Nickel-Catalyzed Defluorinative Reductive Cross-Coupling Reaction

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Nickel-Catalyzed Defluorinative Reductive Cross-Coupling Reaction of gem-Difluoroalkenes with Thiosulfonate or Selenium Sulfonate Jian Li, Weidong Rao, Shun-Yi Wang, and Shun-Jun Ji J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01387 • Publication Date (Web): 19 Aug 2019 Downloaded from pubs.acs.org on August 20, 2019

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The Journal of Organic Chemistry

Nickel-Catalyzed Defluorinative Reductive Cross-Coupling Reaction of gemDifluoroalkenes with Thiosulfonate or Selenium Sulfonate Jian Li,† Weidong Rao‡ Shun-Yi Wang,*,† and Shun-Jun Ji*,† †

Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, China. ‡ Jiangsu Key Laboratory of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China. E-mail: [email protected]; [email protected]

RECEIVED DATE *CORRESPONDING AUTHOR FAX: 86-512-65880307.

ABSTRACT: A nickel-catalyzed defluorinative reductive cross-coupling of gem-difluoroalkenes with thiosulfonate or selenosulfonates is described. The reaction involves the formation of thiolated or selenylated monofluoroolefins via regio-selective C-F bond cleavage and C-S or C-Se bond formation and features easily available substrates, mild reaction conditions and high E-selectivity. One of the derivatives by further cross coupling with PhMgBr exhibited aggregation induced emission (AIE) enhancementeffect. KEYWORDS:

nickel-catalyzed,

defluorinative

reductive

cross-coupling,

gem-difluoroalkenes,

thiosulfonate or selenosulfonates. 1. INTRODUCTION Monofluoroalkenes have emerged as a class of important fluorine-containing fragments because of stable conformation and enhanced peptidases, which are ideal amidebond mimics.1 Recently, the construction of monofluoroalkenes has gained considerable attention in medicinal chemistry and drugdiscovery. Among the methods developed for the synthesis of monofluoroalkenes, cross-coupling of gem-difluoroalkenes with nucleophiles has proved to be an efficient and prevailing strategy (Scheme 1, 1 ACS Paragon Plus Environment

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a). The direct nucleophilic substitution reaction has emerged as an effective strategy to construct C–C2, C–O3，C–N4 and C–S5 bonds. However, the major drawback of these methods are the unavoidable disubstitution products and poor E/Z-selectivity. More recently, Teck-Peng Loh, Xingwei Li and Lutz Ackermann groups repoted the strategy of transition metal-catalyzed C–H activation of arenes with αfluoroalkenylation for the construction of monofluoroolefins, respectively (Scheme 1, b).6 Toste group developed a palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes with boronic acids.7 Hosoya group also disclosed a coupling of various (poly)fluoroalkenes with (Bnep)2 or (Bpin)2 via copper catalysis.8 Through a similar strategy, Cao group copper-catalyzed defluorinative reactions via C-B or C-Si bonds formation

under

mild

reaction

conditions.9

Despite

these

successes,

a

novel,

efficient

monofluoroalkenylation involving of radical pathway has been achieved recenty.10 Scheme 1. Nickel-Catalyzed Defluorinative Reductive Cross-Coupling Reactions

During the past decade, nickel-catalyzed reductive cross-coupling reactions gained attentions substantially, which have been recognized a useful tool for the direct coupling of two electrophiles represents under mild conditions.11 Fu’s group report the first nickel-catalyzed defluorinative reductive cross-coupling of gem-difluoroalkenes with secondary and tertiary alkyl halides, which allows C(sp2)C(sp3) formation12 (Scheme 1, c). To the best of our knowledge, in such an active field, using nickelcatalyzed defluorinative reductive cross-coupling strategy to construct C(sp2)-S bonds has not been achieved. Meanwhile, our group has developed a nickel-catalyzed reductive thiolation and selenylation 2 ACS Paragon Plus Environment

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of unactivated alkyl bromides (Scheme 1, d).13 Benzenesulfonothioate is a important and useful synthon, which has some advantages compared to other sulfuration agents14 such as thiols, disulfides, sulfenyl halides, sulfonium salts, N-thioimides quinone mono O,S-acetal, p-toluenesulfonyl hydrazide S-acetals, arylsulfonyl chlorides, sulfinic acids, and p-tolylsulfinate. As a electrophile, benzenesulfonothioate is stable to air, easy to be prepared or commercially available, without unpleasant odors.15 As a continuation of our intrests in C-S bonds and C-Se bonds formation reactions, herein, we report a nickel-catalyzed defluorinative reductive cross-coupling reaction of thiosulfonate or selenosulfonates with gem-difluoroalkenes, which allows thiolation and selenylation of gem-difluoroalkenes under mild conditions with high E-selectivity and excellent functional group toleration (Scheme 1, e). 2. RESULTS AND DISCUSSION We initiated the study by the reaction of methyl 4-(2, 2-difluorovinyl) benzoate 1a and S-phenyl benzenesulfonothioate 2a. It was found that the reaction of 1a and 2a catalyzed by NiBr2 with 4, 4'-ditert-butyl-2, 2'-bipyridine in the presence of Mn powder as the reductant in DMF successfully afforded the defluorinative E/Z mixture products methyl 4-(2-fluoro-2-(phenylthio) vinyl) benzoates 3a and 3a’ (E:Z = 92:8) in 78% total yield (Table 1, entry 1). It should be noted that no desired product was detected in the absence of NiBr2 or Mn (Table 1, entries 2-3). To our delight, the reaction of 1a and 2a proceeded smoothly to afford 3a and 3a’ (E:Z = 71:29) in 93% yield without adding additional ligand (Table 1, entry 4). Other nickel catalysts such as NiCl2 or NiF2 showed no catalytic activity at all (Table 1, entries 5-6). The use of other thiolation reagent (such as 1, 2-diphenyldisulfane) and reducing reagent (Zn) decreased the yields of product (Table 1, entries 7-9). We further investigated the effects of the ligands on E/Z selectivities of this transformation. Several ligands such as diamine ligands, PPh3 and PCy3 (Table 1 entries 10-13) were screened. Pleasingly, 4,4'-dimethyl-2,2'-bipyridine L3 was identified as the ideal ligand for this reaction and afforded the desired product 3a in 93% yield with excellent stereoselectivity (E/Z>98:2) (Table 1, entry 11). This promising result indicated that the suitable ligand was essential to improve the stereoselectivity. When we carefully checked the side product of the reaction of 1a and 2a, trisubstituted alkene 3a’’ was also observed in 6% yield even though 3a was obtained in 93% yield at the same time. Further optimization studies of different solvents such as DMA, DMSO or DMF/THF=1:1 revealed that DMF is the best solvent for this reaction (Table 1, entries 14-16). Table 1. Screening of Reaction Conditionsa,d

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[S]

Solvent

yield (%)b

E:Z

L1

2a

DMF

78

92:8

L1

2a

DMF

0

-

Mn

L1

2a

DMF

0

-

Mn

-

2a

DMF

93

71:29

NiCl2

Mn

-

2a

DMF

0

-

6

NiF2

Mn

-

2a

DMF

0

-

7

NiBr2

Mn

-

PhSSPh

DMF

98:2

15

NiBr2

Mn

L3

2a

DMSO

64

>98:2

16

NiBr2

Mn

L3

2a

DMF/THF=1:1

76

>98:2

a 1a (0.1 mmol, 1.0 equiv.), 2a (0.12 mmol, 1.2 equiv.), [Ni] (10.0 mol%), Ligand (15.0 mol%), Mn (0.2 mmol, 2.0 equiv.), DMF (0.5 mL), N2 atmosphere, 40 °C, 24h. bYields were determined by GC with 1,1'-biphenyl as the internal standard.. c0.1 mmol NaBr was added.d E/Z selectivity was determined by 19F NMR spectra.

With these optimized reaction conditions and the limitation of the reaction in hand, we investigated the scope of gem-difluoroalkenes with more bulky S-(2, 6-dimethylphenyl) benzenesulfonothioate 2a’ (Scheme 2). Notably, the reaction of 1a and 2a’ chemoselective gave thiolated monofluoroolefin 3b in 98% yields with excellent stereoselectivity. Various substitutions on (2,2-difluorovinyl)benzene such as CN, CH3SO2 and CF3 were well tolerated. The reaction of methyl 2-(2,2-difluorovinyl)benzoate with 2a’ also could give the desired product 3c in 97% yield with E/Z>98:2 stereoselectivity. 4-(2,2Difluorovinyl)benzonitrile and 1-(2,2-difluorovinyl)-4-(methylsulfonyl)benzene reacted with 2a’ to furnish the desired products 3d and 3e in high yields with similar excellent stereoselectivity, respectively. The reaction of 1-(2,2-difluorovinyl)-4-(trifluoromethyl)benzene could also undergo smoothly to result in 3f in 70% yield with E/Z>98:2 stereoselectivity. Notably, the reaction of gemdifluoroalkene 3,3'-(2,2-difluoroethene-1,1-diyl) bis((trifluoromethyl) benzene) 1g with 2a’ led to 3g in 4 ACS Paragon Plus Environment

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98% yield under a standard condition. Unfortunately, substrates containing electron-donating groups on the aromatic ring failed to give the desired products. Scheme 2. Scope of gem-Difluoroalkenes 1a,b

a o

Standard conditions: 1 (0.1 mmol), 2a’ (0.12 mmol), NiBr2 (10 mol%), Mn (2 equiv), L3 (15 mol%), DMF (0.5 mL) at 40 C under Ar for 24h. bYields of isolated product.

Next, we further explored the scope of benzenesulfonothioates and various substituted benzenesulfonothioate were applied to the reaction with (2,2-difluoroethene-1,1-diyl)dibenzene 1h (Scheme 3). Most of S-aryl benzenesulfonothioate underwent smoothly with 1h to give the desired products in excellent yields in absence of ligand. Substrates containing halide substituents or methyl in ortho, or para position were amenable to the reaction conditions to furnish the desired products 4a-f in 66-98% yields under the modified conditions. Subsequently, the reactions of S-alkyl benzenesulfonothioates with 1h were also investigated. It was found that higher thiosulfonate loading and higher temperature led to satisfactory results (4g-j). To our delight, the secondary thiosulfonates were also compatible with 1h. Cyclobutyl (4k), cyclopentyl (4l) and cycloheptyl (4m) thioethers were successfully obtained in 62–96% yields under the modified reaction conditions. Next, a variety of thiosulfonates with diverse synthetic valuable functional groups converted to the desired products successfully. Substituents bearing functionalized groups such as thiophene, alcohol, silane and amino, were well-tolerated under these mild reaction conditions to afford the desired products 4n-q in moderate to good yields. It is worth mentioning that the cysteine derivative 4r was successfully observed in 74% yield. Scheme 3 Scope of Thiosulfonates 2a,c 5 ACS Paragon Plus Environment


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a

Standard conditions: 1h (0.1 mmol), 2 (0.12 mmol), NiBr2 (10 mol%), Mn (2 equiv), DMF (0.5 mL) at 40 oC under Ar for 24h. b0.15 mmol 2 was used at 100 oC cYields of isolated product.

Encouraged by the promising results of the sucessfully synthesis of α-fluorovinyl thioethers, we turned our attention to explore the nickel-catalyzed defluorinative cross-coupling reaction scope of benzenesulfonoselenoates with 1h and study the construction of α-fluorovinyl selenides (Scheme 4). Similarly, the reactions of various Se-primary alkyl benzenesulfonoselenoates led to the corresponding α-fluorovinyl

selenides

4s-u

in

73%

to

92%

yields.

Additional,

Se-secondary

alkyl

benzenesulfonoselenoates were also investigated in the reactions with 1h. We could obtain the cyclobutyl (4v), cyclopentyl (4w), and cyclohexyl (4x) α-fluorovinyl selenides. A series of selenides was synthesized in good yields using similar conditions at 100 °C 6 ACS Paragon Plus Environment

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Scheme 4 Scope of Selenosulfonatesa,b

a b

Standard conditions: 1h (0.1 mmol), 5 (0.15 mmol), NiBr2 (10 mol%), Mn (2 equiv), DMF (0.5 mL) at 100 oC for 24h. Yields of isolated product.

To evaluate the application of this reductive cross coupling reactions, the gram-scale reaction of 1h (3 mmol) with 2l (3 mmol) in the presecne of only 2 mol% nickel catalyst was investigated. It should be mentioned that the decreased catalyst could also give the desired product 4l in insignificant reduced yield (92%) (Scheme 5). Scheme 5. Gram-Scale Reactions

Meanwhile, to explore the versatile synthetic utility of this method, we studied the oxidation reaction of cyclopentyl(1-fluoro-2,2-diphenylvinyl)sulfane 4l. (α-fluoro)vinyl sulfone derivative 6 was obtained in 92% yield through the simple oxidation of 4l by m-CPBA (Scheme 6). Scheme 6 Oxidation of Cyclopentyl(1-fluoro-2,2-diphenylvinyl)sulfane 4l

The hydrogenation of vinyl fluorides to corresponding alkyl fluorides remains underrepresented.16 Notably, methyl 4-(2-fluoro-2-(phenylsulfonyl)ethyl)benzoate 7 was obtained in 65% yield through the simple oxidation of 3a and subsequently hydrogenation (Scheme 7). Scheme 7 Oxidation and Hydrogenation of 3a 7 ACS Paragon Plus Environment


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As described above, not only sulfides, but also monofluoroalkenes are verstaile intermediates for the the assembly of useful functionalized molecules. With (1-fluoro-2,2-diphenylvinyl)(phenyl)sulfane 4a in hand, 4a was subjected to the Pd(PPh3)4-catalyzed coupling reaction with PhMgBr.9a To our delight, phenyl(1,2,2-triphenylvinyl)sulfane 8 was observed in 75% yield (Scheme 8). Then, we studied the UVvis spectra of 8 in DMSO (Fig. 1) and PL spectra of 8 EtOH–water mixtures with different fractions of water (Fig. 2). Phenyl(1,2,2-triphenylvinyl)sulfane 8 shows an absorption maximum at 336 nm. Evidently, phenyl(1,2,2-triphenylvinyl)sulfane 8 is a luminogen that exhibits an aggregationinduced emission (AIE) enhancement effect.17 Addition of a large amount of water (fw≥ 70%) into the EtOH solution of 8 causes its molecules to aggregate and boosts the light emission (Fig. 2). This promising result provides a new protocol to design and develop new functionalzied potential AIE molecules. Scheme 8 Synthesis of Sulfer-Containing AIE Luminogens 8

Fig 1 UV-vis Absorption Spectrum of 8 in DMSO


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Fig 2 PL Spectra of 8 in EtOH–Water Mixtures with Different Fractions of Water (fw); c = 1μM, λex = 336 nm (Figure 2 was photographed by Jian Li) On the basis of above experimental results and literature reports, a plausible reaction mechanism was proposed in Scheme 9. First, NiBr2 reacts with Mn in the presence of ligand to furnish active Ni0-Ln complex A. The reaction of Ni0-Ln complex with sulfonothioates 2 gives NiII intermediate B via oxidative addition. Next, the reduction of B affords NiI–SR complex C. The addition of C to difluoroalkene leads to NiI intermediate D. Subsequently, conformationally favorable 3 is formed through a β-F elimination process with the formation of NiI species E. E can be further reduced to Ni0Ln complex A to finish the catalytic cycle. Scheme 9 Proposed Mechanism

3. CONCLUSION In summary, we have developed a nickel-catalyzed defluorinative reductive coupling reactions of gem-difluoroalkenes with sulfonothioates or sulfonoselenoates. This simple and mild transformation provides a convenient route for the preparation of thiolated or selenylated monofluoroolefins, which complements the nickel-catalyzed reductive coupling reaction. The sucessfully preparation of phenyl(1,2,2-triphenylvinyl)sulfane provides a new and useful method to design and develop new functionalzied AIE molecules based on the skeleton of aryl(1,2,2-triarylvinyl)sulfane. 4. EXPERIMENTAL SECTION 9 ACS Paragon Plus Environment


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1. General Information All the solvents for routine isolation of products and chromatography were reagent grade. Flash chromatography was performed using silica gel (300−400 mesh) with the indicated solvents. Melting points were recorded on an electrothermal digital melting point apparatus and were uncorrected. IR spectra were recorded on a spectrophotometer using KBr optics. 1H NMR and 13C NMR spectra were recorded on a 400 MHz (1H NMR) and 100 MHz (13C NMR) spectrometer using CDCl3 or DMSO-d6 as solvent and TMS as internal standard. The 1H NMR data are reported as the chemical shift in parts per million, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet), coupling constant in hertz, and number of protons. High resolution mass spectra were obtained using a high resolution ESI-TOF mass spectrometer and high resolution CI-TOF mass spectrometer. 2.1. General procedures for the synthesis gem-difluoroalkenes. 1a-1d18, 1e19, 1f20 and1g-1h21 were prepared following the reported procedures. 2.2. Procedure for the preparation of PhSO2SNa.22 Sodium benzenesulfinate (10 g, 61 mmol) and sulfur (1.95 g, 61 mmol) were dissolved in anhydrous pyridine (60 mL) to give a yellow solution. The reaction was stirred under argon (heat source: oil bath) and after 1 h gave a white suspension. Et2O was added to the suspension, and the reaction was filtered and washed with anhydrous diethyl ether. Recrystallization from anhydrous ethanol afforded PhSO2SNa (10.5 g, 88%) as a white crystalline solid. 2.3. General procedure for the preparation of PhSO2SAr.23 A mixture of PhSO2Na (4 equiv), diaryl disulphide (1 equiv) and NBS (2 equiv) in MeCN was stirred at room temperature (heat source: oil bath). After the completion of the reaction, as monitored by TLC, the reaction mixture was washed with water and extracted with ethyl acetate. The organic phase was separated and dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the resulting residue was purified by column chromatography to provide the desired aryl-thiosulfonates. 2.4. General procedure for the preparation of PhSO2SAlkyl.24 To a solution of PhSO2SNa (1 equiv) in DMF was added Alkyl bromide or Alkyl iodine (2 equiv) and the reaction mixture was stirred at room temperature (heat source: oil bath). After the completion of the reaction, as monitored by TLC, the reaction mixture was diluted with ethyl acetate and washed with 7 water. The organic phase was separated and dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the resulting residue was purified by column chromatography to provide the desired alkylthiosulfonates. 2.5. General procedure for the preparation of 3b-3g. In glovebox, an oven-dried screw-capped 8 mL vial equipped with a magnetic stir bar was charged with gem-difluoroalkenes 1b-1g (0.1 mmol) and O-phenyl 2,6-dimethylbenzenesulfonothioate 2a’ (33.4 mg 0.12 mmol) NiBr2 (2.2 mg, 0.01 mmol), 4,4'-Dimethyl-2,2'-bipyridyl (L3, 2.8 mg, 0.015 mmol ) and Mn powder (11.0 mg, 0.2 mmol). DMF (0.5 mL) was added via syringe. The resulting solution was stirred for 24 h at 40 oC (heat source: oil bath). After this time, the crude reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography. 2.6. General procedure for the preparation of 4a-4f. In glovebox, an oven-dried screw-capped 8 mL vial equipped with a magnetic stir bar was charged with (2,2-difluoroethene-1,1-diyl)dibenzene 1h (21.6 mg, 0.1 mmol) and benzenesulfonothioate 2a-2f (0.12 mmol) NiBr2 (2.2 mg, 0.01 mmol), and Mn powder (11.0 mg, 0.2 mmol). DMF (0.5 mL) was added via syringe. The resulting solution was stirred for 24 h at 40 oC (heat source: oil bath). After this time, the crude reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography. 2.7. General procedure for the preparation of 4g-4x. In glovebox, an oven-dried screw-capped 8 mL vial equipped with a magnetic stir bar was charged with (2,2-difluoroethene-1,1-diyl)dibenzene 1h (21.6 mg, 0.1 mmol) and benzenesulfonoselenoate 2g-2r or benzenesulfonoselenoate 5s-5x (0.15 mmol) NiBr2 (2.2 mg, 0.01 mmol), and Mn powder (11.0 mg, 0.2 mmol). DMF (0.5 mL) was added via syringe. The resulting solution was stirred for 24 h at 100 oC (heat source: oil bath). After this time, the crude reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography. S-(2-((Tert-butoxycarbonyl)amino)ethyl) benzenesulfonothioate (2q) (1.33g, 84%)Following General Procedure for the preparation of PhSO2SAlkyl using corresponding alkyl bromide 1H NMR (400 MHz, Chloroform-d) δ 8.03 – 7.88 (m, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.6 Hz, 2H), 4.93 (s, 1H), 3.40 (q, J = 6.0 Hz, 2H), 3.12 (t, J = 6.4 Hz, 2H), 1.43 (s, 9H). Methyl (tert-butoxycarbonyl)(phenoxysulfonothioyl)-L-alaninate (2r) (1.35g, 72%)Following General Procedure for the preparation of PhSO2SAlkyl using corresponding alkyl iodine 1H NMR (400 MHz, Chloroform-d) δ 8.02 – 7.85 (m, 2H), 7.66 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.6 Hz, 2H), 5.37 (d, J = 6.5 Hz, 1H), 4.64 – 4.40 (m, 1H), 3.74 (s, 3H), 3.60 – 3.34 (m, 2H), 1.44 (s, 9H). Methyl (E)-4-(2-fluoro-2-(phenylthio)vinyl)benzoate (3a) White solid (26 mg, 93%), mp: 77.5-80.5 ℃. IR (neat, ν, cm-1): 2920, 2850, 1711, 1408, 1275, 1178, 1112, 1050, 868, 747, 687, 588, 494 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 8.00 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 7.3 Hz, 2H), 7.40 – 7.29 (m, 3H), 6.27 (d, J = 32.3 Hz, 1H), 3.91 (s, 3H); 19F NMR (377 MHz, CDCl3) δ 82.4; 13C{1H}NMR (101 MHz, CDCl3) δ 166.8, 154.8 (d, JC-F= 310.7 Hz), 137.5 (d, JC-F= 5.5 Hz), 131.3, 130.9, 130.0, 129.6, 129.3 (d, JC+ F= 2.7 Hz), 128.7 (d, JC-F=8.1 Hz), 128.3, 115.8 (d, JC-F= 12.0 Hz), 52.3 ppm. HRMS (CI-TOF) m/z: [M + H] Calcd for C16H14FO2S 289.0693; Found 289.0689. Methyl 4-(2,2-bis(phenylthio)vinyl)benzoate (3a’’) White solid (2 mg, 6%), mp: 66.4-74.1 ℃. IR (neat, ν, cm-1): 2952, 2919, 2849, 1717, 1603, 1435, 1275, 1187, 1106, 738, 686, 528 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.3 Hz, 2H), 7.32 (s, 5H), 7.25 (s, 5H), 7.00 (s, 1H), 3.90 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 166.9, 140.4, 135.4, 134.4, 133.3, 133.2, 133.0, 131.3, 129.6, 129.3, 129.2, 129.0, 128.9, 128.4, 127.6, 52.3 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C22H19O2S2 379.0821; Found 379.0827. Methyl (E)-4-(2-((2,6-dimethylphenyl)thio)-2-fluorovinyl)benzoate (3b) White solid (25 mg, 98%), mp: 92.1-98.5 ℃. IR (neat, ν, cm-1): 3051, 2956, 2924, 2853, 1712, 1605, 1460, 1436, 1277, 1185, 1110, 1036, 1017, 962, 878, 820, 763, 696, 580, 497, 448 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.94 (d, J = 8.5 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 7.27 – 7.19 (m, 1H), 7.15 (d, J = 7.5 Hz, 2H), 5.78 (d, J =


Page 11 of 17 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


34.7 Hz, 1H), 3.89 (s, 3H), 2.57 (s, 6H); 19F NMR (376 MHz, CDCl3) δ -85.0; 13C{1H}NMR (101 MHz, CDCl3) δ 166.9, 156.6 (d, JC-F= 305.7 Hz), 143.9, 138.0 (d, JC-F= 4.7 Hz), 130.1, 129.9, 128.8, 128.5 (d, JC-F= 2.5 Hz), 128.0 (d, JC-F= 8.0 Hz), 127.3 (d, JC-F= 1.2 Hz), 109.4 (d, JC-F= 10.1 Hz), 52.2, 22.0 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C18H18FO2S 317.1006; Found 317.1010. Methyl (E)-2-(2-((2,6-dimethylphenyl)thio)-2-fluorovinyl)benzoate (3c) White solid (24 mg, 97%), mp: 58.3-63.8 ℃. IR (neat, ν, cm-1): 2949, 2918, 2848, 1718, 1637, 1462, 1434, 1278, 1253, 1138, 1253, 1138, 1081, 1025, 776, 743, 697, 570 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.87 (dd, J = 7.9, 1.3 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 8.3 Hz, 1H), 7.28 – 7.18 (m, 2H), 7.15 (d, J = 7.3 Hz, 2H), 6.62 (d, J = 34.1 Hz, 1H), 3.82 (s, 3H), 2.61 (s, 6H); 19F NMR (376 MHz, CDCl3) δ -90.6; 13C{1H}NMR (101 MHz, CDCl3) δ 167.8, 156.4 (d, JC-F= 303.5 Hz), 144.0, 133.7 (d, JC-F= 3.7 Hz), 132.0, 130.7, 130.5 (d, JC-F= 10.4 Hz), 129.9, 128.67, 128.5, 127.8, 127.1 (d, JC+ F= 30.8 Hz), 108.6 (d, JC-F= 8.8 Hz), 52.2, 22.0 ppm. HRMS (CI-TOF) m/z: [M + H] Calcd for C18H18FO2S 317.1006; Found 317.1018. (E)-4-(2-((2,6-Dimethylphenyl)thio)-2-fluorovinyl)benzonitrile (3d) White solid (21 mg, 98%), mp: 74.1-81.6 ℃. IR (neat, ν, cm-1): 2956, 2923, 2852, 2224, 1626, 1602, 1460, 1259, 1080, 1014, 868, 793, 700, 553 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.59 – 7.37 (m, 4H), 7.29 – 7.22 (m, 1H), 7.17 (d, J = 7.5 Hz, 2H), 5.69 (d, J = 34.4 Hz, 1H), 2.56 (s, 6H); 19F NMR (376 MHz, CDCl3) δ -83.9; 13 C{1H}NMR (101 MHz, CDCl3) δ 158.0 (d, JC-F= 305.8 Hz), 143.9, 138.0 (d, JC-F= 3.4 Hz), 132.4, 130.3, 128.9, 128.5 (d, JC-F= 8.2 Hz), 126.9 (d, JC-F= 1.8 Hz), 119.0, 110.2 (d, JC-F= 3.0 Hz), 108.0 (d, JC-F= 9.6 Hz), 22.0 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C17H15FNS 284.0904; Found 284.0903. (E)-(2,6-Dimethylphenyl)(1-fluoro-2-(4-(methylsulfonyl)phenyl)vinyl)sulfane (3e) White solid (27 mg, 98%), mp: 99.5-106.8 ℃. IR (neat, ν, cm-1): 2956, 2919, 2850, 1733, 1592, 1460, 1377, 1147, 1081, 957, 761, 666, 534 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.84 (d, J = 8.6 Hz, 2H), 7.54 (d, J = 8.6 Hz, 2H), 7.29 – 7.22 (m, 1H), 7.17 (d, J = 7.7 Hz, 2H), 5.74 (d, J = 34.4 Hz, 1H), 3.02 (s, 3H), 2.57 (s, 6H); 19 F NMR (376 MHz, CDCl3) δ -84.0 (d, J = 1Hz); 13C{1H}NMR (101 MHz, CDCl3) δ 158.2 (d, J = 304.9 Hz), 143.9, 138.9 (d, J = 4.6 Hz), 130.3, 128.9, 128.8, 128.7, 127.8, 126.9 (d, J = 1.8 Hz), 107.8 (d, J = 9.6 Hz), 44.7, 22.0 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C17H18FO2S2 337.0727; Found 337.0737. (E)-(2,6-Dimethylphenyl)(1-fluoro-2-(4-(trifluoromethyl)phenyl)vinyl)sulfane (3f) Yellow oil (18 mg, 70%). IR (neat, ν, cm-1): 3057, 2958, 2927, 2856, 1615, 1462, 1413, 1322, 1164, 1114, 1067, 1017, 858, 827, 772, 604 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.76 – 7.35 (m, 4H), 7.33 – 7.01 (m, 3H), 5.78 (d, J = 34.4 Hz, 1H), 2.57 (s, 6H); 19F NMR (376 MHz, CDCl3) δ -62.6, -85.5. 13C{1H}NMR (101 MHz, CDCl3) δ 156.0 (d, JC-F= 305.5 Hz), 143.3, 136.3 (d, JC-F= 3.0 Hz), 129.5, 128.5 (d, JC-F= 2.8 Hz), 128.2, 127.7 (d, JC-F= 8.0 Hz), 126.6 (d, JC-F= 0.8 Hz), 124.9 (q, JC-F= 3.9 Hz), 123.6 (q, JC-F= 270.2 Hz),108.4(d, JC-F= 10.3 Hz), 21.4 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C17H15F4S 327.0825; Found 327.0807. (2,6-Dimethylphenyl)(1-fluoro-2,2-bis(3-(trifluoromethyl)phenyl)vinyl)sulfane (3g) White solid (40 mg, 98%), mp: 54.0-58.2 ℃. IR (neat, ν, cm-1): 2955, 2925, 2854, 1606, 1462, 1443, 1328, 1259, 1162, 1124, 905, 808, 784, 775, 701, 686, 646, 550, 447 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.66 (d, J = 7.6 Hz, 1H), 7.60 (s, 1H), 7.58 – 7.45 (m, 4H), 7.43 – 7.28 (m, 2H), 7.22 – 7.16 (m, 1H), 7.11 (d, J = 7.5 Hz, 2H), 2.44 (s, 6H); 19F NMR (376 MHz, CDCl3) δ -62.7, -87.7; 13C{1H}NMR (101 MHz, CDCl3) δ 154.9 (d, JC-F= 305.8 Hz), 143.54, 138.2 (d, JC-F= 5.2 Hz), 137.2 (d, JC-F= 2.8 Hz), 134.0 (d, JC-F= 1.2 Hz), 132.6 (d, JC-F= 3.9 Hz), 131.0 (t, JC-F= 32.0 Hz) 129.87, 129.24, 128.85, 128.58, 127.3 (t, JC-F= 3.6Hz), 127.2 (d, JC-F= 2.1 Hz), 126.0 (q, JC-F= 3.8 Hz), 125.2 (d, JC-F= 3.8 Hz), 124.4 (d, JC-F= 3.0 Hz), 124.1 (q, JC-F= 270.7 Hz), 121.4 (d, JC-F= 16.3 Hz), 22.16 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C24H18F7S 471.1012; Found 471.1010. (1-Fluoro-2,2-diphenylvinyl)(phenyl)sulfane (4a) White solid (28 mg, 93%), mp: 67.8-72.96 ℃. IR (neat, ν, cm-1): 3055, 3018, 2962, 2917, 2849, 1609, 1580, 1479, 1441, 1179, 1479, 1441, 1093, 1071, 738, 696 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.43 – 7.35 (m, 2H), 7.35 – 7.16 (m, 13H). 19F NMR (376 MHz, CDCl3) δ -88.5. 13C{1H}NMR (101 MHz, CDCl3) δ 150.0 (d, JC-F= 302.2 Hz), 138.6 (d, JC-F= 3.7 Hz), 137.0 (d, JC-F= 2.4 Hz), 132.6 (d, JC-F= 2.2 Hz), 130.8 (d, JC-F= 17.0 Hz), 130.3 (d, JC-F= 3.0 Hz), 129.8 (d, JC-F= 2.7 Hz), 129.7, 129.4, 128.3, 128.2, 128.0, 128.0, 127.4 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C20H16FS 307.0951; Found 307.0952. (1-Fluoro-2,2-diphenylvinyl)(4-fluorophenyl)sulfane (4b) White solid (28 mg, 86%), mp: 60.1-64.6 ℃. IR (neat, ν, cm-1): 2957, 2923, 2853, 2361, 1589, 1488, 1442, 1222, 1078, 930, 826, 767, 734, 694, 675, 613, 497 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.53 – 7.17 (m, 12H), 7.01 (td, J = 8.8, 2.5 Hz, 2H).; 19F NMR (376 MHz, CDCl3) δ -89.1, -113.53; 13C{1H}NMR (101 MHz, CDCl3) δ 162.7 (d, JC-F= 246.5 Hz), 151.8, 148.8, 138.4 (d, JC-F= 3.9 Hz), 136.9 (d, JC-F= 2.5 Hz), 132.9 (d, JC-F= 8.2 Hz), 130.4 (d, JC-F= 3.0 Hz), 129.8 (d, JC-F= 5.4 Hz), 128.4, 128.2, 128.1, 128.0, 127.2, 116.5 (d, JC-F= 22.2 Hz) ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C20H15F2S 325.0857; Found 325.0863. (4-Chlorophenyl)(1-fluoro-2,2-diphenylvinyl)sulfane (4c) White solid (33 mg, 97%), mp: 79.3-83.5 ℃ IR (neat, ν, cm-1):2361, 2325, 1473, 1079, 1008, 929, 815, 766, 693, 674, 616, 483 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.29 (ddt, J = 19.6, 10.9, 6.2 Hz, 14H); 19F NMR (376 MHz, CDCl3) δ -89.2; 13C{1H}NMR (101 MHz, CDCl3) δ 149.6 (d, JC-F= 302.2 Hz), 138.4 (d, JC-F= 3.9 Hz), 136.8 (d, JC-F= 2.5 Hz), 133.7, 131.2, 131.1 (d, JC-F= 2.6 Hz), 130.3 (d, JC-F= 3.2 Hz), 129.8 (d, JC-F= 5.3 Hz), 129.5, 128.4, 128.3, 128.2, 128.1 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C20H15ClFS 341.0562; Found 341.0572. (4-Bromophenyl)(1-fluoro-2,2-diphenylvinyl)sulfane (4d) White solid (25 mg, 66%), mp: 77.1-78.6 ℃. IR (neat, ν, cm-1):3054, 3019, 2920, 2850, 2362, 1580, 1441, 1179, 1069, 931, 755, 738, 695, 613 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.41 (tt, J = 4.6, 2.0 Hz, 2H), 7.38 – 7.19 (m, 12H); 19F NMR (376 MHz, CDCl3) δ -89.1; 13C{1H}NMR (101 MHz, CDCl3) δ 149.4 (d, JC-F= 302.1 Hz), 138.4 (d, JC-F= 3.8 Hz), 136.8 (d, JC-F= 2.9 Hz) , 132.5, 131.8 (d, JC-F= 2.5 Hz), 131.4, 131.3 (d, JC-F= 0.6 Hz), 130.2 (d, JC-F= 3.1 Hz), 129.8(d, JC-F= 5.4 Hz), 128.4, 128.3, 128.2, 128.1, 121.6 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C20H15BrFS 385.0056; Found 385.0060. (1-Fluoro-2,2-diphenylvinyl)(p-tolyl)sulfane (4e) White solid (29 mg, 90%), mp: 69.5-88.8 ℃. IR (neat, ν, cm-1): 2954, 2920, 2851, 1599, 1473, 1443, 1377, 1177, 1079, 1008, 815, 766, 693, 674, 616, 555, 483 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.61 – 6.99 (m, 14H), 2.34 (s, 3H); 19F NMR (376 MHz, CDCl3) δ -88.7; 13C{1H}NMR (101 MHz, CDCl3) δ 150.6 (d, JC-F= 302.2 Hz), 138.7 (d, JC-F= 3.9 Hz), 137.8, 137.1, 130.54, 130.4 (d, JC-F= 3.0 Hz), 130.1, 129.8 (d, JC-F= 5.2 Hz), 129.6, 128.6, 128.3, 128.2, 128.0, 127.8, 21.3 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C21H18FS 321.1108; Found 321.1119. (1-Fluoro-2,2-diphenylvinyl)(o-tolyl)sulfane (4f) White solid (31 mg, 98%), mp: 32.1-35.2 ℃. IR (neat, ν, cm-1): 3055, 2956, 2918, 2850, 1606, 1493, 1441, 1182, 1082, 1054, 966, 931, 833, 752, 693, 674, 615, 559, 437 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.49 (dd, J = 3.4, 1.9 Hz, 1H), 7.37 – 7.21 (m, 10H), 7.16 (d, J = 2.8 Hz, 3H), 2.30 (s, 3H); 19F NMR (376 MHz, CDCl3) δ -88.9; 13C{1H}NMR (101



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MHz, CDCl3) δ 149.9 (d, JC-F= 301.7 Hz), 138.5 (t, JC-F= 2 Hz), 137.1 (d, JC-F= 2.8 Hz), 131.5 (d, JC-F= 1.6 Hz), 130.71, 130.3 (d, JC-F= 3.1 Hz), 130.0 (d, JC-F= 16.7 Hz), 129.8 (d, JC-F= 5.4 Hz), 128.4, 128.2, 128.0, 127.9, 127.8, 126.8, 77.5, 77.2, 76.8, 20.5 ppm. HRMS (CITOF) m/z: [M + H]+ Calcd for C21H18FS 321.1108; Found 321.1107. (1-Fluoro-2,2-diphenylvinyl)(methyl)sulfane (4g) Colourless oil (22 mg, 90%). IR (neat, ν, cm-1): 3054, 3022, 2928, 1599, 1493, 1442, 1315, 1181, 1082, 970, 932, 753, 694, 672, 614, 492, 456 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.49 – 7.05 (m, 10H), 2.32 (s, 3H); 19 F NMR (376 MHz, CDCl3) δ -93.7; 13C{1H}NMR (101 MHz, CDCl3) δ 152.6 (d, JC-F= 301.4 Hz), 138.5 (d, JC-F= 4.9 Hz), 137.3 (d, JC-F= 2.2 Hz) 130.5 (d, JC-F= 3.1 Hz), 129.6 (d, JC-F= 5.2 Hz), 128.3, 128.2, 127.8, 127.4, 125.4 (d, JC-F= 16.7 Hz), 14.91 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C15H14FS: 245.0795; Found 245.0793. Decyl(1-fluoro-2,2-diphenylvinyl)sulfane (4h) Yellow oil (22 mg, 95%). IR (neat, ν, cm-1):2954, 2923, 2852, 1600, 1494, 1443, 1181, 1080, 933, 753, 695, 673, 615cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.50 – 7.11 (m, 10H), 2.77 (t, J = 7.3 Hz, 2H), 1.64 (p, J = 7.3 Hz, 2H), 1.25 (s, 14H), 0.88 (t, J = 6.8 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ -91.3. 13C{1H}NMR (101 MHz, CDCl3) δ 152.3 (d, JC-F= 301.0 Hz), 138.7 (d, JC-F= 4.7 Hz), 137.4 (d, JC-F= 2.2 Hz), 130.6 (d, JC-F= 3.1 Hz), 129.6 (d, JC-F= 5.3 Hz), 128.2, 128.1, 127.7, 127.4, 126.6 (d, JC-F= 17.3 Hz), 32.1 (d, JC-F= 2.1 Hz), 32.1, 29.9, 29.7, 29.6, 29.4, 29.3, 28.7, 22.8, 14.3 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C24H32FS: 371.2203; Found 371.2203. Benzyl(1-fluoro-2,2-diphenylvinyl)sulfane (4i) Yellow oil (31 mg, 98%). IR (neat, ν, cm-1): 3057, 3028, 2926, 1599, 1493, 1442, 1180, 1069, 932, 753, 693, 615, 471 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.32 – 7.15 (m, 13H), 6.90 – 6.75 (m, 2H), 3.97 (s, 2H); 19F NMR (376 MHz, CDCl3) δ -90.4; 13C{1H}NMR (101 MHz, CDCl3) δ 151.7 (d, JC-F= 302.2 Hz), 138.5 (d, JC-F= 4.6 Hz), 137.3 (d, JC-F= 2.5 Hz), 137.2, 130.4 (d, JC-F= 3.1 Hz), 129.6 (d, JC-F= 5.2 Hz), 129.2, 129.0, 128.7, 128.1, 128.1, 127.6, 127.6, 127.5, 36.6 ppm. HRMS (CITOF) m/z: [M + H]+ Calcd for C21H18FS: 321.1108; Found 321.1117. (1-Fluoro-2,2-diphenylvinyl)(3-phenylpropyl)sulfane (4j) yellow oil (34 mg, 98%). IR (neat, ν, cm-1):3058, 3025, 2928, 2853, 1601, 1494, 1442, 1280, 1072, 932, 753, 694, 673, 615 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.37 – 7.09 (m, 15H), 2.77 (t, J = 7.1 Hz, 2H), 2.67 – 2.60 (m, 2H), 2.03 – 1.91 (m, 2H); 19F NMR (376 MHz, CDCl3) δ -91.2; 13C{1H}NMR (101 MHz, CDCl3) δ 152.0 (d, JC-F= 301.1 Hz), 141.2, 138.6 (d, JC-F= 4.7 Hz), 137.3 (d, JC-F= 2.3 Hz), 130.6 (d, JC-F= 3.1 Hz), 129.6 (d, JC-F= 5.3 Hz), 128.55, 128.50, 128.26, 128.13, 127.72, 127.44, 127.1 (d, JC-F= 17.1 Hz), 126.09, , 34.50, 31.5 (d, JC-F= 1.8 Hz), 31.30 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C23H22FS: 349.1421; Found 349.1417. Cyclobutyl(1-fluoro-2,2-diphenylvinyl)sulfane (4k) Yellow oil (24 mg, 62%). IR (neat, ν, cm-1): 2979, 2931, 2854, 1618, 1493, 1441, 1265, 1179, 1069, 915, 836, 754, 693, 616, 531, 463 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.44 – 7.09 (m, 10H), 3.84 (p, J = 8.0 Hz, 1H), 2.37 (ddp, J = 14.2, 7.9, 3.6 Hz, 2H), 2.14 (pd, J = 9.9, 3.1 Hz, 2H), 2.05 – 1.81 (m, 2H); 19F NMR (376 MHz, CDCl3) δ -87.5; 13 C{1H}NMR (101 MHz, CDCl3) δ 152.7 (d, JC-F= 300.4 Hz), 138.7 (d, JC-F= 4.7 Hz), 137.4 (d, JC-F= 2.2 Hz), 130.6 (d, JC-F= 3.3 Hz), 129.7 (d, JC-F= 5.3 Hz), 128.3, 128.2, 127.7, 127.4, 126.8 (d, JC-F= 17.1 Hz), 39.9, 31.1, 18.9 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C18H18FS: 285.1108; Found 285.1100. Cyclopentyl(1-fluoro-2,2-diphenylvinyl)sulfane (4l) White solid (29 mg, 96%), mp: 38.2-42.6 ℃. IR (neat, ν, cm-1): 2953, 2867, 1619, 1491, 1442, 1180, 1066, 933, 913, 755, 694, 617 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.54 – 6.95 (m, 10H), 3.74 – 3.43 (m, 1H), 2.17 – 1.87 (m, 2H), 1.81 – 1.44 (m, 6H); 19F NMR (376 MHz, CDCl3) δ -87.7; 13C{1H}NMR (101 MHz, CDCl3) δ 153.1 (d, JC-F= 300.2 Hz), 138.7 (d, JC-F= 4.7 Hz), 137.5 (d, JC-F= 2.3 Hz), 130.6 (d, JC-F= 3.2 Hz), 129.7 (d, JC-F= 5.2 Hz), 128.2, 128.1, 127.6, 127.4, 127.1 (d, JC-F= 17.5 Hz), 45.2, 33.5, 24.7 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C19H20FS: 299.1264; Found 299.1263. Cycloheptyl(1-fluoro-2,2-diphenylvinyl)sulfane (4m) White solid (28 mg, 87%), mp: 29.3-32.1 ℃. IR (neat, ν, cm-1):3053, 2922, 2851, 1614, 1492, 1441, 1225, 1180, 1069, 931, 754, 692, 675, 617 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.43 – 7.06 (m, 10H), 3.40 (tt, J = 8.6, 4.2 Hz, 1H), 2.02 (dq, J = 10.8, 4.2 Hz, 2H), 1.70 – 1.39 (m, 10H); 19F NMR (376 MHz, CDCl3) δ -87.7; 13C{1H}NMR (101 MHz, CDCl3) δ 152.7 (d, JC-F= 299.6 Hz), 138.8 (d, JC-F= 4.6 Hz), 137.5 (d, JC-F= 2.3 Hz), 130.6 (d, JC-F= 3.1 Hz), 129.7 (d, JC-F= 5.3 Hz), 128.2, 128.1, 127.9 (d, JC-F= 17.8 Hz), 127.5, 127.4, 46.7, 34.7, 28.2, 25.9 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C21H24FS: 327.1577; Found 327.1571. 4-((1-Fluoro-2,2-diphenylvinyl)thio)butyl thiophene-2-carboxylate (4n) Yellow oil (40 mg, 98%). IR (neat, ν, cm-1): 2954, 2854, 1705, 1599, 1418, 1256, 1094, 1072, 750, 6958, 673, 615cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.77 (d, J = 3.7 Hz, 1H), 7.49 (d, J = 5.0 Hz, 1H), 7.27 (td, J = 21.2, 19.4, 7.3 Hz, 10H), 7.05 (t, J = 4.6 Hz, 1H), 4.27 (t, J = 5.7 Hz, 2H), 2.84 (t, J = 6.4 Hz, 2H), 1.89 – 1.69 (m, 4H); 19F NMR (376 MHz, CDCl3) δ -91.5; 13C{1H}NMR (101 MHz, CDCl3) δ 162.2, 151.7 (d, JC-F= 301.0 Hz), 138.5 (d, JC-F= 4.7 Hz), 137.2 (d, JC-F= 2.3 Hz), 133.8, 133.5, 132.4, 130.5 (d, JC-F= 3.1 Hz), 129.6 (d, JC-F= 5.3 Hz), 128.3, 128.1, 127.8, 127.7, 127.4, 127.3 (d, JC+ F= 16.9 Hz), 64.5, 31.6, 27.6, 26.4 ppm. HRMS (ESI-TOF) m/z: [M + Na] Calcd for C23H21FNaO2S2: 435.0859; Found 435.0855. 6-((1-Fluoro-2,2-diphenylvinyl)thio)hexan-1-ol (4o) Colourless oil (30 mg, 90%). IR (neat, ν, cm-1): 3340, 2930, 2856, 1599, 1494, 1442, 1180, 1070, 932, 839, 754, 839, 754, 695, 673, 615 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.41 – 7.07 (m, 10H), 3.56 (t, J = 6.6 Hz, 2H), 2.76 (t, J = 7.3 Hz, 2H), 2.12 (s, 1H), 1.63 (dt, J = 12.8, 6.3 Hz, 2H), 1.53 – 1.42 (m, 2H), 1.32 (dd, J = 7.1, 3.3 Hz, 4H); 19F NMR (376 MHz, CDCl3) δ -91.3; 13C{1H}NMR (101 MHz, CDCl3) δ 152.0 (d, JC-F= 300.9 Hz), 138.5 (d, JC-F= 4.8 Hz), 137.2(d, JC-F= 2.3 Hz), 130.4 (d, JC-F= 3.2 Hz), 129.5 (d, JC-F= 5.3 Hz), 128.1, 128.0, 127.6, 127.3, 126.7 (d, JC-F= 17.1 Hz), 62.6, 32.5, 31.9, 29.7, 28.3, 25.3 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C20H23FNaOS: 353.1346; Found 353.1343. Tert-butyl(2-((1-fluoro-2,2-diphenylvinyl)thio)ethoxy)dimethylsilane (4p) Colourless oil (33 mg, 86%). IR (neat, ν, cm-1): 2953, 2928, 2856, 1741, 1602, 1443, 1254, 1086, 834, 753, 695, 673, 615 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.50 – 7.17 (m, 10H), 3.91 (t, J = 6.9 Hz, 2H), 3.02 (t, J = 6.9 Hz, 2H), 0.98 (s, 9H), 0.15 (s, 6H); 19F NMR (376 MHz, CDCl3) δ -91.7; 13C{1H}NMR (101 MHz, CDCl3) δ 151.8 (d, JC-F= 301.3 Hz), 138.5 (d, JC-F= 4.2 Hz), 137.4 (d, JC-F= 2.1 Hz), 130.6 (d, JC-F= 3.1 Hz), 129.7 (d, JC-F= 5.2 Hz), 128.3, 128.1, 127.7, 127.4, 126.2 (d, JC-F= 16.6 Hz), 62.8, 34.2, 26.0, 18.4, -5.2 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H29FNaOSSi: 411.1585; Found 411.1585. Tert-butyl (2-((1-fluoro-2,2-diphenylvinyl)thio)ethyl)carbamate (4q) White solid (25 mg, 66%), mp: 66.2-67.8 ℃. IR (neat, ν, cm-1): 3397, 3055, 2973, 2922, 2966, 1687, 1622, 1513, 1364, 1173, 1085, 1047, 763, 749, 696, 615, 506 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.60 – 7.05 (m, 10H), 4.73 (s, 1H), 3.51 – 3.23 (m, 2H), 2.89 (t, J = 6.2 Hz, 2H), 1.42 (s, 9H); 19F NMR (376 MHz, CDCl3) δ -91.1; 13 C{1H}NMR (101 MHz, CDCl3) δ 154.2 (d, JC-F= 302.2 Hz), 149.6, 140.7, 138.4 (d, JC-F= 4.3 Hz), 137.0 (d, JC-F= 2.6 Hz), 130.5 (d, JC-F=


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3.2 Hz), 129.7 (d, JC-F= 5.3 Hz), 128.5, 128.2, 128.0, 127.78, 40.4, 32.5, 28.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H24FNNaO2S: 396.1404; Found 396.1394. Methyl N-(tert-butoxycarbonyl)-S-(1-fluoro-2,2-diphenylvinyl)-L-cysteinate (4r) White solid (32 mg, 74%), mp: 83.9-84.5 ℃. IR (neat, ν, cm-1): 3394, 3057, 2977, 2950, 2923, 1761, 1683, 1509, 1366, 1149, 1088, 1060, 765, 748, 695, 615, 503 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.39 – 7.18 (m, 10H), 5.30 (d, J = 6.0 Hz, 1H), 4.61 (dt, J = 8.2, 4.5 Hz, 1H), 3.67 (s, 3H), 3.35 – 3.16 (m, 2H), 1.43 (s, 9H); 19F NMR (376 MHz, CDCl3) δ -92.0; 13C{1H}NMR (101 MHz, CDCl3) δ 170.80, 155.0, 150.3 (d, JC-F= 301.8 Hz), 138.2 (d, JC-F= 4.6 Hz), 136.9 (d, JC-F= 2.2 Hz), 130.5 (d, JC-F= 3.1 Hz), 129.6 (d, JC-F= 5.3 Hz), 128.4, 128.1, 127.9, 127.6, 127.1 (d, JC-F= 16.4 Hz), 53.8, 52.7, 33.9, 29.8, 28.4 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H26FNNaO4S: 454.1459; Found 454.1485. (1-Fluoro-2,2-diphenylvinyl)(hexyl)selane (4s) Yellow oil (25 mg, 92%). IR (neat, ν, cm-1): 2924, 2854, 1739, 1597, 1442, 1372, 1597, 1442, 1372, 1237, 1069, 1046, 933, 910, 750, 695, 666, 605 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.44 – 7.08 (m, 10H), 2.82 (t, J = 7.4 Hz, 2H), 1.72 (p, J = 7.3 Hz, 2H), 1.38 – 1.21 (m, 6H), 0.87 (t, J = 6.8 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ -87.0; 13C{1H}NMR (101 MHz, CDCl3) δ 148.5 (d, JC-F= 321.6 Hz), 139.1 (d, JC-F= 5.8 Hz), 137.2, 137.2, 130.6 (d, JC-F= 3.1 Hz), 129.4 (d, JC-F= 5.4 Hz), 128.4, 128.2, 127.9, 127.4 (d, JC-F= 10.7 Hz), 127.2, 31.4, 30.7, 29.4, 26.4, 26.4, 22.7, 14.2 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C20H24FSe: 363.1022; Found 363.1022. (1-Fluoro-2,2-diphenylvinyl)(octyl)selane (4t) Yellow oil (20 mg, 73%). IR (neat, ν, cm-1): 3055, 3018, 2962, 2917, 2849, 1609, 1580, 1479, 1441, 1179, 1479, 1441, 1093, 1071, 738, 696 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.46 – 7.07 (m, 10H), 2.82 (t, J = 7.4 Hz, 2H), 1.72 (p, J = 7.3 Hz, 2H), 1.40 – 1.14 (m, 10H), 0.87 (t, J = 6.9 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ -87.0; 13C{1H}NMR (101 MHz, CDCl3) δ 1548.5 (d, JC-F= 321.6 Hz), 139.1 (d, JC-F= 6.1 Hz), 137.2, 137.2, 130.6 (d, JC-F= 3.2 Hz), 129.5 (d, JC-F= 5.4 Hz), 128.4, 128.2, 127.9, 127.5 (d, JC-F= 10.8 Hz), 127.3, 31.9, 30.8, 29.8, 29.3, 29.2, 26.4 (d, JC-F= 3.9 Hz), 22.8, 14.2 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C22H28FSe: 391.1335; Found 391.1341. Decyl(1-fluoro-2,2-diphenylvinyl)selane (4u) Yellow oil (23 mg, 84%). IR (neat, ν, cm-1): 2922, 2852, 1597, 1494, 1442, 1181. 1069, 932, 750, 694, 666, 605 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.64 – 6.99 (m, 10H), 2.82 (t, J = 7.4 Hz, 2H), 1.72 (p, J = 7.3 Hz, 2H), 1.25 (s, 14H), 0.88 (t, J = 6.7 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ -86.9; 13C{1H}NMR (101 MHz, CDCl3) δ 148.5 (d, JC-F= 321.5 Hz), 139.1 (d, JC-F= 6.2 Hz), 137.2, 130.6 (d, JC-F= 2.9 Hz), 129.4 (d, JC-F= 5.3 Hz), 128.4, 128.1, 127.8, 127.5 (d, JC-F= 10.8 Hz), 127.2, 32.0, 30.8, 29.8, 29.7, 29.6, 29.4, 29.12, 26.4 (d, JC-F= 3.9 Hz), 22.8, 14.23 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C24H32FSe: 419.1648; Found 419.1644. Cyclobutyl(1-fluoro-2,2-diphenylvinyl)selane (4v) White solid (21 mg, 62%), mp: 37.2-41.6 ℃. IR (neat, ν, cm-1): 2953, 2919, 2850, 1595, 1491, 1461, 1441, 1254, 1177, 1071, 936, 764, 748, 696, 664, 605, 480 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.39 – 7.16 (m, 10H), 4.05 (p, J = 8.1 Hz, 1H), 2.57 – 2.35 (m, 2H), 2.26 (pd, J = 9.1, 2.7 Hz, 2H), 2.12 – 1.87 (m, 2H); 19F NMR (376 MHz, CDCl3) δ -83.5; 13 C{1H}NMR (101 MHz, CDCl3) δ 150.0 (d, JC-F= 320.9Hz), 139.1(d, JC-F= 5.0 Hz), 137.2, 130.6 (d, JC-F= 3.1 Hz), 129.5 (d, JC-F= 5.4 Hz), 128.4, 128.2, 128.0, 127.9, 127.3, 35.6, 32.0, 20.4 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C18H18FSe: 333.0552; Found 333.0542. Cyclopentyl(1-fluoro-2,2-diphenylvinyl)selane (4w) White solid (33 mg, 95%), mp: 39.7-43.4 ℃. IR (neat, ν, cm-1): 2954, 2920, 2851, 1492, 1441, 1179, 1060, 932, 751, 694, 604 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.70 – 6.83 (m, 11H), 3.70 (dt, J = 12.8, 6.9 Hz, 1H), 2.23 – 1.90 (m, 2H), 1.87 – 1.47 (m, 6H); 19F NMR (376 MHz, CDCl3) δ -83.4; 13C{1H}NMR (101 MHz, CDCl3) δ 149.9 (d, JC-F= 320.7 Hz), 139.1 (d, JC-F= 6.0 Hz), 137.3, 130.6 (d, JC-F= 3.1 Hz), 129.5 (d, JC-F= 5.4 Hz), 128.4, 128.2, 128.0, 127.8, 127.3, 41.1, 34.1, 25.0 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C19H20FSe: 347.0709; Found 347.0714. Cyclohexyl(1-fluoro-2,2-diphenylvinyl)selane (4x) Yellow oil (22 mg, 92%). IR (neat, ν, cm-1): 2926, 2851, 1714, 1596, 1494, 1442, 1257, 1183, 1064, 991, 931, 750, 694, 666, 605, 480 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.28 (td, J = 20.8, 19.0, 4.7 Hz, 10H), 3.46 (dt, J = 14.1, 7.1 Hz, 1H), 2.07 (d, J = 12.7 Hz, 2H), 1.79 – 1.66 (m, 2H), 1.59 (d, J = 10.9 Hz, 2H), 1.43 – 1.14 (m, 4H); 19F NMR (376 MHz, CDCl3) δ -83.4; 13C{1H}NMR (101 MHz, CDCl3) δ 149.2 (d, JC-F= 318.9 Hz), 139.3 (d, JC-F= 5.9 Hz), 137.3, 130.7 (d, JC-F= 3.0 Hz), 129.6 (d, JC-F= 5.4 Hz), 129.0 (d, JC-F= 10.9 Hz), 128.3, 128.2, 127.8, 127.3, 42.6, 34.4, 26.9, 25.8 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C20H22FSe: 361.0865; Found 361.0854. (2-(Cyclopentylsulfonyl)-2-fluoroethene-1,1-diyl)dibenzene (6) White solid (0.82g, 92%), mp: 134.1-136.2 ℃. IR (neat, ν, cm-1): 3056, 2959, 2875, 1625, 1493, 1443, 1321, 1186, 1149, 1098, 921, 832, 765, 695, 626, 589, 555, 493, 469 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.65 – 7.07 (m, 10H), 3.64 (dddd, J = 11.7, 9.3, 6.8, 3.5 Hz, 1H), 2.05 (ddq, J = 25.4, 13.3, 7.1 Hz, 4H), 1.88 – 1.70 (m, 2H), 1.70 – 1.60 (m, 2H); 19F NMR (376 MHz, CDCl3) δ -118.31; 13C{1H}NMR (101 MHz, CDCl3) δ 150.0 (d, JC-F= 296.0 Hz), 135.3, 133.9 (d, JC-F= 4.1 Hz), 132.2 (d, JC-F= 7.2 Hz), 130.3 (d, JC-F= 3.1 Hz), 129.8 (d, JC-F= 5.2 Hz), 129.5, 129.2, 128.5, 128.2, 61.5, 26.7, 26.1 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C19H20FO2S: 331.1163; Found 331.1174. Methyl 2-(2-fluoro-2-(phenylthio)ethyl)benzoate (7) White solid (61 mg, 92%), mp: 85.9-87.2 ℃. IR (neat, ν, cm-1): 2961, 2917, 2849, 1694, 1574, 1416, 1260, 1084, 796, 748, 714, 667, 612, 551, 522, 418 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 8.04 – 7.94 (m, 3H), 7.71 (t, J = 7.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 2H), 7.47 (td, J = 7.5, 1.4 Hz, 1H), 7.36 (td, J = 7.7, 1.2 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 5.54 (ddd, J = 49.0, 10.1, 2.5 Hz, 1H), 4.10 (ddd, J = 37.9, 14.1, 2.4 Hz, 1H), 3.92 (s, 3H), 3.27 (td, J = 14.2, 10.1 Hz, 1H); 19F NMR (377 MHz, CDCl3) δ -179.1; 13C{1H}NMR (101 MHz, CDCl3) δ 167.6, 135.7, 135.3 (d, JC-F=1.0 Hz), 134.7, 133.3, 132.6, 131.5, 129.8, 129.7, 129.4, 128.0, 102.1 (d, JC-F=218Hz), 52.5, 33.3 (d, JC-F=19.3 Hz) ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C16H16FO4S: 323.0748; Found 323.0754. Phenyl(1,2,2-triphenylvinyl)sulfane (8) Light green solid (42 mg, 65%), mp: 134.2-136.4 ℃. IR (neat, ν, cm-1): 2946, 2009, 1472, 1439, 1260, 1024, 796, 761, 741, 697, 624, 593, 474, 430 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.38 (dd, J = 8.1, 1.3 Hz, 2H), 7.34 – 7.25 (m, 5H), 7.21 – 7.14 (m, 2H), 7.11 – 6.91 (m, 11H); 13C{1H}NMR (101 MHz, CDCl3) δ 146.5, 143.9, 142.6, 139.3, 135.9, 134.1, 131.2, 130.9, 129.8, 129.7, 128.6, 128.3, 127.8, 127.7, 127.4, 127.2, 126.8, 125.9 ppm. HRMS (CI-TOF) m/z: [M + H]+ Calcd for C26H21S: 365.1358; Found 323. 365.1357.



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ASSOCIATED CONTENT Supporting Information Available. The copies of 1H and 13C and 19F NMR spectra of the products. This material is available free of charge via the Internet at http://pubs.acs.org. ACKNOWLEDGMENT We gratefully acknowledge the National Natural Science Foundation of China (21772137, 21542015 and 21672157), PAPD, the project of scientific and technologic infrastructure of Suzhou (SZS201708), the Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (No.16KJA150002), Soochow University. REFERENCES (1) (a) Landelle, G.; Bergeron, M.; Turcotte-Savard, M.-O.; Paquin, J.-F. Synthetic Approaches to Monofluoroalkenes. Chem. Soc. Rev. 2011, 40, 2867-2908. (b) Okoromoba, O. E.; Han, J.; Hammond, G. B.; Xu, B. Designer HF-based Fluorination Reagent: Highly Regioselective Synthesis of Fluoroalkenes and gem-Difluoromethylene Compounds from Alkynes. J. Am. Chem. Soc. 2014, 136, 14381-14384. (c) Rousée, K.; Schneider, C.; Couve-Bonnaire, S.; Pannecoucke, X.; Levacher, V.; Hoarau, C. Pd- and Cu-Catalyzed Stereo- and Regiocontrolled Decarboxylative/C-H Fluoroalkenylation of Heteroarenes Chem. - Eur. J. 2014, 20, 15000-15004. (d) Sommer, H.; Fürstner, A. Stereospecific Synthesis of Fluoroalkenes by Silver-Mediated Fluorination of Functionalized Alkenylstannanes. Chem. - Eur. J. 2017, 23, 558-562. (e) Liu, T.-L.; Wu, J. E.; Zhao, Y. Divergent Reactivities in Fluoronation of Allylic Alcohols: Synthesis of Z-Fluoroalkenes via Carbon–Carbon Bond Cleavage. Chem. Sci. 2017, 8, 3885-3890. (f) Zhao, Y.; Jiang, F.; Hu, J. Spontaneous Resolution of Julia-Kocienski Intermediates Facilitates Phase Separation to Produce Z- and E-Monofluoroalkenes. J. Am. Chem. Soc. 2015, 137, 5199-5203. (g) Lin, J.; Toscano, P. J.; Welch, J. T. Inhibition of Dipeptidyl Peptidase IV by Fluoroolefin-Containing NPeptidyl-O-Hydroxylamine Peptidomimetics. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 14020-14024. (h) Dutheuil, G.; CouveBonnaire, S.; Pannecoucke, X. Diastereomeric Fluoroolefins as Peptide Bond Mimics Prepared by Asymmetric Reductive Amination of α-Fluoroenones. Angew. Chem., Int. Ed. 2007, 46, 1290-1292. (2) (a) Xiong, Y.; Zhang, X.; Huang, T.; Cao, S. N-(α-Fluorovinyl)azoles by The Reaction of Difluoroalkenes with Azoles. J. Org. Chem. 2014, 79, 6395-6402. (b) Zhang, X.; Lin, Y.; Zhang, J.; Cao, S. Base-Mediated Direct Fluoroalkenylation of 2-Phenyl-1,3,4-oxadiazole, Benzothiazole and Benzoxazole with gem-Difluoroalkenes. RSC Adv. 2015, 5, 7905-7908. (c) Landelle, G. G.; Champagne, P. A.; Barbeau, X. Stereocontrolled Approach to Bromofluoroalkenes and Their use For the Synthesis of tri- and tetrasubstituted Fluoroalkenes. Org. Lett. 2009, 11, 681-684. (3) Wang, M.; Liang, F.; Xiong, Y.; Cao, S. Synthesis of Fluorovinyl Aryl Ethers by A Three-Component Reaction of gemDifluoroalkenes with Arylboronic Acids and Oxygen. RSC Adv. 2015, 5, 11996-11999. (4) Zhang, J.; Xu, C.; Wu, W.; Cao, S. Mild and Copper-Free Stereoselective Cyanation of gem-Difluoroalkenes by Using Benzyl Nitrile as a Cyanating Reagent. Chem. - Eur. J. 2016, 22, 9902-9908.


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Fluoromethylation

and

Subsequent

Transformation

of

Alkyl

and

Benzyl

Halides

Using

Fluorobis(phenylsulfonyl)methane Org. Lett. 2009 11, 1127. (17) For selected examples on AIE attributes: (a) Hong, Y.; Lam, J. W. Y.; T, B. Z. Aggregation-Induced Emission. Chem. Soc. Rev., 2011, 40, 5361–5388. (b) Hong, Y.; Lam J. W. Y.; Tang, B. Z. Aggregation-Induced Emission: Phenomenon, Mechanism and Applications. Chem. Commun. 2009, 0, 4332-4353. (c) Wu, Y. T.; Kuo, M. Y.; Chang, Y. T.; C.; Shin, C.;


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