 Hz, 2H),
d
6.89 (d, J ¼ 8.8 Hz, 2H), 6.05e5.90 (m, 1H), 5.82 (ddt, J ¼ 10.1, 4.0,
2.1 Hz, 1H), 5.56e5.39 (m, 1H), 3.83 (s, 3H), 2.18e2.07 (m, 1H),
2.07e1.91 (m, 2H), 1.84 (ttd, J ¼ 17.8, 9.7, 9.0, 3.1 Hz, 2H), 1.73e1.65
4.5.11. Cyclohex-2-en-1-yl 4-chlorobenzoate (3ka) [9d]
Colorless oil (105 mg, 89 %). Hex/EA as the eluent (Hex/
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d 8.03e7.91 (m, 2H), 7.38
(m, 1H). 13C NMR (101 MHz, CDCl3)
d 166.0, 163.3, 132.7, 131.7, 126.1,
(d, J ¼ 8.5 Hz, 2H), 5.99 (dt, J ¼ 8.9, 3.2 Hz,1H), 5.81 (ddd, J ¼ 8.0, 3.4,
1.7 Hz, 1H), 5.56e5.40 (m, 1H), 2.18e2.08 (m, 1H), 2.07e1.92 (m,
2H), 1.90e1.76 (m, 2H), 1.69 (tdt, J ¼ 13.7, 5.8, 3.5 Hz, 1H). 13C NMR
123.3, 113.6, 77.5, 77.2, 76.8, 68.3, 55.5, 28.6, 25.1, 19.1.
4.5.5. Cyclohex-2-en-1-yl 3-methylbenzoate (3ea) [9d]
(101 MHz, CDCl3) d 165.4, 139.2, 133.1, 131.1, 129.4, 128.7, 125.6, 77.5,
Colorless oil (101 mg, 93 %). Hex/EA as the eluent (Hex/
77.2, 76.8, 69.0, 69.0, 28.5, 25.0, 19.0.
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
7.86 (d, J ¼ 7.3 Hz, 2H),
d
7.38e7.27 (m, 2H), 6.07e5.92 (m, 1H), 5.84 (ddt, J ¼ 10.0, 4.0, 2.1 Hz,
1H), 5.51 (qd, J ¼ 4.3, 2.6 Hz, 1H), 2.39 (s, 3H), 2.18e2.09 (m, 1H),
2.08e1.94 (m, 2H), 1.86 (dddd, J ¼ 25.3, 12.8, 7.7, 3.1 Hz, 2H), 1.70
4.5.12. Cyclohex-2-en-1-yl 2-bromobenzoate (3la) [9d]
Colorless oil (112 mg, 80 %). Hex/EA as the eluent (Hex/
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
7.79 (dd, J ¼ 7.6, 1.8 Hz,
d
(tdt, J ¼ 13.9, 5.9, 3.6 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d 166.4,
1H), 7.72e7.59 (m, 1H), 7.35 (dtd, J ¼ 20.2, 7.4, 1.4 Hz, 2H), 6.04 (dt,
J ¼ 10.7, 3.6 Hz, 1H), 5.96e5.81 (m, 1H), 5.55 (dd, J ¼ 3.6, 1.7 Hz, 1H),
2.21e2.11 (m, 1H), 2.11e1.94 (m, 3H), 1.91e1.81 (m, 1H), 1.77e1.67
138.1, 133.5, 132.8, 130.8, 130.1, 128.2, 126.8, 125.9, 77.5, 77.2, 76.8,
68.6, 28.5, 25.0, 21.3, 19.1.
(m, 1H). 13C NMR (101 MHz, CDCl3)
d 166.1, 134.3, 133.3, 133.0,132.3,
4.5.6. Cyclohex-2-en-1-yl 4-methylbenzoate (3fa) [9d]
131.2, 127.2, 125.3, 121.5, 77.5, 77.2, 76.8, 69.6, 28.3, 25.0, 18.9.
Colorless oil (99 mg, 91 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
7.94 (d, J ¼ 8.2 Hz, 2H), 7.21 (d,
4.5.13. Cyclohex-2-en-1-yl 4-bromobenzoate (3ma) [9d]
J ¼ 8.0 Hz, 2H), 5.99 (dt, J ¼ 8.9, 3.2 Hz, 1H), 5.83 (ddd, J ¼ 12.4, 3.9,
2.1 Hz, 1H), 5.58e5.42 (m, 1H), 2.39 (s, 3H), 2.13 (ddd, J ¼ 16.5, 3.9,
1.9 Hz, 1H), 2.08e1.93 (m, 2H), 1.85 (ddtt, J ¼ 19.2, 9.7, 6.7, 2.8 Hz,
2H), 1.69 (tdt, J ¼ 13.9, 5.9, 3.5 Hz, 1H). 13C NMR (101 MHz, CDCl3)
Colorless oil (104 mg, 74 %). Hex/EA as the eluent (Hex/
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d 7.96e7.83 (m, 2H),
7.62e7.46 (m, 2H), 5.99 (dt, J ¼ 9.8, 3.6 Hz, 1H), 5.90e5.70 (m, 1H),
5.59e5.37 (m,1H), 2.12 (dtdt, J ¼ 15.4, 5.8, 3.9,1.9 Hz,1H), 2.07e1.91
(m, 2H), 1.83 (dtdd, J ¼ 23.7, 10.0, 5.6, 3.1 Hz, 2H), 1.69 (tdt, J ¼ 13.7,
d
166.3, 143.4, 132.7, 129.7, 129.0, 128.1, 126.0, 77.5, 77.2, 76.8, 68.4,
5.9, 3.5 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d 165.5, 133.1, 131.7,
28.5, 25.0, 21.7, 21.6, 19.0.
131.2, 129.8, 127.9, 125.6, 77.5, 77.2, 76.8, 69.0, 28.5, 25.0, 19.0.
4.5.7. Cyclohex-2-en-1-yl [1,10-biphenyl]-4-carboxylate (3ga) [22]
Colorless oil (130 mg, 93 %). Hex/EA as the eluent (Hex/
4.5.14. Cyclohex-2-en-1-yl 4-iodobenzoate (3na) [9b]
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d 8.22e8.09 (m, 2H), 7.65
Colorless oil (129 mg, 79 %). Hex/EA as the eluent (Hex/
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d 7.91e7.58 (m, 4H),
6.09e5.88 (m, 1H), 5.80 (dt, J ¼ 10.1, 2.0 Hz, 1H), 5.55e5.39 (m, 1H),
2.12 (dd, J ¼ 16.4, 4.1 Hz, 1H), 2.06e1.91 (m, 2H), 1.90e1.75 (m, 2H),
(dd, J ¼ 13.9, 7.8 Hz, 4H), 7.47 (t, J ¼ 7.4 Hz, 2H), 7.40 (t, J ¼ 7.2 Hz,
1H), 6.10e5.97 (m, 1H), 5.96e5.83 (m, 1H), 5.65e5.50 (m, 1H),
2.24e2.13 (m, 1H), 2.12e1.98 (m, 2H), 1.91 (tdd, J ¼ 13.7, 7.1, 4.2 Hz,
2H), 1.74 (ddt, J ¼ 13.5, 8.1, 2.7 Hz, 1H). 13C NMR (101 MHz, CDCl3)
1.69 (td, J ¼ 8.8, 4.5 Hz,1H). 13C NMR (101 MHz, CDCl3)
d 165.7,137.7,
d
166.1, 145.5, 140.1, 132.9, 130.2, 129.6, 128.9, 128.1, 127.3, 127.0,
133.1, 131.1, 130.3, 125.6, 100.6, 77.5, 77.2, 76.8, 69.0, 28.4, 25.0, 19.0.
125.9, 77.5, 77.2, 76.8, 68.7, 28.5, 25.0, 19.1.
4.5.15. Cyclohex-2-en-1-yl 4-(trifluoromethyl)benzoate (3oa) [22]
4.5.8. Cyclohex-2-en-1-yl 4-(tert-butyl) benzoate (3ha) [9d]
Colorless oil (127 mg, 94 %). Hex/EA as the eluent (Hex/
Colorless oil (116 mg, 90 %). Hex/EA as the eluent (Hex/
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
8.15 (d, J ¼ 8.1 Hz, 2H),
d
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d
8.00 (d, J ¼ 8.4 Hz, 2H),
7.68 (d, J ¼ 8.2 Hz, 2H), 6.13e5.92 (m, 1H), 5.83 (ddd, J ¼ 8.0, 3.5,
1.7 Hz, 1H), 5.60e5.45 (m, 1H), 2.19e2.10 (m, 1H), 2.09e1.94 (m,
2H), 1.86 (dtdd, J ¼ 20.2, 13.0, 5.5, 3.2 Hz, 2H), 1.71 (dddt, J ¼ 13.6,
7.45 (d, J ¼ 8.4 Hz, 2H), 5.99 (dt, J ¼ 6.7, 3.7 Hz, 1H), 5.92e5.75 (m,
1H), 5.61e5.41 (m, 1H), 2.20e2.08 (m, 1H), 2.08e1.93 (m, 2H), 1.86
(tdt, J ¼ 15.2, 9.6, 7.4 Hz, 2H),1.70 (ddtd, J ¼ 13.7, 8.7, 5.9, 3.3 Hz,1H),
8.2, 5.6, 3.0 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d 165.1, 134.5, 134.2,
1.33 (s, 9H). 13C NMR (101 MHz, CDCl3)
d
166.2, 156.3, 132.6, 129.5,
134.2,134.2,133.4, 130.1,125.5,125.4,125.4,125.3,125.2,122.5, 77.5,
128.1, 126.0, 125.2, 77.5, 77.2, 76.8, 68.3, 35.0, 31.2, 28.5, 25.0, 19.0.
77.2, 76.8, 69.4, 28.5, 25.0, 19.0. 19F NMR (471 MHz, CDCl3)
d
ꢁ63.11.
7

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
4.5.16. Cyclohex-2-en-1-yl 4-cyanobenzoate (3pa) [22]
133.9, 133.2, 133.0, 131.4, 130.1, 128.6, 127.9, 127.7, 126.2, 125.9,
125.8, 124.5, 77.5, 77.2, 76.8, 68.8, 28.5, 25.0, 19.1.
Colorless oil (99 mg, 87 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
8.12 (d, J ¼ 8.0 Hz, 2H), 7.71 (d,
J ¼ 8.0 Hz, 2H), 6.01 (d, J ¼ 9.9 Hz, 1H), 5.80 (d, J ¼ 8.7 Hz, 1H), 5.50
4.5.23. Cyclohex-2-en-1-yl 3-phenylpropanoate (3ya) [22]
(s, 1H), 2.22e2.08 (m, 1H), 2.08e1.92 (m, 2H), 1.91e1.76 (m, 2H),
Colorless oil (105 mg, 91 %). Hex/EA as the eluent (Hex/
1.69 (dp, J ¼ 13.5, 4.3, 3.3 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d
164.6,
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
7.18 (q, J ¼ 7.4 Hz, 2H),
d
134.7, 133.6, 132.2, 130.2, 125.1, 118.1, 116.2, 77.5, 77.2, 76.8, 69.7,
28.3, 25.0, 18.9.
7.11 (d, J ¼ 7.4 Hz, 3H), 5.84 (dd, J ¼ 8.6, 4.8 Hz, 1H), 5.66e5.50 (m,
1H), 5.27e5.08 (m, 1H), 2.86 (t, J ¼ 7.8 Hz, 2H), 2.53 (t, J ¼ 7.8 Hz,
2H), 2.04e1.82 (m, 2H), 1.75 (td, J ¼ 13.2, 12.2, 4.6 Hz, 1H), 1.66e1.48
4.5.17. Cyclohex-2-en-1-yl 4-hydroxybenzoate (3ra)
(m, 3H). 13C NMR (101 MHz, CDCl3)
d 172.6,140.6,132.7,128.5,128.4,
Colorless oil (44 mg, 40 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
126.2, 125.7, 77.5, 77.2, 76.8, 68.1, 36.2, 31.1, 28.3, 24.9, 18.9.
v/v). 1H NMR (400 MHz, CDCl3)
d
7.95 (d, J ¼ 8.2 Hz, 2H), 6.87 (d,
J ¼ 8.3 Hz, 2H), 6.08e5.91 (m, 1H), 5.90e5.74 (m, 1H), 5.47 (d,
J ¼ 1.8 Hz, 1H), 2.18e2.08 (m, 1H), 2.08e1.98 (m, 1H), 1.97e1.91 (m,
1H), 1.90e1.79 (m, 2H), 1.71 (dd, J ¼ 8.0, 3.2 Hz, 1H). 13C NMR
4.5.24. Cyclopent-2-en-1-yl benzoate (4a) [9a]
Colorless oil (78 mg, 83 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
8.03 (d, J ¼ 7.6 Hz, 2H), 7.53 (t,
(101 MHz, CDCl3)
d
166.6, 166.6, 160.4, 160.4, 132.9, 132.1, 125.9,
J ¼ 7.4 Hz, 1H), 7.41 (t, J ¼ 7.6 Hz, 2H), 6.15 (d, J ¼ 4.4 Hz, 1H), 5.95 (d,
J ¼ 4.2 Hz, 2H), 2.59 (td, J ¼ 15.0, 13.2, 6.8 Hz, 1H), 2.40 (tt, J ¼ 12.1,
6.3 Hz, 2H), 1.96 (ddt, J ¼ 13.6, 11.2, 3.5 Hz, 1H). 13C NMR (101 MHz,
123.0, 115.3, 77.5, 77.2, 76.8, 68.6, 28.6, 25.5, 25.1, 24.2, 19.1. HR-MS
(ESI) calcd for C14H14NaO3 [MþNa]þ 241.0835, found: 241.0830.
CDCl3) d 166.6,137.8, 132.8,130.8,129.6,129.4,128.3, 81.2, 77.5, 77.2,
4.5.18. Cyclohex-2-en-1-yl 2,4-dihydroxybenzoate (3sa)
76.8, 31.3, 30.0.
Colorless oil (39 mg, 34 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
11.11 (s,1H), 7.74 (d, J ¼ 8.7 Hz,1H),
4.5.25. Cyclopent-2-en-1-yl 4-methoxybenzoate (4b) [9b]
6.46e6.29 (m, 2H), 6.09e5.95 (m, 1H), 5.87e5.73 (m, 1H),
5.59e5.39 (m, 1H), 2.14 (ddd, J ¼ 18.2, 4.9,1.9 Hz,1H), 2.09e2.03 (m,
1H), 1.97e1.87 (m, 2H), 1.86e1.77 (m, 1H), 1.71 (dd, J ¼ 7.6, 3.5 Hz,
Colorless oil (90 mg, 82 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (500 MHz, CDCl3)
d
7.97 (d, J ¼ 8.5 Hz, 2H), 6.88 (d,
J ¼ 8.5 Hz, 2H), 6.12 (d, J ¼ 5.4 Hz, 1H), 6.02e5.81 (m, 2H), 3.83 (s,
1H). 13C NMR (101 MHz, CDCl3)
d 169.8, 163.8, 162.3, 133.5, 132.1,
3H), 2.56 (dd, J ¼ 12.4, 8.0 Hz, 1H), 2.44e2.29 (m, 2H), 1.95 (dq,
125.4, 107.9, 106.4, 103.2, 77.5, 77.2, 76.8, 69.1, 28.5, 25.0, 18.9. HR-
J ¼ 13.0, 5.3, 4.5 Hz, 1H). 13C NMR (126 MHz, CDCl3)
d 166.4, 163.3,
MS (ESI) calcd for C13H15O4 [MþH]þ 235.0965, found: 235.0960.
137.5, 131.6, 129.6, 123.2, 113.5, 80.8, 77.4, 77.2, 76.9, 55.4, 31.2, 30.0.
4.5.19. Cyclohex-2-en-1-yl 2,6-dimethoxybenzoate (3ta) [22]
Colorless oil (76 mg, 58 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
4.5.26. Cyclopent-2-en-1-yl 4-(trifluoromethyl)benzoate (4c)
Colorless oil (103 mg, 80 %). Hex/EA as the eluent (Hex/
v/v). 1H NMR (400 MHz, CDCl3)
d
7.32e7.27 (m, 1H), 6.57 (d,
EA ¼ 10:1, v/v). 1H NMR (500 MHz, CDCl3)
8.13 (d, J ¼ 8.1 Hz, 2H),
d
J ¼ 8.4 Hz, 2H), 6.08e5.94 (m, 1H), 5.93e5.79 (m, 1H), 5.59 (qd,
J ¼ 5.3, 3.6 Hz, 1H), 3.83 (s, 6H), 2.18e2.03 (m, 2H), 2.03e1.90 (m,
2H), 1.83 (tdt, J ¼ 12.9, 5.7, 3.4 Hz, 1H), 1.74e1.63 (m, 1H). 13C NMR
7.67 (d, J ¼ 8.1 Hz, 2H), 6.18 (d, J ¼ 5.6 Hz, 1H), 5.95 (t, J ¼ 7.9 Hz, 2H),
2.67e2.52 (m, 1H), 2.50e2.30 (m, 2H),1.98 (ddt, J ¼ 10.6, 8.0, 4.4 Hz,
1H). 13C NMR (126 MHz, CDCl3)
d 165.4, 138.3, 134.5, 134.2, 134.0,
(101 MHz, CDCl3)
d
166.4,157.5,132.8,130.9,125.9,113.8,104.2, 77.5,
130.1, 129.1, 125.5, 125.4, 125.4, 125.4, 124.9, 122.7, 82.0, 77.4, 77.2,
77.2, 76.8, 69.1, 56.1, 28.4, 25.0, 19.0.
76.9, 31.3, 29.9. 19F NMR (471 MHz, CDCl3)
d
ꢁ63.10. HR-MS (ESI)
calcd for C13H11F3NaO2 [MþNa]þ 279.0603, found: 279.0599.
4.5.20. Cyclohex-2-en-1-yl thiophene-2-carboxylate (3ua) [9d]
Colorless oil (87 mg, 83 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
4.5.27. Benzoic acid indan-2-yl ester (4h) [28]
v/v). 1H NMR (400 MHz, CDCl3)
d
7.77 (d, J ¼ 2.8 Hz, 1H), 7.51 (d,
Colorless oil (100 mg, 84 %). Hex/EA as the eluent (Hex/
J ¼ 4.8 Hz, 1H), 7.05 (t, J ¼ 4.2 Hz, 1H), 6.02e5.92 (m, 1H), 5.80 (dd,
J ¼ 10.0, 3.2 Hz, 1H), 5.44 (d, J ¼ 5.0 Hz, 1H), 2.10 (dd, J ¼ 17.9, 5.0 Hz,
1H), 2.05e1.98 (m, 1H), 1.93 (ddt, J ¼ 13.7, 8.9, 4.1 Hz, 1H), 1.88e1.75
(m, 2H), 1.66 (dddd, J ¼ 16.9, 13.7, 7.4, 4.6 Hz, 1H). 13C NMR
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
d 8.23e8.01 (m, 2H), 7.58
(t, J ¼ 6.5 Hz, 2H), 7.51e7.42 (m, 2H), 7.37 (d, J ¼ 3.5 Hz, 2H), 7.31 (dq,
J ¼ 8.2, 4.1 Hz, 1H), 6.53 (dt, J ¼ 7.3, 4.3 Hz, 1H), 3.31e3.18 (m, 1H),
3.06e2.94 (m, 1H), 2.77e2.62 (m, 1H), 2.39e2.21 (m, 1H). 13C NMR
(101 MHz, CDCl3)
d
162.1, 134.6, 133.3, 133.1, 132.3, 127.8, 125.6, 77.5,
(101 MHz, CDCl3) d 166.6, 144.4, 141.2, 132.9, 130.5, 129.7, 129.0,
77.2, 76.8, 69.1, 28.5, 25.0, 19.0.
128.3, 126.8, 125.7, 124.9, 79.0, 77.5, 77.2, 76.8, 32.5, 30.3.
4.5.21. Cyclohex-2-en-1-yl furan-2-carboxylate (3va) [9d]
4.5.28. (E)-(2-cyclohexylvinyl)benzene (6a) [9b]
Colorless oil (77 mg, 80 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
Colorless oil (69 mg, 74 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
7.53 (s, 1H), 7.13 (d, J ¼ 3.5 Hz, 1H),
v/v). 1H NMR (400 MHz, CDCl3)
d
7.37 (d, J ¼ 7.3 Hz, 2H), 7.30 (t,
6.50e6.41 (m, 1H), 6.06e5.87 (m, 1H), 5.76 (d, J ¼ 9.2 Hz, 1H), 5.45
(d, J ¼ 4.9 Hz, 1H), 2.09 (dd, J ¼ 18.5, 4.7 Hz, 1H), 2.03e1.88 (m, 2H),
1.80 (tdd, J ¼ 16.2, 7.3, 3.9 Hz, 2H), 1.69e1.59 (m, 1H). 13C NMR
J ¼ 7.7 Hz, 2H), 7.20 (t, J ¼ 7.2 Hz, 1H), 6.37 (d, J ¼ 16.0 Hz, 1H), 6.20
(dd, J ¼ 16.0, 6.9 Hz, 1H), 2.15 (dtt, J ¼ 10.9, 7.1, 3.5 Hz, 1H), 1.85 (d,
J ¼ 3.3 Hz, 1H), 1.81 (s, 2H), 1.78 (t, J ¼ 3.4 Hz, 1H), 1.73e1.68 (m, 1H),
1.37e1.33 (m, 1H), 1.32e1.28 (m, 1H), 1.24 (dt, J ¼ 10.9, 3.9 Hz, 2H),
(101 MHz, CDCl3) d 158.4, 146.1, 145.0, 133.2, 125.4, 117.7, 111.7, 77.4,
77.1, 76.8, 68.8, 28.3, 24.9, 18.9.
1.19 (d, J ¼ 3.3 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d 138.2, 137.0,
128.6, 127.4, 126.9, 126.1, 77.5, 77.2, 76.8, 41.3, 33.1, 26.3, 26.2.
4.5.22. Cyclohex-2-en-1-yl 2-naphthoate (3xa) [9d]
Colorless oil (113 mg, 90 %). Hex/EA as the eluent (Hex/
4.5.29. (E)-1-(2-cyclohexylvinyl) 4-methoxybenzene (6b) [29]
Colorless oil (81 mg, 75 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
EA ¼ 10:1, v/v). 1H NMR (400 MHz, CDCl3)
8.97 (d, J ¼ 8.6 Hz, 1H),
d
8.21 (d, J ¼ 7.2 Hz, 1H), 8.00 (d, J ¼ 8.2 Hz, 1H), 7.88 (d, J ¼ 8.2 Hz,
1H), 7.63 (t, J ¼ 7.7 Hz, 1H), 7.52 (dt, J ¼ 15.8, 7.6 Hz, 2H), 6.06 (d,
J ¼ 10.1 Hz, 1H), 5.97 (d, J ¼ 11.2 Hz, 1H), 5.67 (s, 1H), 2.23e2.13 (m,
1H), 2.04 (ddq, J ¼ 21.2, 13.1, 5.2, 4.5 Hz, 3H), 1.89 (ddd, J ¼ 16.4, 13.1,
v/v). 1H NMR (400 MHz, CDCl3)
d
7.32 (d, J ¼ 8.3 Hz, 2H), 6.88 (d,
J ¼ 8.3 Hz, 2H), 6.34 (d, J ¼ 16.0 Hz, 1H), 6.08 (dd, J ¼ 15.9, 7.0 Hz,
1H), 3.83 (s, 3H), 2.20e2.09 (m, 1H), 1.88e1.78 (m, 4H), 1.75e1.69
(m, 1H), 1.39e1.31 (m, 2H), 1.23 (t, J ¼ 11.4 Hz, 3H). 13C NMR
9.6 Hz, 1H), 1.80e1.71 (m, 1H). 13C NMR (101 MHz, CDCl3)
d
167.3,
(101 MHz, CDCl3) d 158.7, 134.9, 131.0, 127.1, 126.7, 114.0, 77.5, 77.2,
8

X.-Y. Chen, S. Yang, B.-P. Ren et al.
Tetrahedron xxx (xxxx) xxx
(2021) 1776e1808.
76.8, 55.4, 41.3, 33.2, 26.3, 26.2.
[3] (a) S.A. Girard, T. Knauber, C.J. Li, Angew. Chem. Int. Ed. 53 (2014) 74e100;
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4.5.30. (E)-1-(2-cyclohexylvinyl) 4-(trifluoromethyl)benzene (6c)
[29]
Colorless oil (80 mg, 63 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
(b) S. Arshadi, A. Banaei, A. Monfared, S. Ebrahimiasl, A. Hosseinian, RSC Adv. 9
(2019) 17101e17118.
v/v). 1H NMR (400 MHz, CDCl3)
d
7.54 (d, J ¼ 8.2 Hz, 2H), 7.43 (d,
[5] (a) A. Das, P. Theato, Chem. Rev. 116 (2015) 1434e1495;
J ¼ 8.1 Hz, 2H), 6.38 (d, J ¼ 16.0 Hz, 1H), 6.28 (dd, J ¼ 16.0, 6.6 Hz,
1H), 2.16 (dtd, J ¼ 10.9, 7.3, 3.3 Hz, 1H), 1.87e1.74 (m, 4H), 1.73e1.67
(m, 1H), 1.36e1.31 (m, 1H), 1.31e1.20 (m, 3H), 1.17 (dd, J ¼ 13.1,
ꢀ
(b) A.G.A. Sa, A.C.d. Meneses, P.H. H.d. Araújo, D.d. Oliveira, Trends Food Sci.
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3847e3855;
3.7 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d 141.7, 139.7, 128.5, 126.3,
126.2, 125.6, 125.5, 77.5, 77.2, 76.8, 41.4, 32.9, 26.3, 26.1. 19F NMR
(471 MHz, CDCl3)
ꢁ62.34.
(b) P.T.M. Ha, T.D. Le, S.H. Doan, T.T. Nguyen, N.T.H. Le, N.T.S. Phan, Tetrahe-
dron 73 (2017) 5883e5891;
(c) P. Macias-Benitez, F.J. Moreno-Dorado, F.M. Guerra, J. Org. Chem. 85 (2020)
6027e6043;
d
(d) B. Lu, F. Zhu, D. Wang, H. Sun, Q. Shen, Tetrahedron Lett. 58 (2017)
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4.5.31. (E)-(2-cyclopentylvinyl)benzene (6d) [9b]
Colorless oil (58 mg, 68 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
7.37 (d, J ¼ 7.7 Hz, 2H), 7.30 (t,
J ¼ 7.5 Hz, 2H), 7.20 (t, J ¼ 7.3 Hz, 1H), 6.39 (d, J ¼ 15.8 Hz, 1H), 6.23
(dd, J ¼ 15.8, 7.7 Hz, 1H), 2.62 (h, J ¼ 8.0 Hz, 1H), 1.88 (dq, J ¼ 11.3,
6.3 Hz, 2H), 1.73 (dq, J ¼ 7.0, 4.1 Hz, 2H), 1.63 (td, J ¼ 7.8, 4.5 Hz, 2H),
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12193e12196.
1.42 (dq, J ¼ 15.1, 8.2 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d 138.1,
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135.8, 128.6, 128.0, 126.8, 126.1, 77.5, 77.2, 76.8, 44.0, 33.4, 25.4.
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4.5.32. (E)-styrylcyclooctane (6e) [9b]
Colorless oil (75 mg, 70 %). Hex/EA as the eluent (Hex/EA ¼ 10:1,
v/v). 1H NMR (400 MHz, CDCl3)
d
7.38 (d, J ¼ 7.8 Hz, 2H), 7.31 (t,
J ¼ 7.4 Hz, 2H), 7.22 (d, J ¼ 7.4 Hz, 1H), 6.36 (d, J ¼ 15.9 Hz, 1H), 6.25
(dd, J ¼ 15.8, 7.3 Hz, 1H), 2.42 (d, J ¼ 8.4 Hz, 1H), 1.80 (q, J ¼ 11.1,
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3834e3837.
10.2 Hz, 4H), 1.63e1.55 (m, 11H). 13C NMR (101 MHz, CDCl3)
d 138.3,
137.9, 128.6, 127.0, 126.8, 126.1, 77.5, 77.2, 76.8, 41.5, 32.0, 27.6, 26.1,
25.2.
Declaration of competing interest
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Tetrahedron 76 (2020) 131569;
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
Acknowledgments
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 21671068) and “Dengfeng
Plan” High-level Hospital Construction Opening Project of Foshan
Fourth People's Hospital (No. FSSYKF-2020012).
Appendix A. Supplementary data
(b) F.-H. Wang, Z.-Y. Liu, S. Yang, L. Shi, D.-Z. Lin, H.-Y. Liu, G.-Q. Yuan, Synth.
Commun. 51 (2021) 2053e2062.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132377.
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