Alkyl Thiolation of Ketene

Sep 25, 2018 - The sulfenylation of the vinyl C–H bond in ketene dithioacetals leading to the synthesis of polythiolated alkenes is achieved via the...
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Article Cite This: ACS Omega 2018, 3, 11890−11895

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Metal-Free Vinyl C−H Sulfenylation/Alkyl Thiolation of Ketene Dithioacetals for the Synthesis of Polythiolated Alkenes Leiling Deng and Yunyun Liu* College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, P. R. China

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S Supporting Information *

ABSTRACT: The sulfenylation of the vinyl C−H bond in ketene dithioacetals leading to the synthesis of polythiolated alkenes is achieved via the promotion of molecular iodine. In addition, alkyl thiols also exhibit tolerance to the C−H bond elaboration reaction for the synthesis of corresponding alkylthiolated ketene dithioacetals.

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INTRODUCTION Ketene dithioacetals are a class of highly important synthons showing widespread applications in the synthesis of diverse organic molecules.1 Thanks to their multiple reactive sites as well as enriched transformation pathways, dithioacetals have been used as main building blocks in constructing a large variety of different organic products such as N-heterocycles,2 S-heterocycles,3 O-heterocycles,4 heterocycles featuring more than one heteroatoms,5 and full carbon cyclic compounds of different ring sizes.6 Notably, besides the pivotal role as building blocks in the synthesis of those cyclic molecules, the ketene dithioacetal backbone is also a typical alkene precursor showing attractiveness in the synthesis of polyfunctionalized alkenes via direct elaboration on the vinyl C−H bond. For example, the cross-coupling of the α-C−H bond forming new C−C bond7 and C−O bond8 has been successfully realized in the presence of various transition-metal catalysts. Following the daily increasing interest in developing metalfree organic synthesis,9 the direct functionalization on the vinyl C−H bond in the heteroatom-activated alkenes has advanced significantly.10 In this context, the transition-metal-free C−H coupling of the vinyl C−H bond in ketene dithioacetals also has attracted extensive interest and successful examples have been reported. In 2015, Xu, Wang, and co-workers developed the phosphorylation reaction of the α-C−H bond in ketene dithioacetals via the promotion of K2S2O8.11 Later on, the same group reported thiocyanation of the same C−H bond in ketene dithioacetals mediated by N-chlorosuccinimide.12 Rather recently, Lei and co-workers realized the C−H alkylation of ketene dithioacetals on the α-site via the oxidation of di-tert-butyl peroxide.13 Despite these advances, however, the overall examples on the successful α-C−H coupling of ketene dithioacetals for the construction of divergent new chemical bonds without relying on transition-metal catalysis are yet limited. Therefore, establishing transition-metal-free methods enabling the vinyl C−H coupling of ketene dithioacetals is highly demanding. Previously, Singh et al. reported CuI-catalyzed C−H methylthiolation of ketene © 2018 American Chemical Society

dithioacetals using dimethyl sulfoxide (DMSO) in the presence of molecular iodine;14a despite the applications of DMSO as a reagent in this and many other synthetic methods,14b−e an applicable metal-free alkyl thiolation reaction on the vinyl C−H bond of ketene dithioacetals has not yet been realized.15 Since the transition-metal-free C−H crosscoupling forming the C−S bond has recently gained noteworthy progress,16 we envision that it is possible to achieve the metal-free C−S bond-forming reactions via the cross-coupling of the vinyl C−H bond in the ketene dithioacetals with a proper sulfur substrate and catalytic conditions. Herein, we report our results on the vinyl C−H sulfenylation and alkyl thiolation reactions of the ketene dithioacetals by employing sulfonyl hydrazines as the sulfenylating/thiolating reagents under metal-free conditions.

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RESULTS AND DISCUSSION To begin with, the ketene dithioacetal 1a and tosyl hydrazine 2a were tentatively employed in the presence of molecular iodine, and the α-sulfenylated ketene dithioacetal 3a was produced with 25% yield by heating in dimethylformamide (DMF) at 100 °C (entry 1, Table 1). Inspired by this successful sulfenylation transformation, we then conducted systematical optimization experiments to improve the yield of 3a. First, a series of different organic solvents, including N,Ndimethylacetamide (DMAC), toluene, dioxane, DMSO, ethyl lactate (EL), water, EtOH, and tetrahydrofuran (THF) were individually employed. It was found that only those polar solvents with high boiling point can mediate the reaction, and among them, DMAC exhibited the best effect (entries 2−9, Table 1). By using DMAC as the medium, the iodo-promoter was also varied, but no better candidate was identified (entries 10−12, Table 1). Subsequently, increasing the loading of I2 was found to be helpful in enhancing the yield of 3a (entries Received: August 8, 2018 Accepted: September 12, 2018 Published: September 25, 2018 11890

DOI: 10.1021/acsomega.8b01946 ACS Omega 2018, 3, 11890−11895

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Table 1. Optimization on the Reaction conditiona

entry

promoter

solvent

T (°C)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13c 14d 15e 16e,f 17e,g 18e,f 19e,f 20e,f,h

I2 I2 I2 I2 I2 I2 I2 I2 I2 KI NaI KIO3 I2 I2 I2 I2 I2 I2 I2 I2

DMF DMAC toluene dioxane DMSO EL H2O EtOH THF DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC

100 100 100 100 100 100 100 reflux reflux 100 100 100 100 100 100 100 100 80 120 120

25 29 trace nr 20 24 trace trace trace 13 10 trace 33 40 48 72 70 trace 65 trace

the vinyl C−H alkyl thiolation for the synthesis of αalkylthiolated ketene dithioacetals was also realized with satisfactory results by employing alkyl sulfonyl hydrazines as the substrates (3r and 3s, Table 2). Finally, the utilization of ethyl thiolated ketene dithioacetal afforded product 3t with high yield, demonstrating the additional compatibility of the reaction to thiolated ketenes with different S-alkyl structures. According to the result from the control experiment (entry 20, Table 1) and the well-documented C−H sulfenylation reactions reported in the literature,17 a mechanism for the present reactions is proposed. As shown in Scheme 1, the sulfonyl hydrazine 2 can be transformed into disulfide 5 via the intermediate 4 resulting from a featured reductive coupling in the presence of I2.17a The thermo-induced homolytic cleavage on 5 then provides the arylthio free radical 6. The subsequent addition of 6 to ketene dithioacetal 1 led to the formation of intermediate 7. The reaction of 7 and molecular iodine then provides intermediate 8, and the successive elimination of HI from the intermediate 8 yields products 3.

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CONCLUSIONS In conclusion, herein, we have developed a transition-metalfree method for the direct α-sulfenylation and alkyl thiolation of ketene dithioacetals via direct C−H bond coupling functionalization. The metal-free conditions, broad substrate tolerance, and simple operation ensure the present method a useful option for the synthesis of useful polythiolated alkene derivatives.

a

General conditions: 1a (0.2 mmol), 2a (0.2 mmol), and promoter (0.5 equiv) in 2 mL of solvent, stirred for 12 h. bYield of the isolated product. cI2 (1 equiv). dI2 (2 equiv). eI2 (3 equiv). f2a (0.3 mmol). g 2a (0.4 mmol). hIn the presence of TEMPO (4 equiv).

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EXPERIMENTAL SECTION

General. All experiments were conducted under an open air atmosphere. The ketene dithioacetals 118 and commercially unavailable sulfonyl hydrazines 219,20 were synthesized following reported processes. Other chemicals and solvents used in the experiments were commercially available and were used without additional treatment. The 1H and 13C NMR spectra were recorded in 400 MHz apparatus. The frequencies for 1H NMR and 13C NMR test are 400 and 100 MHz, respectively. The NMR chemical shifts were reported in ppm using the internal standard of tetramethylsilane (TMS). The melting points were measured in an X-4A instrument, and the temperature was not corrected. HRMS data were acquired in a spectrometer equipped with a time-of-flight analyzer under electrospray ionization (ESI) mode. General Procedure for the Synthesis of Polythiolated Ketene Dithioacetals 3. A 25 mL round-bottom flask was charged with ketene dithioacetal 1 (0.2 mmol), sulfonyl hydrazine 2 (0.3 mmol), molecular iodine (0.6 mmol), and DMAC (2 mL). Then, the resulting mixture was stirred at 100 °C for 12 h (TLC). Upon completion, 5 mL of water was added to the vessel. Subsequently, ethyl acetate (3 × 8 mL) was used to extract the resulting suspension. The organic phases were combined and washed with a small amount of water three times. After drying with anhydrous Na2SO4 and filtration, the acquired solution was employed to reduce pressure to remove the solvent. The resulting residue was then purified with flash silica gel column chromatography to provide target products, wherein mixed petroleum ether and ethyl acetate (v/v = 15:1) was used as the eluent. 3,3-Bis(methylthio)-1-(p-tolyl)-2-(p-tolylthio)prop-2-en-1one (3a). Yield: 72%, 51.8 mg; yellow solid; mp 82−84 °C; 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.4 Hz, 2H), 7.17 (d,

13−15, Table 1). In addition, evident improvement was achieved by increasing the amount of 2a to 1.5 equiv mole (entries 16−17, Table 1). At last, the impact of the reaction temperature was also examined, but no improved yield of the target product was observed by heightening or lowering the temperature (entries 18−19, Table 1). Under the optimized conditions, a control experiment in the presence of a freeradical scavenger (TEMPO) was conducted, wherein only a trace amount of the product was observed, indicating that this reaction might proceed via a free-radical mechanism (entry 20, Table 1). With the optimized parameters in hand, the synthetic scope of sulfenylation was successively investigated. As outlined in Table 2, ketene dithioacetals functionalized with various aryl substitutions exhibited excellent tolerance to the synthesis. Those substrates containing alkyl (3a, 3c, and 3d, Table 2), alkoxyl (3e, Table 2), halogen (3g, 3h, 3i, and 3k, Table 2), and trifluoromethyl (3j, Table 2) in the phenyl ring of 1 as well as the unsubstituted phenyl ketene dithioacetal (3b, Table 2) took part in the reaction to provide corresponding products with moderate to good yields. In addition, naphthyl- and heteroaryl (thiophenyl)-functionalized ketene dithioacetals were also successfully utilized for the target synthesis (3f, 3l, Table 2). Among these synthesized products, the strong electron-donating effect of the aryl ring in the ketene dithioacetal component led to the synthesis of the polythiolated products with lower yield (3e, 3f, and 3l, Table 2). On the contrary, thiophenol with both electron-donating and -withdrawing substituents could also participate in the reaction to provide the expected products (3m, 3o, 3p, and 3q, Table 2). More notably, alongside the successful C−H sulfenylation, 11891

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Table 2. Application Scope of the Ketene Dithioacetal C−H Sulfenylation/Alkyl Thiolationa,b

General conditions: ketene dithioacetal 1 (0.2 mmol), sulfonyl hydrazine 2 (0.3 mmol), and I2 (0.6 mmol) in DMAC (2 mL), stirred at 100 °C for 12 h. bIsolated yield based on 1.

a

HRMS: calcd for C18H19OS3 (M + H)+, 347.0592; found, 347.0591. 3,3-Bis(methylthio)-1-(o-tolyl)-2-(p-tolylthio)prop-2-en-1one (3c). Yield: 70%, 50.4 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.51 (d, J = 7.6 Hz, 1H), 7.22 (d, J = 7.6 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H), 7.03 (t, J = 9.2, 8.0 Hz, 3H), 6.87 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H), 2.18 (s, 3H), 2.09 (s, 3H), 2.06 (s, 3H); 13C NMR (100 MHz, CDCl3): 192.7, 141.4, 140.4, 138.7, 135.9, 134.9, 134.2, 131.8, 131.7, 131.0, 129.6, 127.5, 125.2, 21.2, 20.9, 18.4, 16.6. ESI-HRMS: calcd for C19H21OS3 (M + H)+, 361.0749; found, 361.0748. 3,3-Bis(methylthio)-1-(m-tolyl)-2-(p-tolylthio)prop-2-en1-one (3d). Yield: 66%, 47.5 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.54 (t, J = 7.0 Hz, 2H), 7.33−7.25 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H), 2.34 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3): 191.2, 140.2, 138.8, 138.2, 136.2, 134.2, 134.1, 133.0, 129.6, 129.5, 128.2, 127.1, 126.7, 21.3, 21.2, 18.4, 16.4; ESI-HRMS: calcd for C19H21OS3+ (M + H)+, 361.0749; found, 361.0748. 1-(4-Methoxyphenyl)-3,3-bis(methylthio)-2-(p-tolylthio)prop-2-en-1-one (3e). Yield: 54%, 40.8 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.74 (s, 1H), 7.72 (s, 1H), 7.17 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.86 (s, 1H),

Scheme 1. Proposed Reaction Mechanism

J = 8.0 Hz, 4H), 6.93 (d, J = 8.0 Hz, 2H), 2.48 (s, 3H), 2.38 (s, 3H), 2.23 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3): 190.6, 144.1, 140.4, 138.8, 134.2, 133.8, 132.5, 129.6, 129.4, 129.1, 127.1, 21.8, 21.2, 18.4, 16.4; ESI-HRMS: calcd for C19H21OS3 (M + H)+, 361.0749; found, 361.0750. 3,3-Bis(methylthio)-1-phenyl-2-(p-tolylthio)prop-2-en-1one (3b). Yield: 65%, 45.0 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 7.6 Hz, 2H), 7.50 (d, J = 7.4 Hz, 1H), 7.37 (d, J = 7.6 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H); 13 C NMR (100 MHz, CDCl3): 190.9, 140.1, 138.8, 136.3, 134.3, 133.2, 129.6, 129.3, 128.3, 127.0, 21.2, 18.4, 16.4. ESI11892

DOI: 10.1021/acsomega.8b01946 ACS Omega 2018, 3, 11890−11895

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(400 MHz, CDCl3): δ 7.92 (dd, J = 2.8, 1.2 Hz, 1H), 7.32 (dd, J = 5.2, 1.2 Hz, 1H), 7.23−7.17 (m, 3H), 6.96 (d, J = 8.0 Hz, 2H), 2.48 (s, 3H), 2.24 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3): 184.8, 141.6, 140.5, 138.8, 134.1, 133.9, 133.4, 129.6, 127.4, 127.2, 126.1, 21.2, 18.6, 16.5; ESI-HRMS: calcd for C16H17OS4 (M + H)+, 353.0157; found, 353.0155. 3,3-Bis(methylthio)-2-(phenylthio)-1-(p-tolyl)prop-2-en-1one (3m). Yield: 50%, 34.9 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.25−7.06 (m, 5H), 2.49 (s, 3H), 2.38 (s, 3H), 2.18 (s, 3H); 13C NMR (100 MHz, CDCl3): 190.6, 144.2, 139.0, 134.7, 133.7, 131.1, 129.4, 129.1, 128.8, 128.37, 21.8, 18.5, 16.5; ESI-HRMS: calcd for C18H19OS3 (M + H)+, 347.0592; found, 347.0590. 3,3-Bis(methylthio)-2-(naphthalen-2-ylthio)-1-(p-tolyl)prop-2-en-1-one (3n). Yield: 48%, 38.2 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.77 (s, 1H), 7.72 (t, 1H), 7.63 (dd, J = 8.4, 3.6 Hz, 4H), 7.46−7.38 (m, 2H), 7.36 (dd, J = 8.0, 2.0 Hz, 1H), 7.13 (d, J = 8.4 Hz, 2H), 2.51 (s, 3H), 2.35 (s, 3H), 2.21 (s, 3H); 13C NMR (100 MHz, CDCl3): 190.6, 144.2, 138.4, 136.0, 133.7, 133.3, 132.8, 132.7, 130.1, 129.5, 129.1, 128.6, 128.4, 127.6, 126.6, 126.4, 21.7, 18.6, 16.5; ESIHRMS: calcd for C22H21OS3 (M + H)+, 397.0749; found, 397.0753. 2-((4-Fluorophenyl)thio)-3,3-bis(methylthio)-1-(p-tolyl)prop-2-en-1-one (3o). Yield: 53%, 38.8 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 8.0 Hz, 2H), 7.19 (dd, J = 8.6, 5.4 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 6.73 (t, J = 8.8, 8.4 Hz, 2H), 2.40 (s, 3H), 2.30 (s, 3H), 2.08 (s, 3H); 13C NMR (100 MHz, CDCl3): 190.4, 164.3 (d, 1JC−F = 248.0 Hz), 161.8, 144.4, 139.7, 136.5 (d, 3JC−F = 8.3 Hz), 136.5, 133.6, 133.0, 129.4, 129.2, 125.9 (d, 4JC−F = 3.3 Hz), 125.9, 116.0 (d, 2 JC−F = 21.9 Hz), 115.8, 21.7, 18.4, 16.4; ESI-HRMS: calcd for C18H18FOS3 (M + H)+, 365.0498; found, 365.0499. 2-((4-Chlorophenyl)thio)-3,3-bis(methylthio)-1-(p-tolyl)prop-2-en-1-one (3p). Yield: 43%, 32.5 mg; yellow solid; mp 95−97 °C;1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.4 Hz, 2H), 7.25−7.17 (m, 4H), 7.11 (d, J = 8.4 Hz, 2H), 2.49 (s, 3H), 2.39 (s, 3H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3): 190.5, 144.4, 137.7, 136.2, 134.6, 133.5, 129.8, 129.4, 129.3, 129.0, 21.8, 18.5, 16.5; ESI-HRMS: calcd for C18H18ClOS3 (M + H)+, 381.0203; found, 381.0204. 3,3-Bis(methylthio)-2-((4-nitrophenyl)thio)-1-(p-tolyl)prop-2-en-1-one (3q). Yield: 58%, 45.2 mg; yellow solid; mp 99−101 °C; 1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 8.8 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 2.51 (s, 3H), 2.41 (s, 3H), 2.29 (s, 3H): 13C NMR (100 MHz, CDCl3): 190.6, 148.7, 146.4, 144.7, 143.1, 133.0, 129.6, 129.5, 129.4, 123.9, 21.8, 19.0, 16.7; ESI-HRMS: calcd for C18H18NO3S3 (M + H)+, 392.0443; found, 392.0444. 2,3,3-Tris(methylthio)-1-(p-tolyl)prop-2-en-1-one (3r). Yield: 78%, 44.3 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.87 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 2.43 (s, 6H), 2.13 (s, 3H), 2.09 (s, 3H); 13C NMR (100 MHz, CDCl3): 190.8, 144.8, 141.7, 133.6, 129.6, 129.5, 128.4, 21.8, 18.3, 16.2, 16.0; ESI-HRMS: calcd for C13H17OS3 (M + H)+, 285.0436; found, 285.0436. 2-(Ethylthio)-3,3-bis(methylthio)-1-(p-tolyl)prop-2-en-1one (3s). Yield: 66%, 39.6 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 2.61 (q, J = 7.3 Hz, 2H), 2.43 (d, J = 3.6 Hz, 6H), 2.10 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):

6.84 (s, 1H), 3.85 (s, 3H), 2.48 (s, 3H), 2.23 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3): 189.6, 163.7, 140.8, 138.8, 134.4, 131.8, 131.7, 129.5, 129.3, 127.0, 113.6, 55.5, 21.2, 18.4, 16.4; ESI-HRMS: calcd for C19H21O2S3 (M + H)+, 377.0698; found, 377.0696. 3,3-Bis(methylthio)-1-(naphthalen-2-yl)-2-(p-tolylthio)prop-2-en-1-one (3f). Yield: 52%, 41.3 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 8.29 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.79 (s, 2H), 7.56 (dt, J = 22.8, 7.8, 7.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 2H), 2.52 (s, 3H), 2.18 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3): 190.9, 140.2, 138.9, 135.7, 134.3, 133.7, 133.2, 132.5, 131.3, 129.7, 129.6, 128.5, 128.3, 127.8, 127.0, 126.7, 124.6, 21.1, 18.5, 16.5. ESI-HRMS: calcd for C22H21OS3 (M + H)+, 397.0749; found, 397.0748. 1-(4-Chlorophenyl)-3,3-bis(methylthio)-2-(p-tolylthio)prop-2-en-1-one (3g). Yield: 61%, 46.4 mg; yellow solid; mp 80−82 °C; 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H), 2.24 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3): 189.7, 139.6, 139.4, 139.0, 134.7, 134.3, 133.7, 130.6, 129.7, 128.7, 126.8, 21.2, 18.5, 16.4; ESI-HRMS: calcd for C18H18ClOS3 (M + H)+, 381.0203; found, 381.0202. 1-(4-Bromophenyl)-3,3-bis(methylthio)-2-(p-tolylthio)prop-2-en-1-one (3h). Yield: 64%, 54.1 mg; yellow solid; mp 104−107 °C; 1H NMR (400 MHz, CDCl3): δ 7.59 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H), 2.24 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3): 189.9, 139.3, 139.0, 135.1, 134.2, 131.7, 130.7, 129.7, 128.3, 126.8, 21.2, 18.5, 16.4; ESI-HRMS: calcd for C18H18BrOS3 (M + H)+, 424.9698; found, 424.9700. 1-(4-Fluorophenyl)-3,3-bis(methylthio)-2-(p-tolylthio)prop-2-en-1-one (3i). Yield: 62%, 45.0 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.75 (dd, J = 8.8, 5.6 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 7.03 (t, J = 8.4 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H), 2.24 (s, 3H), 2.18 (s, 3H); 13C NMR (100 MHz, CDCl3): 189.4, 167.0 (d, 1JC−F = 253.8 Hz), 164.5, 139.8, 139.0, 134.3, 133.2, 132.7 (d, 4JC−F = 2.0 Hz), 132.7, 131.9 (d, 3JC−F = 10.0 Hz), 131.8, 129.6, 126.8, 115.6 (d, 2JC−F = 22.0 Hz), 115.4, 21.1, 18.5, 16.4; ESI-HRMS: calcd for C18H18FOS3 (M + H)+, 365.0498; found, 365.0497. 3,3-Bis(methylthio)-2-(p-tolylthio)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one (3j). Yield: 70%, 57.9 mg; yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 2.51 (s, 3H), 2.24 (s, 3H), 2.17 (s, 3H); 13 C NMR (100 MHz, CDCl3): 189.8, 139.2, 139.0, 138.7, 135.3, 134.4, 134.1, 129.7, 129.4, 126.8, 125.4(d, J = 3.9 Hz), 125.3, 125.0, 21.1, 18.5, 16.5; ESI-HRMS: calcd for C19H18F3OS3 (M + H)+, 415.0466; found, 415.0465. 1-(3-Chlorophenyl)-3,3-bis(methylthio)-2-(p-tolylthio)prop-2-en-1-one (3k). Yield: 60%, 45.8 mg; yellow solid; mp 90−93 °C; 1H NMR (400 MHz, CDCl3): δ 7.65 (s, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.46 (d, J = 6.8 Hz, 1H), 7.31 (t, J = 8.0, 7.6 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 2.50 (s, 3H), 2.24 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3): 189.7, 139.1, 139.0, 138.0, 134.6, 134.6, 134.2, 133.0, 129.7, 129.6, 129.0, 127.3, 126.8, 21.2, 18.5, 16.5; ESI-HRMS: calcd for C18H18ClOS3 (M + H)+, 381.0203; found, 381.0203. 3,3-Bis(methylthio)-1-(thiophen-2-yl)-2-(p-tolylthio)prop2-en-1-one (3l). Yield: 57%, 40.3 mg; yellow liquid; 1H NMR 11893

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190.9, 144.7, 140.6, 133.4, 130.3, 129.6, 129.5, 27.5, 21.8, 18.3, 16.2, 14.4; ESI-HRMS: Calcd for C14H19OS3 (M + H)+, 299.0592; found, 299.0593. 3,3-Bis(ethylthio)-1-(p-tolyl)-2-(p-tolylthio)prop-2-en-1one (3t). Yield: 73%, 56.8 mg; yellow solid; mp 66−69 °C; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 8.4 Hz, 2H), 7.15 (dd, J = 8.0, 3.2 Hz, 4H), 6.91 (d, J = 8.0 Hz, 2H), 2.97 (q, J = 7.3 Hz, 2H), 2.69 (q, J = 7.4 Hz, 2H), 2.37 (s, 3H), 2.22 (s, 3H), 1.39 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 190.7, 144.0, 143.1, 138.7, 134.4, 133.8, 129.5, 129.5, 129.4, 129.0, 127.2, 29.1, 27.8, 21.7, 21.2, 15.2, 14.5; ESI-HRMS: calcd for C21H25OS3 (M + H)+, 389.1062; found, 389.1065.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.8b01946. 1 H and 13C NMR spectra for all products (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (Y.L). ORCID

Yunyun Liu: 0000-0002-5553-1672 Author Contributions

All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is financially supported by the National Natural Science Foundation of China (21562024). REFERENCES

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