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Article

A Facile and Mild Synthesis of Trisubstituted Allylic Sulfones from Morita-Baylis-Hillman Carbonates

by
Lin Jiang
1,2,*,
Yong-Gen Li
1,
Jiang-Feng Zhou
1,
Yong-Ming Chuan
1,2,
Hong-Li Li
1,2 and
Ming-Long Yuan
1,2,*
1
Engineering Research Center of Biopolymer Functional Materials of Yunnan, School of Chemistry and Biotechnology, Yunnan Minzu University, Kunming 650500, China
2
Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Chemistry and Biotechnology, Yunnan Minzu University, Kunming 650500, China
*
Authors to whom correspondence should be addressed.
Molecules 2015, 20(5), 8213-8222; https://doi.org/10.3390/molecules20058213
Submission received: 1 April 2015 / Revised: 29 April 2015 / Accepted: 4 May 2015 / Published: 7 May 2015
(This article belongs to the Special Issue Design and Synthesis of Novel Conjugated and Non Conjugated Small Molecules)
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Abstract

:
An efficient and catalyst-free synthesis of trisubstituted allylic sulfones through an allylic sulfonylation reaction of Morita-Baylis-Hillman (MBH) carbonates with sodium sulfinates has been developed. Under the optimized reaction conditions, a series of trisubstituted allylic sulfones were rapidly prepared in good to excellent yields (71%–99%) with good to high selectivity (Z/E from 79:21 to >99:1). Compared with known synthetic methods, the current protocol features mild reaction temperature, high efficiency and easily available reagents.

Graphical Abstract

1. Introduction

Morita-Baylis-Hillman (MBH) adducts and their derivatives are very useful multifunctional synthons in organic chemistry [1,2,3,4,5]. Since the pioneering work of Lu and co-workers in 2004, MBH carbonates have triggered much interest among chemistry researchers [6]. The most extensively studied transformation pattern of this type of MBH derivatives is the allylic substitution with a pronucleophile in the presence of a Lewis basic catalyst [7,8,9]. Based on the substitution position on MBH carbonates, the transformations could be divided into the following two styles: substitution at the β-position through a SN2'-SN2' cascade or substitution at the β'-position via a single SN2' route (Scheme 1). Compared with the former route, which is widely employed in asymmetric synthesis to access versatile multifunctional chiral molecules [10,11,12,13,14,15,16], the latter route has been often used for the preparation of trisubstituted alkenes [17,18,19,20].
Molecules 20 08213 g001 550
Scheme 1. Allylic substitution reaction of Morita-Baylis-Hillman (MBH) carbonates.
Scheme 1. Allylic substitution reaction of Morita-Baylis-Hillman (MBH) carbonates.
Molecules 20 08213 g001
Allylic sulfone derivatives are important intermediates in organic synthesis [21,22,23,24]. Recent studies have revealed that these compounds exhibit remarkable biological activities [25]. The use of MBH adducts or their acetates as good starting materials for the trisubstituted allylic sulfones has been reported in some instances [26,27,28,29,30,31,32,33,34]. Although many sulfonyl precursors including sulfinate [26,27,28,29], p-toluenesulfonylmethylcyanide [30], arenesulfonyl cyanide [31], sulfinyl chloride [32], sulfonylhydrazide [33] and sulfinic acid [34] have been employed in this type of allylic sulfonylation, sulfinate is undoubtedly a cheap and easily available reagent. However, either a high reaction temperature [26,27] (70–80 °C, 6–16 h) or unconventional organic solvent (ionic liquids or polyethylene glycol) [28,29], accompanied with tedious work-up procedures, were required to ensure a high yield of the desired products. Since MBH carbonates usually exhibit much superior reactivity to MBH acetates, we envisaged that they would be more susceptible to the nucleophilic attack by sulfinate. Herein, we report a new protocol in which MBH carbonates 1 and sodium sulfinates 2 undergo a smooth and rapid SN2' pathway to realize the trisubstituted allylic sulfones 3 under mild and catalyst-free reaction conditions (Scheme 2).
Molecules 20 08213 g002 550
Scheme 2. Allylic sulfonylation of MBH carbonates 1 with sodium sulfinates 2.
Scheme 2. Allylic sulfonylation of MBH carbonates 1 with sodium sulfinates 2.
Molecules 20 08213 g002

2. Results and Discussion

2.1. Optimization Studies

Preliminary studies were carried out by using MBH carbonate 1a (R = Ph, EWG = CO2Me) and sodium benzenesulfinate (2a, Ar = Ph). The screening results are presented in Table 1. Firstly, the model reaction was investigated with different solvents at ambient temperature (Table 1, entries 1–6). Among the solvents tested, toluene and chloroform gave poor conversion (Table 1, entries 1 and 2), and PhCF3 afforded only a trace amount of the final adduct 3a after 72 h (Table 1, entry 3). Although 1,2-dichloroethane (DCE) and tetrahydrofuran (THF) afforded 3a in high yield (Table 1, entries 4 and 5), acetonitrile was a superior solvent with regard to both conversion rate and product yield (92%, Table 1, entry 6). Next, it was found that when the reaction temperature was raised to 40 °C, nearly full conversion could be achieved within a significantly shortened reaction time and the expected product was furnished in 96% yield (Table 1, entry 7). Finally, the examination of the reaction with a decreased concentration of substrate 1a revealed no influence on product yield, whereas the reaction time was prolonged (Table 1, entry 8).
Table
Table 1. Optimization of reaction conditions using MBH carbonate 1a and sodium benzenesulfinate 2a a.
Table 1. Optimization of reaction conditions using MBH carbonate 1a and sodium benzenesulfinate 2a a.
EntrySolventT (°C)Time (h)Yield (%) b,c
1toluene253637
2CHCl3254817
3PhCF32572trace
4DCE253682
5THF253687
6MeCN253692
7MeCN40296 d
8 eMeCN40596
a Reaction conditions: Unless otherwise noted, reactions were performed with 1a (0.1 mmol) and sodium benzenesulfinate 2a (0.15 mmol) in solvent (1 mL) at indicated temperature; b Isolated yield of two inseparable isomers; c Major isomer of 3a was determined to be Z by comparison of its NMR data with the one reported in literature [35]; d Z/E = 96:4, determined by 1H-NMR analysis; e 2 mL of solvent was used.

2.2. Synthesis of Trisubstituted Allylic Sulfones 3a–o

On the basis of the above optimized reaction parameters (0.1 mmol of MBH carbonate 1a and 0.15 mmol of sodium benzenesulfinate (2a) to perform the reaction in 1 mL of MeCN at 40 °C), this protocol was then extended to other MBH carbonates or sulfinates to investigate the scope and limitation of the method. As shown in Table 2, MBH carbonates 1 could generally be converted within 2 h and corresponding products 3 were obtained in good to excellent yields (71%–99%) with good to high selectivity (Z/E from 79:21 to >99:1) (Table 2, entries 1–15). Different substituents on the phenyl group were first explored. The results showed that the electronic nature or position of substituents had minimal influence on reaction efficiency in terms of reaction rate and product yield in general (78%–98%, Table 2, entries 1–9). Besides, 1-naphthyl group-substituted MBH carbonate 1j was a suitable substrate, albeit with lower yield (71%, Table 2, entry 10). Meanwhile, two heteroaromatic substrates 1k and 1l also showed high reactivity, providing 3k and 3l in high yields (85% and 96%, Table 2, entries 11 and 12). It is worth mentioning that the MBH carbonate 1m, which was prepared from an aliphatic aldehyde, could participate in this reaction to produce the desired product 3m in high yield (91%, Table 2, entry 13). In addition, MBH carbonate 1n, which was derived from acrylonitrile, could also be transformed in excellent yield under the catalyst-free reaction conditions (99%, Table 2, entry 14). To our delight, sodium p-toluenesulfinate 2b (Ar = p-MeC6H4) was well tolerated and the desired product 3o was provided in 95% yield (Table 2, entry 15).
Table
Table 2. Substrate scope for allylic sulfonylation of MBH carbonates 1 with sodium sulfinates 2 a.
Table 2. Substrate scope for allylic sulfonylation of MBH carbonates 1 with sodium sulfinates 2 a.
EntryREWGArYield (%) bZ/E c,d
1Ph (1a)CO2MePh96 (3a)96:4
2o-ClC6H4 (1b)CO2MePh88 (3b)95:5
3p-ClC6H4 (1c)CO2MePh96 (3c)85:15
4p-NO2C6H4 (1d)CO2MePh83 (3d)79:21
5m-BrC6H4 (1e)CO2MePh93 (3e)94:6
6p-MeOC6H4 (1f)CO2MePh78 (3f)88:12
7 Molecules 20 08213 i001 (1g)CO2MePh98 (3g)90:10
8m-MeC6H4 (1h)CO2MePh96 (3h)88:12
9p-MeC6H4 (1i)CO2MePh92 (3i)96:4
101-naphthyl (1j)CO2MePh71 (3j)96:4
112-furyl (1k)CO2MePh85 (3k)>99:1
122-thienyl (1l)CO2MePh96 (3l)81:19
13n-propyl (1m)CO2MePh91 (3m)82:18
14Ph (1n)CNPh99 (3n)<1:99
15Ph (1a)CO2Mep-MeC6H495 (3o)84:16
a Reaction conditions: Unless otherwise noted, reactions were performed with MBH carbonate 1 (0.1 mmol) and sodium sulfinate 2 (0.15 mmol) in MeCN (1 mL) at 40 °C for 2 h; b Isolated yield of two inseparable isomers; c Olefin geometry was assigned by analogy with that of 3a; d Z/E ratio was determined by 1H-NMR analysis.

3. Experimental Section

3.1. General Information

TLC was performed on glass-backed silica plates. Flash column chromatography was performed using silica gel (200–300 mesh) eluting with ethyl acetate and petroleum ether. UV light was used to visualize products. 1H-NMR spectra were recorded at 400 MHz, and 13C-NMR spectra were recorded at 100 MHz (Avance 400, Bruker, Faellanden, Switzerland). Tetramethylsilane was used as the internal standard. Chemical shifts are reported in ppm downfield from the solvent signal (CDCl3, δ = 7.27 ppm) for 1H-NMR and relative to the central CDCl3 resonance (δ = 77.0 ppm) for 13C-NMR spectroscopy. Coupling constants are given in Hz. ESI-HRMS was recorded on a Waters SYNAPT G2 (Milford, MA, USA). In experiments requiring dry solvents, DCE, chloroform and toluene were distilled from CaH2. PhCF3 was stored over 4 Å molecular sieves. THF was dried over sodium metal. Acetonitrile was dried over P2O5. All other chemicals were used without purification as commercially available. MBH carbonates were prepared by the reported procedure [36].

3.2. General Procedure for Preparation of Trisubstituted Allylic Sulfones 3a–o

MBH carbonate 1 (0.1 mmol) and sodium sulfinate 2 (0.15 mmol) were mixed in MeCN (1 mL) and heated at 40 °C for 2 h. Then, the reaction mixture was concentrated under reduced pressure and the residue was diluted with toluene and purified by flash column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired product 3a–o. Products 3a [33], 3d [26], 3f [26], 3k [26], 3l [27], 3n [33] and 3o [26] are known compounds.
(Z)-Methyl 3-phenyl-2-[(phenylsulfonyl)methyl]acrylate (3a). Colourless liquid; 96% yield; Z/E = 96:4; 1H-NMR: δ = 7.95 (s, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.63–7.59 (m, 1H), 7.52–7.47 (m, 4H), 7.39–7.37 (m, 3H), 4.49 (s, 2H), 3.60 (s, 3H) ppm; 13C-NMR: δ = 167.0, 146.6, 139.6, 133.9, 133.8, 129.9, 129.4, 129.2, 129.0, 128.7, 121.1, 55.3, 52.5 ppm; ESI-HRMS: calcd. For C17H16O4S+Na 339.0667, found 339.0661.
(Z)-Methyl 3-(2-chlorophenyl)-2-[(phenylsulfonyl)methyl]acrylate (3b). Colourless liquid; 88% yield; Z/E = 95:5; 1H-NMR: δ = 7.94 (m, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.55–7.53 (m, 2H), 7.43–7.40 (m, 2H), 7.30–7.27 (m, 1H), 7.23–7.21 (m, 2H), 4.31 (s, 2H), 3.55 (s, 3H) ppm; 13C-NMR: δ = 165.5, 142.4, 138.5, 133.3, 133.0, 131.5, 129.9, 129.2, 129.0, 128.3, 128.1, 127.7, 126.3, 122.3, 54.2, 51.8 ppm; ESI-HRMS: calcd. For C17H15ClO4S+Na 373.0277, found 373.0273.
(Z)-Methyl 3-(4-chlorophenyl)-2-[(phenylsulfonyl)methyl]acrylate (3c). Colourless liquid; 96% yield; Z/E = 85:15; 1H-NMR: δ = 7.89 (s, 1H), 7.85 (d, J = 8.0 Hz, 2H), 7.64–7.61 (m, 1H), 7.53–7.49 (m, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.44 (s, 2H), 3.57 (s, 3H) ppm; 13C-NMR: δ = 165.6, 144.0, 138.3, 134.9, 132.9, 131.1, 129.6, 128.1, 127.5, 120.4, 54.1, 51.5 ppm; ESI-HRMS: calcd. For C17H15ClO4S+H 351.0458, found 351.0459.
(Z)-Methyl 3-(4-nitrophenyl)-2-[(phenylsulfonyl)methyl]acrylate (3d). Pale yellow solid; 83% yield; Z/E = 79:21; 1H-NMR: δ = 8.24 (d, J = 8.0 Hz, 2H), 7.98 (s, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.69–7.64 (m, 3H), 7.55–7.52 (m, 2H), 4.40 (s, 2H), 3.63 (s, 3H) ppm; 13C-NMR: δ = 165.0, 142.5, 139.0, 133.1, 128.8, 128.2, 127.7, 127.5, 123.2, 122.9, 122.4, 53.9, 51.7 ppm; ESI-HRMS: calcd. For C17H15NO6S+Na 384.0518, found 384.0518.
(Z)-Methyl 3-(3-bromophenyl)-2-[(phenylsulfonyl)methyl]acrylate (3e). Pale yellow solid; 93% yield; Z/E = 94:6; 1H-NMR: δ = 7.85–7.83 (m, 3H), 7.68–7.64 (m, 1H), 7.53–7.42 (m, 5H), 7.28–7.24 (m, 1H), 4.46 (s, 2H), 3.67 (s, 3H) ppm; 13C-NMR: δ = 166.6, 144.6, 139.1, 135.7, 134.0, 132.6, 131.9, 130.4, 129.3, 128.7, 127.4, 123.0, 122.7, 55.0, 52.7 ppm; ESI-HRMS: calcd. For C17H15BrO4S+Na 416.9772, found 416.9772.
(Z)-Methyl 3-(4-methoxyphenyl)-2-[(phenylsulfonyl)methyl]acrylate (3f). Colourless liquid; 78% yield; Z/E = 88:12; 1H-NMR: δ = 7.92 (s, 1H), 7.89 (d, J = 8.0 Hz, 2H), 7.62–7.58 (m, 3H), 7.54–7.50 (m, 2H), 6.93 (d, J = 8.0 Hz, 2H), 4.52 (s, 2H), 3.85 (s, 3H), 3.51 (s, 3H) ppm; 13C-NMR: δ = 167.3, 161.3, 146.5, 139.6, 133.8, 131.7, 129.1, 128.7, 126.3, 118.1, 114.4, 55.6, 55.5, 52.3 ppm; ESI-HRMS: calcd. For C18H18O5S+Na 369.0773, found 369.0771.
(Z)-Methyl 3-(3,4-dimethoxyphenyl)-2-[(phenylsulfonyl)methyl]acrylate (3g). Viscous liquid; 98% yield; Z/E = 90:10; 1H-NMR: δ = 7.93 (s, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.65–7.62 (m, 1H), 7.55–7.51 (m, 2H), 7.43 (s, 1H), 7.20–7.17 (m, 1H), 6.90 (d, J = 8.0 Hz, 1H), 4.53 (s, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 3.50 (s, 3H), ppm; 13C-NMR: δ = 166.1, 149.8, 148.1, 145.8, 138.6, 132.7, 128.0, 127.6, 125.5, 122.7, 117.2, 111.5, 110.1, 55.3, 55.0, 54.8, 51.2 ppm; ESI-HRMS: calcd. For C19H20O6S+K 415.0618, found 415.0618.
(Z)-Methyl 2-[(phenylsulfonyl)methyl]-3-(m-tolyl)acrylate (3h). Colourless liquid; 96% yield; Z/E = 88:12; 1H-NMR: δ = 7.88 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.59–7.54 (m, 1H), 7.47–7.43 (m, 2H), 7.24–7.20 (m, 2H), 7.16–7.13 (m, 2H), 4.47 (s, 2H), 3.58 (s, 3H), 2.31(s, 3H) ppm; 13C-NMR: δ = 165.9, 145.5, 138.3, 137.4, 132.6, 129.5, 128.8, 127.7, 127.5, 125.1, 119.7, 54.1, 51.4, 20.3 ppm; ESI-HRMS: calcd. For C18H18O4S+Na 353.0823, found 353.0827.
(Z)-Methyl 2-[(phenylsulfonyl)methyl]-3-(p-tolyl)acrylate (3i). Colourless liquid; 92% yield; Z/E = 96:4; 1H-NMR: δ = 7.93 (s, 1H), 7.87 (d, J = 8.0 Hz, 2H), 7.63–7.60 (m, 1H), 7.52–7.48 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 4.50 (s, 2H), 3.56 (s, 3H), 2.38 (s, 3H) ppm; 13C-NMR: δ = 166.0, 145.6, 139.3, 138.5, 132.7, 129.8, 128.5, 128.5, 128.0, 127.6, 118.7, 54.3, 51.3, 20.4 ppm; ESI-HRMS: calcd. For C18H18O4S+Na 353.0823, found 353.0820.
(Z)-Methyl 3-(naphthalen-2-yl)-2-[(phenylsulfonyl)methyl]acrylate (3j). Colourless liquid; 71% yield; Z/E = 96:4; 1H-NMR: δ = 8.35 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.62–7.59 (m, 3H), 7.46–7.33 (m, 4H), 7.29–7.26 (m, 1H), 7.21–7.17 (m, 2H), 4.38 (s, 2H), 3.66 (s, 3H) ppm; 13C-NMR: δ = 166.7, 144.6, 139.2, 133.4, 133.3, 131.0, 130.7, 129.8, 128.9, 128.6, 128.1, 126.7, 126.4, 126.4, 125.3, 124.3, 123.5, 55.1, 52.6 ppm; ESI-HRMS: calcd. For C21H18O4S+Na 389.0823, found 389.0825.
(Z)-Methyl 3-(furan-2-yl)-2-[(phenylsulfonyl)methyl]acrylate (3k). Semi-solid; 85% yield; Z/E > 99:1; 1H-NMR: δ = 7.84 (s, 1H), 7.83–7.82 (m, 1H), 7.53–7.50 (m, 2H), 7.44–7.39 (m, 3H), 6.67 (d, J = 4.0 Hz, 1H), 6.40 (m, 1H), 4.79 (s, 2H), 3.59 (s, 3H) ppm;13C-NMR: δ = 166.9, 150.0, 145.8, 139.4, 133.6, 130.7, 128.7, 128.7, 119.1, 115.5, 112.3, 55.5, 52.4 ppm; ESI-HRMS: calcd. For C15H14O5S+H 307.0640, found 307.0649.
(Z)-Methyl 2-[(phenylsulfonyl)methyl]-3-(thiophen-2-yl)acrylate (3l). Light brown liquid; 96% yield; Z/E = 81:19; 1H-NMR: δ = 8.03 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.60–7.56 (m, 1H), 7.53–7.46 (m, 5H), 7.08–7.06 (m, 1H), 4.61 (s, 2H), 3.50 (s, 3H) ppm; 13C-NMR: δ = 165.7, 138.4, 137.3, 135.7, 133.2, 132.8, 129.9, 128.0, 127.6, 126.8, 115.1, 55.0, 51.3 ppm; ESI-HRMS: calcd. For C15H14O4S2+H 323.0412, found 323.0417.
(Z)-Methyl 2-[(phenylsulfonyl)methyl]hex-2-enoate (3m). viscous liquid; 91% yield; Z/E = 82:18; 1H-NMR: δ = 7.86–7.81 (m, 2H), 7.64–7.61 (m, 1H), 7.54–7.51 (m, 2H), 7.12 (t, J = 8.0 Hz, 1H), 4.24 (s, 2H), 3.48 (s, 3H), 2.20–2.14 (m, 2H), 1.49–1.40 (m, 2H), 0.91 (t, J = 8.0 Hz, 3H) ppm; 13C-NMR: δ = 166.2, 151.9, 139.0, 133.9, 129.2, 128.9, 120.8, 54.2, 52.1, 31.6, 21.7, 14.0 ppm; ESI-HRMS: calcd. For C14H18O4S+Na 305.0823, found 305.0829.
(E)-3-Phenyl-2-[(phenylsulfonyl)methyl]acrylonitrile (3n). Colourless liquid; 99% yield; Z/E < 1:99; 1H-NMR: δ = 7.94–7.92 (m, 2H), 7.74–7.68 (m, 3H), 7.63–7.59 (m, 2H), 7.47–7.41 (m, 3H), 7.09 (s, 1H), 4.05 (s, 2H) ppm; 13C-NMR: δ = 151.9, 137.6, 134.7, 132.5, 131.7, 129.6, 129.3, 129.1, 128.8, 117.1, 98.0, 61.4 ppm; ESI-HRMS: calcd. For C16H13NO2S+Na 306.0565, found 306.0566.
(Z)-Methyl 3-phenyl-2-(tosylmethyl)acrylate (3o). Colourless liquid; 95% yield; Z/E = 84:16; 1H-NMR: δ = 7.93 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.47 (m, 2H), 7.37 (m, 3H), 7.27 (d, J = 8.0 Hz, 2H), 4.48 (s, 2H), 3.62 (s, 3H), 2.42 (s, 3H) ppm; 13C-NMR: δ = 167.1, 146.3, 144.8, 136.3, 133.8, 129.7, 129.3, 128.8, 128.6, 121.2, 55.2, 52.5, 21.7 ppm; ESI-HRMS: calcd. For C18H18O4S+Na 353.0823, found 353.0827.

4. Conclusions

In summary, we have established a method for the allylic sulfonylation of MBH carbonates with sodium sulfinates under catalyst-free reaction conditions. A series of functionalized trisubstituted allylic sulfones were rapidly generated in good to excellent yields (71%–99%) with good to high selectivity (Z/E from 79:21 to >99:1). Compared with known synthetic methods, the current protocol features mild reaction temperature (40 °C), high efficiency (full conversion within 2 h) and easily available reagents. Thus, it should provide an efficient and facile access to the trisubstituted allylic sulfones. Further studies on expanding the substrate scope and chemical transformations of the trisubstituted allylic sulfones are currently underway.

Supplementary Materials

Supplementary materials can be accessed at: https://www.mdpi.com/1420-3049/20/05/8213/s1.

Acknowledgments

We are grateful for financial support from the National Natural Science Foundation of China (21302163), Scientific Research Foundation of Yunnan Education Office (2013Z037), Youth Scientific Research Foundation of Yunnan Minzu University (2012QN03) and Graduate Students Innovation Foundation of Yunnan Minzu University (2014YJY85).

Author Contributions

L.J. and M.-L.Y. designed research; L.J. wrote the paper as well; Y.-G.L. and J.-F.Z. performed the experiments; Y.-M.C. analyzed the data; H.-L.L. revised the manuscript. All authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References and Notes

  1. Basavaiah, D.; Reddy, B.S.; Badsara, S.S. Recent contributions from the Baylis-Hillman reaction to organic chemistry. Chem. Rev. 2010, 110, 5447–5674. [Google Scholar] [CrossRef] [PubMed]
  2. Ma, G.-N.; Jiang, J.-J.; Shi, M.; Wei, Y. Recent extensions of the Morita-Baylis-Hillman reaction. Chem. Commun. 2009, 5496–5514. [Google Scholar] [CrossRef]
  3. Declerck, V.; Martinez, J.; Lamaty, F. Aza-Baylis-Hillman reaction. Chem. Rev. 2009, 109, 1–48. [Google Scholar] [CrossRef]
  4. Gowrisankar, S.; Lee, H.S.; Kim, S.H.; Lee, K.Y.; Kim, J.N. Recent advances in the Pd-catalyzed chemical transformations of Baylis-Hillman adducts. Tetrahedron 2009, 65, 8769–8780. [Google Scholar] [CrossRef]
  5. Wei, Y.; Shi, M. Multifunctional chiral phosphine organocatalysts in catalytic asymmetric Morita-Baylis-Hillman and related reactions. Acc. Chem. Res. 2010, 43, 1005–1018. [Google Scholar] [CrossRef] [PubMed]
  6. Du, Y.; Han, X.; Lu, X. Alkaloids-catalyzed regio- and enantioselective allylic nucleophilic substitution of tert-butyl carbonate of the Morita-Baylis-Hillman products. Tetrahedron Lett. 2004, 45, 4967–4971. [Google Scholar] [CrossRef]
  7. Liu, T.-Y.; Xie, M.; Chen, Y.-C. Organocatalytic asymmetric transformations of modied Morita-Baylis-Hillman adducts. Chem. Soc. Rev. 2012, 41, 4101–4112. [Google Scholar] [CrossRef] [PubMed]
  8. Rios, R. Organocatalytic enantioselective methodologies using Morita-Baylis-Hillman carbonates and acetates. Catal. Sci. Technol. 2012, 2, 267–278. [Google Scholar] [CrossRef]
  9. Wei, Y.; Shi, M. Recent advances in organocatalytic asymmetric Morita-Baylis-Hillman/aza-Morita-Baylis-Hillman reactions. Chem. Rev. 2013, 113, 6659–6690. [Google Scholar] [CrossRef] [PubMed]
  10. Zhan, G.; Zhou, Q.-Q.; Du, W.; Chen, Y.-C. Enantioselective N-allylic alkylation of N-propargylsulfonamides with Morita-Baylis-Hillman carbonates and sequential electrophilic cyclization. Synthesis 2014, 46, 3383–3393. [Google Scholar] [CrossRef]
  11. Yang, H.-B.; Zhao, Y.-Z.; Sang, R.; Shi, M. (DHQ)2AQN-Catalyzed asymmetric substitution of isatin-derived hydrazones with O-BoC-protected Morita-Baylis-Hillman adducts: A strategy for synthesizing enantioenriched Azo compounds incorporating an oxindole scaffold. J. Org. Chem. 2014, 79, 3519–3528. [Google Scholar] [CrossRef] [PubMed]
  12. Companyó, X.; Geant, P.-Y.; Mazzanti, A.; Moyano, A.; Rios, R. Catalytic asymmetric one-pot synthesis of α-methylene-γ-lactams. Tetrahedron 2014, 70, 75–82. [Google Scholar] [CrossRef]
  13. Yan, Y.; En, D.; Zhuang, Z.; Guo, Y.; Liao, W.-W. Synthesis of densely functionalized α-methylene γ-butyrolactones via an organ Catalytic one-pot allylic-alkylation-cyclization reaction. Tetrahedron Lett. 2014, 55, 479–482. [Google Scholar] [CrossRef]
  14. Mao, H.; Lin, A.; Shi, Y.; Mao, Z.; Zhu, X.; Li, W.; Hu, H.; Cheng, Y.; Zhu, C. Construction of enantiomerically enriched diazo compounds using diazo esters as nucleophiles: Chiral Lewis base catalysis. Angew. Chem. Int. Ed. 2013, 52, 6288–6292. [Google Scholar] [CrossRef]
  15. Wang, Q.-G.; Zhou, Q.-Q.; Deng, J.-G.; Chen, Y.-C. An asymmetric allylic alkylation-smiles rearrangement sulfinate addition sequence to construct chiral cyclic sulfones. Org. Lett. 2013, 15, 4786–4789. [Google Scholar] [CrossRef] [PubMed]
  16. Companyó, X.; Mazzanti, A.; Moyano, A.; Janecka, A.; Rios, R. First one-pot organocatalytic synthesis of α-methylene-γ-lactones. Chem. Commun. 2013, 49, 1184–1186. [Google Scholar] [CrossRef]
  17. Drewes, S.E.; Roos, G.H.P. Synthetic potential of the tertiary-amine-catalysed reaction of activated vinyl carbanions with aldehydes. Tetrahedron 1988, 44, 4653–4670. [Google Scholar] [CrossRef]
  18. Basavaiah, D.; Rao, P.D.; Hyma, R.S. The Baylis-Hillman reaction: A novel carbon-carbon bond forming reaction. Tetrahedron 1996, 52, 8001–8062. [Google Scholar] [CrossRef]
  19. Li, G.; Wei, H.-X.; Gao, J.J.; Caputo, T.D. TiCl4-Mediated Baylis-Hillman and aldol reactions without the direct use of a Lewis base. Tetrahedron Lett. 2000, 41, 1–5. [Google Scholar] [CrossRef]
  20. Basavaiah, D.; Pandiaraju, S.; Padmaja, K. The Friedel-Crafts chemistry: Acetates of the Baylis-Hillman adducts as novel stereodefined β-electrophiles. Synlett 1996, 393–395. [Google Scholar] [CrossRef]
  21. Quiclet-Sire, B.; Seguin, S.; Zard, S.Z. A new radical allylation reaction of dithiocarbonates. Angew. Chem. Int. Ed. 1998, 37, 2864–2866. [Google Scholar] [CrossRef]
  22. Kim, S.; Lim, C.J. Tin-free radical-mediated C-C-bond formations with alkyl allyl sulfones as radical precursors. Angew. Chem. Int. Ed. 2002, 41, 3265–3267. [Google Scholar] [CrossRef]
  23. Wróbel, Z. Silane-mediated direct condensation of nitroarenes with cinnamyl-type sulfones. The way to 2-aryl-4-X-quinolines and their hetero analogs. Tetrahedron 1998, 54, 2607–2618. [Google Scholar] [CrossRef]
  24. Jiang, L.; Lei, Q.; Huang, X.; Cui, H.-L.; Zhou, X.; Chen, Y.-C. Lewis base assisted Brønsted base catalysis: Direct regioselective asymmetric vinylogous alkylation of allylic sulfones. Chem. Eur. J. 2011, 17, 9489–9493. [Google Scholar] [CrossRef] [PubMed]
  25. Neamati, N.; Kabalka, G.W.; Venkataiah, B.; Dayam, R. Small Molecules for Treating Cancer and Abnormal Cell Proliferation Disorders. U.S. Patent WO 2,007,081,966 A3, 9 January 2007. [Google Scholar]
  26. Wang, Q.; Sheng, S.-R.; Lin, S.-Y.; Guo, L.; Wei, M.-H.; Huang, X. Liquid-phase synthesis of methyl (2Z)-2-arylsulfonylmethyl-2-alkenoates from PEG-supported α-phenylselenopropionate. Chin. J. Chem. 2007, 25, 1027–1030. [Google Scholar] [CrossRef]
  27. Karnakar, K.; Shankar, J.; Murthy, S.N.; Nageswar, Y.V.D. Synthesis of allyl aryl sulfone derivatives from Baylis-Hillman acetates in water. Helv. Chim. Acta 2011, 94, 875–880. [Google Scholar] [CrossRef]
  28. Kabalka, G.W.; Venkataiah, B.; Dong, G. Preparation of substituted allyl acetates and sulfones from Baylis-Hillman adducts in ionic liquid media. Tetrahedron Lett. 2003, 44, 4673–4675. [Google Scholar] [CrossRef]
  29. Chandrasekhar, S.; Saritha, B.; Jagadeshwer, V.; Narsihmulu, C.; Vijay, D.; Sarma, G.D.; Jagadeesh, B. Hydroxy-assisted catalyst-free Michael addition-dehydroxylation of Baylis-Hillman adducts in poly(ethylene glycol). Tetrahedron Lett. 2006, 47, 2981–2984. [Google Scholar] [CrossRef]
  30. Srivastava, V.P.; Yadav, L.D.S. Direct sulfonylation of Baylis-Hillman alcohols and diarylmethanols with TosMIC in ionic liquid-[Hmim]HSO4: An unexpected reaction. Tetrahedron Lett. 2011, 52, 4622–4626. [Google Scholar] [CrossRef]
  31. Reddy, L.R.; Hu, B.; Prashad, M.; Prasad, K. An unexpected reaction of arenesulfonyl cyanides with allylic alcohols: Preparation of trisubstituted allyl sulfones. Angew. Chem. Int. Ed. 2009, 48, 172–174. [Google Scholar] [CrossRef]
  32. Li, H.-H.; Dong, D.-J.; Jin, Y.-H.; Tian, S.-K. An expeditious entry to benzylic and allylic sulfones through byproduct-catalyzed reaction of alcohols with sulfinyl chlorides. J. Org. Chem. 2009, 74, 9501–9504. [Google Scholar] [CrossRef] [PubMed]
  33. Li, X.; Xu, X.; Tang, Y. Tetrabutylammonium iodide catalyzed allylic sulfonylation of Baylis-Hillman acetates with sulfonylhydrazides in water. Org. Biomol. Chem. 2013, 11, 1739–1742. [Google Scholar] [CrossRef] [PubMed]
  34. Liu, C.-R.; Li, M.-B.; Cheng, D.-J.; Yang, C.-F.; Tian, S.-K. Catalyst-free alkylation of sulfinic acids with sulfonamides via sp3 C-N bond cleavage at room temperature. Org. Lett. 2009, 11, 2543–2545. [Google Scholar] [CrossRef] [PubMed]
  35. The NMR characteristic data of 3a are consistent with that of (Z)-methyl 3-phenyl-2-((phenylsulfonyl)methyl)acrylate, which were reported in the ESI section of Ref. [33].
  36. Feng, J.; Lu, X.; Kong, A.; Han, X. A highly regio- and stereo-selective [3+2] annulation of allylic compounds and 2-substituted 1,1-dicyanoalkenes through a catalytic carbon-phosphorus ylide reaction. Tetrahedron 2007, 63, 6035–6041. [Google Scholar] [CrossRef]
  • Samples Availability: Samples of the compounds 3a–o are available from the authors.

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MDPI and ACS Style

Jiang, L.; Li, Y.-G.; Zhou, J.-F.; Chuan, Y.-M.; Li, H.-L.; Yuan, M.-L. A Facile and Mild Synthesis of Trisubstituted Allylic Sulfones from Morita-Baylis-Hillman Carbonates. Molecules 2015, 20, 8213-8222. https://doi.org/10.3390/molecules20058213

AMA Style

Jiang L, Li Y-G, Zhou J-F, Chuan Y-M, Li H-L, Yuan M-L. A Facile and Mild Synthesis of Trisubstituted Allylic Sulfones from Morita-Baylis-Hillman Carbonates. Molecules. 2015; 20(5):8213-8222. https://doi.org/10.3390/molecules20058213

Chicago/Turabian Style

Jiang, Lin, Yong-Gen Li, Jiang-Feng Zhou, Yong-Ming Chuan, Hong-Li Li, and Ming-Long Yuan. 2015. "A Facile and Mild Synthesis of Trisubstituted Allylic Sulfones from Morita-Baylis-Hillman Carbonates" Molecules 20, no. 5: 8213-8222. https://doi.org/10.3390/molecules20058213

APA Style

Jiang, L., Li, Y. -G., Zhou, J. -F., Chuan, Y. -M., Li, H. -L., & Yuan, M. -L. (2015). A Facile and Mild Synthesis of Trisubstituted Allylic Sulfones from Morita-Baylis-Hillman Carbonates. Molecules, 20(5), 8213-8222. https://doi.org/10.3390/molecules20058213

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