Ligand-Promoted Iridium-Catalyzed Transfer Hydrogenation of Terminal Alkynes with Ethanol and Its Application.

A ligand-promoted iridium-catalyzed transfer hydrogenation of terminal alkynes with ethanol and its application has been developed. Highly chemical selectivity control is achieved based on ligand regulation. 1,2-Bis(diphenylphosphino)ethane was found to be critical for the transfer hydrogenation of alkynes. The general applicability of this procedure is highlighted by the synthesis of 30 terminal alkenes with a good yield. In addition, we conducted drug effect studies of phenelzine using zebrafish as the vertebrate model. Phenelzine shows a significant effect on promoting vascular proliferation and inhibiting nerve growth. The results of these studies have an important reference value for promoting drug research in cerebrovascular diseases, epilepsy, mania, and psychosis.

Introduction

Transfer hydrogenation of unsaturated compounds has attracted much attention due to its widespread use in the synthesis of synthetic intermediates, natural products, fragrances, pharmaceuticals, and agrochemical products.[1] To date, several catalytic systems applicable to alkyne transfer hydrogenation,[2] represented by Lindlar reduction,[3] have been reported. Among all the transfer hydrogenation, the metal-catalyzed transfer semireduction is attracting much attention because of its critical advantage over the conventional semihydrogenation method,[4] which suffers from problems with overreduction as well as safety concerns.[5] While effective, these methods often employ flammable, explosive, corrosive, or expensive hydrogenation reagents (Scheme ), in short do not conform to the current standards of sustainable chemistry. Therefore, the development of methods that use cheap, safe, and convenient reagents is highly desirable. Undoubtedly, ethanol (EtOH) is the best choice for a transfer hydrogenation agent, and the development of methods for synthesizing alkenes with EtOH as the hydrogen source is desirable. Very recently, Grützmacher,[6] Swamy,[7] and Huang[8] reported an elegant work for transfer hydrogenation with EtOH. Unfortunately, the semihydrogenation of terminal alkynes cannot be achieved by all three systems. Subsequently, our research group developed a method for ligand-controlled iridium-catalyzed semihydrogenation of alkynes with EtOH: highly stereoselective synthesis of E- and Z-alkenes.[9] However, the reaction temperature of this method is harsh, and there is no systematic investigation of the terminal acetylene substrate. Herein, we report an example of ligand-promoted iridium-catalyzed transfer hydrogenation of terminal alkynes with EtOH and its application (Scheme ).

Scheme 1

Different Strategies for Transfer Hydrogenation of Terminal Alkynes

Results and Discussion

Based on our previous work, we commenced our studies by treating phenyl acetylene and EtOH with 2.5 mol % [Ir(cod)Cl]2 as a catalyst, using 1,2-bis(diphenylphosphino)ethane (DPPE) as a ligand. Initially, we screened various reaction temperatures, and 70 °C was found to be the best choice, furnishing the corresponding styrene in 91% yield (Table , entry 6). If the temperature drops to 50 °C, only 79% yield of styrene was obtained. Notably, the yield was significantly reduced when the temperature increased up to 120 °C (Table , entry 1). These results showed that too high or too low a temperature was unfavorable to the reaction progress. To investigate whether other alcohols can also give better yields, different alcohols such as isopropanol, methanol, cyclopropylmethanol, benzyl alcohol, pinacol, and EG were tested (Table , entries 9–14), but the results are not as good as EtOH. To further increase the conversion rate to styrene, we replaced DPPE with large sterically hindering ligands or small sterically hindering ligands (Table , entries 15–19). Regrettably, the expected results were not obtained. These results showed that too large or too small steric hindrance were not conducive to the reaction progressing. Therefore, we performed subsequent reactions of terminal alkynes with EtOH in the presence of [Ir(COD)Cl]2/DPPE at 70 °C for 24 h.

Table 1

Effects of Solvent, Temperature, and Liganda

entry	ligand	ROH	T (°C)	yield 2a (%)b	yield 3a (%)b
1	DPPE	EtOH	120	0	100
2	DPPE	EtOH	110	58	42
3	DPPE	EtOH	100	60	15
4	DPPE	EtOH	90	65	trace
5	DPPE	EtOH	80	72	0
6	DPPE	EtOH	70	91	0
7	DPPE	EtOH	60	83	0
8	DPPE	EtOH	50	79	0
9	DPPE	MeOH	70	76	0
10	DPPE	iPrOH	70	73	0
11	DPPE	CPMO	70	50	0
12	DPPE	PhCH2OH	70	trace	0
13	DPPE	pinacol	70	66	0
14c	DPPE	EG	70	72	0
15	Ph3P	EtOH	70	56	0
16d	DPPBde	EtOH	70	trace	0
17e	DIPAMP	EtOH	70	27	0
18f	BINAP	EtOH	70	9	0
19g	DPPE + COD	EtOH	70	56	0
20	none	EtOH	70	0	0
21	DPPE	none	70	0	0
22h	DPPE	EtOH	70	0	0

Reaction conditions: phenylacetylene (0.2 mmol), EtOH (0.4 mmol), [Ir(cod)Cl]2 (10 μmol), ligand (0.04 mmol), THF (1.5 mL), at 70 °C under N2 for 24 h.

Yields were determined by GC analysis.

EG = 2-diphenylphosphinobenzaldehyde.

DPPBde = 2-diphenylphosphinobenzaldehyde.

DIPAMP = ethylenebis(2-methoxyphenylphenylphosphine).

BINAP = 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene.

COD = 1,5-cyclooctadiene.

[Ir(cod)Cl]2 was not added.

With the optimized reaction conditions in hand, a series of arylacetylenes were investigated for extending the substrate scope (Table ). This ligand-promoted iridium-catalyzed transfer hydrogenation of terminal alkynes with EtOH displayed good functional group tolerance. Arylacetylene with electron-neutral or electron-donating groups on the aryl rings, such as alkyl, phenyl, and methoxyl, all gave the corresponding arylethylenes in good yields. Aryls containing an electron-withdrawing group such as fluoro, chloro, bromo, trifluoromethyl, cyano, and nitro were also tolerated and afforded the corresponding arylethylenes (2e–2m, 2q, 2r, 2t, 2v, and 2w) in moderate to good yields. Moreover, the reaction of arylacetylene containing two trifluoromethyl substituents at the meta positions of the aromatic rings also gave the corresponding arylethylene product 2z in good yields. To our delight, N-containing heteroaryl and naphthyl with higher steric hindrance also show good compatibility. Notably, the retention of the F, Cl, and Br atoms in the structures of the products should make the products considerably useful in organic transformations. Unfortunately, amino- and amide-substituted alkynes are not suitable for this reaction.

Table 2

Ligand-Promoted Iridium-Catalyzed Transfer Hydrogenation of Activated Terminal Alkynesa

Reaction conditions: substrate 1 (0.2 mmol), EtOH (0.4 mmol), [Ir(cod)Cl]2 (10 μmol), DPPE (0.04 mmol), THF (1.5 mL), at 70 °C under N2 for 20 h.

30 h.

48 h.

Gram-scale synthesis.

To explore the ability of the developed catalytic method to deliver alkylethylenes, a further transfer hydrogenation of alkylacetylenes was examined. The substrate scope was surveyed to investigate the versatility of this iridium-catalyzed transfer hydrogenation of alkylacetylenes, with use of a combination of DPPE as the ligand. The alkylethylene products were obtained in moderate to good yields for the tested substrates. The results, which were summarized in Table , showed that unactivated alkylacetylenes also gave the corresponding alkylethylenes. This shows that the method is applicable not only to activated arylacetylenes, but also to nonactivated alkylacetylenes. Notably, it is necessary to extend the reaction time and increase the temperature to achieve better conversion of the substrate because of the low activity of the nonactivated terminal alkyne.

Table 3

Ligand-Promoted Iridium-Catalyzed Transfer Hydrogenation of Unactivated Terminal Alkynesa

Reaction conditions: substrate 1 (0.2 mmol), EtOH (0.4 mmol), [Ir(cod)Cl]2 (10 μmol), DPPE (0.04 mmol), THF (1.5 mL), at 100 °C under N2 for 20 h.

The synthetic utility of the current method was tested by performing a gram-scale ligand-promoted iridium-catalyzed transfer hydrogenation of terminal alkynes with EtOH under the optimized conditions. Target compound styrene 2u was obtained in 72% yield. Phenelzine is a nonselective and irreversible monoamine oxidase inhibitor of the hydrazine class which is used as an antidepressant and anxiolytic,[10] and it can be conveniently synthesized from styrene (Scheme a). So can it be used for anticancer drugs? Based on this assumption, we conducted molecular docking studies of Ras homologue gene family, member A (RhoA) and phenelzine. RhoA is a small GTPase protein in the Rho family. Given that its overexpression is found in many malignancies, RhoA activity has been linked within several cancer applications because of its significant involvement in cancer signaling cascades.[11] The studies were performed to help visualize possible interactions between RhoA and phenelzine. The results showed that phenelzine may have cation–anion electrostatic interactions with Lys 1006. Based on this docking result, phenelzine is highly likely to be a potent inhibitor of RhoA. The results of the docked poses of RhoA and phenelzine are shown in Scheme b. To further explore phenelzine’s role in blood vessel growth, we conducted drug effect studies of phenelzine using zebrafish as a vertebrate model. The test results showed treatment of zebrafish embryos with 0.01–1 μg/mL phenelzine resulted in potent angiogenic defects (Scheme c). The results of this study are similar to our previous work,[12] and it will be of great significance for promoting drug research in cardiovascular and cerebrovascular diseases. Meanwhile, we examined the activity of phenelzine in nerve growth using zebrafish as a vertebrate model. The test results showed treatment of zebrafish embryos with 0.01–1 μg/mL phenelzine resulted in significant neuro suppressive effects (Scheme d). The results of this study will be of great significance in research on drugs for treating epilepsy, mania, and psychosis.

Scheme 2

Strategic Application

Molecular docking studies, the drug effect of phenelzine treatment on vascular in the trunk of Tg(kdrl:EGFP) zebrafish embryos at 48 hpf and the drug effect of phenelzine treatment on the central nervous system in the trunk of Tg(hb9:gfp) zebrafish embryos at 50 hpf. (A–D) control group and 1, 0.1, and 0.01 μg/mL 3n treated groups. Scale bar, 75 μm.

To gain a better understanding the role of ligand, reductant, and iridium in the transfer hydrogenation of terminal alkynes, some additional experiments were conducted. First, control experiments showed that the absence of EtOH, ligand, or [Ir(cod)Cl]2, shut down the reaction (Table , entries 20–22), implying that each of the components was essential to this reaction. Based on this result and our previous work, we proposed the following catalytic cycle (Scheme ). Ir(I) first underwent ligand coordination with the metal center to generate an active catalytic species A, leading to subsequent oxidative addition to provide the Ir–H species. The coordination of alkyne to Ir–H species followed by the insertion of the alkyne into the Ir–H bond would lead to the formation of alkenyl iridium complex C. Subsequent β-H elimination would afford intermediate D. Then, intermediate D underwent reductive elimination to obtain aryl ethylene while regenerating the catalytic species A.

Scheme 3

Proposed Mechanisms

Conclusions

In conclusion, we have successfully developed a highly efficient ligand-promoted iridium-catalyzed transfer hydrogenation of terminal alkynes using EtOH as transfer hydrogenation agents. The new method is compatible with multiple functional groups, especially nonactivated alkyl ethylenes. Moreover, we performed molecular docking experiments with phenelzine which indicated that this compound might be an inhibitor of Rho A. The results of this study have an important reference value for anticancer drugs such as prostate cancer and gastric cancer. The value of our approach for practical applications was demonstrated by studying the effects of treatment with phenelzine using zebrafish as the vertebrate model. The results of the study show that it can cause potent angiogenesis defects and neuro-suppressive effects. This will be of great significance for promoting drug research in cerebrovascular diseases, epilepsy, mania, and psychosis. Further investigation of animal experiments, cheaper metals and transfer hydrogenation with water are under way in our laboratory.

Experimental Section

General Information

Unless stated otherwise, all reactions were conducted in pressure tubes under N2. All solvents were received from commercial sources without further purification. Commercially available reagents were used as received. Noncommercially available substrates were synthesized following reported protocols. Thin-layer chromatography was visualized using a combination of UV and potassium permanganate staining techniques. Silica gel (particle size 40–63 μm) was used for flash column chromatography. NMR spectra were recorded on a Bruker AV 400 spectrometer at 400 MHz (1H NMR), 100 MHz (13C NMR). Proton and carbon chemical shifts are reported relative to the solvent used as an internal reference. High-resolution mass spectra were recorded on an Ion Spec FT-ICR mass spectrometer with an ESI resource. The results of molecular docking experiments were completed using a Molecular Operating Environment (MOE).

Typical Procedure for Synthesis of Terminal Ethylene

To a 15 mL pressure tube were added arylacetylene 1 (0.20 mmol), [Ir(cod)Cl]2 (5 mmol, 3.6 mg), and DPPE (0.04 mmol, 15.9 mg) under N2, and then EtOH (0.4 mmol, 23 mL) and tetrahydrofuran (THF) (1.5 mL) were added. The resulting solution was stirred at 70 or 100 °C for 24 h. After the reaction was completed, the solution was cooled to room temperature, and diluted with ethyl acetate (10 mL). The combined organic phases were washed with brine, and the aqueous phase was extracted with ethyl acetate. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (n-hexane or n-hex/EtOAc = 100:1) to afford the desired product.

Gram-Scale Synthesis

According to the typical procedure: to a 250 mL pressure tube were added 4-ethynylbiphenyl (5.61 mmol, 1.0 g), [Ir(cod)Cl]2 (140 mmol, 94 mg), DPPE (1.12 mmol, 446 mg) under N2, and then EtOH (11.2 mmol, 1.14 mL), and THF (35 mL) were added. The resulting solution was stirred at 70 °C for 24 h. After column purification (n-hexane), 4-phenylstyrene was obtained (728 mg, 72% yield).

Zebrafish Experiments

At 6 hpf, embryos were screened under an anatomical microscope to remove the morphologically abnormal individuals. Around 10 healthy embryos were loaded into each well of 96-well plate in E3 solution. At the setting time, E3 solutions were replaced with different phenelzine treatment solutions. The control and treated groups were analyzed at different intervals. At 55 hpf, the Tg(fli1a:nEGFP) zebrafish embryos were collected for imaging. At 55 hpf, for confocal imaging embryos were anesthetized with E3/0.16 mg/mL tricaine/1% 1-phenyl-2-thiourea (Sigma) and embedded in 0.8% low-melt agarose. Confocal imaging was performed with a Leica TCS-SP8 LSM. Analysis was performed using Imaris software.

Styrene (2a)[13]

The product was obtained as colorless liquid (18.9 mg, 91% yield). 1H NMR (400 MHz, CDCl3): 7.42–7.40 (m, 2H), 7.34–7.30 (m, 2H), 7.26–7.23 (m, 1H), 6.75–6.68 (m, 1H), 5.75 (d, J = 17.6 Hz, 1H), 5.24 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 137.7, 137.0, 128.7, 127.9, 126.3, 113.9.

1-Methyl-2-vinylbenzene (2b)[13]

The product was obtained as colorless liquid (18.9 mg, 80% yield). 1H NMR (400 MHz, CDCl3): 7.51–7.49 (m, 1H), 7.20–7.16 (m, 3H), 7.00–6.93 (m, 1H), 5.66 (d, J = 17.6 Hz, 1H), 5.32 (d, J = 10.8 Hz, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): 137.0, 135.5, 135.0, 130.4, 127.8, 126.2, 125.5, 115.3, 19.8.

1-Methyl-3-vinylbenzene (2c)[13]

The product was obtained as colorless liquid (19.4 mg, 82% yield). 1H NMR (400 MHz, CDCl3): 7.24–7.23 (m, 3H), 7.10–7.06 (m, 1H), 6.74–6.67 (m, 1H), 5.75 (d, J = 17.6 Hz, 1H), 5.24 (d, J = 10.8 Hz, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): 138.2, 137.7, 137.1, 128.7, 128.6, 127.1, 123.5, 113.7, 21.5.

1-Methyl-4-vinylbenzene (2d)[13]

The product was obtained as colorless liquid (22.2 mg, 94% yield). 1H NMR (400 MHz, CDCl3): 7.37–7.35 (m, 2H), 7.19–7.17 (m, 2H), 6.77–6.70 (m, 1H), 5.76 (d, J = 17.6 Hz, 1H), 5.23 (d, J = 10.8 Hz, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): 137.7, 136.9, 135.0, 129.3, 126.2, 112.9, 21.3.

1-Chloro-2-vinylbenzene (2e)[13]

The product was obtained as colorless liquid (23.0 mg, 83% yield). 1H NMR (400 MHz, CDCl3): 7.58 (d, J = 7.6 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 7.26–7.11 (m, 3H), 5.76 (d, J = 17.6 Hz, 1H), 5.40 (d, J = 10.8 Hz, 1H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3): 135.8, 133.3, 133.2, 129.7, 128.9, 126.9, 126.7, 116.6.

1-Chloro-3-vinylbenzene (2f)[13]

The product was obtained as colorless liquid (22.2 mg, 80% yield). 1H NMR (400 MHz, CDCl3): 7.39 (s, 1H), 7.26–7.22 (m, 3H), 6.68–6.61 (m, 1H), 5.75 (d, J = 17.6 Hz, 1H), 5.30 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 139.5, 135.7, 134.6, 129.9, 127.9, 126.3, 124.6, 115.5.

1-Chloro-4-vinylbenzene (2g)[13]

The product was obtained as colorless liquid (25.2 mg, 91% yield). 1H NMR (400 MHz, CDCl3): 7.35–7.28 (m, 4H), 6.71–6.64 (m, 1H), 5.73 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 136.2, 135.9, 133.6, 128.9, 127.6, 114.6.

1-Bromo-2-vinylbenzene (2h)[14]

The product was obtained as colorless liquid (28.9 mg, 79% yield). 1H NMR (400 MHz, CDCl3): 7.57–7.55 (m, 2H), 7.31–7.27 (m, 1H), 7.14–7.04 (m, 2H), 5.71 (d, J = 17.6 Hz, 1H), 5.38 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 137.6, 135.9, 133.0, 129.2, 127.6, 126.9, 123.7, 116.8.

1-Bromo-3-vinylbenzene (2i)[14]

The product was obtained as colorless liquid (29.3 mg, 80% yield). 1H NMR (400 MHz, CDCl3): 7.56 (s, 1H), 7.40–7.31 (m, 2H), 7.22–7.18 (m, 1H), 6.69–6.61 (m, 1H), 5.76 (d, J = 17.6 Hz, 1H), 5.31 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 139.8, 135.6, 130.8, 130.2, 129.3, 125.0, 122.9, 115.5.

1-Bromo-4-vinylbenzene (2j)[14]

The product was obtained as colorless liquid (33.0 mg, 90% yield). 1H NMR (400 MHz, CDCl3): 7.45–7.42 (m, 2H), 7.28–7.25 (m, 2H), 6.68–6.61 (m, 1H), 5.74 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 136.7, 135.9, 131.8, 127.9, 121.8, 114.8.

1-Fluoro-2-vinylbenzene (2k)[15]

The product was obtained as colorless liquid (18.6 mg, 76% yield). 1H NMR (400 MHz, CDCl3): 7.52–7.48 (m, 1H), 7.24–7.21 (m, 1H), 7.13–7.02 (m, 2H), 6.93–6.86 (m, 1H), 5.84 (d, J = 17.6 Hz, 1H), 5.39 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 160.5 (d, JC–F = 253.9 Hz), 129.5 (d, JC–F = 4.0 Hz), 129.2 (d, JC–F = 8.4 Hz), 127.2 (d, JC–F = 3.7 Hz), 125.5 (d, JC–F = 12.1 Hz), 124.2 (d, JC–F = 3.5 Hz), 116.6 (d, JC–F = 4.7 Hz), 115.8 (d, JC–F = 21.9 Hz).

1-Fluoro-3-vinylbenzene (2l)[15]

The product was obtained as colorless liquid (21.2 mg, 87% yield). 1H NMR (400 MHz, CDCl3): 7.28–7.22 (m, 1H), 7.15–7.08 (m, 2H), 6.95–6.91 (m, 1H), 6.70–6.63 (m, 1H), 5.74 (d, J = 17.6 Hz, 1H), 5.29 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 163.3 (d, JC–F = 243.6 Hz), 140.0 (d, JC–F = 7.5 Hz), 136.0 (d, JC–F = 2.5 Hz), 130.1 (d, JC–F = 8.3 Hz), 122.3 (d, JC–F = 2.8 Hz), 114.7 (d, JC–F = 21.3 Hz), 112.7 (d, JC–F = 21.6 Hz).

1-Fluoro-4-vinylbenzene (2m)[16]

The product was obtained as colorless liquid (21.7 mg, 89% yield). 1H NMR (400 MHz, CDCl3): 7.42–7.38 (m, 2H), 7.06–7.02 (m, 2H), 6.74–6.67 (m, 1H), 5.69 (d, J = 17.6 Hz, 1H), 5.24 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 162.6 (d, JC–F = 246.2 Hz), 135.8, 133.8, 127.9 (d, JC–F = 8.0 Hz), 115.5 (d, JC–F = 21.4 Hz), 113.6.

1-Methoxy-2-vinylbenzene (2n)[17]

The product was obtained as colorless liquid (24.4 mg, 91% yield). 1H NMR (400 MHz, CDCl3): 7.48 (d, J = 7.6 Hz, 1H), 7.26–7.23 (m, 1H), 7.09–7.02 (m, 1H), 6.96–6.92 (m, 1H), 6.88 (d, J = 8.4 Hz, 1H), 5.74 (d, J = 17.6 Hz, 1H), 5.27 (d, J = 11.2 Hz, 1H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3): 156.9, 1131.8, 129.0, 126.9, 126.7, 120.8, 114.6, 111.0, 55.6.

1-Methoxy-3-vinylbenzene (2o)[18]

The product was obtained as colorless liquid (19.8 mg, 74% yield). 1H NMR (400 MHz, CDCl3): 7.29–7.25 (m, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.98 (s, 1H), 6.86–6.83 (m, 1H), 6.76–6.69 (m, 1H), 5.77 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 10.8 Hz, 1H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3): 159.9, 139.1, 136.9, 129.6, 119.0, 114.2, 113.5, 111.6, 55.3.

1-Methoxy-4-vinylbenzene (2p)[16]

The product was obtained as colorless liquid (22.0 mg, 82% yield). 1H NMR (400 MHz, CDCl3): 7.36–7.33 (m, 2H), 6.87–6.85 (m, 2H), 6.70–6.63 (m, 1H), 5.60 (d, J = 17.6 Hz, 1H), 5.12 (d, J = 10.8 Hz, 1H), 3.81 (s, 3H); 13C NMR (100 MHz, CDCl3): 159.5, 136.4, 130.6, 127.5, 114.0, 111.7, 55.4.

1-(Trifluoromethyl)-3-vinylbenzene (2q)[17]

The product was obtained as colorless liquid (27.5 mg, 80% yield). 1H NMR (400 MHz, CDCl3): 7.65 (s, 1H), 7.59–7.42 (m, 3H), 6.78–6.71 (m, 1H), 5.83 (d, J = 17.6 Hz, 1H), 5.37 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 138.4, 135.7, 131.2 (d, JC–F = 3.2 Hz), 129.5, 129.1, 124.5 (q, JC–F = 3.7 Hz), 124.3 (q, JC–F = 270.6 Hz), 123.1 (q, JC–F = 3.8 Hz), 115.9.

1-(Trifluoromethyl)-4-vinylbenzene (2r)[16]

The product was obtained as colorless liquid (24.1 mg, 70% yield). 1H NMR (400 MHz, CDCl3): 7.60–7.49 (m, 4H), 6.79–6.72 (m, 1H), 5.86 (d, J = 17.6 Hz, 1H), 5.39 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 141.1, 141.1, 135.8, 129.8 (q, JC–F = 32.2 Hz), 126.5, 125.6 (q, JC–F = 3.6 Hz), 124.3 (d, JC–F = 270.1 Hz), 116.6.

1-(tert-Butyl)-4-vinylbenzene (2s)[16]

The product was obtained as colorless liquid (28.2 mg, 86% yield). 1H NMR (400 MHz, CDCl3): 7.42–7.41 (m, 4H), 6.80–6.72 (m, 1H), 5.79–5.74 (m, 1H), 5.27–5.25 (m, 1H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3): 151.9, 136.9, 135.0, 126.1, 125.6, 113.1, 34.7, 31.4.

4-Vinylbenzonitrile (2t)[13]

The product was obtained as colorless liquid (23.2 mg, 90% yield). 1H NMR (400 MHz, CDCl3): 7.62–7.60 (m, 2H), 7.49–7.47 (m, 2H), 6.76–6.69 (m, 1H), 5.87 (d, J = 17.6 Hz, 1H), 5.45 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 142.0, 135.5, 132.5, 126.8, 119.0, 117.8, 111.2.

4-Vinyl-1,1′-biphenyl (2u)[16]

The product was obtained as a white solid (24.5 mg, 68% yield). 1H NMR (400 MHz, CDCl3): 7.62–7.57 (m, 4H), 7.50–7.43 (m, 4H), 7.37–7.33 (m, 1H), 6.08–6.73 (m, 1H), 5.80 (d, J = 17.6 Hz, 1H), 5.29 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 140.9, 140.7, 136.8, 136.6, 128.9, 127.5, 127.4, 127.1, 126.8, 114.0.

1-Nitro-4-vinylbenzene (2v)[13]

The product was obtained as colorless liquid (22.6 mg, 76% yield). 1H NMR (400 MHz, CDCl3): 8.17–8.15 (m, 2H), 7.53–7.51 (m, 2H), 6.80–6.73 (m, 1H), 5.92 (d, J = 17.6 Hz, 1H), 5.49 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 147.2, 143.9, 135.0, 126.9, 124.0, 118.7.

1-Nitro-3-vinylbenzene (2w)[19]

The product was obtained as colorless liquid (27.7 mg, 93% yield). 1H NMR (400 MHz, CDCl3): 8.26 (s, 1H), 8.12–8.09 (m, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 6.81–6.74 (m, 1H), 5.90 (d, J = 17.6 Hz, 1H), 5.45 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 139.2, 134.7, 132.0, 129.4, 122.4, 120.8, 117.5.

3-Vinylpyridine (2x)[19]

The product was obtained as colorless liquid (14.1 mg, 67% yield). 1H NMR (400 MHz, CDCl3): 8.57 (d, J = 4.0 Hz, 1H), 7.65–7.61 (m, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.16–7.13 (m, 1H), 6.85–6.78 (m, 1H), 6.22–6.17 (m, 1H), 5.49–5.46 (m, 1H); 13C NMR (100 MHz, CDCl3): 155.8, 149.6, 137.1, 136.6, 122.5, 121.3, 118.3.

1-Vinylnaphthalene (2y)[16]

The product was obtained as a white solid (24.3 mg, 79% yield). 1H NMR (400 MHz, CDCl3): 7.83–7.79 (m, 3H), 7.76 (s, 1H), 7.66–7.63 (m, 1H), 7.49–7.42 (m, 2H), 6.93–6.86 (m, 1H), 5.88 (d, J = 17.6 Hz, 1H), 5.35 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 137.1, 135.2, 133.7, 133.3, 128.3, 128.2, 127.8, 126.5, 126.4, 126.1, 123.3, 114.3.

1,3-Bis(trifluoromethyl)-5-vinylbenzene (2z)[20]

The product was obtained as colorless liquid (36.9 mg, 77% yield). 1H NMR (400 MHz, CDCl3): 7.81–7.76 (m, 3H), 6.81–6.74 (m, 1H), 5.92 (d, J = 17.6 Hz, 1H), 5.50 (d, J = 10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 139.7, 134.5, 132.1 (q, JC–F = 33.0 Hz), 126.3, 123.4 (q, JC–F = 267.8 Hz), 121.5–121.3 (m), 118.1.

Allylbenzene (2α)[21]

The product was obtained as colorless liquid (17.9 mg, 76% yield). 1H NMR (400 MHz, CDCl3): 7.33–7.30 (m, 2H), 7.24–7.20 (m, 3H), 6.05–5.94 (m, 1H), 5.12–5.08 (m, 2H), 3.41 (d, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): 140.2, 137.6, 128.7, 128.6, 126.2, 115.9, 40.4.

But-3-en-1-ylbenzene (2β)[21]

The product was obtained as colorless liquid (18.0 mg, 68% yield). 1H NMR (400 MHz, CDCl3): 7.29–7.15 (m, 5H), 5.90–5.80 (m, 1H), 5.06–4.97 (m, 2H), 2.72–2.68 (m, 2H), 2.40–2.34 (m, 2H); 13C NMR (100 MHz, CDCl3): 142.0, 138.2, 128.6, 128.4, 125.9, 115.0, 35.7, 35.5.

Non-1-ene (2γ)[22]

The product was obtained as colorless liquid (11.2 mg, 50% yield). 1H NMR (400 MHz, CDCl3): 5.86–5.79 (m, 1H), 5.02–4.92 (m, 2H), 2.08–2.03 (m, 2H), 1.40–1.29 (m, 8H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 139.4, 114.2, 34.0, 31.9, 29.1, 29.0, 22.8, 14.2.

Pentadec-1-ene (2ϕ)[22]

The product was obtained as colorless liquid (12.5 mg, 33% yield). 1H NMR (400 MHz, CDCl3): 5.85–5.79 (m, 1H), 5.02–4.92 (m, 2H), 2.06–2.02 (m, 2H), 1.31–1.27 (m, 20H), 0.89 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): 139.4, 114.2, 34.0, 32.1, 29.9, 29.9, 29.9, 29.8, 29.7, 29.6, 29.4, 29.2, 22.9, 14.3.