Skip to main content
NCBI home page
ACS Omega logoLink to ACS Omega
. 2018 Sep 25;3(9):11890–11895. doi: 10.1021/acsomega.8b01946

Metal-Free Vinyl C–H Sulfenylation/Alkyl Thiolation of Ketene Dithioacetals for the Synthesis of Polythiolated Alkenes

Leiling Deng 1, Yunyun Liu 1,*
PMCID: PMC6645039  PMID: 31459275

Abstract

graphic file with name ao-2018-01946n_0005.jpg

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.

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 metal-free 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 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−14e 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 cross-coupling 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.

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,N-dimethylacetamide (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 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 free-radical 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).

Table 1. Optimization on the Reaction conditiona.

graphic file with name ao-2018-01946n_0002.jpg

entry promoter solvent T (°C) yield (%)b
1 I2 DMF 100 25
2 I2 DMAC 100 29
3 I2 toluene 100 trace
4 I2 dioxane 100 nr
5 I2 DMSO 100 20
6 I2 EL 100 24
7 I2 H2O 100 trace
8 I2 EtOH reflux trace
9 I2 THF reflux trace
10 KI DMAC 100 13
11 NaI DMAC 100 10
12 KIO3 DMAC 100 trace
13c I2 DMAC 100 33
14d I2 DMAC 100 40
15e I2 DMAC 100 48
16e,f I2 DMAC 100 72
17e,g I2 DMAC 100 70
18e,f I2 DMAC 80 trace
19e,f I2 DMAC 120 65
20e,f,h I2 DMAC 120 trace
Open in a new tab
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.

b

Yield of the isolated product.

c

I2 (1 equiv).

d

I2 (2 equiv).

e

I2 (3 equiv).

f

2a (0.3 mmol).

g

2a (0.4 mmol).

h

In the presence of TEMPO (4 equiv).

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, the vinyl C–H alkyl thiolation for the synthesis of α-alkylthiolated 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.

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

graphic file with name ao-2018-01946n_0003.jpg

graphic file with name ao-2018-01946n_0004.jpg

Open in a new tab
a

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.

b

Isolated yield based on 1.

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.

Scheme 1. Proposed Reaction Mechanism.

Scheme 1

Open in a new tab

Conclusions

In conclusion, herein, we have developed a transition-metal-free 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.

Experimental Section

General

All experiments were conducted under an open air atmosphere. The ketene dithioacetals 1(18) 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-1-one (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, 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-1-one (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); 13C 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. ESI-HRMS: calcd for C18H19OS3 (M + H)+, 347.0592; found, 347.0591.

3,3-Bis(methylthio)-1-(o-tolyl)-2-(p-tolylthio)prop-2-en-1-one (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-en-1-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), 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); 13C 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)prop-2-en-1-one (3l)

Yield: 57%, 40.3 mg; yellow liquid; 1H NMR (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-1-one (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; ESI-HRMS: 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, 2JC–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-1-one (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): 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-1-one (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.

Acknowledgments

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

Supporting Information Available

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.8b01946.

  • 1H and 13C NMR spectra for all products (PDF)

Author Contributions

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

The authors declare no competing financial interest.

Supplementary Material

ao8b01946_si_001.pdf (4.1MB, pdf)

References

  1. a Dieter R. K. α-Oxo ketene dithioacetals and related compounds: versatile three-carbon synthons. Tetrahedron 1986, 42, 3029–3096. 10.1016/s0040-4020(01)87376-2. [DOI] [Google Scholar]; b Kolb M. Ketene dithioacetals in organic synthesis: recent developments. Synthesis 1990, 171–190. 10.1055/s-1990-26824. [DOI] [Google Scholar]; c Junjappa H.; Ila H.; Asokan C. V. α-Oxoketene-S,S-, N,S- and N,N-acetals: Versatile intermediates in organic synthesis. Tetrahedron 1990, 46, 5423–5506. 10.1016/s0040-4020(01)87748-6. [DOI] [Google Scholar]; d Pan L.; Bi X.; Liu Q. Recent developments of ketene dithioacetal chemistry. Chem. Soc. Rev. 2013, 42, 1251–1286. 10.1039/c2cs35329f. [DOI] [PubMed] [Google Scholar]
  2. a Wu T.; Pan L.; Xu X.; Liu Q. Regiodivergent heterocyclization: a strategy for the synthesis of substituted pyrroles and furans using α-formyl ketene dithioacetals as common precursors. Chem. Commun. 2014, 50, 1797–1800. 10.1039/c3cc48546c. [DOI] [PubMed] [Google Scholar]; b Rao H. S. P.; Sivakumar S. Aroylketene dithioacetal chemistry: facile synthesis of 4-aroyl-3-methylsulfanyl-2-tosylpyrroles from aroylketene dithioacetals and TosMIC. Beilstein J. Org. Chem. 2007, 3, 31. 10.1186/1860-5397-3-31. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Upta A. K.; Ila H.; Junjappa H. Cycloaromatization ofα-oxoketene dithioacetals with lithioacetonitrile and lithiopropionitrile: a facile route to substituted and annelated pyridines. Tetrahedron 1990, 46, 2561–2572. 10.1016/s0040-4020(01)82036-6. [DOI] [Google Scholar]; d Zhao Y.-L.; Yang S.-C.; Di C.-H.; Han X.-D.; Liu Q. Highly efficient synthesis of 3-amino-/alkylthio-cyclobut-2-en-1-ones based on the cyclization of acyl ketene dithioacetals. Chem. Commun. 2010, 46, 7614–7616. 10.1039/c0cc02470h. [DOI] [PubMed] [Google Scholar]
  3. a Marino J. P.; Kostusyk J. L. A direct synthesis of substituted thiophenes α-oxoketene dithioacetals. II. Tetrahedron Lett. 1979, 20, 2493–2496. 10.1016/s0040-4039(01)86329-2. [DOI] [Google Scholar]; b Kumara C. S. P.; Gowda G. B.; Kumar K. S. V.; Ramesh N.; Sadashiva M. P.; Junjappa H. Base catalyzed reaction of 1,4-dithiane-2,5-diol with α-oxoketene dithioacetals: a new general method for the synthesis of 2-methylthio-3-aroyl/heteroaroyl thiophenes. Tetrahedron Lett. 2016, 57, 4302–4305. 10.1016/j.tetlet.2016.08.033. [DOI] [Google Scholar]
  4. a Okazaki R.; Negishi Y.; Inamoto N. Reactions of .alpha.-oxo ketene dithioacetals with dimethylsulfonium methylide: a new versatile synthesis of furans and butenolides. J. Org. Chem. 1984, 49, 3819–3824. 10.1021/jo00194a028. [DOI] [Google Scholar]; b Yang X.; Hu F.; Di H.; Cheng X.; Li D.; Kan X.; Zou X.; Zhang Q. A convenient base-mediated synthesis of 3-aryol-4-methyl (or benzyl)-2-methylthio furans from α-oxo ketene dithioacetals and propargyl alcohols via domino coupling/annulations. Org. Biomol. Chem. 2014, 12, 8947–8951. 10.1039/c4ob01300j. [DOI] [PubMed] [Google Scholar]; c Fu Z.; Wang M.; Ma Y.; Liu Q.; Liu J. Synthesis of functionalized allylic sulfoxides and their use in the construction of 2,3,4-trisubstituted furans via a [3 + 2] annulation. J. Org. Chem. 2008, 73, 7625–7630. 10.1021/jo801406p. [DOI] [PubMed] [Google Scholar]; d Rao H. S. P.; Sivakumar S. Condensation of α-Aroylketene Dithioacetals and 2-Hydroxyarylaldehydes Results in Facile Synthesis of a Combinatorial Library of 3-Aroylcoumarins#. J. Org. Chem. 2006, 71, 8715–8723. 10.1021/jo061372e. [DOI] [PubMed] [Google Scholar]; e Lou J.; Wang Q.; Wu K.; Wu P.; Yu Z. Iron-Catalyzed Oxidative C-H Functionalization of Internal Olefins for the Synthesis of Tetrasubstituted Furans. Org. Lett. 2017, 19, 3287–3290. 10.1021/acs.orglett.7b01431. [DOI] [PubMed] [Google Scholar]
  5. a Purkayastha M. L.; Ila H.; Junjappa H. I. H. Regioselective synthesis of alkylthioisoxazoles and 3-alkylthioisoxazoles from acylketene dithioacetals. Synthesis 1989, 20–24. 10.1002/chin.198923173. [DOI] [Google Scholar]; b Peruncheralathan S.; Khan T. A.; Ila H.; Junjappa H. Regioselective Synthesis of 1-Aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-Aryl-3-(methylthio)-4,5-substituted/annulated Pyrazoles. J. Org. Chem. 2005, 70, 10030–10035. 10.1021/jo051771u. [DOI] [PubMed] [Google Scholar]; c Huang Z.-T.; Shi X. Synthesis of Heterocyclic KeteneN,S-Acetals and Their Reactions with Esters of α,β-Unsaturated Acids. Synthesis 1990, 162–167. 10.1055/s-1990-26822. [DOI] [Google Scholar]; d Chauhan S. M. S.; Junjappa H. The Use of α-KetoketeneS,S-Diacetals for a Novel Pyrimidine Synthesis. Synthesis 1974, 880–882. 10.1055/s-1974-23465. [DOI] [Google Scholar]; e Dhanalakshmi P.; Thimmarayaperumal S.; Shanmugam S. Metal catalyst free one-pot synthesis of 2-arylbenzimidazoles from α-aroylketene dithioacetals. RSC Adv. 2014, 4, 12028–12036. 10.1039/c3ra47761d. [DOI] [Google Scholar]
  6. a Liu C.; Gu Y. Synthesis of Densely Substituted 1,3-Butadienes through Acid-Catalyzed Alkenylations of α-Oxoketene Dithioacetals with Aldehydes. J. Org. Chem. 2014, 79, 9619–9627. 10.1021/jo5017234. [DOI] [PubMed] [Google Scholar]; b Yadav K. M.; Mohanta P. K.; Ila H.; Junjappa H. Regioselective synthesis of substituted 1-methyl- and 2-methylnaphthalenes. Tetrahedron 1996, 52, 14049–14056. 10.1016/0040-4020(96)80832-5. [DOI] [Google Scholar]; c Thimmarayaperumal S.; Shanmugam S. Base-promoted selective synthesis of 2H-pyranones and tetrahydronaphthalenes via domino reactions. ACS Omega 2017, 2, 4900–4910. 10.1021/acsomega.7b00627. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Liu X.; Zhang L.; Xu X.; Wang S.; Pan L.; Zhang Q.; Liu Q. Aerobic copper-catalyzed oxidative [6C+1C] annulation: an efficient route to seven-membered carbocycles. Chem. Commun. 2014, 50, 8764–8767. 10.1039/c4cc03095h. [DOI] [PubMed] [Google Scholar]; e Dong J.; Pan L.; Xu X.; Liu Q. α-Trifluoromethyl-(indol-3-yl)methanols as trifluoromethylated C31,3-dipoles: [3+2] cycloaddition for the synthesis of 1-(trifluoromethyl)-cyclopenta[b]indole alkaloids. Chem. Commun. 2014, 50, 14797–14800. 10.1039/c4cc05895j. [DOI] [PubMed] [Google Scholar]
  7. a Yu H.; Jin W.; Sun C.; Chen J.; Du W.; He S.; Yu Z. Palladium-Catalyzed Cross-Coupling of Internal Alkenes with Terminal Alkenes to Functionalized 1,3-Butadienes Using CH Bond Activation: Efficient Synthesis of Bicyclic Pyridones. Angew. Chem., Int. Ed. 2010, 49, 5792–5797. 10.1002/anie.201002737. [DOI] [PubMed] [Google Scholar]; b Wang Q.; Lou J.; Wu P.; Wu K.; Yu Z. Iron-Mediated Oxidative C-H Alkylation of S,S -Functionalized Internal Olefins via C(sp 2 )-H/C(sp 3 )-H Cross-Coupling. Adv. Synth. Catal. 2017, 359, 2981–2998. 10.1002/adsc.201700654. [DOI] [Google Scholar]; c Fang Z.; Ning Y.; Mi P.; Liao P.; Bi X. Catalytic C-H α-Trifluoromethylation of α,β-Unsaturated Carbonyl Compounds. Org. Lett. 2014, 16, 1522–1525. 10.1021/ol5004498. [DOI] [PubMed] [Google Scholar]; d Tian S.; Song X.; Zhu D.; Wang M. Alternative Palladium-Catalyzed Vinylic C–H Difluoroalkylation of Ketene Dithioacetals Using Bromodifluoroacetate Derivatives. Adv. Synth. Catal. 2018, 360, 1414–1419. 10.1002/adsc.201701554. [DOI] [Google Scholar]
  8. a Liu Z.; Huang F.; Lou J.; Wang Q.; Yu Z. Copper-promoted direct C-H alkoxylation of S,S-functionalized internal olefins with alcohols. Org. Biomol. Chem. 2017, 15, 5535–5540. 10.1039/c7ob01234a. [DOI] [PubMed] [Google Scholar]; b Liang D.; Wang M.; Dong Y.; Guo Y.; Liu Q. Palladium-catalyzed oxidative C-O cross-coupling of ketene dithioacetals and carboxylic acids. RSC Adv. 2014, 4, 6564–6567. 10.1039/c3ra47282e. [DOI] [Google Scholar]
  9. For reviews, see:; a Bhunia A.; Yetra S. R.; Biju A. T. Recent advances in transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions using arynes. Chem. Soc. Rev. 2012, 41, 3140–3152. 10.1039/c2cs15310f. [DOI] [PubMed] [Google Scholar]; b Sun C.-L.; Shi Z.-J. Transition-metal-free coupling reactions. Chem. Rev. 2014, 114, 9219–9280. 10.1021/cr400274j. [DOI] [PubMed] [Google Scholar]; c Wan J.-P.; Gao Y.; Wei L. Recent advances in transition-metal-free oxygenation of alkene C=C double bonds for carbonyl generation. Chem.—Asian J. 2016, 11, 2092–2102. 10.1002/asia.201600671. [DOI] [PubMed] [Google Scholar]
  10. a Guo Y.; Xiang Y.; Wei L.; Wan J.-P. Thermoinduced Free-Radical C-H Acyloxylation of Tertiary Enaminones: Catalyst-Free Synthesis of Acyloxyl Chromones and Enaminones. Org. Lett. 2018, 20, 3971–3974. 10.1021/acs.orglett.8b01536. [DOI] [PubMed] [Google Scholar]; b Wang F.; Sun W.; Wang Y.; Jiang Y.; Loh T.-P. Highly Site-Selective Metal-Free C-H Acyloxylation of Stable Enamines. Org. Lett. 2018, 20, 1256–1260. 10.1021/acs.orglett.8b00222. [DOI] [PubMed] [Google Scholar]; c Wan J.-P.; Zhong S.; Xie L.; Cao X.; Liu Y.; Wei L. KIO3-Catalyzed Aerobic Cross-Coupling Reactions of Enaminones and Thiophenols: Synthesis of Polyfunctionalized Alkenes by Metal-Free C-H Sulfenylation. Org. Lett. 2016, 18, 584–587. 10.1021/acs.orglett.5b03608. [DOI] [PubMed] [Google Scholar]; d Gao Y.; Hu C.; Wen C.; Wan J.-P. Tunable Synthesis of Disulfide-Functionalized Enaminones and 1,4-Thiazines via the Reactions of Enaminones and β-Aminoethanethiol. ACS Omega 2017, 2, 7784–7789. 10.1021/acsomega.7b01422. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Wan J.-P.; Cao S.; Hu C.; Wen C. Iodine-Catalyzed, Ethyl-Lactate-Mediated Synthesis of 1,4-Benzothiazines via Metal-Free Cascade Enaminone Transamination and C–H Sulfenylation. Asian J. Org. Chem. 2018, 7, 328–331. 10.1002/ajoc.201700680. [DOI] [Google Scholar]; f Sun J.; Zhang-Negrerie D.; Du Y. Oxidative Coupling of Enamines and DisulfidesviaTetrabutylammonium Iodide/tert-Butyl Hydroperoxide-Mediated Intermolecular Oxidative C(sp2)–S Bond Formation Under Transition Metal-Free Conditions. Adv. Synth. Catal. 2016, 358, 2035–2040. 10.1002/adsc.201501099. [DOI] [Google Scholar]
  11. Zhu L.; Yu H.; Guo Q.; Chen Q.; Xu Z.; Wang R. C-H Bonds Phosphorylation of Ketene Dithioacetals. Org. Lett. 2015, 17, 1978–1981. 10.1021/acs.orglett.5b00728. [DOI] [PubMed] [Google Scholar]
  12. Chen Q.; Lei Y.; Wang Y.; Wang C.; Wang Y.; Xu Z.; Wang H.; Wang R. Direct thiocyanation of ketene dithioacetals under transition-metal-free conditions. Org. Chem. Front. 2017, 4, 369–372. 10.1039/c6qo00676k. [DOI] [Google Scholar]
  13. Wen J.; Zhang F.; Shi W.; Lei A. Metal-Free Direct Alkylation of Ketene Dithioacetals by Oxidative C(sp2 )–H/C(sp3 )–H Cross-Coupling. Chem.—Eur. J. 2017, 23, 8814–8817. 10.1002/chem.201701664. [DOI] [PubMed] [Google Scholar]
  14. a Shukla G.; Srivastava A.; Nagaraju A.; Raghuvanshi K.; Singh M. S. Iodine-Mediated Copper-Catalyzed Efficientα-C(sp2)-Thiomethylation ofα-Oxoketene Dithioacetals with Dimethyl Sulfoxide in One Pot. Adv. Synth. Catal. 2015, 357, 3969–3976. 10.1002/adsc.201500634. [DOI] [Google Scholar]; b Magolan J.; Jones-Mensah E.; Karki M. Dimethyl sulfoxide as a synthon in organic chemistry. Synthesis 2016, 48, 1421–1436. 10.1055/s-0035-1560429. [DOI] [Google Scholar]; c Wu X.-F.; Natte K. The applications of dimethyl sulfoxide as reagent in organic synthesis. Adv. Synth. Catal. 2016, 358, 336–352. 10.1002/adsc.201501007. [DOI] [Google Scholar]; d Wu X.-F.; Gong J.-L.; Qi X. A powerful combination: recent achievements on using TBAI and TBHP as oxidation system. Org. Biomol. Chem. 2014, 12, 5807–5817. 10.1039/c4ob00276h. [DOI] [PubMed] [Google Scholar]; e Wu X.-F. Toward Greener Oxidative Transformations: Base-Metal Catalysts and Metal-Free Reactions. Chem. Rec. 2015, 15, 949–963. 10.1002/tcr.201500207. [DOI] [PubMed] [Google Scholar]
  15. Anjaiah C. H.; Sunitha V.; Abraham L. C.-H.; Ashok D. Antimicrobial activity and microwave assisted synthesis of 1-(4-chlorophenyl)-3,3-bis(methylthio)-2 -(arylthio)prop-2-en-1-ones. Der Pharma Chemica 2017, 9, 57–59. [Google Scholar]
  16. For reviews, see:; a Liu Y.; Xiong J.; Wei L. Recent Advances in the C(sp2)-S Bond Formation Reactions by Transition Metal-Free C(sp2)-H Functionalization. Chin. J. Org. Chem. 2017, 37, 1667–1680. 10.6023/cjoc201702009. [DOI] [Google Scholar]; b Dong D.-Q.; Hao S.-H.; Yang D.-S.; Li L.-X.; Wang Z.-L. Sulfenylation of C-H bonds for C-S bond formation under metal-free conditions. Eur. J. Org. Chem. 2017, 6576–6592. 10.1002/ejoc.201700853. [DOI] [Google Scholar]
  17. a Pang X.; Xiang L.; Yang X.; Yan R. Iodine-Mediated Synthesis of Aromatic Thioethers with Aromatic Amines and Sulfonyl Hydrazides in High RegioselectivityviaC(sp2)H Bond Functionalization. Adv. Synth. Catal. 2016, 358, 321–325. 10.1002/adsc.201500943. [DOI] [Google Scholar]; b Yang Y.; Zhang S.; Tang L.; Hu Y.; Zha Z.; Wang Z. Catalyst-free thiolation of indoles with sulfonyl hydrazides for the synthesis of 3-sulfenylindoles in water. Green Chem. 2016, 18, 2609–2613. 10.1039/c6gc00313c. [DOI] [Google Scholar]; c Kang X.; Yan R.; Yu G.; Pang X.; Liu X.; Li X.; Xiang L.; Huang G. Iodine-Mediated Thiolation of Substituted Naphthols/Naphthylamines and Arylsulfonyl Hydrazides via C(sp2)-H Bond Functionalization. J. Org. Chem. 2014, 79, 10605–10610. 10.1021/jo501778h. [DOI] [PubMed] [Google Scholar]; d Guo Y.; Zhong S.; Wei L.; Wan J.-P. Transition-metal-free synthesis of 3-sulfenylated chromones via KIO3-catalyzed radical C(sp2)-H sulfenylation. Beilstein J. Org. Chem. 2017, 13, 2017–2022. 10.3762/bjoc.13.199. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Yu Q.; Yang Y.; Wan J.-P.; Liu Y. Copper-catalyzed C5-H sulfenylation of unprotected 8-aminoquinolines using sulfonyl hydrazides. J. Org. Chem. 2018, 83, 11385–11391. 10.1021/acs.joc.8b01658. [DOI] [PubMed] [Google Scholar]
  18. Konreddy A. K.; Toyama M.; Ito W.; Bal C.; Baba M.; Sharon A. Synthesis and Anti-HCV Activity of 4-Hydroxyamino α-Pyranone Carboxamide Analogues. ACS Med. Chem. Lett. 2014, 5, 259–263. 10.1021/ml400432f. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yu X.; Li X.; Wan B. Palladium-catalyzed desulfitative arylation of azoles with arylsulfonyl hydrazides. Org. Biomol. Chem. 2012, 10, 7479. 10.1039/c2ob26270c. [DOI] [PubMed] [Google Scholar]
  20. Wan J.-P.; Hu D.; Bai F.; Wei L.; Liu Y. Stereoselective Z-halosulfonylation of terminal alkynes using sulfonohydrazides and CuX (X = Cl, Br, I). RSC Adv. 2016, 6, 73132–73135. 10.1039/c6ra13737g. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao8b01946_si_001.pdf (4.1MB, pdf)

Articles from ACS Omega are provided here courtesy of American Chemical Society

RESOURCES