Photoinduced copper-catalyzed dual decarboxylative coupling of α,β-unsaturated carboxylic acids with redox-active esters

Article abstract of DOI:10.1016/j.tet.2021.132259

The first photoinduced copper-catalyzed dual decarboxylative cross-coupling of α,β-unsaturated carboxylic acids and redox-active esters has been developed. This reaction enabled C(sp²)–C(sp³) bond formation, which afforded a variety of synthetically valuable alkene derivatives. Many α,β-unsaturated carboxylic acids and redox-active ester derivatives were tolerant to this reaction. The reaction also tolerated many common functional groups.

Full text of DOI:10.1016/j.tet.2021.132259

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Photoinduced copper-catalyzed dual decarboxylative coupling of
unsaturated carboxylic acids with redox-active esters
a,b-
, b,
Xiao-Yu Lu a *, Ang Gao a, Qi-Le Liu a, Ze-Jie Xia a
a College of Materials and Chemical Engineering, Chuzhou University, Hui Feng Road 1, Chuzhou, 239000, PR China
b School of Chemistry and Chemical Engineering, AnHui University, Hefei, 230601, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The first photoinduced copper-catalyzed dual decarboxylative cross-coupling of
boxylic acids and redox-active esters has been developed. This reaction enabled C(sp2)eC(sp3) bond
formation, which afforded a variety of synthetically valuable alkene derivatives. Many -unsaturated
carboxylic acids and redox-active ester derivatives were tolerant to this reaction. The reaction also
tolerated many common functional groups.
a,b-unsaturated car-
Received 23 March 2021
Received in revised form
6 May 2021
Accepted 24 May 2021
Available online xxx
a,b
© 2021 Elsevier Ltd. All rights reserved.
Keywords:
Photoinduced
Copper-catalyzed
Decarboxylative
Unsaturated carboxylic acids
Redox-active esters
1. Introduction
bond formation methods [18e20]. The photoredox catalytic
decarboxylative cross-coupling of cinnamic acids has attracted
In the past few decades, transition metal-catalyzed cross-
coupling reactions have become powerful methods for constructing
carbonecarbon bonds. They have shown wide applicability for the
synthesis of pharmaceutically-active compounds, agricultural
chemicals, natural products, and functional materials [1e4]. Cin-
namic acids are abundant compounds with broad structural di-
versity, natural and synthetic sources, and are common in many
drug molecules and active natural products [5e8]. Recently, syn-
thetic chemists have used inexpensive, stable, readily-available,
and environmentally-friendly cinnamic acids (as per extraction by
carbon dioxide) to construct CeC bonds, and various decarbox-
ylative cross-couplings of cinnamic acids have been realized
[9e13]; however, reported reactions require the use of transition
metals and high temperatures to overcome unfavorable thermo-
dynamics [14e17]. Therefore, the development of mild and eco-
friendly decarboxylative coupling reactions of cinnamic acids is
highly desired.
considerable attention, but most of these reactions use costly and
scarce iridium- or ruthenium-based photoredox catalysts because
of their excellent photochemical properties [21e27]. As an alter-
native, copper salts are earth-abundant, inexpensive, and have low
toxicities [28,29]. The development of copper as a photocatalyst
under visible-light irradiation is still in its infancy [30e38]; thus,
the photoinduced copper-catalyzed decarboxylative cross-coupling
of cinnamic acids has rarely been reported (Scheme 1a) [39] (see
Scheme 2).
Herein, we report the first example of the photoinduced copper-
catalyzed dual decarboxylative cross-coupling of a,b-unsaturated
carboxylic acids with redox-active esters (Scheme 1b). The reaction
was tolerant to many synthetically valuable functional groups.
Suitable substrates included primary, secondary, and tertiary car-
boxylic acids derived redox esters. The E isomer was preferred
because of the thermodynamic stability of the product. Our pho-
tocatalytic dual decarboxylative cross-coupling method provides a
route for the modification of complex organic molecules containing
carboxylic acids and requires neither rare metals nor preformed
metal photocatalyst.
Recently, researchers have used mild photoinduced radical
decarboxylative functionalization to create several nontraditional
* Corresponding author. College of Materials and Chemical Engineering, Chuzhou
University, Hui Feng Road 1, Chuzhou, 239000, PR China.
E-mail address: xiaoyulu@mail.ustc.edu.cn (X.-Y. Lu).
https://doi.org/10.1016/j.tet.2021.132259
0040-4020/© 2021 Elsevier Ltd. All rights reserved.
Please cite this article as: X.-Y. Lu, A. Gao, Q.-L. Liu et al., Photoinduced copper-catalyzed dual decarboxylative coupling of a,b-unsaturated
carboxylic acids with redox-active esters, Tetrahedron, https://doi.org/10.1016/j.tet.2021.132259

X.-Y. Lu, A. Gao, Q.-L. Liu et al.
Tetrahedron xxx (xxxx) xxx
substrate scope of the photoinduced copper-catalyzed dual decar-
boxylative reaction (Table 2). Many substituted
a,b-unsaturated
carboxylic acids, coupled with a series of aliphatic carboxylic acid
derived redox-active esters, provided good yields and preferential E
selectivity. Both electron-rich (such as methoxy, phenyl) and
electron-poor (such as trifluoromethyl) cinnamic acids afforded
products in excellent yields. This reaction was tolerant to many
synthetically useful functional groups, including fluorine (3d), es-
ters (3f), tetrahydropyran (3i, 3j), amides (3k), and alkenes (3l).
Beyond the styrene system, heterocycles such as furan (3m), thio-
phene (3n), and pyridine (3o), were also compatible, providing the
corresponding products in good yields. Unprotected phenolic hy-
droxyl (3h) and aryl carboxylic acids (3g) were also compatible
with our method. Acyclic primary carboxylic acid derived redox-
active esters (3n, 3p) also participated in the coupling reaction.
Quaternary carboxylic acid derived redox-active esters were also
suitable, giving the substituted quaternary alkene derivatives in
high E-product stereoselectivity. We also tested some quaternary
carboxylic acid derived redox-active ester substrates, and they all
provided high yields (3q, 3r, 3s, 3t, 3u). To further demonstrate the
compatibility of the copper-catalyzed dual decarboxylative cross-
Scheme 1. Photoinduced copper-catalyzed decarboxylative coupling of
rated carboxylic acids.
a,b-unsatu-
2. Results and discussion
We first selected cinnamic acid (1a) and a cyclohexyl carboxylic
acid derived redox-active NHPI ester (2a) as model reactants. Based
on previous research, we first used Cu(MeCN)4PF6 as catalyst, L1
and Xantphos as ligands, and DMAc as solvent under irradiation by
20 W blue LEDs at room temperature. We obtained the product in
49% yield (entry 1). We then screened a series of solvents, including
DMF, CH3CN, THF, DMSO, and CH2Cl2 (entry 2e6), but only THF
provided a better yield than DMAc (entry 4). We then evaluated a
range of nitrogen ligands, also in THF solvent (entry 7e10). Unfor-
tunately, only the L4 ligand provided 15% yield (entry 7), and almost
no product was obtained using other nitrogen ligands (entry 8e10).
Finally, we obtained the optimal reaction conditions by adjusting
the ratio of the amounts of reactants (entry 11e14). A control
experiment indicated that no reaction occurred in the absence of
Cu(MeCN)4PF6 or blue LEDs (entry 15 and 16).
coupling, we examined several
a,b-unsaturated carboxylic acids
containing other coupling units. Aryl chloride (3v) and aryl bromide
(3w) were well-tolerated, as was aryl tosylate (3x). These experi-
ments demonstrate the broad compatibility and selectivity of the
reaction and provide opportunities for convenient transformations
at the retained coupling units by using other cross-coupling
reactions.
We next demonstrated the photoinduced copper-catalyzed dual
decarboxylative cross-coupling reactions for the late-stage modi-
fication of natural products and drug molecules containing car-
boxylic acids. Treatment of a gemfibrozil derivative afforded
product 4a in 70% yield. Treating dehydrocholic acid derived redox-
active esters containing three base-sensitive ketone groups affor-
ded the desired product 4b in 67% yield. Modification of a myco-
phenolic acid derived redox-active ester produced the
corresponding product 4c in moderate yield and tolerated the hy-
droxyl group. These results extensively demonstrate the broad
applicability of this reaction for modifying complex natural prod-
ucts and drug molecules.
With the optimized conditions in hand, we next investigated the
Table 1
Optimization of the reaction conditions.
To gain insight into the reaction mechanism, we conducted
control experiments. First, when we added 1 eq. of TEMPO (a
common radical scavenger) to the model reaction, we obtained no
desired product (Scheme 3, Eq. 1). Critically, treating (Z)-cinnamic
acid with redox-active esters also afforded the trans-alkene prod-
uct, which indicates that the stereoconvergent reaction proceeded
by a radical process (Scheme 3, Eq. 2). Based on the above results
and previous reports [30,40e43], a possible reaction mechanism
was proposed, as depicted in Scheme 3. Initially, Cuþ1 was excited
to a reducing excited state (Cuþ1)* by visible light irradiation. Next,
a single-electron transfer from (Cuþ1)* to NHP esters generated
Cuþ2 and a radical anion I, which then fragmented, followed by CO2
evolution to produce an alkyl radical (Rꢀ). Radical addition of alkyl
Entry
Ligand
Solvent
Yield%
1a
L1
L1
L1
L1
L1
L1
L4
L3
L2
dtbpy
L1
L1
L1
L1
L1
L1
DMAc
DMF
CH3CN
THF
DMSO
CH2Cl2
THF
49
47
42
63
51
32
15
trace
trace
trace
32
31
26
78
0
0
2a
3a
4a
5a
6a
7a
8a
THF
THF
THF
THF
9a
10a
radical Rꢀ to cinnamic acid provided the
b-radical carboxylate II
11b
intermediate. The photoexcited Cuþ2 then oxidized DABCO to give
DABCOþꢀ. Then, DABCOþꢀ was oxidized, accepting an electron from
b
12
13
dioeane
DMAc
THF
b
14c
15d
16e
b
-radical carboxylate II to complete the redox cycle. Finally,
THF
THF
decarboxylation of III generated the product.
a
3. Conclusion
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol) in 1 mL solvent irradiated by
20 W blue LEDs for 48 h under Ar. 1a (0.4 mmol), 2a (0.2 mmol).
b
1a (0.4 mmol), 2a (0.2 mmol).
1a (0.2 mmol), 2a (0.6 mmol).
No Cu Salt.
Here, we disclose the first photoinduced copper-catalyzed dual
decarboxylative cross-coupling of a,b-unsaturated carboxylic acids
c
d
e
with aliphatic carboxylic acid derived redox-active esters. This re-
No Blue LEDs. The yield was determined by GC using biphenyl as internal
standard (see Table 1).
action enabled C(sp2)eC(sp3) bond formation to access a variety of
2

X.-Y. Lu, A. Gao, Q.-L. Liu et al.
Tetrahedron xxx (xxxx) xxx
Table 2
Scope of the dual decarboxylative couplinga.
a
Reaction conditions: Cu(MeCN)4PF6 (10 mol%), L1 (15 mol%), xantphos (15 mol%), DABCO (50 mol%), acrylic acids (0.2 mmol) and redox active ester (0.6 mmol). E/Z ratio
was determined by 1H NMR analysis.
synthetically valuable alkene derivatives. A series of
a
,b
-unsatu-
%), DABCO (50 mol%), a,b-unsaturated carboxylic acids (0.2 mmol)
rated carboxylic acids and redox-active esters derivatives was
tolerant. The reaction was tolerant to many critical functional
groups. Primary, secondary, and tertiary carboxylic acids derived
redox-active esters were all suitable substrates. The E isomer was
preferred due to the thermodynamic stability of the product. This
also provides a route for modifying complex natural products and
drug molecules containing carboxylic acids.
and redox active ester (0.6 mmol) were added to a schlenk tube
equipped with a stir bar. The vessel was evacuated and filled with
argon (three cycles). Anhydrous THF (1 mL) were added by syringe.
The resulting reaction mixture was stirred under the irradiation of a
20 W blue LEDs (465 nm) at room temperature for 48 h under Ar.
The resulting solution was purified by column chromatography.
4.2. (E)-(2-cyclohexylvinyl)benzene (3a)
4. Experimental section
White liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.35 (d,
4.1. General procedure
J ¼ 7.4 Hz, 2H), 7.29 (t, J ¼ 7.6 Hz, 2H), 7.18 (t, J ¼ 7.2 Hz, 1H), 6.35 (d,
J ¼ 16.0 Hz, 1H), 6.18 (dd, J ¼ 16.0, 6.9 Hz, 1H), 2.18e2.09 (m, 1H),
1.85e1.73 (m, 4H), 1.72e1.64 (m, 1H), 1.37e1.14 (m, 5H). 13C NMR
In air, Cu(MeCN)4PF6 (10 mol%), L1 (15 mol%), xantphos (15 mol
3

X.-Y. Lu, A. Gao, Q.-L. Liu et al.
Tetrahedron xxx (xxxx) xxx
6H), 3.83 (s, 3H), 2.16e2.05 (m, 1H), 1.86e1.66 (m, 5H), 1.37e1.12
(m, 5H). 13C NMR (101 MHz, Chloroform-d)
d 153.22, 137.09, 136.40,
133.80,127.09,102.84, 60.89, 56.00, 41.08, 32.95, 26.12, 26.01. HRMS
(ESI) calcd for C17H25O3 (M þ Hþ): 277.1798; found: 277.1796.
4.5. (E)-1-(2-cyclohexylvinyl)-3-fluorobenzene (3d)
White liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.24e7.20 (m,
1H), 7.11e7.01 (m, 2H), 6.90e6.82 (m, 1H), 6.30 (d, J ¼ 16.0 Hz, 1H),
6.18 (dd, J ¼ 16.0, 6.8 Hz, 1H), 2.12 (dtt, J ¼ 13.7, 6.7, 3.3 Hz, 1H),
1.85e1.73 (m, 4H), 1.71e1.65 (m, 1H), 1.35e1.13 (m, 5H). 19F NMR
(376 MHz, Chloroform-d)
form-d)
129.79 (d, J ¼ 8.5 Hz), 126.24 (d, J ¼ 2.5 Hz), 121.81 (d, J ¼ 2.6 Hz),
113.44 (d, J ¼ 21.4 Hz), 112.29 (d, J ¼ 21.6 Hz), 41.08, 32.79, 26.10,
25.97. HRMS (ESI) calcd for C14H18F (M þ Hþ): 205.1387; found:
205.1390.
d
ꢁ113.98. 13C NMR (101 MHz, Chloro-
d
163.11 (d, J ¼ 244.7 Hz), 140.46 (d, J ¼ 7.7 Hz), 138.23,
Scheme 2. Modification of natural products and drug molecules.
4.6. (E)-1-(2-cyclohexylvinyl)-3-(trifluoromethyl)benzene (3e)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d
7.59e7.54 (m, 1H), 7.46e7.36 (m, 2H), 7.24e7.19 (m, 1H), 6.65 (d,
J ¼ 16.0 Hz, 1H), 6.53 (dd, J ¼ 16.0, 6.8 Hz, 1H), 2.52e2.43 (m, 1H),
2.18e2.08 (m, 4H), 2.06e1.99 (m, 1H), 1.69e1.49 (m, 5H). 19F NMR
(376 MHz, Chloroform-d)
form-d)
126.06, 125.59 (q, J ¼ 3.2 Hz), 123.26 (q, J ¼ 3.8 Hz), 122.56 (q,
J ¼ 3.8 Hz), 41.15, 32.77, 26.09, 25.96. HRMS (ESI) calcd for C15H18F3
(M þ Hþ): 255.1355; found: 255.1357.
d
ꢁ113.98. 13C NMR (101 MHz, Chloro-
d
138.85, 129.80 (q, J ¼ 237.7 Hz), 129.16, 129.15, 128.86,
4.7. (E)-4-(2-cyclohexylvinyl)phenyl acetate (3f)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d
7.42e7.30 (m, 2H), 7.08e6.93 (m, 2H), 6.32 (d, J ¼ 16.0 Hz, 1H),
6.12 (dd, J ¼ 16.0, 6.9 Hz, 1H), 2.29 (s, 3H), 2.12 (dt, J ¼ 7.5, 3.9 Hz,
1H), 1.87e1.64 (m, 5H), 1.39e1.06 (m, 5H). 13C NMR (101 MHz,
Chloroform-d)
d 169.73, 149.52, 137.30, 136.06, 126.95, 126.39,
121.65, 41.27, 33.05, 26.29, 26.16, 21.29. HRMS (ESI) calcd for
C
16H21O2 (M þ Hþ): 245.1536; found: 245.1539.
4.8. (E)-2-(2-cyclohexylvinyl)benzoic acid (3g)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 8.00 (dd,
Scheme 3. Mechanism experiments and proposed catalytic cycle.
J ¼ 7.9,1.1 Hz,1H), 7.58 (d, J ¼ 7.9 Hz,1H), 7.49 (td, J ¼ 7.7,1.2 Hz,1H),
7.32e7.27 (m, 1H), 7.23 (d, J ¼ 15.9 Hz, 1H), 6.11 (dd, J ¼ 15.9, 6.9 Hz,
1H), 2.26e2.17 (m, 1H), 1.89e1.67 (m, 5H), 1.38e1.18 (m, 5H). 13C
(101 MHz, Chloroform-d)
d 138.02, 136.84, 128.43, 127.16, 126.70,
NMR (101 MHz, Chloroform-d)
d 172.88, 140.96, 140.21, 132.95,
125.90, 41.14, 32.93, 26.15, 26.03. HRMS (ESI) calcd for C14H19
131.37, 127.54, 127.01, 126.65, 126.30, 41.40, 32.96, 26.31, 26.14.
(M þ Hþ): 187.1481; found: 187.1486.
HRMS (ESI) calcd for C15H19O2 (M þ Hþ): 231.1380; found: 231.1385.
4.3. (E)-4-(2-cyclohexylvinyl)-1,2-dimethoxybenzene (3b)
4.9. (E)-4-(2-cyclohexylvinyl)phenol (3h)
White solid. 1H NMR (400 MHz, Chloroform-d)
d 6.91 (d,
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.23 (d,
J ¼ 1.8 Hz, 1H), 6.87 (dd, J ¼ 8.2, 1.8 Hz, 1H), 6.79 (d, J ¼ 8.2 Hz, 1H),
6.28 (d, J ¼ 15.9 Hz, 1H), 6.04 (dd, J ¼ 15.9, 7.0 Hz, 1H), 3.90 (s, 3H),
3.86 (s, 3H), 2.16e2.05 (m, 1H), 1.85e1.72 (m, 4H), 1.68 (d,
J ¼ 12.6 Hz, 1H), 1.35e1.25 (m, 2H), 1.24e1.13 (m, 3H). 13C NMR
J ¼ 8.6 Hz, 2H), 6.77 (d, J ¼ 8.6 Hz, 2H), 6.28 (d, J ¼ 16.0 Hz, 1H), 6.03
(dd, J ¼ 16.0, 7.0 Hz, 1H), 5.08 (s, 1H), 2.17e1.99 (m, 1H), 1.88e1.72
(m, 4H), 1.73e1.61 (m, 1H), 1.39e1.09 (m, 5H). 13C NMR (101 MHz,
Chloroform-d)
d 154.37, 134.81, 131.02, 127.16, 126.41, 115.33, 41.06,
33.03, 26.14, 26.04. HRMS (ESI) calcd for C14H19O (M þ Hþ):
(101 MHz, Chloroform-d)
d 148.88, 148.07, 134.94, 131.11, 126.76,
118.77, 111.05, 108.32, 55.84, 55.70, 41.06, 33.02, 26.12, 26.02. HRMS
203.1430; found: 203.1436.
(ESI) calcd for C16H23O2 (M þ Hþ): 247.1693; found: 247.1692.
4.10. (E)-4-styryltetrahydro-2H-pyran (3i)
4.4. (E)-5-(2-cyclohexylvinyl)-1,2,3-trimethoxybenzene (3c)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.36 (dd,
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
2H), 6.27 (d, J ¼ 15.9 Hz, 1H), 6.08 (dd, J ¼ 15.9, 6.9 Hz, 1H), 3.87 (s,
d
6.57 (s,
J ¼ 8.3, 1.2 Hz, 2H), 7.30 (td, J ¼ 6.9, 6.5, 1.8 Hz, 2H), 7.24e7.18 (m,
1H), 6.39 (d, J ¼ 16.0 Hz, 1H), 6.16 (dd, J ¼ 16.0, 6.8 Hz, 1H),
4

X.-Y. Lu, A. Gao, Q.-L. Liu et al.
Tetrahedron xxx (xxxx) xxx
4.05e3.97 (m, 2H), 3.47 (td, J ¼ 11.7, 2.3 Hz, 2H), 2.44e2.34 (m, 1H),
1.75e1.66 (m, 2H), 1.63e1.54 (m, 2H). 13C NMR (101 MHz, Chloro-
4.16. (E)-3-(2-cyclohexylvinyl)pyridine (3o)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 8.55 (s,
form-d)
d
137.64, 134.72, 128.66, 128.37, 127.22, 126.15, 67.86, 38.50,
32.74. HRMS (ESI) calcd for C13H17O (M þ Hþ): 189.1274; found:
1H), 8.41 (d, J ¼ 4.2 Hz, 1H), 7.68 (d, J ¼ 7.9 Hz, 1H), 7.23 (dd, J ¼ 7.8,
189.1277.
4.9 Hz, 1H), 6.43e6.15 (m, 2H), 2.15 (t, J ¼ 14.4, 6.5, 3.3 Hz, 1H),
1.85e1.74 (m, 4H), 1.69 (d, J ¼ 12.7 Hz, 1H), 1.38e1.10 (m, 5H). 13
C
NMR (101 MHz, Chloroform-d)
d 147.71, 147.49, 139.69, 133.94,
4.11. (E)-4-(2-([1,10-biphenyl]-4-yl)vinyl)tetrahydro-2H-pyran (3j)
132.93, 123.71, 123.63, 41.39, 32.84, 26.21, 26.08. HRMS (ESI) calcd
for C13H18N (M þ Hþ): 188.1434; found: 188.1436.
Pale-yellow solid. 1H NMR (400 MHz, Chloroform-d)
d 7.64e7.54
(m, 4H), 7.48e7.42 (m, 4H), 7.39e7.31 (m, 1H), 6.44 (d, J ¼ 15.9 Hz,
1H), 6.22 (dd, J ¼ 16.0, 6.8 Hz, 1H), 4.08e3.99 (m, 2H), 3.49 (td,
J ¼ 11.7, 2.2 Hz, 2H), 2.47e2.37 (m, 1H),1.78e1.70 (m, 2H),1.66e1.55
4.17. (E)-pent-1-ene-1,5-diyldibenzene (3p)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.36 (dd,
J ¼ 8.2, 1.2 Hz, 2H), 7.33e7.27 (m, 4H), 7.23e7.18 (m, 4H), 6.41 (d,
J ¼ 15.8 Hz, 1H), 6.25 (dt, J ¼ 15.8, 6.8 Hz, 1H), 2.72e2.65 (m, 2H),
2.31e2.23 (m, 2H), 1.87e1.78 (m, 2H). 13C NMR (101 MHz, Chloro-
(m, 2H). 13C NMR (101 MHz, Chloroform-d)
d 140.71, 139.79, 136.53,
134.72, 128.72, 127.76, 127.17, 126.84, 126.40, 67.69, 38.39, 32.58.
HRMS (ESI) calcd for C19H21O (M þ Hþ): 265.1587; found: 265.1589.
form-d)
d 142.50, 137.93, 130.69, 130.34, 128.62, 128.44, 127.00,
126.06, 125.86, 35.53, 32.67, 31.16. HRMS (ESI) calcd for C17H19
4.12. Tert-butyl (E)-3-styrylpiperidine-1-carboxylate (3k)
(M þ Hþ): 223.1481; found: 223.1480.
Pale-yellow solid. 1H NMR (400 MHz, Chloroform-d)
d 7.37e7.28
4.18. (E)-1-(3,3-dimethylbut-1-en-1-yl)-4-methoxybenzene (3q)
(m, 4H), 7.22 (d, J ¼ 7.1 Hz, 1H), 6.45 (d, J ¼ 16.0 Hz, 1H), 6.09 (dd,
J ¼ 16.1, 7.0 Hz, 1H), 3.98 (d, J ¼ 13.2 Hz, 2H), 2.83e2.74 (m, 1H), 2.68
(s, 1H), 2.37e2.27 (m, 1H), 1.96e1.90 (m, 1H), 1.71 (dt, J ¼ 13.1,
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
3.6 Hz, 1H), 1.57e1.51 (m, 1H), 1.47 (s, 9H), 1.42e1.32 (m, 1H). 13
C
d
7.33e7.28 (m, 2H), 6.88e6.81 (m, 2H), 6.26 (d, J ¼ 16.2 Hz, 1H),
6.13 (d, J ¼ 16.2 Hz, 1H), 3.81 (s, 3H), 1.12 (s, 9H). 13C NMR (101 MHz,
NMR (101 MHz, Chloroform-d)
d 154.99, 137.49, 131.92, 129.90,
Chloroform-d) d 158.71, 139.95, 130.96, 127.18, 123.97, 114.03, 55.42,
128.65, 127.32, 126.16, 79.53, 49.21, 44.30, 39.49, 31.01, 28.60, 24.86.
HRMS (ESI) calcd for C18H26NO2 (M þ Hþ): 288.1958; found:
288.1963.
33.38, 29.83. HRMS (ESI) calcd for C13H19O (M þ Hþ): 191.1430;
found: 191.1432.
4.19. (E)-1-(3,3-dimethylpent-1-en-1-yl)-4-methoxybenzene (3r)
4.13. (E)-(2-(cyclohex-3-en-1-yl)vinyl)benzene (3l)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.33 (d,
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.38 (d,
J ¼ 8.7 Hz, 2H), 6.87 (d, J ¼ 8.8 Hz, 2H), 6.26 (d, J ¼ 16.2 Hz, 1H), 6.06
J ¼ 7.4 Hz, 2H), 7.32 (t, J ¼ 7.6 Hz, 2H), 7.21 (t, J ¼ 7.3 Hz, 1H), 6.43 (d,
J ¼ 16.0 Hz,1H), 6.26 (dd, J ¼ 15.9, 7.2 Hz,1H), 5.74 (d, J ¼ 1.9 Hz, 2H),
2.50e2.42 (m, 1H), 2.28e2.19 (m, 1H), 2.15 (dt, J ¼ 6.2, 3.7 Hz, 2H),
2.04e1.94 (m, 1H), 1.91e1.83 (m, 1H), 1.56e1.49 (m, 1H). 13C NMR
(d, J ¼ 16.2 Hz, 1H), 3.82 (s, 3H), 1.44 (q, J ¼ 7.5 Hz, 2H), 1.10 (s, 6H),
0.87 (t, J ¼ 7.5 Hz, 3H). 13C NMR (101 MHz, Chloroform-d)
d 158.70,
138.64, 131.06, 127.14, 125.28, 114.00, 55.38, 36.39, 35.70, 26.93,
9.17. HRMS (ESI) calcd for C14H21O (M þ Hþ): 205.1587; found:
205.1586.
(101 MHz, Chloroform-d)
d 137.96, 135.85, 128.61, 128.09, 127.12,
126.99, 126.16, 126.12, 37.25, 31.52, 28.87, 24.97. HRMS (ESI) calcd
for C14H17 (M þ Hþ): 185.1325; found: 185.1328.
4.20. (3r,5r,7r)-1-((E)-4-methoxystyryl)adamantane (3s)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.30 (d,
4.14. Tert-butyl (E)-3-(2-(furan-2-yl)vinyl)piperidine-1-
carboxylate (3m)
J ¼ 8.7 Hz, 2H), 6.85 (d, J ¼ 8.7 Hz, 2H), 6.20 (d, J ¼ 16.2 Hz, 1H), 5.98
(d, J ¼ 16.2 Hz, 1H), 3.81 (s, 3H), 2.03 (s, 3H), 1.82e1.64 (m, 12H). 13
C
NMR (101 MHz, Chloroform-d)
d 158.69, 140.25, 131.11, 127.14,
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
123.90, 114.01, 55.42, 42.47, 37.04, 35.16, 28.64. HRMS (ESI) calcd for
d
7.34e7.29 (m, 1H), 6.34 (dd, J ¼ 3.2,1.9 Hz,1H), 6.25 (d, J ¼ 16.2 Hz,
C
19H25O (M þ Hþ): 269.1900; found: 269.1903.
1H), 6.16 (d, J ¼ 3.1 Hz, 1H), 6.03 (dd, J ¼ 16.1, 7.0 Hz, 1H), 3.95 (d,
J ¼ 12.7 Hz, 2H), 2.80e2.72 (m, 1H), 2.67 (s, 1H), 2.27 (dt, J ¼ 6.8,
3.5 Hz, 1H), 1.90 (dd, J ¼ 9.2, 3.7 Hz, 1H), 1.75e1.66 (m, 2H), 1.46 (s,
9H), 1.32 (dd, J ¼ 19.0, 7.2 Hz, 1H). 13C NMR (101 MHz, Chloroform-
4.21. (E)-1-methoxy-4-(2-(1-methylcyclohexyl)vinyl)benzene (3t)
Pale-yellow solid. 1H NMR (400 MHz, Chloroform-d)
d
7.34e7.28
d)
d 154.97, 152.99, 141.65, 130.72, 118.53, 111.32, 107.05, 79.56,
(m, 2H), 6.91e6.80 (m, 2H), 6.28 (d, J ¼ 16.4 Hz, 1H), 6.09 (d,
J ¼ 16.4 Hz, 1H), 3.81 (s, 3H), 1.65e1.57 (m, 2H), 1.56e1.49 (m, 4H),
1.46e1.34 (m, 4H), 1.08 (s, 3H). 13C NMR (101 MHz, Chloroform-d)
49.17, 44.12, 39.22, 30.88, 28.59, 24.68. HRMS (ESI) calcd for
C
16H24NO3 (M þ Hþ): 278.1751; found: 278.1752.
d
158.69, 139.10, 131.19, 127.07, 125.35, 114.01, 55.41, 38.18, 36.16,
4.15. (E)-2-(5-phenylpent-1-en-1-yl)thiophene (3n)
27.77, 26.48, 22.59. HRMS (ESI) calcd for C16H23O (M þ Hþ):
231.1743; found: 231.1748.
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d
7.34e7.31 (m, 2H), 7.22 (dt, J ¼ 7.7, 1.0 Hz, 3H), 7.11 (dt, J ¼ 5.0,
4.22. Tert-butyl (E)-4-(4-methoxystyryl)-4-methylpiperidine-1-
carboxylate (3u)
0.9 Hz, 1H), 6.96 (dd, J ¼ 5.1, 3.5 Hz, 1H), 6.90e6.88 (m, 1H),
6.58e6.51 (m, 1H), 6.15e6.05 (m, 1H), 2.71e2.66 (m, 2H), 2.28e2.21
(m, 2H), 1.87e1.78 (m, 2H). 13C NMR (101 MHz, Chloroform-d)
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d
143.16, 142.38, 130.66, 128.59, 128.44, 127.34, 125.88, 124.39,
d
7.34e7.22 (m, 2H), 6.85 (d, J ¼ 8.7 Hz, 2H), 6.29 (d, J ¼ 16.4 Hz,1H),
123.60, 123.26, 35.47, 32.44, 30.99. HRMS (ESI) calcd for C15H17
S
6.02 (d, J ¼ 16.4 Hz, 1H), 3.80 (s, 3H), 3.58e3.44 (m, 2H), 3.40e3.30
(M þ Hþ): 229.1045; found: 229.1048.
(m, 2H), 1.70e1.62 (m, 2H), 1.49e1.39 (m, 11H), 1.12 (s, 3H). 13C NMR
5

X.-Y. Lu, A. Gao, Q.-L. Liu et al.
Tetrahedron xxx (xxxx) xxx
(101 MHz, Chloroform-d)
d
158.96, 155.09, 136.50, 130.47, 127.18,
4.28. 7-Hydroxy-5-methoxy-6-((2E,6E)-7-(4-methoxyphenyl)-3-
126.74, 114.06, 79.36, 55.41, 40.68, 37.09, 34.78, 28.58, 27.05. HRMS
methylhepta-2,6-dien-1-yl)-4-methylisobenzofuran-1(3H)-one (4c)
(ESI) calcd for C20H30NO3 (M þ Hþ): 332.2220; found: 332.2225.
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.67 (d,
4.23. (E)-4-(4-chlorostyryl)tetrahydro-2H-pyran (3v)
J ¼ 2.0 Hz, 1H), 7.18 (dd, J ¼ 8.5, 6.4 Hz, 2H), 6.78 (d, J ¼ 8.7 Hz, 2H),
6.32e6.19 (m, 1H), 6.04e5.92 (m, 1H), 5.26e5.14 (m, 3H), 3.79 (s,
3H), 3.73 (s, 3H), 3.39 (d, J ¼ 6.9 Hz, 2H), 2.44e2.23 (m, 2H), 2.13 (d,
J ¼ 12.2 Hz, 5H), 1.81 (s, 3H). 13C NMR (101 MHz, Chloroform-d)
Pale-yellow solid. 1H NMR (400 MHz, Chloroform-d)
d 7.31e7.20
(m, 4H), 6.33 (dd, J ¼ 16.0, 1.2 Hz, 1H), 6.13 (dd, J ¼ 16.0, 6.8 Hz, 1H),
4.03e3.95 (m, 2H), 3.46 (td, J ¼ 11.7, 2.3 Hz, 2H), 2.42e2.29 (m, 1H),
1.74e1.66 (m, 2H), 1.62e1.48 (m, 2H). 13C NMR (101 MHz,
d
173.09, 163.70, 158.63, 153.73, 143.98, 135.28, 130.76, 129.99,
129.29, 128.45, 126.99, 122.51, 116.76, 113.88, 113.62, 106.42, 70.14,
61.09, 55.38, 39.60, 31.49, 22.73, 16.31, 11.65. HRMS (ESI) calcd for
Chloroform-d) d 136.14, 135.39, 132.73, 128.76, 127.36, 127.22, 67.80,
38.47, 32.63. HRMS (ESI) calcd for C13H16ClO (M þ Hþ): 223.0884;
C
25H29O5 (M þ Hþ): 409.2010; found: 409.2013.
found: 223.0887.
Declaration of competing interest
4.24. (E)-4-(3-bromostyryl)tetrahydro-2H-pyran (3w)
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.
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.50 (t,
J ¼ 1.8 Hz, 1H), 7.35e7.30 (m, 1H), 7.26e7.23 (m, 1H), 7.16 (t,
J ¼ 7.8 Hz,1H), 6.31 (d, J ¼ 16.1 Hz,1H), 6.16 (dd, J ¼ 16.0, 6.7 Hz,1H),
4.05e3.97 (m, 2H), 3.46 (td, J ¼ 11.7, 2.3 Hz, 2H), 2.38 (dtd, J ¼ 10.6,
6.7, 2.9 Hz, 1H), 1.72e1.66 (m, 2H), 1.61e1.52 (m, 2H). 13C NMR
Acknowledgement
(101 MHz, Chloroform-d)
d 139.84, 136.31, 130.14, 130.04, 128.99,
We are grateful for the support from National Natural Science
Foundation of China (22001029), Natural Science Foundation of
Anhui Province (2008085QB92), and University Natural Science
Research Key Project of Anhui Province (KJ2020A0708).
127.08, 124.89, 122.86, 67.78, 38.47, 32.58. HRMS (ESI) calcd for
C
13H16BrO (M þ Hþ): 267.0379; found: 267.0381.
4.25. (E)-4-(2-cyclohexylvinyl)phenyl 4-methylbenzenesulfonate
(3x)
Appendix A. Supplementary data
Pale-yellow liquid. 1H NMR (400 MHz, Chloroform-d)
d 7.69 (d,
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132259.
J ¼ 8.3 Hz, 2H), 7.30 (d, J ¼ 8.1 Hz, 2H), 7.24e7.20 (m, 2H), 6.91e6.85
(m, 2H), 6.27 (d, J ¼ 16.0 Hz, 1H), 6.11 (dd, J ¼ 16.0, 6.9 Hz, 1H), 2.44
(s, 3H), 2.10 (ddp, J ¼ 10.4, 6.8, 3.3 Hz, 1H), 1.79e1.64 (m, 5H),
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d 148.37,
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d 7.29e7.19
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7