Jian Gao,
Junyi Lai and
Gaoqing Yuan*
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, P. R. China. E-mail: gqyuan@scut.edu.cn
First published on 28th July 2015
With water as the reaction medium, a green and efficient method has been developed for the synthesis of (E)-vinyl sulfones via I2-mediated decarboxylative cross-coupling reactions of sodium sulfinates with cinnamic acids. This synthetic route could effectively avoid the use of toxic organic solvents and transition metal catalysts, and the target products could be obtained with moderate to excellent yields under green and mild conditions.
Vinyl sulfones, as key functional units, exhibit a broad range of biological and parmaceutical activities in biological and medicinal chemistry,6 and show great synthetic value as building blocks in organic transformations.7 To date various synthetic methods have been developed,8 mainly including (1) direct coupling reaction of alkenes or alkynes with sulfone resources (sulfinic acid,9 sodium sulfinate,10 sulfonyl hydrazide,11 thiols12 and dimethyl sulfoxide5b,13), and (2) decarboxylative coupling reaction of cinnamic acids with sodium sulfinate (Scheme 1).14 In Scheme 1, there have been some new and efficient Pd- or Cu-catalyzed decarboxylative coupling reactions for the synthesis vinyl sulfones from cinnamic acid and sodium sulfinate. However, all of them need toxic metals, ligands, oxidants and high temperature (Scheme 1a–c).
It is noteworthy that Jiang's group has reported a simple and efficient route for the synthesis of vinyl sulfones without any catalysts (Scheme 1d), and very recently Kuhakarn's group has reported a highly efficient method by PhI(OAc)2 mediated decarboxylative sulfonylation in a very short time (Scheme 1e). However, both of them still suffer from toxic organic solvents and high temperature. It is well known that water as green reaction medium has practical advantages over organic solvents and attracted increasing attention in organic synthesis.15 Herein, we reported a green and efficient method for the synthesis of vinyl sulfones via I2-mediated decarboxylative cross-coupling reaction of sodium sulfinates with cinnamic acids, using water as a solvent at lower temperature.
Firstly, we chose trans-cinnamic acid (1a) and sodium 4-methyl benzenesulfinate (2a) as model substrates to examine various reaction conditions, and the results were shown in Table 1. We did not get the desired product when the reaction of 1a with 2a was performed with 1 equiv. of I2 in the absence of a base at room temperature for 5 h (entry 1). In the presence of base K2CO3 (1.0 equiv.), (E)-1-methyl-4-(styrylsulfonyl)benzene (3a) could be obtained with 10% yield (entry 2). We attempted to prolong reaction time to 10 h, but the yield of 3a was not obviously improved (only 23%, entry 3). Luckily, when the reaction temperature was raised to 40 °C, the yield of 3a was drastically increased to 72% (entry 4). Higher temperatures (50 °C, 60 °C and 70 °C, entries 5–7) were further tested, and a best yield was obtained (91%, entry 6). When 0.5 equiv. of I2 or 0.5 equiv. of K2CO3 was added to the reaction system, the yield of 3a declined to approximately half of the best yield (entries 8 and 9). Besides, the reaction efficiency was not improved when excess K2CO3 (2.0 equiv.) was used (entry 10). At last, various bases (Cs2CO3, NaOAc, KOH, CH3ONa and Et3N) and solvents (CH3CN, DMF, EtOAc, CH3OH and DMSO) were screened, respectively. These results showed that K2CO3 was an optimal base and water was the most suitable solvent in this process (entries 11–20).
Entry | I2 (equiv.) | Base (equiv.) | Solvent | Time (h) | Temp. (°C) | Yieldb (%) |
---|---|---|---|---|---|---|
a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), base (1.0 equiv.), I2 (1.0 equiv.), H2O (2 mL) at 60 °C for 10 h.b Determined by GC-MS using dodecane as the internal standard.c Under N2 atmosphere. | ||||||
1 | 1.0 | No | H2O | 5 | rt | Trace |
2 | 1.0 | K2CO3 (1.0) | H2O | 5 | rt | 10 |
3 | 1.0 | K2CO3 (1.0) | H2O | 10 | rt | 23 |
4 | 1.0 | K2CO3 (1.0) | H2O | 10 | 40 | 72 |
5 | 1.0 | K2CO3 (1.0) | H2O | 10 | 50 | 80 |
6 | 1.0 | K2CO3 (1.0) | H2O | 10 | 60 | 91 |
7 | 1.0 | K2CO3 (1.0) | H2O | 10 | 70 | 84 |
8 | 0.5 | K2CO3 (1.0) | H2O | 10 | 60 | 40 |
9 | 1.0 | K2CO3 (0.5) | H2O | 10 | 60 | 41 |
10 | 1.0 | K2CO3 (2.0) | H2O | 10 | 60 | 80 |
11 | 1.0 | Cs2CO3 (1.0) | H2O | 10 | 60 | 90 |
12 | 1.0 | NaOAc (1.0) | H2O | 10 | 60 | 14 |
13 | 1.0 | KOH (1.0) | H2O | 10 | 60 | 30 |
14 | 1.0 | CH3ONa (1.0) | H2O | 10 | 60 | 35 |
15 | 1.0 | Et3N (1.0) | H2O | 10 | 60 | 22 |
16 | 1.0 | K2CO3 (1.0) | CH3CN | 10 | 60 | 7 |
17 | 1.0 | K2CO3 (1.0) | DMF | 10 | 60 | 5 |
18 | 1.0 | K2CO3 (1.0) | EtOAc | 10 | 60 | 3 |
19 | 1.0 | K2CO3 (1.0) | CH3OH | 10 | 60 | 52 |
20 | 1.0 | K2CO3 (1.0) | DMSO | 10 | 60 | 5 |
21c | 1.0 | K2CO3 (1.0) | H2O | 10 | 60 | 87 |
With the optimal reaction conditions in hand, the scope of substrates was investigated and the results are summarized in Table 2. On one hand, we examined the reaction of sodium 4-methyl benzenesulfinate (2a) with cinnamic acid derivatives in the standard reaction conditions. Some cinnamic acids which have electron-withdrawing substituents on the phenyl ring (4-CN, 4-F, 4-Cl, 4-Br, 4-CF3 and 2,6-2Cl) could proceed smoothly to afford the corresponding products in available yields (63–84%) (3d–h, 3m). Also, cinnamic acids with electron-donating substituents on the phenyl ring (4-Me, 4-MeO, 4-t-Bu, 2-Me, 2-MeO and 3-Me) were examined, and the yields of the corresponding products ranged from 69% to 81% (3b–c, 3i–l). These results did not obviously change in comparison with those of substrates having electron-withdrawing substituents. In addition, (E)-2-(2-tosylvinyl)pyridine (3n) and (E)-2-(2-tosylvinyl)thiophene (3o) could be obtained with 55% and 57% yields, respectively. On the other hand, the reactions of trans-cinnamic acid (1a) with various sodium sulfinates were tested. Various sodium sulfinates with 4-H, 4-F, 4-Cl and 4-Br groups substituted on phenyl rings all proceeded smoothly to give good yields (78–83%) (3p–s). Moreover, (E)-(2-(methyl sulfonyl)vinyl)benzene (3t) was obtained with 45% yield.
It is worth noting that the reaction was performed on a 1.0 g scale to afford 3a with 81% yield, indicating that the reaction is scalable and practical (Scheme 2).
To understand the reaction mechanism better, some control experiments have been explored. The desired product 3a was obtained with a good yield under nitrogen atmosphere, which eliminated the influence of oxygen on this reaction very well (Table 1, entry 21). The reaction of 1a with 2a was proceeded under the standard conditions in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), and no 3a was detected by GC, which implied a radical pathway should be involved (Scheme 3a). When using 4-methylbenzene-1-sulfonyl iodide as the substrate instead of 2a and iodine, the yield of 3a was almost unchanged (Scheme 3b). The result suggested that 4-methylbenzene-1-sulfonyl iodide should be an intermediate in this transformation. The synthetic procedure of 4-methylbenzene-1-sulfonyl iodide was given in the ESI.† In addition, it should be pointed out that I2 is almost converted to iodine anions after the reaction in two steps (i.e., the reaction of ArSO2Na with I2, and the reaction of ArSO2I with cinnamic acid) in the present standard conditions, which is confirmed by iodometric titration.
Based on the results of control experiments, a possible reaction mechanism was proposed in Scheme 4. It is easy to generate intermediate A from sodium sulfinate and iodine, and the intermediate A undergoes homolysis to give a sulfonyl radical (B) and an iodine radical.16 Subsequently, the radical B is added to the double bond of cinnamic acid to afford intermediate C,14b–e,17 which is combined with iodine or iodine radical to generate intermediate D.10b,d Finally, the intermediate D undergoes the elimination of carbon dioxide and hydrogen iodide to provide the desired vinyl sulfones with the help of a base.14c,17
In conclusion, we have developed a green and efficient method for the synthesis of vinyl sulfones via I2-mediated decarboxylative coupling reaction using environmentally friendly water as the reaction medium. This reaction shows its fascinating application prospect in organic synthesis. Compared with the reported methods, this route seems to be greener and more efficient.
Footnote |
† Electronic supplementary information (ESI) available: Detailed experimental procedures, characterization of products, and NMR spectral charts. See DOI: 10.1039/c5ra10896a |
This journal is © The Royal Society of Chemistry 2015 |