K₂S₂O₈/I₂ promoted syntheses of α-thio-β-dicarbonyl compounds via oxidative C–S coupling reactions under transition metal-free and solvent-free conditions

Abstract

A K₂S₂O₈/I₂ promoted C–S coupling reaction of β-diketones with disulfides has been described. The resulting α-thio-β-diketone compounds were obtained in good to excellent yields. Both diaryl and dialkyl disulfides coupled well with a variety of β-diketones under transition metal-free and solvent-free conditions.

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Introduction

Due to their versatile synthetic applications as intermediates in many organic transformations, the preparation of thioaryl carbonyl compounds has recently gained much attention.¹ α-Thio-β-dicarbonyl compounds such as, α-arylthiodialkyl malonates are useful synthons for the syntheses of a number of heterocyclic frameworks like coumarins and α-pyrones etc.² Meanwhile, α-thio-β-diketones have also been shown to represent interesting examples of strong intramolecular hydrogen bonding.³

Various synthetic methods have been reported in the literatures for the preparation of thioaryl carbonyl compounds including: (1) the sulfenylation of enolates with various sulfenylating agents such as sulphenyl halides,⁴ disulfides,⁵ (2) nucleophilic substitution of α-halogenated ketones with sulphur surrogates,⁶ (3) via transition-metal catalyzed C–S bond formation.⁷ A cesium carbonate and diphenyl diselenide promoted direct α-phenylthiolation of carbonyl compounds using diaryl disulfides has been also reported by Nishiyama and co-workers (eqn (1)).⁸ Bolm and co-workers⁹ have reported an interesting Cu(OAc)₂–H₂O catalyzed C–S coupling of β-diketones with diaryl disulfide to afford α-thioaryl carbonyl compounds (eqn (2)). Recently, oxidant-promoted C–C, C–heteroatom bond forming reactions emerged as an interesting class of synthetic methodology.¹⁰ As our ongoing research on C–S coupling reactions,^10a,b,11 we herein report a novel transition metal-free and solvent-free K₂S₂O₈/I₂ promoted synthesis of α-thio-β-dicarbonyl compounds via the C–S coupling between β-diketones and disulfides at room temperature (eqn (3)).

Results and discussion

Accordingly, first we have carried out the oxidative C–S coupling reaction between acetylacetone (1a) and bis(4-methoxyphenyl)disulfide (2a) under the influence of I₂ at room temperature. Which after 48 h provided the corresponding α-thio-β-diketones compound 3a in 27% isolated yield (Table 1, entry 1). To our delight, a 88% yield of product was obtained when H₂O₂ was used as an oxidant (Table 1, entry 2). Other oxidants were screened to obtained optimal reaction conditions (Table 1, entries 3–8). K₂S₂O₈ is the best of these oxidants, providing product 3a in 99% isolated yield (Table 1, entry 6). Decreasing the amount of I₂ (Table 1, entry 9), K₂S₂O₈ (Table 1, entry 10) and reaction time (Table 1, entry 11) diminished the yield of 3a. A 96% yield of 3a was obtained when NIS was used as additive instead of I₂ (Table 1, entry 12).

Table 1 Optimization of reaction conditions^a

Entry	Oxidant (equiv.)	Additive	Yield^b (%)
a Reaction conditions: 2,4-pentanedione 1a (1.0 mL), bis(4-methoxyphenyl)disulfide 2a (0.5 mmol), K2S2O8 (5.0 eq.), I2 (0.3 mmol), at room temperature for 48 h.b Isolated yield.c I2 (0.2 mmol).d 36 h (TBHP = tert-butyl hydroperoxide, BPO = benzoyl peroxide, AcOOH = peracetic acid, DTBP = di-tert-butyl peroxide).
1	—	I2	27
2	H2O2 (5)	I2	88
3	DTBP (5)	I2	53
4	TBHP (5)	I2	58
5	BPO (5)	I2	24
6	K2S2O8 (5)	I2	99
7	AcOOH (5)	I2	36
8	TBPB (5)	I2	84
9^c	K2S2O8 (5)	I2	49
10^d	K2S2O8 (5)	I2	73
11	K2S2O8 (4)	I2	58
12	K2S2O8 (5)	NIS	96

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To generalize and expand the scope of this methodology, we have carried out this K₂S₂O₈/I₂ promoted oxidative C–S coupling reaction between variety of dicarbonyl compound 1a–1d and diaryl disulfides 2a–2g under optimized reaction conditions which provided the resulting α-thio-β-diketones compounds 3b–3u in good to excellent yields (Table 2). This system shows good functional group tolerance, functional groups including fluoro (Table 2, entries 3, 10 and 16), chloro (Table 2, entries 4, 11 and 17), bromo (Table 2, entries 5, 12 and 18), trifluoromethyl (Table 2, entries 2, 9 and 15) are all tolerated under the reaction conditions employed. Disulfides containing both the electron donating (Table 2, entry 7) and electron withdrawing group (Table 2, entries 2, 9 and 15) coupled well with dicarbonyl compounds, providing the products in good to excellent yields.

Table 2 Reactions of various 1,3-diketones 1 with disulfides 2^a

Entry	1	R^3	Product		Yield^b (%)
a Reaction conditions: various 1,3-diketones (1.0 mL), disulfides (0.5 mmol), K2S2O8 (5.0 eq.), I2 (0.3 mmol), at room temperature for 48 h.b Isolated yield.c 1,3-diketones (5.0 mmol) and CH3CN (1.5 mL) was used as solvent.
1	1a	Ph (2b)		3b	72
2	1a	4-CF3Ph (2c)		3c	64
3	1a	4-FPh (2d)		3d	76
4	1a	4-ClPh (2e)		3e	95
5	1a	4-BrPh (2f)		3f	91
6	1a	4-MePh (2g)		3g	58
7	1b	2a		3h	95
8	1b	2b		3i	89
9	1b	2c		3j	83
10	1b	2d		3k	85
11	1b	2e		3l	94
12	1b	2f		3m	83
13	1b	2g		3n	90
14	1c	2b		3o	90
15	1c	2c		3p	86
16	1c	2d		3q	84
17	1c	2e		3r	67
18	1c	2f		3s	83
19	1c	2g		3t	93
20	1d	2b		3u	80^c
21	1a	n-C4H9 (2h)		3v	71
22	1a	n-C12H25 (2i)		3w	92
23	1b	2h		3x	51
24	1b	2i		3y	71

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Dialkyl disulfides could also be used as the coupling partners for the oxidative C–S coupling reaction as shown in Table 2 (entries 21–24). Dialkyl disulfides 4a & 4b underwent oxidative C–S coupling reaction with dicarbonyl compound 1a–1c under the influence of K₂S₂O₈/I₂ at 70 °C, provided the products 3v–3yin 51–92% yields.

To check the possibility of radical mechanism, we have carried out the reaction of 1a with 2a under optimized conditions using K₂S₂O₈–I₂ in presence of TEMPO and found that there was no effect on the product formation, hence the radical mechanism is ruled out (eqn (4)). Next, we have treated 3-iodopentane-2,4-dione (5) with disulphide 2a using oxidant K₂S₂O₈ under optimized conditions, provided the desired product 3a in 65% yield (eqn (5)).^12a Based on these experiments, we proposed plausible mechanism for this transformation as shown in Scheme 1. Initially, in presence of I₂, disulfide 2 can attack on dicarbonyl compounds 1 to provide the desired product 3 along with the formation of HI and R³SI (4) as shown in path A. Alternatively, the enol form of dicarbonyl compounds 1 can also undergo a similar kind of reaction to generate product 3 along with HI and R³SI (4) (path B). It is known that in presence of oxidant HI can reoxidize into molecular iodine.^12b Since the R³SI (4) is very reactive species, the enol form of dicarbonyl compounds 1 can react with 4 to provide the desired product 3 according to path C.

Scheme 1 Plausible mechanism.

Conclusions

In conclusion, we have developed an interesting transition metal free K₂S₂O₈/I₂ promoted syntheses of α-thio-β-dicarbonyl compounds via the oxidative C–S coupling reaction between β-diketones 1 and disulfide 2 at room temperature under solvent free conditions. The resulting α-thio-β-diketones compounds 3 were obtained in good to excellent yields. The system shows good functional group tolerance as the functional groups such as fluoro, chloro, bromo, trifluoromethyl and methoxy are all tolerated by the reaction conditions employed.

Experimental

General information

All chemicals were purchased from commercial suppliers and used without further purification. Flash chromatography was performed on Merck silica gel 60 (230–400 mesh). NMR spectra were recorded on a Varian Unity Inova-600 or a Varian Mercury-400 instrument using CDCl₃ as solvent. Chemical shifts are reported in parts per million (ppm) and referenced to the residual solvent resonance. Coupling constant (J) are reported in hertz (Hz). Standard abbreviations indicating multiplicity were used as follows: s = singlet, d = doublet, t = triplet, dd = double of doublet, q = quartet, m = multiplet, b = broad. Melting points (m.p.) were determined using a Büchi 535 apparatus and are reported uncorrected. GC-MS analyses were performed on a GC-MS analysis on HP 5890 GC equipped with HP 5972 MS. High-resolution mass spectra were carried out on a Jeol JMS-HX 110 spectrometer by the services at the National Chung Hsing University.

General procedure and representative example for Table 1: 3-((4-methoxyphenyl)thio) pentane-2,4-dione (entry 6, 3a):^1d

A sealed vial equipped with a magnetic stir bar was charged with pentane-2,4-dione 1a (1.0 mL), 1,2-bis(4-methoxyphenyl)disulfane 2a (0.5 mmol, 139 mg), oxidant (5.0 equiv.) and additive (0.3 mmol) and then the reaction mixture was stirred for 48 h at room temperature. The resulting solution was directly filtered through a pad of silica gel then washed with ethyl acetate (3 × 10 mL) and concentrated to give the crude material which was then purified by flash silica gel column chromatography (eluent: hexane) to afford the desired product 3a as a yellow solid (236 mg, 99% yield). ¹H NMR (400 MHz, CDCl₃): δ 2.35 (s, 6H), 3.77 (s, 3H), 6.83 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 24.4, 55.3, 103.0, 114.9, 126.8, 128.3, 157.9, 198.0.

General procedure for Table 2

A sealed vial equipped with a magnetic stir bar was charged with 1,3-diketone 1 (1.0 mL), disulfide 2 (0.5 mmol), K₂S₂O₈ (5.0 mmol) and I₂ (0.3 mmol) and then the reaction mixture was stirred for 48 h at room temperature. The resulting solution was then directly filtered through a pad of silica gel then washed with ethyl acetate (3 × 10 mL) and concentrated to give the crude material which was then purified by column chromatography (SiO₂, hexane) to yield 3.

3-(Phenylthio) pentane-2,4-dione 3b (Table 2, entry 1):^1d. The title compound was prepared following the general procedure for Table 2 using pentane-2,4-dione (1.0 mL), diphenyl disulfide (0.109 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3b as a yellow liquid (150 mg, 72% yield). ¹H NMR (400 MHz, CDCl₃): δ 2.33 (s, 6H), 7.08–7.14 (m, 3H), 7.27 (t, J = 7.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 24.3, 101.5, 124.6, 125.2, 129.0, 129.2, 134.8, 137.7, 198.3.

3-{(4-(Trifluoromethyl)phenyl)thio}pentane-2,4-dione 3c (Table 2, entry 2). The title compound was prepared following the general procedure for Table 2 using pentane-2,4-dione (1.0 mL), 1,2-bis(4-(trifluoromethyl)phenyl)disulfane (0.1772 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3c as a yellow liquid (177 mg, 64% yield). ¹H NMR (400 MHz, CDCl₃): δ 2.32 (s, 6H), 7.19 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃): δ 24.2 (d, J = 12.9 Hz), 100.3 (d, J = 2.0 Hz), 124.1 (q, J = 270.2 Hz), 124.3, 126.0 (q, J = 3.8 Hz), 127.4 (q, J = 32.6 Hz), 142.9, 198.4; ¹⁹F NMR (376 MHz, CDCl₃): δ −63.9 (s); HRMS-EI calcd for C₁₂H₁₁F₃O₂S: 276.0432, found: 276.0434.

3-{(4-Fluorophenyl)thio}pentane-2,4-dione 3d (Table 2, entry 3). The title compound was prepared following the general procedure for Table 2 using pentane-2,4-dione (1.0 mL), 1,2-bis(4-fluorophenyl)disulfane (0.0942 mL, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3d as a yellow liquid (172 mg, 76% yield). ¹H NMR (400 MHz, CDCl₃): δ 2.34 (s, 6H), 6.97–7.02 (m, 2H), 7.05–7.08 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 24.3, 102.1, 116.2 (d, J = 21.9 Hz), 126.5 (d, J = 8.1 Hz), 132.7 (d, J = 3.6 Hz), 159.8, 162.2, 198.1; ¹⁹F NMR (376 MHz, CDCl₃): δ −119.0 (s); HRMS-EI calcd for C₁₁H₁₁FO₂S: 226.0464, found: 226.0456.

3-{(4-Chlorophenyl)thio}pentane-2,4-dione 3e (Table 2, entry 4). The title compound was prepared following the general procedure for Table 2 using pentane-2,4-dione (1.0 mL), 1,2-bis(4-chlorophenyl)disulfane (0.160 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3e as a white solid (230 mg, 95% yield). M.P. = 68–69 °C; ¹H NMR (400 MHz, CDCl₃): δ 2.33 (s, 6H), 7.02 (d, J = 8.8 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 24.2, 101.2, 125.8, 129.2, 131.0, 136.3, 198.2; HRMS-EI calcd for C₁₁H₁₁ClO₂S: 242.0168, found: 242.0160.

3-{(4-bromophenyl)thio}pentane-2,4-dione 3f (Table 2, entry 5). The title compounds was prepared following the general procedure for Table 2 using pentane-2,4-dione (1.0 mL), 1,2-bis(4-bromophenyl)disulfane (0.1881 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3f as a white solid (261 mg, 91% yield). M.P. = 70–71 °C; ¹H NMR (400 MHz, CDCl₃): δ 2.33 (s, 6H), 6.96 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 24.2, 101.0, 118.7, 126.1, 132.1, 136.9, 198.1; HRMS-EI calcd for C₁₁H₁₁BrO₂S: 285.9663, found: 285.9659.

3-(p-Tolylthio)pentane-2,4-dione 3g (Table 2, entry 6). The title compounds was prepared following the general procedure for Table 2 using pentane-2,4-dione (1.0 mL), 1,2-di-p-tolyldisulfane (0.123 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3g as a yellow liquid (129 mg, 58% yield). ¹H NMR (400 MHz, CDCl₃): δ 2.31 (s, 3H), 2.34 (s, 6H), 6.99 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 20.8, 24.3, 102.0, 124.8, 129.9, 134.1, 135.0, 198.1; HRMS-EI calcd for C₁₂H₁₄O₂S: 222.0715, found: 222.0719.

4-{(4-Methoxyphenyl)thio}heptane-3,5-dione 3h (Table 2, entry 7). The title compounds was prepared following the general procedure for Table 2 using heptane-3,5-dione (1.0 mL), 1,2-bis(4-methoxyphenyl)disulfane (0.1435 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3h as a colorless liquid (253 mg, 95% yield). ¹H NMR (400 MHz, CDCl₃): δ 1.10 (t, J = 7.4 Hz, 6H), 2.74 (q, J = 7.3 Hz, 4H), 3.77 (s, 3H), 6.83 (d, J = 6.8 Hz, 2H), 7.02 (d, J = 6.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 9.5, 29.9, 55.3, 101.4, 114.9, 126.5, 128.9, 157.8, 201.0; HRMS-EI calcd for C₁₄H₁₈O₃S: 266.0977, found: 266.0973.

4-(Phenylthio)heptane-3,5-dione 3i (Table 2, entry 8). The title compounds was prepared following the general procedure for Table 2 using heptane-3,5-dione (1.0 mL), diphenyl disulfide (0.109 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3i as a yellow liquid (210 mg, 89% yield). ¹H NMR (400 MHz, CDCl₃): δ 1.09 (t, J = 7.3 Hz, 6H), 2.60–2.90 (m, 4H), 7.02–7.13 (m, 3H), 7.26 (t, J = 7.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 9.4, 29.8, 99.9, 124.4, 125.0, 129.0, 138.2, 201.2; HRMS-EI calcd for C₁₃H₁₆O₂S: 236.0871, found: 236.0875.

4-{(4-(Trifluoromethyl)phenyl)thio}heptane-3,5-dione 3j (Table 2, entry 9). The title compounds was prepared following the general procedure for Table 2, heptane-3,5-dione (1.0 mL), 1,2-bis(4-(trifluoromethyl)phenyl)disulfane (0.1772 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3j as a yellow liquid (252 mg, 83% yield). ¹H NMR (400 MHz, CDCl₃): δ 1.12 (t, J = 7.2 Hz, 6H), 2.40–3.10 (m, 4H), 7.20 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃): δ 9.4, 29.9, 98.8, 124.1 (q, J = 270.1 Hz), 124.2, 126.0 (q, J = 3.8 Hz), 127.2 (q, J = 38.9 Hz), 143.5, 201.4; ¹⁹F NMR (376 MHz, CDCl₃): δ −63.9 (s); HRMS-EI calcd. for C₁₄H₁₅F₃O₂S: 304.0745, found: 304.0741.

4-{(4-Fluorophenyl)thio}heptane-3,5-dione 3k (Table 2, entry 10). The title compounds was prepared following the general procedure for Table 2 using heptane-3,5-dione (1.0 mL), 1,2-bis(4-fluorophenyl)disulfane (0.0942 mL, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3k as a yellow liquid (216 mg, 85% yield). ¹H NMR (400 MHz, CDCl₃): δ 1.10 (t, J = 7.2 Hz, 6H), 2.50–2.90 (m, 4H), 6.96–7.07 (m, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 9.4, 29.8, 100.5, 116.2 (d, J = 21.9 Hz), 126.2 (d, J = 7.3 Hz), 133.2, 159.7, 162.1, 201.1; ¹⁹F NMR (376 MHz, CDCl₃): δ −119.2 (s); HRMS-EI calcd for C₁₃H₁₅FO₂S: 254.0777, found: 254.0770.

4-{(4-Chlorophenyl)thio}heptane-3,5-dione 3l (Table 2, entry 11). The title compounds was prepared following the general procedure for Table 2 using heptane-3,5-dione (1.0 mL), 1,2-bis(4-chlorophenyl)disulfane (0.160 g, 0.5 mmol, 1.0 equiv.), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3l as a yellow liquid (254 mg, 94% yield). ¹H NMR (400 MHz, CDCl₃) δ 1.09 (t, J = 7.4 Hz, 6H), 2.60–2.90 (m, 4H), 7.01 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 9.4, 29.8, 99.6, 125.6, 129.1, 130.8, 136.8, 201.1; HRMS-EI calcd for C₁₃H₁₅ClO₂S: 270.0481, found: 270.0485.

4-{(4-bromophenyl)thio}heptane-3,5-dione 3m (Table 2, entry 12). The title compounds was prepared following the general procedure for Table 2 using heptane-3,5-dione (1.0 mL), 1,2-bis(4-bromophenyl)disulfane (0.1881 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3m as a yellow liquid (284 mg, 83% yield). ¹H NMR (400 MHz, CDCl₃): δ 1.09 (t, J = 7.1 Hz, 6H), 2.60–2.90 (m, 4H), 6.95 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 9.4, 29.8, 99.5, 118.5, 125.9, 132.0, 137.5, 201.1; HRMS-EI calcd for C₁₃H₁₅BrO₂S: 313.9976, found: 313.9968.

4-(p-Tolylthio)heptane-3,5-dione 3n (Table 2, entry 13). The title compounds was prepared following the general procedure for Table 2 using heptane-3,5-dione (1.0 mL), 1,2-di-p-tolyldisulfane (0.123 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3n as a yellow liquid (225 mg, 90% yield). ¹H NMR (400 MHz, CDCl₃): δ 1.09 (t, J = 7.4 Hz, 6H), 2.28 (s, 3H), 2.60–2.90 (m, 4H), 6.97 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 9.4, 20.7, 29.8, 100.4, 124.6, 129.8, 134.6, 134.7, 201.1; HRMS-EI calcd for C₁₄H₁₈O₂S: 250.1028, found: 250.1019.

2,6-Dimethyl-4-(phenylthio)heptane-3,5-dione 3o (Table 2, entry 14). The title compounds was prepared following the general procedure for Table 2 using 2,6-dimethylheptane-3,5-dione (1.0 mL), diphenyl disulfide (0.109 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3o as a white liquid (238 mg, 90% yield). ¹H NMR (400 MHz, CDCl₃): δ 0.93 (d, J = 6.8 Hz, 12H), 3.41–3.51 (m, 2H), 7.06–7.14 (m, 3H), 7.25–7.29 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 19.4, 33.7, 98.1, 124.3, 124.9, 129.0, 139.0, 205.5; HRMS-EI calcd for C₁₅H₂₀O₂S: 264.1184, found: 264.1189.

2,6-Dimethyl-4-{(4-(trifluoromethyl)phenyl)thio}heptane-3,5-dione 3p (Table 2, entry 15). The title compounds was prepared following the general procedure for Table 2 using 2,6-dimethylheptane-3,5-dione (1.0 mL), 1,2-bis(4-(trifluoromethyl)phenyl)disulfane (0.1772 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3p as a yellow solid (286 mg, 86% yield). M.P. = 41–42 °C; ¹H NMR (400 MHz, CDCl₃): δ 0.93–1.27 (m, 12H), 3.35–3.45 (m, 2H), 7.19 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃): δ 19.4 (d, J = 178.1 Hz), 33.8 (d, J = 17.6 Hz), 96.9, 124.1 (q, J = 270.1 Hz), 124.1, 125.9 (q, J = 3.7 Hz), 127.2 (q, J = 32.5 Hz), 144.3, 205.7; ¹⁹F NMR (376 MHz, CDCl₃): δ −63.8 (s); HRMS-EI calcd for C₁₆H₁₉F₃O₂S: 332.1058, found: 332.1060.

4-{(4-Fluorophenyl)thio}-2,6-dimethylheptane-3,5-dione 3q (Table 2, entry 16). The title compounds was prepared following the general procedure for Table 2 using 2,6-dimethylheptane-3,5-dione (1.0 mL), 1,2-bis(4-fluorophenyl)disulfane (0.0942 mL, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3q as a yellow solid (237 mg, 84% yield). M.P. = 48–49 °C; ¹H NMR (400 MHz, CDCl₃): δ 1.08 (d, J = 6.4 Hz, 6H), 1.14 (d, J = 6.8 Hz, 6H), 3.42–3.52 (m, 2H), 6.95–7.07 (m, 5H); ¹³C NMR (100 MHz, CDCl₃): δ 19.4, 33.8, 98.6, 116.1 (d, J = 21.9 Hz), 126.0 (d, J = 7.3 Hz), 134.1, 159.7, 162.1, 205.5; ¹⁹F NMR (376 MHz, CDCl₃): δ −119.4 (s); HRMS-EI calcd for C₁₅H₁₉FO₂S: 282.1090, found: 282.1085.

4-{(4-Chlorophenyl)thio}-2,6-dimethylheptane-3,5-dione 3r (Table 2, entry 17). The title compounds was prepared following the general procedure for Table 2 using 2,6-dimethylheptane-3,5-dione (1.0 mL), 1,2-bis(4-chlorophenyl)disulfane (0.160 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3r as a yellow solid (200 mg, 67% yield). M.P. = 41–42 °C; ¹H NMR (400 MHz, CDCl₃): δ 0.80–1.40 (m, 12H), 3.37–3.47 (m, 2H), 7.01 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 19.5, 33.8, 97.8, 125.5, 129.1, 130.8, 137.7, 205.5; HRMS-EI calcd for C₁₅H₁₉ClO₂S: 298.0794, found: 298.0797.

4-{(4-Bromophenyl)thio}-2,6-dimethylheptane-3,5-dione 3s (Table 2, entry 18). The title compounds was prepared following the general procedure for Table 2 using 2,6-dimethylheptane-3,5-dione (1.0 mL), 1,2-bis(4-bromophenyl)disulfane (0.1881 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3s as a yellow liquid (285 mg, 83% yield). ¹H NMR (400 MHz, CDCl₃): δ 0.80–1.35 (m, 12H), 3.35–3.46 (m, 2H), 6.94 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 9.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 19.5, 33.8, 97.7, 118.5, 125.9, 132.0, 138.4, 205.6; HRMS-EI calcd for C₁₅H₁₉BrO₂S: 342.0289, found: 342.0284.

2,6-Dimethyl-4-(p-tolylthio)heptane-3,5-dione 3t (Table 2, entry 19). The title compounds was prepared following the general procedure for Table 2 using 2,6-dimethylheptane-3,5-dione (1.0 mL), 1,2-di-p-tolyldisulfane (0.123 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3t as a yellow liquid (259 mg, 93% yield). ¹H NMR (400 MHz, CDCl₃): δ 1.07 (d, J = 6.4 Hz, 12H), 2.28 (s, 3H), 3.42–3.52 (m, 2H), 6.96 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 19.5, 20.7, 33.7, 98.4, 124.4, 129.8, 134.6, 135.4, 205.4; HRMS-EI calcd for C₁₆H₂₂O₂S: 278.1341, found: 278.1349.

1-Phenyl-2-(phenylthio)butane-1,3-dione 3u (Table 2, entry 20). A sealed vial equipped with a magnetic stir bar was charged with 1-phenylbutane-1,3-dione (0.743 g, 5.0 mmol), diphenyl disulfide (0.109 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol) and CH₃CN (1.5 mL). After being stirred for 48 hours at room temperature, the resulting solution was directly filtered through a pad of silica gel then washed with ethyl acetate (3 × 10 mL) and concentrated to give the crude material which was then purified by flash silica gel column chromatography (eluent: hexane) to afford the desired product 3u as a yellow solid. (216 mg, 80% yield). M.P. = 57–58 °C; ¹H NMR (400 MHz, CDCl₃): δ 2.42 (s, 3H), 7.11–7.15 (m, 3H), 7.24–7.34 (m, 4H), 7.40–7.44 (m, 1H), 7.63 (d, J = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 25.7, 100.7, 124.8, 125.2, 127.7, 128.4, 129.2, 131.1, 135.6, 138.6, 190.6, 203.3; HRMS-EI calcd for C₁₆H₁₄O₂S: 270.0715, found: 270.0713.

General procedure for compounds 3v–3y

A sealed vial equipped with a magnetic stir bar was charged with 1,3-diketone (1.0 mL), dialkyl disulfide (0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol). The reaction mixture was then stirred for 48 hours at 70 °C. The resulting solution was directly filtered through a pad of silica gel then washed with ethyl acetate (3 × 10 mL) and concentrated to give the crude material which was then purified by column chromatography (SiO₂, hexane) to yield 3.

3-(Butylthio)pentane-2,4-dione 3v (Table 2, entry 21). The title compounds was prepared following the general procedure for compounds 3v–3y using pentane-2,4-dione (1.0 mL), 1,2-dibutyldisulfane (0.098 mL, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3v as a colorless liquid (133 mg, 71% yield). ¹H NMR (400 MHz, CDCl₃): δ 0.92 (t, J = 7.3 Hz, 3H), 1.37–1.46 (m, 2H), 1.49–1.57 (m, 2H), 2.44 (s, 6H), 2.50 (t, J = 7.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 13.7, 22.0, 24.5, 31.2, 36.5, 104.7, 197.4; HRMS-EI calcd for C₉H₁₆O₂S: 188.0871, found: 188.0870.

3-(Dodecylthio)pentane-2,4-dione 3w (Table 2, entry 22). The title compounds was prepared following the general procedure for compounds 3v–3y using pentane-2,4-dione (1.0 mL), 1,2-didodecyldisulfane (0.2014 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 5b as a yellow liquid (276 mg, 92% yield). ¹H NMR (400 MHz, CDCl₃): δ 0.88 (t, J = 7.2 Hz, 3H), 1.26–1.38 (m, 18H), 1.50–1.57 (m, 2H), 2.43 (s, 6H), 2.48 (t, J = 7.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 14.1, 22.7, 24.5, 28.9, 29.2, 29.3, 29.3, 29.5, 29.6, 29.6, 31.9, 36.9, 104.7, 197.4; HRMS-EI calcd for C₁₇H₃₂O₂S: 300.2123, found: 300.2124.

4-(Butylthio)heptane-3,5-dione 3x (Table 2, entry 23). The title compounds was prepared following the general procedure for compounds 3v–3y heptane-3,5-dione (1.0 mL), 1,2-dibutyldisulfane (0.098 mL, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 5c as a yellow liquid (110 mg, 51% yield). ¹H NMR (400 MHz, CDCl₃): δ 0.92 (t, J = 7.2 Hz, 3H), 1.16 (t, J = 7.4 Hz, 6H), 1.36–1.45 (m, 2H), 1.49–1.56 (m, 2H), 2.49 (t, J = 7.4 Hz, 2H), 2.85 (q, J = 7.2 Hz, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 9.7, 13.6, 22.0, 29.9, 31.2, 37.0, 103.4, 200.4; HRMS-EI calcd. for C₁₁H₂₀O₂S: 216.1184, found: 216.1180.

4-(Dodecylthio)heptane-3,5-dione 3y (Table 2, entry 24). The title compounds was prepared following the general procedure for compounds 3v–3y heptane-3,5-dione (1.0 mL), 1,2-didodecyldisulfane (0.2014 g, 0.5 mmol), K₂S₂O₈ (1.3653 g, 5.0 mmol) and I₂ (76 mg, 0.3 mmol), then purified by column chromatography (SiO₂, hexane) to provide 5d as a yellow liquid (233 mg, 71% yield). ¹H NMR (400 MHz, CDCl₃): δ 0.87 (t, J = 6.8 Hz, 3H), 1.15 (t, J = 7.6 Hz, 6H), 1.26–1.38 (m, 18H), 1.49–1.57 (m, 2H), 2.47 (t, J = 7.6 Hz, 2H), 2.85 (q, J = 7.6 Hz, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 9.6, 14.0, 22.6, 28.9, 29.1, 29.2, 29.3, 29.4, 29.5, 29.6, 29.9, 31.8, 33.7, 37.3, 103.4, 200.3; HRMS-EI calcd for C₁₉H₃₆O₂S: 328.2436, found: 328.2437.

Acknowledgements

The National Science Council, Taiwan (NSC 101-2113-M-005-008-MY3), the National Chung Hsing University and the Centre of Nanoscience and Nanotechnology (NCHU) are gratefully acknowledged for financial support. We also thank Prof. Fung-E Hong (NCHU) for sharing his GC-MS instruments. C.F.L. is a Golden-Jade Fellow of Kenda Foundation, Taiwan.

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Footnotes

† Electronic supplementary information (ESI) available: For 1H and 13C spectra of compounds 3 and 4 See DOI: 10.1039/c5ra07204b

‡ Both authors contributed equally to this work.

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