CC BY-NC-ND 4.0 · SynOpen 2021; 05(01): 91-99
DOI: 10.1055/a-1422-9411
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Simple and Efficient Synthesis of Allyl Sulfones through Cs2CO3-Mediated Radical Sulfonylation of Morita–Baylis–Hillman Adducts with Thiosulfonates

Angothu Shankar
,
Md. Waheed
,
We thank the Department of Science & Technology - Promotion of University Research and Scientific Excellence (DST-PURSE; SR/PURSE Phase 2/32/G) and the Council of Scientific and Industrial Research (CSIR-EMR-II; 02(0340)/18/EMR-II) for funding support. A.S. and M.W. thank CSIR-SRF and UGC-SRF, respectively, for their Research Fellowships.
 


Abstract

A highly efficient and eco-friendly method has been developed for the synthesis of allyl sulfones using Morita–Baylis–Hillman (MBH) adducts and thiosulfonates under mild conditions. The Cs2CO3-promoted radical sulfonylation provided a series of allyl sulfones in good to high yields with high stereoselectivities. A wide variety of MBH bromides/acetates as well as thiosulfonates were tolerated and reliable in scaled-up synthesis. A plausible mechanism is proposed to rationalize the radical sulfonylation.


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Thiosulfonates (R1SO2-SR2)[1] have emerged as powerful reactants to synthesize many valuable organosulfur compounds.[2] Also known as sulfonothioates or S-esters of thiosulfonic acid, they generally show low toxicity. Typically, thiosulfonates serve as electrophilic sulfenylating reagents,[3] generating a sulfonyl moiety as by-product. Additionally, homolytic cleavage of the S–S(O2) bond of thiosulfonates generates sulfonyl and sulfenyl radicals under thermal or photochemical conditions.[4] As a result, thiosulfonates have been utilized to install two distinct C–S bonds (sulfenyl and sulfonyl) through atom transfer thiosulfonylation.[5] Despite these achievements, thiosulfonates have rarely been explored as sulfonylating agents.[6]

On the other hand, allyl aryl sulfones are attractive intermediates in organic synthesis[7] and they are widely distributed pharmacophores,[8] for instance in anticancer agents,[8a] cysteine protease inhibitors,[8b] [c] TSH receptor antagonists,[8d] and antibacterial agents[8e] (Figure [1]). Therefore, the development of efficient and straightforward methods for the synthesis of allyl sulfones continues to attract considerable attention. In this context, various sulfonyl reagents[9] [10] (sulfinates,[9] arylsulfonyl cyanides,[10a] arenesulfonylmethyl isocyanide,[10b] and sulfinyl chlorides,[10c] sulfonyl hydrazines,[10d] and sulfinic acids[10e]) have been used for the sulfonylation of Morita–Baylis–Hillman (MBH) adducts for the synthesis of allyl sulfone derivatives (Scheme [1a]). Compared to these sulfonyl reactants, aryl thiosulfonates[1c] are usually stable crystalline solids, easy to handle and widely accessible starting precursors. Accordingly, we envisaged that thiosulfonates could be alternative starting materials to offer an opportunity for the synthesis of allyl sulfones. This fact motivated us to develop a possible new strategy for radical sulfonylation of Morita–Baylis–Hillman (MBH) adducts under mild conditions (Scheme [1b]). Of note, the multifunctional MBH allyl bromides and MBH acetates can be easily prepared and have been widely studied.[11] As part of our ongoing research programme on organosulfur chemistry[12] and the utilization of thiosulfonates,[3c] [d] [5e] [6c] [12b] [c] we report herein a simple and efficient radical sulfonylation of MBH allyl bromides/acetates with thiosulfonates in the presence of Cs2CO3 to access a range of (hetero)aryl/alkyl allyl sulfones. To our knowledge, radical sulfonylation using thiosulfonates has not been previously explored.[6`] [d] [e]

Zoom Image
Figure 1 Representative biologically active allyl sulfones
Zoom Image
Scheme 1 Allyl sulfonylation of MBH adducts using various sulfonyl reagents

At the outset, our optimization investigations began with S-phenyl benzenesulfonothioate (1a) and (Z)-methyl 2-(bromomethyl)-3-phenylacrylate (2a) as model substrates (Table [1]). Initially, the reaction between 1a and 2a in a 1:1.5 ratio in the presence of Cs2CO3 in EtOH provided the allyl sulfone 3aa in 65% yield (entry 1). On reversing the ratios of 1a and 2a (1.5:1) the desired product 3aa was produced in 79% yield (entry 2). Various solvents, such as DMF, CH3CN, 1,4-dioxane, DMSO and toluene were screened (entries 3–7). Among these solvents, CH3CN proved the best choice for the transformation, giving 3aa in 80% yield (entry 4). In CH3CN at 80 °C, the yield of the reaction between 1a, 2a and Cs2CO3 (1:1.5:2 ratio) was improved considerably, giving 3aa in 91% yield (entry 8). To our satisfaction, use of 1 equiv of Cs2CO3 provided the desired allyl sulfone (3aa) in 96% yield (entry 9). Using 1.2 equiv of 2a or 1.5 equiv of Cs2CO­3 or performing the reaction at room temperature were not beneficial (entries 10–12).

Table 1 Optimization for the Sulfonylation of MBH Bromide with Thiosulfonatea

Entry

1a (equiv)

2a (equiv)

Base (equiv)

Solvent

Temp (°C)

Time (h)

Yield of 3aa (%)b

1

1.0

1.5

Cs2CO3 (2.0)

EtOH

90

6

65

2

1.5

1.0

Cs2CO3 (2.0)

EtOH

90

6

79

3

1.5

1.0

Cs2CO3 (2.0)

DMF

90

6

47

4

1.5

1.0

Cs2CO3 (2.0)

CH3CN

80

5

80

5

1.5

1.0

Cs2CO3 (2.0)

dioxane

80

5

32

6

1.5

1.0

Cs2CO3 (2.0)

DMSO

90

6

47

7

1.5

1.0

Cs2CO3 (2.0)

toluene

90

6

25

8

1.0

1.5

Cs2CO3 (2.0)

CH3CN

80

4

91

9

1.0

1.5

Cs2CO3 (1.0)

CH3CN

80

4

96

10

1.0

1.2

Cs2CO3 (1.0)

CH3CN

80

5

79

11

1.0

1.5

Cs2CO3 (1.5)

CH3CN

80

4

91

12

1.0

1.5

Cs2CO3 (1.0)

CH3CN

rt

8

33

13

1.0

1.5

K2CO3 (1.0)

CH3CN

80

5

60

14

1.0

1.5

Na2CO3 (1.0)

CH3CN

80

8

trace

15

1.0

1.5

DABCO (1.0)

CH3CN

80

8

NR

16

1.0

1.5

c

CH3CN

80

8

NR

a All reactions were carried out on a 0.2 mmol scale.

b Isolated yields.

c Without Cs2CO3.

We then examined other bases (K2CO3, Na2CO3 and DABCO) but all afforded diminished yields (Table [1], entries 13–15). No reaction was observed in the absence of Cs2CO3, indicating that it plays a vital role in the sulfonylation process (entry 16). Only sulfonylated 3aa was obtained in all cases; the other anticipated allyl thioether (3aa′) did not form, probably due to the lower stability of the thiyl radical (ArS).[13]

Zoom Image
Scheme 2 Substrate scope for the synthesis of allyl sulfones via radical sulfonylation of MBH bromides with thiosulfonates. Reagents and conditions (performed on a 0.5 mmol scale of thiosulfonate): 1 (1.0 equiv), MBH bromide 2 (1.5 equiv), Cs2CO3 (1.0 equiv) in MeCN (2.5 mL) at 80 °C. Isolated yields are given. Z/E ratio based on 1H NMR analysis.

With the reaction conditions optimized, we then explored a broad range of thiosulfonates (1ai) and MBH allyl bromides (2an) to furnish a series of allyl sulfones (3aai and 3abn) in good to excellent yields and stereoselectivities (Scheme [2]). Various alkyl and halo-substituted thiosulfonates (1af) reacted smoothly with 2a, providing the corresponding allyl sulfones 3aafa in 69–95% yields; an exception was 4-bromophenyl thiosulfonate (1f), which afforded moderate yields. In addition, 1/2-naphthyl and thiophenyl derived thiosulfonates 1gi also served as suitable substrates to furnish the expected allyl sulfones in high yields. A variety of para-, meta- and ortho-substituted allyl bromides 2bg were readily sulfonylated with 1a to give the anticipated allyl sulfones in 57–96% yields. The position and electronic nature of substituents on the phenyl ring of MBH bromides had a limited effect on this sulfonylation process. Additionally, different heteroaryl allyl sulfones 3ahaj were produced in satisfactory yields from the corresponding allyl bromides. Interestingly, the alkenyl and alkyl-substituted MBH bromides 2km reacted well with 1a, giving the synthetically useful alkyl allyl sulfones in acceptable yields. The substrate scope was further extended to ethyl acrylate derived MBH bromide 2n, and the corresponding products 3an and 3bn were obtained in 96% and 98% yield, respectively.

Inspired by these results, we sought to evaluate the scope of MBH acetates 4 with S-aryl arylsulfonothioate (1a/b). Under the same conditions, acetate 4a was smoothly sulfonated with S-aryl arylsulfonothioate (1a/b), to give the desired products 3aa and 3ba in 86% and 81% yields, respectively, with slightly inferior stereoselectivities as compared to the allyl bromides (Scheme [3]).[14] Several aryl and heteroaryl derived substrates (4b,d,e,hj) reacted well with 1a to form expected products (3ab,d,e,hj) in reasonable yields. Similarly, the alkyl sulfones 3al and 3am were obtained in 69% and 79% yield, respectively, from the corresponding MBH acetates 4l/m under the standard conditions. It is worth noting that these allyl sulfones, particularly allyl (hetero)aryl sulfones, show activity against cancer and abnormal cell proliferation activity.[8a] The E/Z stereochemistry of the allyl sulfones was assigned based on the 1H NMR chemical shift values of the olefinic protons as compared with the reported values.[15]

Zoom Image
Scheme 3 Substrate scope for the synthesis of allyl sulfones via radical sulfonylation of MBH acetates with thiosulfonates. Reagents and conditions (performed on a 0.5 mmol scale of thiosulfonates): 1 (1.0 equiv), MBH acetate 4 (1.5 equiv), Cs2CO3 (1.0 equiv) in MeCN (2.5 mL) at 80 °C. Isolated yield are given. Z/E ratio based on 1H NMR analysis.

Furthermore, the scope of the sulfonylation reaction could be extended to other representative classes of allyl bromides, such as acrylonitrile derived MBH allyl bromide (2o) or cinnamyl bromide (2p), as presented in Scheme [4]. Disappointingly, they did not provide the desired allyl sulfones 3ao and 3ap under the same conditions.

Zoom Image
Scheme 4 Study of other allyl bromides 2o/p and gram-scale synthesis

The efficacy of radical sulfonylation was demonstrated at gram-scale under the optimal conditions (see the Supporting Information). Thus, a 5 mmol scale reaction of S-phenyl benzenesulfonothioate (1a) (1.25 g) and (Z)-methyl 2-(bromomethyl)-3-phenylacrylate (2a) (1.90 g) gave 3aa in 72% yield (1.14 g). Similarly, allyl sulfone 3aj was obtained in 78% yield (1.25 g) from acetate 4j. Thus, the protocol is scalable with little deviation of the outcome (Scheme [4]).

Several control experiments were performed to gain insight into the reaction mechanism (Scheme [5]). The standard reaction was performed with radical scavengers (BHT or TEMPO), in an attempt to define whether the reaction involved an ionic or radical pathway. With BHT, the product 3aa formed in <10% yield; whereas the reaction was totally inhibited with TEMPO (Scheme [5] i). These experiments suggest the process involves a radical sulfonylation pathway and this is in keeping with the known homolytic cleavage of thiosulfonate 1a to generate sulfonyl radical (I) and thiyl radical (II)[13] species (Scheme [5] ii).[4] Based on the above results and on literature precedent,[4] [6] [13] a plausible mechanism is proposed for this transformation (Scheme [5]). The radical initiation of PhSSO2Ph (1a)[6d] [e] may lead to sulfonyl radical (I) and thiyl radical (II) in the presence of Cs2CO3. Subsequent propagation of 2a will form allyl radical (A) and termination product sulfonyl bromide (PhSO2Br).[16] Finally, the termination product triggers the sulfonylation of A with PhSO2Br to give the expected allyl sulfone 3aa. Similarly, sulfonyl radical can add onto MBH acetate to form radical B and eliminate an acetyl radical to afford the desired allyl sulfone 3aa. Overall, in this process, the Cs2CO3 might be playing a dual role as a radical initiator and as a base to trap the bromine radical.

Zoom Image
Scheme 5 Control experiments and a plausible mechanism

In conclusion, we have described the Cs2CO3-promoted radical sulfonylation of Morita–Baylis–Hillman (MBH) bromides with thiosulfonates under mild conditions. A series of allyl sulfones was readily generated in good to high yields with high stereoselectivities. Various aryl, heteroaryl, alkenyl and alkyl MBH bromides/acetates and aryl/hetereoaryl thiosulfonates with diverse substitution patterns and broad functional group compatibility were elaborated. Furthermore, the MBH acetates efficiently furnished the corresponding allyl sulfones in high yields. The protocol was proven to be applicable to gram-scale synthesis, which can be challenging with other approaches. A plausible mechanism is presented to rationalize the experimental outcome.


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Synthesis of Allyl Sulfones; General Procedure 1 (GP1)

A heat gun-dried Schleck tube was charged with thiosulfonate (0.5 mmol, 1.0 equiv), Morita–Baylis–Hillman allyl bromide (0.75 mmol, 1.5 equiv) or Morita–Baylis–Hillman acetate (0.75 mmol, 1.5 equiv) and Cs2CO3 (0.5 mmol, 1.0 equiv) in CH3CN (2.5 mL). The reaction mixture was stirred at 80 °C for 4 h and monitored by TLC until the reaction was judged to be either complete or to be proceeding no further. The reaction was quenched by addition of water (10 mL) followed by extraction with EtOAc (3 × 20 mL). The combined organic layers were washed with brine (2 × 10 mL), dried over anhydrous Na2SO­4, filtered and the solvent was removed under reduced pressure. The resulting residue was subjected to flash chromatography (silica gel, eluting with 10–20% EtOAc/petroleum ether) to afford the desired allyl sulfones.


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Methyl (Z)-3-Phenyl-2-[(phenylsulfonyl)methyl]acrylate (3aa)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3aa.

Yield: 150.3 mg (95%); colorless solid; mp 63–65 °C (Lit.[6] 64–66 °C); Rf = 0.38 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>97:3) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.95 (s, 1 H), 7.85 (dd, J = 8.4, 1.2 Hz, 2 H), 7.60 (tt, J = 7.4, 1.2 Hz, 1 H), 7.52–7.46 (m, 4 H), 7.39–7.35 (m, 3 H), 4.49 (s, 2 H), 3.59 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.9, 146.5, 139.3, 133.8, 133.7, 129.8, 129.2 (2C), 129.1 (2C), 128.8 (2C), 128.6 (2C), 120.9, 55.2, 52.5.

The title compound is known in the literature and the data are consistent with reported values.[10e]


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Methyl (Z)-3-Phenyl-2-(tosylmethyl)acrylate (3ba)

Obtained by following GP1 using S-(p-tolyl) 4-methylbenzenesulfonothioate 1b (139.1 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3ba.

Yield: 145.4 mg (88%); colorless liquid Rf = 0.50 (20% EtOAc in petroleum ether); mixture of Z/E isomers (75:25) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.83 (s, 1 H), 7.61 (d, J = 8.3 Hz, 2 H), 7.38–7.35 (m, 2 H), 7.29–7.26 (m, 3 H), 7.17 (d, J = 8.0 Hz, 2 H), 4.38 (s, 2 H), 3.52 (s, 3 H), 2.32 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 167.1, 146.5, 146.2, 144.8, 136.4, 133.8, 129.8, 129.7 (2C), 129.3, 129.1, 128.9, 128.8, 128.6, 121.2, 55.2, 52.5, 21.7.

The title compound is known in the literature and the data are consistent with reported values.[9a] [10d]


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Methyl (Z)-2-{[(4-(tert-Butyl)phenyl)sulfonyl]methyl}-3-phenyl­acrylate (3ca)

Obtained by following GP1 using S-(4-(tert-butyl)phenyl) 4-(tert-butyl­benzenesulfonothioate 1c (128.5 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO­3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title­ compound 3ca.

Yield: 128.3 mg (69%); colorless solid; mp 100–102 °C; Rf = 0.42 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>99:1) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.93 (s, 1 H), 7.76 (dt, J = 8.6, 2.0 Hz, 2 H), 7.50 (dt, J= 8.8, 2.1 Hz, 2 H), 7.48–7.45 (m, 2 H), 7.39–7.34 (m, 3 H), 4.48 (s, 2 H), 3.57 (s, 3 H), 1.34 (s, 9 H).

13C NMR (101 MHz, CDCl3): δ = 167.1, 157.8, 146.3, 136.3, 133.8, 129.8, 129.3 (2C), 128.9 (2C), 128.6 (2C), 126.1 (2C), 121.2, 55.2, 52.4, 35.4, 31.2 (3C).

LCMS (ESI): m/z 373.00 [M + H]+.


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Methyl (Z)-2-{[(4-Fluorophenyl)sulfonyl]methyl}-3-phenyl­acrylate (3da)

Obtained by following GP1 using S-(4-fluorophenyl)4-fluorobenzenesulfonothioate 1d (143.1 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3da.

Yield: 133.8 mg (80%); colorless solid; mp 72–74 °C; Rf = 0.37 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>97:1) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.93 (s, 1 H), 7.85–7.78 (m, 2 H), 7.45–7.41 (m, 2 H), 7.39–7.35 (m, 3 H), 7.12 (t, J = 8.5 Hz, 2 H), 4.50 (s, 2 H), 3.66 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.0 (d, J = 256.4 Hz), 166.9, 146.5, 135.3 (d, J = 3.1 Hz), 133.7, 131.5 (d, J = 9.7 Hz), 129.9, 129.2 (3C), 128.9 (3C), 120.9, 116.4 (d, J = 22.6 Hz), 55.1, 52.6.

LCMS (ESI): m/z 334.90 [M]+.


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Methyl (Z)-2-{[(4-Chlorophenyl)sulfonyl]methyl}-3-phenyl­acrylate (3ea)

Obtained by following GP1 using S-(4-chlorophenyl)-4-chlorobenzenesulfonothioate 1e (175.4 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3ea.

Yield: 136.8 mg (78%); colorless solid; mp 86–88 °C; Rf = 0.35 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>97:3) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.92 (s, 1 H), 7.71 (dt, J = 8.6, 1.9 Hz, 2 H), 7.41–7.35 (m, 7 H), 4.51 (s, 2 H), 3.66 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.9, 146.5, 140.7, 137.6, 133.6, 130.1 (2C), 129.8, 129.4 (2C), 129.1 (2C), 128.9 (2C), 120.9, 55.0, 52.6.

LCMS (ESI): m/z 351.90 [M + H]+.


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Methyl (Z)-2-{[(4-Bromophenyl)sulfonyl]methyl}-3-phenyl­acrylate (3fa)

Obtained by following GP1 using S-(4-bromophenyl)-4-bromobenzenesulfonothioate 1f (204.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3fa.

Yield: 136.3 mg (69%); yellow solid; mp 99–101 °C; Rf = 0.33 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>98:2) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.93 (s, 1 H), 7.64 (dt, J = 8.7, 2.0 Hz, 2 H), 7.57 (dt, J = 8.7, 2.0 Hz, 2 H), 7.40–7.36 (m, 5 H), 4.51 (s, 2 H), 3.67 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.9, 146.6, 138.0, 133.6, 132.4 (2C), 130.2 (2C), 129.9, 129.3, 129.1 (2C), 128.9 (2C), 120.8, 54.9, 52.7.

The title compound has been reported in the literature and the data are consistent with reported values.[10d]


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Methyl (Z)-2-[(Naphthalen-1-ylsulfonyl)methyl]-3-phenyl­acrylate (3ga)

Obtained by following GP1 using S-(naphthalen-1-yl) naphthalene-1-sulfonothioate 1g (175.2 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol), for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3ga.

Yield: 144.6 mg (79%); colorless solid; mp 119–121 °C; Rf = 0.35 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>95:5) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 H), 7.84–7.77 (m, 4 H), 7.69 (dd, J = 8.7, 1.7 Hz, 1 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.27 (d, J = 7.8 Hz, 2 H), 7.17–7.11 (m, 3 H), 4.47 (s, 2 H), 3.36 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.9, 146.3, 136.2, 135.4, 133.6, 132.1, 130.5, 129.6, 129.5, 129.4, 129.3, 129.0 (2C), 128.7 (2C), 128.0, 127.6, 123.2, 121.1, 55.1, 52.4.

LCMS (ESI): m/z 366.95 [M]+.


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Methyl (Z)-2-((Naphthalen-2-ylsulfonyl)methyl)-3-phenyl­acrylate (3ha)

Obtained by following GP1 using S-(naphthalen-2-yl) naphthalene-2-sulfonothioate 1h (175.2 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3ha.

Yield: 141.2 mg (77%); colorless solid; mp 116–118 °C; Rf = 0.37 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>95:5) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 8.27 (s, 1 H), 7.84–7.77 (m, 4 H), 7.69 (d, J = 8.5 Hz, 1 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.29–7.25 (m, 2 H), 7.14 (d, J = 7.4 Hz, 3 H), 4.47 (s, 2 H), 3.34 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.6, 146.0, 135.7, 135.0, 133.2, 131.7, 130.1, 129.3, 129.1, 129.04, 128.96, 128.7 (2C), 128.3 (2C), 127.6, 127.3, 122.8, 120.7, 54.7, 52.0.

LCMS (ESI): m/z 366.95 [M]+.


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Methyl (Z)-3-Phenyl-2-[(thiophen-2-ylsulfonyl)methyl]acrylate (3ia)

Obtained by following GP1 using S-(thiophen-2-yl) thiophene-2-sulfonothioate 1i (115.1 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-phenylacrylate 2a (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3ia.

Yield: 130.6 mg (81%); colorless liquid; Rf = 0.37 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>93:7) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.99 (s, 1 H), 7.67 (dd, J = 5.0, 1.3 Hz, 1 H), 7.60 (dd, J = 3.8, 1.3 Hz, 1 H), 7.47 (dd, J = 6.4, 3.1 Hz, 2 H), 7.39–7.36 (m, 3 H), 7.08 (dd, J = 5.0, 3.8 Hz, 1 H), 4.59 (s, 2 H), 3.67 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.9, 146.7, 140.0, 134.9, 134.7, 133.6, 129.8, 129.2 (2C), 128.8 (2C), 127.9, 120.8, 56.2, 52.6.

LCMS (ESI): m/z 322.90 [M]+.


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Methyl (Z)-3-(4-Chlorophenyl)-2-[(phenylsulfonyl)methyl]acrylate­ (3ab)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol) methyl (Z)-2-(bromomethyl)-3-(4-chlorophenyl) acrylate 2b (217.1 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol), for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3ab.

Yield: 157.8 mg (90%); liquid; Rf = 0.20 (30% EtOAc in petroleum ether); mixture of Z/E isomers (>95:5) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.88 (s, 1 H), 7.84 (dd, J = 8.3, 1.0 Hz, 2 H), 7.62 (t, J = 7.5 Hz, 1 H), 7.50 (t, J = 7.8 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.34 (d, J = 8.5 Hz, 2 H), 4.43 (s, 2 H), 3.57 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.7, 145.1, 139.4, 136.0, 134.0, 132.2, 130.7 (2C), 129.20 (2C), 129.17 (2C), 128.6 (2C), 121.5, 55.2, 52.6.

The title compound is known in the literature and the data are consistent with reported values.[9f]


#

Methyl (Z)-2-[(Phenylsulfonyl)methyl]-3-(p-tolyl)acrylate (3ac)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(p-tolyl)acrylate 2c (201.8 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound.

Yield: 132.1 mg (80%); colorless liquid; Rf = 0.29 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>96:4) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.92 (s, 1 H), 7.86 (dd, J = 8.3, 1.1 Hz, 2 H), 7.60 (tt, J = 7.4, 1.2 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 2 H), 7.43 (d, J = 8.1 Hz, 2 H), 7.18 (d, J = 8.0 Hz, 2 H), 4.50 (s, 2 H), 3.54 (s, 3 H), 2.36 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 167.1, 146.6, 140.3, 139.4, 133.8, 130.9, 129.6 (2C), 129.5 (2C), 129.1 (2C), 128.6 (2C), 119.7, 55.3, 52.4, 21.5.

The title compound is known in the literature and the data are consistent with reported values.[10e]


#

Methyl (Z)-3-(4-Isopropylphenyl)-2-[(phenylsulfonyl)methyl]acrylate­ (3ad)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(4-isopropylphenyl)acrylate 2d (222.8 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol), for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3ad.

Yield: 102.1 mg (57%); colorless liquid; Rf = 0.39 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>98:2) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.93 (s, 1 H), 7.86 (dd, J = 8.4, 1.2 Hz, 2 H), 7.60 (tt, J = 7.4, 1.2 Hz, 1 H), 7.51–7.45 (m, 4 H), 7.24 (d, J = 8.2 Hz, 2 H), 4.52 (s, 2 H), 3.56 (s, 3 H), 2.91 (sept, J = 6.9 Hz, 1 H), 1.25 (d, J = 6.9 Hz, 6 H).

13C NMR (101 MHz, CDCl3): δ = 167.2, 151.2, 146.7, 139.5, 133.8, 131.3, 129.7 (2C), 129.1 (2C), 128.7 (2C), 127.1 (2C), 119.8, 55.4, 52.4, 34.1, 23.9 (2C).

LCMS (ESI) m/z 359.00 [M + H]+.


#

Methyl (Z)-3-(3-Bromophenyl)-2-[(phenylsulfonyl)methyl]acrylate­ (3ae)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(3-bromophenyl)acrylate 2e (239.9 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3ae.

Yield: 189.7 mg (96%); pale-yellow solid; mp 64–66 °C; Rf = 0.29 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>95:5) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.96 (s, 1 H), 7.84 (dd, J = 8.3, 1.1 Hz, 2 H), 7.64–7.60 (m, 2 H), 7.57 (dd, J = 8.0, 1.1 Hz, 1 H), 7.50 (t, J = 7.7 Hz, 2 H), 7.35 (td, J = 7.5, 0.9 Hz, 1 H), 7.22 (td, J = 7.6, 1.4 Hz, 1 H), 4.36 (s, 2 H), 3.62 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.3, 145.3, 139.4, 134.1, 133.9, 133.0, 130.8, 130.1, 129.2 (2C), 128.5 (2C), 127.7, 124.1, 122.8, 55.0, 52.6.

The title compound is known in the literature and the data are consistent with reported values.[9f]


#

Methyl (Z)-3-(3-Methoxyphenyl)-2-[(phenylsulfonyl)methyl]acrylate­ (3af)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(3-methoxyphenyl)acrylate 2f (213.8 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 20% EtOAc in petroleum ether) yielded title compound 3af.

Yield: 141.0 mg (80%); liquid; Rf = 0.42 (30% EtOAc in petroleum ether); mixture of Z/E isomers (83:17) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.88 (s, 1 H), 7.80 (d, J = 8.0 Hz, 2 H), 7.56 (t, J = 7.9 Hz, 1 H), 7.44 (t, J = 7.0 Hz, 2 H), 7.23 (t, J = 8.0 Hz, 1 H), 7.09 (s, 1 H), 6.98 (d, J = 7.5 Hz, 1 H), 6.87 (d, J = 8.0 Hz, 1 H), 4.46 (s, 2 H), 3.78 (s, 3 H), 3.54 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.7, 159.7, 146.2, 139.3, 134.8, 133.7, 129.7, 129.0 (2C), 128.4 (2C), 121.5, 121.0, 115.9, 113.9, 55.4, 55.2, 52.3.

LCMS (ESI): m/z 346.95 [M]+.


#

Methyl (Z)-3-(2-Bromophenyl)-2-[(phenylsulfonyl)methyl]acrylate­ (3ag)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(2-bromophenyl)acrylate 2g (239.9 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded title compound 3ag.

Yield: 158.1 mg (80%); colorless solid; mp 110–112 °C; Rf = 0.27 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>95:5) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.85–7.79 (m, 3 H), 7.63 (tt, J = 7.4, 1.2 Hz, 1 H), 7.51–7.45 (m, 3 H), 7.44 (s, 1 H), 7.41 (dd, J = 7.7, 0.7 Hz, 1 H), 7.24 (t, J = 7.8 Hz, 1 H), 4.44 (s, 2 H), 3.65 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.5, 144.4, 138.9, 135.7, 134.0, 132.5, 131.9, 130.8, 129.2 (2C), 128.5 (2C), 127.4, 122.9, 122.5, 54.8, 52.7.

The title compound is reported in the literature and the data are consistent with reported values.[10a]


#

Methyl (Z)-2-((Phenylsulfonyl)methyl)-3-(thiophen-2-yl)acrylate (3ah)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(thiophen-2-yl)acrylate 2h (185.0 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3ah.

Yield: 151.5 mg (94%); colorless liquid; Rf = 0.39 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>98:2) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 8.04 (s, 1 H), 7.89 (d, J = 8.2 Hz, 2 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.53–7.47 (m, 4 H), 7.08 (t, J = 3.9 Hz, 1 H), 4.62 (s, 2 H), 3.51 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.8, 139.5, 138.3, 136.8, 134.3, 133.9, 131.0, 129.0 (2C), 128.7 (2C), 127.9, 116.2, 56.0, 52.4.

The title compound is reported in the literature and the data are consistent with reported values.[10a]


#

Methyl (Z)-2-((Phenylsulfonyl)methyl)-3-(1-tosyl-1H-indol-2-yl)-acrylate (3ai)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(1-tosyl-1H-indol-2-yl)acrylate 2i (336.2 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 20% EtOAc in petroleum ether) yielded the title compound 3ai.

Yield: 198.7 mg (78%); colorless solid; mp 137–139 °C; Rf = 0.31 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>94:6) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 8.57 (s, 1 H), 8.09 (s, 1 H), 8.03 (d, J = 8.3 Hz, 1 H), 7.98 (d, J = 7.2 Hz, 2 H), 7.89 (d, J = 8.4 Hz, 2 H), 7.62 (tt, J = 7.4, 2.1 Hz, 1 H), 7.58–7.52 (m, 3 H), 7.41–7.36 (m, 1 H), 7.32–7.26 (m, 3 H), 4.51 (s, 2 H), 3.63 (s, 3 H), 2.35 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.6, 145.7, 139.6, 136.0, 134.9, 134.7, 134.0, 130.3 (2C), 130.0, 129.3 (2C), 128.6 (2C), 127.5, 127.3 (2C), 125.7, 124.0, 119.9, 119.3, 115.9, 113.9, 56.8, 52.6, 21.7.

LCMS (ESI): m/z 509.90 [M]+.


#

Methyl (Z)-3-(2-Chloroquinolin-3-yl)-2-[(phenylsulfonyl)methyl]-acrylate (3aj)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-3-(2-chloroquinolin-3-yl)acrylate 2j (254.1 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 20% EtOAc in petroleum ether) yielded the title compound 3aj.

Yield: 162.6 mg (81%); colorless solid; mp 129–13 °C; Rf = 0.21 (20% EtOAc in petroleum ether); mixture of Z/E isomers (80:20) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 8.74 (s, 1 H), 8.09 (s, 1 H), 8.04 (d, J = 8.5 Hz, 1 H), 7.95 (d, J = 7.7 Hz, 1 H), 7.90 (d, J = 7.3 Hz, 2 H), 7.80 (t, J = 7.7 Hz, 1 H), 7.65 (t, J = 6.9 Hz, 2 H), 7.53 (t, J = 7.7 Hz, 2 H), 4.36 (s, 2 H), 3.63 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.2, 148.3, 143.3, 139.5, 139.3, 138.7, 134.2, 131.8, 129.4 (2C), 128.7, 128.6 (2C), 128.5, 128.4, 128.0, 126.9, 124.0, 55.6, 52.9.

LCMS (ESI): m/z 401.80 [M]+.


#

Methyl (2Z,4E)-5-Phenyl-2-[(phenylsulfonyl)methyl]penta-2,4-dienoate (3ak)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (2Z,4E)-2-(bromomethyl)-5-phenylpenta-2,4-dienoate 2k (222.8 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3ak.

Yield: 97.8 mg (57%); colorless solid; mp 143–145 °C; Rf = 0.35 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>95:5) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.89–7.86 (m, 2 H), 7.62 (dd, J = 7.3, 3.5 Hz, 1 H), 7.56–7.47 (m, 3 H), 7.44 (dd, J = 8.0, 1.6 Hz, 2 H), 7.36 (m, 3 H), 6.96–6.93 (m, 2 H), 4.43 (s, 2 H), 3.53 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.5, 145.8, 143.8, 138.7, 135.8, 134.0, 129.8, 129.1 (2C), 129.0 (2C), 128.9 (2C), 127.9 (2C), 123.0, 118.1, 54.7, 52.3.

The title compound is known in the literature and the data are consistent with reported values.[10a] [d]


#

Methyl (Z)-5-Phenyl-2-[(phenylsulfonyl)methyl]pent-2-enoate (3al)

Obtained by following G1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-5-phenylpent-2-enoate 2l (212.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3al.

Yield: 161.7 mg (94%); colorless liquid; Rf = 0.41 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>92:8) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.95 (dd, J = 8.3, 1.2 Hz, 2 H), 7.73 (tt, J = 7.4, 1.2 Hz, 1 H), 7.63 (t, J = 7.7 Hz, 2 H), 7.43–7.38 (m, 2 H), 7.32 (d, J = 7.4 Hz, 1 H), 7.30 –7.27 (m, 3 H), 4.27 (s, 2 H), 3.57 (s, 3 H), 2.87 (t, J = 7.6 Hz, 2 H), 2.66 (q, J = 7.6 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 166.0, 150.5, 140.5, 138.9, 133.9, 129.1 (2C), 128.8 (2C), 128.6 (2C), 128.5 (2C), 126.4, 121.2, 54.1, 52.2, 34.3, 31.5.

LCMS (ESI): m/z 344.95 [M]+.


#

Methyl (Z)-5-Methyl-2-[(phenylsulfonyl)methyl]hex-2-enoate (3am)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125.0 mg, 0.5 mmol), methyl (Z)-2-(bromomethyl)-5-methylhex-2-enoate 2m (165.8 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 10% EtOAc in petroleum ether) yielded the title compound 3am.

Yield: 134.9 mg (91%); colorless liquid; Rf = 0.30 (20% EtOAc in petroleum ether); mixture of Z/E isomers (80:20) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.83 (dd, J = 8.4, 1.2 Hz, 2 H), 7.62 (tt, J = 7.4, 1.2 Hz, 1 H), 7.51 (t, J = 7.7 Hz, 2 H), 7.14 (t, J = 7.5 Hz, 1 H), 4.22 (s, 2 H), 3.46 (s, 3 H), 2.08 (t, J = 7.2 Hz, 2 H), 1.77–1.67 (m, 1 H), 0.89 (d, J = 6.7 Hz, 6 H).

13C NMR (101 MHz, CDCl3): δ = 166.2, 151.1, 133.9, 129.6, 129.1 (2C), 128.9 (2C), 121.2, 54.3, 52.2, 38.4, 28.2, 22.5 (2C).

LCMS (ESI): m/z 296.95 [M]+.


#

Ethyl (Z)-3-Phenyl-2-[(phenylsulfonyl)methyl]acrylate (3an)

Obtained by following GP1 using S-phenyl benzenesulfonothioate 1a (125 mg, 0.5 mmol), ethyl (Z)-2-(bromomethyl)-3-phenylacrylate 2n (201.8 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3an.

Yield: 158.7 mg (96%); colorless liquid; Rf = 0.40 (20% EtOAc/hexanes); mixture of Z/E isomers (>98:2) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 7.93 (s, 1 H), 7.84 (dd, J = 8.4, 1.2 Hz, 2 H), 7.58 (tt, J = 7.4, 1.2 Hz, 1 H), 7.49–7.44 (m, 4 H), 7.37–7.33 (m, 3 H), 4.49 (s, 2 H), 4.03 (q, J = 7.1 Hz, 2 H), 1.22 (t, J = 7.1 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.6, 146.2, 139.5, 133.85, 133.81, 129.7, 129.3 (2C), 129.1 (2C), 128.9 (2C), 128.6 (2C), 121.3, 61.7, 55.2, 14.2.

The title compound is known in the literature and the data are consistent with reported values.[9d]


#

Ethyl (Z)-3-Phenyl-2-(tosylmethyl)acrylate (3bn)

Obtained by following GP1 using S-(p-tolyl) 4-methylbenzenesulfonothioate 1b (139.1 mg, 0.5 mmol), ethyl (Z)-2-(bromomethyl)-3-phenylacrylate 2n (191.3 mg, 0.75 mmol), and Cs2CO3 (162.5 mg, 0.5 mmol) for 4 h. Purification by flash column chromatography (silica gel, 15% EtOAc in petroleum ether) yielded the title compound 3bn.

Yield: 168.7 mg (98%); colorless liquid; Rf = 0.42 (20% EtOAc in petroleum ether); mixture of Z/E isomers (>98:2) based on 1H NMR analysis.

1H NMR (400 MHz, CDCl3): δ = 8.01 (s, 1 H), 7.80 (d, J = 8.2 Hz, 2 H), 7.56 (dd, J = 6.5, 2.7 Hz, 2 H), 7.47–7.44 (m, 3 H), 7.35 (d, J = 8.2 Hz, 2 H), 4.58 (s, 2 H), 4.16 (q, J = 7.1 Hz, 2 H), 2.51 (s, 3 H), 1.34 (t, J = 7.1 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.6, 146.0, 144.8, 136.5, 133.9, 129.74 (2C), 129.68, 129.3 (2C), 128.8 (2C), 128.7 (2C), 121.5, 61.7, 55.2, 21.7, 14.2.

The title compound is known in the literature and the data are consistent with reported values.[10d]


#
#

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

R.J.R. thanks UGC for a faculty position under the Faculty Recharge Programme. The authors are highly thankful to Dr Ch. Raji Reddy, Associate Editor of SynOpen, for his generous invitation to publish some of their work in this journal.

Supporting Information

  • References

    • 1a Zefirof NS, Zyk NV, Beloglazkina EK, Kutateladze AG. Sulfur Rep. 1993; 14: 223
    • 1b Pannecoucke X, Besset T. Org. Biomol. Chem. 2019; 17: 1683
    • 1c For a general and excellent review on thiosulfonates, see: Mampuys P, McElroy CR, Clark JH, Orru RV. A, Maes BU. W. Adv. Synth. Catal. 2020; 362: 3; and references therein

      Recent leading articles:
    • 2a Wang N, Saidhareddy P, Jiang X. Nat. Prod. Rep. 2020; 37: 246
    • 2b Scott KA, Njardarson JT. Top. Curr. Chem. 2018; 376: 5
    • 2c Ilardi EA, Vitaku E, Njardarson JT. J. Med. Chem. 2014; 57: 2832
    • 2d Haruki H, Pedersen MG, Gorska KI, Pojer F, Johnsson K. Science 2013; 340: 987
    • 2e Deming TJ. Bioconjugate Chem. 2017; 28: 691
    • 2f Organosulfur Chemistry I & II. Page PC. B. Springer; Berlin: 1999
    • 2g Simpkins NS. Sulphones in Organic Synthesis, Vol. 10. Pergamon Press Ltd; Oxford: 2013: 1-367
    • 3a Chen H, Yan Y, Zhang N, Mo Z, Xu Y, Chen Y. Org. Lett. 2021; 23: 376
    • 3b Ielo L, Pillari V, Gajic N, Holzer W, Pace V. Chem. Commun. 2020; 56: 12395
    • 3c Reddy RJ, Shankar A, Kumari AH. Asian J. Org. Chem. 2019; 8: 2269
    • 3d Reddy RJ, Kumar JJ, Kumari AH. Eur. J. Org. Chem. 2019; 3771
    • 3e Fang Y, Rogge T, Ackermann L, Wang S.-Y, Ji S.-J. Nat. Commun. 2018; 9: 2240
    • 3f Kanemoto K, Sugimura Y, Shimizu S, Yoshida S, Hosoya T. Chem. Commun. 2017; 53: 10640
    • 3g Wang W, Peng X, Wei F, Tung C.-H, Xu Z. Angew. Chem. Int. Ed. 2016; 55: 649
    • 3h Yoshida S, Sugimura Y, Hazama Y, Nishiyama Y, Yano T, Shimizu S, Hosoya T. Chem. Commun. 2015; 51: 16613
    • 3i Mampuys P, Zhu Y, Vlaar T, Ruijter E, Orru RV. A, Maes BU. W. Angew. Chem. Int. Ed. 2014; 53: 12849

      For homolytic cleavage of thiosulfonates in EPR studies, see:
    • 4a Gilbert BC, Gill B, Sexton MD. J. Chem. Soc., Chem. Commun. 1978; 78
    • 4b Chatgilialoglu C, Gilbert BC, Gill B, Sexton MD. J. Chem. Soc., Perkin Trans. 2 1980; 1141

      For thiosulfonylation of alkenes and alkynes, see:
    • 5a Zhou X, Peng Z, Wang PG. Liu Q, Jia T. Org. Lett. 2021; 23: 1054
    • 5b Gadde K, Mampuys P, Guidetti A, Ching HY. V, Herrebout WA, Van Doorslaer S, Tehrani KA, Maes BU. W. ACS Catal. 2020; 10: 8765
    • 5c Peng Z, Yin H, Zhang H, Jia T. Org. Lett. 2020; 22: 5885
    • 5d Song T, Li H, Wei F, Tung C.-H, Xu Z. Tetrahedron Lett. 2019; 60: 916
    • 5e Reddy RJ, Kumari AH, Kumar JJ, Nanubolu JB. Adv. Synth. Catal. 2019; 361: 1587
    • 5f Yuan H, Thirupathi N, Gao H, Tung C.-H, Xu Z. Org. Chem. Front. 2018; 5: 1371
    • 5g Li H, Cheng Z, Tung C.-H, Xu Z. ACS Catal. 2018; 8: 8237
    • 5h Li H, Shan C, Tung C.-H, Xu Z. Chem. Sci. 2017; 8: 2610
    • 5i Zhao Q, Lu L, Shen Q. Angew. Chem. Int. Ed. 2017; 56: 11575
    • 5j Zhu D, Shao X, Hong X, Lu L, Shen Q. Angew. Chem. Int. Ed. 2016; 55: 15807
    • 6a Mao K, Bian M, Dai L, Zhang J, Yu Q, Wang C, Rong L. Org. Lett. 2021; 23: 218
    • 6b Liang Q, Walsh PJ, Jia T. ACS Catal. 2020; 10: 2633
    • 6c Reddy RJ, Shankar A, Waheed M, Nanubolu JB. Tetrahedron Lett. 2018; 59: 2014
    • 6d Shyam PK, Jang H.-Y. J. Org. Chem. 2017; 82: 1761
    • 6e Shyam PK, Son S, Jang H.-Y. Eur. J. Org. Chem. 2017; 5025
    • 7a Kim S, Lim CJ. Angew. Chem. Int. Ed. 2002; 41: 3265
    • 7b Quiclet-Sire B, Seguin S, Zard SZ. Angew. Chem. Int. Ed. 1998; 37: 2864
    • 7c Wrobel Z. Tetrahedron 1998; 54: 2607
    • 7d For a review, see: EI-Awa A, Noshi MN, du Jourdin XM, Fuchs PL. Chem. Rev. 2009; 109: 2315
    • 8a Neamati N, Kabalka GW, Venkataiah B, Dayam R. US Patent 0203224, 2007
    • 8b Götz MG, Caffrey CR, Hansell E, McKerrow JH, Powers JC. Bioorg. Med. Chem. 2004; 12: 5203
    • 8c Powers JC, Götz MG. US Patent 0241057, 2006
    • 8d Gershengorn MC. US Patent 0203716, 2009
    • 8e Reck F, Zhou F, Girardot M, Kern G, Eyermann CJ, Hales NJ, Ramsay RR, Gravestock MB. J. Med. Chem. 2005; 48: 499

      For sulfonylation of MBH adducts using sodium sulfinates, see:
    • 9a Kabalka GW, Venkataiah B, Dong G. Tetrahedron Lett. 2003; 44: 4673
    • 9b Chandrasekhar S, Saritha B, Jagadeshwer V, Narsihmulu C, Vijay D, Sarma GD, Jagadeesh B. Tetrahedron Lett. 2006; 47: 2981
    • 9c Wang Q, Sheng SR, Lin SY, Guo L, Wei MH, Huang X. Chin. J. Chem. 2007; 25: 1027
    • 9d Khamri S, Turki T, Amri H. J. Soc. Chim. Tunisie 2008; 10: 149
    • 9e Karnakar K, Shankar J, Murthy SN, Nageswar YV. D. Helv. Chim. Acta 2011; 94: 875
    • 9f Jiang L, Li Y.-G, Zhou J.-F, Chuan Y.-M, Li H.-L, Yuan M.-L. Molecules 2015; 20: 8213

      For sulfonylation of MBH adducts using other sulfonyl agents, see:
    • 10a Reddy LR, Hu B, Prashad M, Prasad K. Angew. Chem. Int. Ed. 2009; 48: 172
    • 10b Li H.-H, Dong D.-J, Jin Y.-H, Tian S.-K. J. Org. Chem. 2009; 74: 9501
    • 10c Garima, Srivastava VP, Yadav LD. S. Tetrahedron Lett. 2011; 52: 4622
    • 10d Li X, Xu X, Tang Y. Org. Biomol. Chem. 2013; 11: 1739
    • 10e Xie P, Wang J, Liu Y, Fan J, Wo X, Fu W, Sun Z, Loh T.-P. Nat. Commun. 2018; 9: 1321

      For selected reviews on MBH reaction, see:
    • 11a Basavaiah D, Tilak RN. New J. Chem. 2018; 42: 14036
    • 11b Kaur K, Namboothiri IN. N. Chimia 2012; 66: 913
    • 11c Basavaiah D, Reddy BS, Badsara BS. Chem. Rev. 2010; 110: 5447
    • 11d Declerck V, Martinez J, Lamaty F. Chem. Rev. 2009; 109: 1
    • 11e Singh V, Batra S. Tetrahedron 2008; 64: 4511
    • 11f Basavaiah D, Rao KV, Reddy RJ. Chem. Soc. Rev. 2007; 36: 1581
    • 12a Reddy RJ, Kumar JJ, Kumari AH, Krishna GR. Adv. Synth. Catal. 2020; 362: 1317
    • 12b Reddy RJ, Waheed M, Krishna GR. Org. Biomol. Chem. 2020; 18: 3243
    • 12c Reddy RJ, Waheed M, Kumar JJ. RSC Adv. 2018; 8: 40446
    • 12d Reddy RJ, Waheed M, Karthik T, Shankar A. New J. Chem. 2018; 42: 980
    • 12e Reddy RJ, Kumari AH. RSC Adv. 2021; 11: 9130
    • 12f Reddy RJ, Kumari AH, Kumar J. J. Org. Biomol. Chem. 2021; DOI: 10.1039/D1OB00111F.

      For reviews of thiyl radicals in organic synthesis, see:
    • 13a Subramanian H, Moorthy R, Sibi MP. Angew. Chem. Int. Ed. 2014; 53: 13660
    • 13b Dénès F, Pichowicz M, Povie G, Renaud P. Chem. Rev. 2014; 114: 2587

      The mixture of Z/E isomers of allyl sulfones was based on the corresponding MBH allyl bromides, see:
    • 14a Basavaiah D, Reddy KR, Kumaragurubaran N. Nat. Protoc. 2007; 2: 2665
    • 14b Basavaiah D. J. Sci. Res. Banaras Hindu Univ. 2019; 63: 169

      In the 1H NMR spectra of aryl substituted products, the vinylic proton cis- to the ester group appears around δ = 7.90 ppm and around δ = 6.85 ppm for the Z- and E-isomers, respectively. Similarly, the vinylic proton of the major Z-isomer appears at around δ = 7.09 ppm and a minor peak for the E-isomer appears at around δ = 6.08 ppm for alkyl substituted products. See:
    • 15a Basavaiah D, Muthukumaran K, Sreenivasulu B. Synthesis 2000; 545
    • 15b Manson PH, Esmile ND. Tetrahedron 1994; 41: 12001
    • 15c Shanmugam P, Singh PR. Synlett 2001; 1314 ; see also ref. 9a
    • 16a Poshkus AC, Herweh JE, Magnotta FA. J. Org. Chem. 1963; 28: 2766
    • 16b Kirihara M, Naito S, Nishimura Y, Ishizuka Y, Iwai T, Takeuchi H, Ogata T, Hanai H, Kinoshita Y, Kishida M, Yamazaki K, Noguchi T, Yamashoji S. Tetrahedron 2014; 70: 2464
    • 16c Silva-Cuevas C, Perez-Arrieta C, Polindara-García LA, Lujan-Montelongo JA. Tetrahedron Lett. 2017; 58: 2244

Corresponding Author

Raju Jannapu Reddy
Department of Chemistry, University College of Science, Osmania University
Hyderabad 500 007
India   
Email: [email protected]   

Publication History

Received: 16 February 2021

Accepted after revision: 08 March 2021

Publication Date:
10 March 2021 (online)

© 2021. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

    • 1a Zefirof NS, Zyk NV, Beloglazkina EK, Kutateladze AG. Sulfur Rep. 1993; 14: 223
    • 1b Pannecoucke X, Besset T. Org. Biomol. Chem. 2019; 17: 1683
    • 1c For a general and excellent review on thiosulfonates, see: Mampuys P, McElroy CR, Clark JH, Orru RV. A, Maes BU. W. Adv. Synth. Catal. 2020; 362: 3; and references therein

      Recent leading articles:
    • 2a Wang N, Saidhareddy P, Jiang X. Nat. Prod. Rep. 2020; 37: 246
    • 2b Scott KA, Njardarson JT. Top. Curr. Chem. 2018; 376: 5
    • 2c Ilardi EA, Vitaku E, Njardarson JT. J. Med. Chem. 2014; 57: 2832
    • 2d Haruki H, Pedersen MG, Gorska KI, Pojer F, Johnsson K. Science 2013; 340: 987
    • 2e Deming TJ. Bioconjugate Chem. 2017; 28: 691
    • 2f Organosulfur Chemistry I & II. Page PC. B. Springer; Berlin: 1999
    • 2g Simpkins NS. Sulphones in Organic Synthesis, Vol. 10. Pergamon Press Ltd; Oxford: 2013: 1-367
    • 3a Chen H, Yan Y, Zhang N, Mo Z, Xu Y, Chen Y. Org. Lett. 2021; 23: 376
    • 3b Ielo L, Pillari V, Gajic N, Holzer W, Pace V. Chem. Commun. 2020; 56: 12395
    • 3c Reddy RJ, Shankar A, Kumari AH. Asian J. Org. Chem. 2019; 8: 2269
    • 3d Reddy RJ, Kumar JJ, Kumari AH. Eur. J. Org. Chem. 2019; 3771
    • 3e Fang Y, Rogge T, Ackermann L, Wang S.-Y, Ji S.-J. Nat. Commun. 2018; 9: 2240
    • 3f Kanemoto K, Sugimura Y, Shimizu S, Yoshida S, Hosoya T. Chem. Commun. 2017; 53: 10640
    • 3g Wang W, Peng X, Wei F, Tung C.-H, Xu Z. Angew. Chem. Int. Ed. 2016; 55: 649
    • 3h Yoshida S, Sugimura Y, Hazama Y, Nishiyama Y, Yano T, Shimizu S, Hosoya T. Chem. Commun. 2015; 51: 16613
    • 3i Mampuys P, Zhu Y, Vlaar T, Ruijter E, Orru RV. A, Maes BU. W. Angew. Chem. Int. Ed. 2014; 53: 12849

      For homolytic cleavage of thiosulfonates in EPR studies, see:
    • 4a Gilbert BC, Gill B, Sexton MD. J. Chem. Soc., Chem. Commun. 1978; 78
    • 4b Chatgilialoglu C, Gilbert BC, Gill B, Sexton MD. J. Chem. Soc., Perkin Trans. 2 1980; 1141

      For thiosulfonylation of alkenes and alkynes, see:
    • 5a Zhou X, Peng Z, Wang PG. Liu Q, Jia T. Org. Lett. 2021; 23: 1054
    • 5b Gadde K, Mampuys P, Guidetti A, Ching HY. V, Herrebout WA, Van Doorslaer S, Tehrani KA, Maes BU. W. ACS Catal. 2020; 10: 8765
    • 5c Peng Z, Yin H, Zhang H, Jia T. Org. Lett. 2020; 22: 5885
    • 5d Song T, Li H, Wei F, Tung C.-H, Xu Z. Tetrahedron Lett. 2019; 60: 916
    • 5e Reddy RJ, Kumari AH, Kumar JJ, Nanubolu JB. Adv. Synth. Catal. 2019; 361: 1587
    • 5f Yuan H, Thirupathi N, Gao H, Tung C.-H, Xu Z. Org. Chem. Front. 2018; 5: 1371
    • 5g Li H, Cheng Z, Tung C.-H, Xu Z. ACS Catal. 2018; 8: 8237
    • 5h Li H, Shan C, Tung C.-H, Xu Z. Chem. Sci. 2017; 8: 2610
    • 5i Zhao Q, Lu L, Shen Q. Angew. Chem. Int. Ed. 2017; 56: 11575
    • 5j Zhu D, Shao X, Hong X, Lu L, Shen Q. Angew. Chem. Int. Ed. 2016; 55: 15807
    • 6a Mao K, Bian M, Dai L, Zhang J, Yu Q, Wang C, Rong L. Org. Lett. 2021; 23: 218
    • 6b Liang Q, Walsh PJ, Jia T. ACS Catal. 2020; 10: 2633
    • 6c Reddy RJ, Shankar A, Waheed M, Nanubolu JB. Tetrahedron Lett. 2018; 59: 2014
    • 6d Shyam PK, Jang H.-Y. J. Org. Chem. 2017; 82: 1761
    • 6e Shyam PK, Son S, Jang H.-Y. Eur. J. Org. Chem. 2017; 5025
    • 7a Kim S, Lim CJ. Angew. Chem. Int. Ed. 2002; 41: 3265
    • 7b Quiclet-Sire B, Seguin S, Zard SZ. Angew. Chem. Int. Ed. 1998; 37: 2864
    • 7c Wrobel Z. Tetrahedron 1998; 54: 2607
    • 7d For a review, see: EI-Awa A, Noshi MN, du Jourdin XM, Fuchs PL. Chem. Rev. 2009; 109: 2315
    • 8a Neamati N, Kabalka GW, Venkataiah B, Dayam R. US Patent 0203224, 2007
    • 8b Götz MG, Caffrey CR, Hansell E, McKerrow JH, Powers JC. Bioorg. Med. Chem. 2004; 12: 5203
    • 8c Powers JC, Götz MG. US Patent 0241057, 2006
    • 8d Gershengorn MC. US Patent 0203716, 2009
    • 8e Reck F, Zhou F, Girardot M, Kern G, Eyermann CJ, Hales NJ, Ramsay RR, Gravestock MB. J. Med. Chem. 2005; 48: 499

      For sulfonylation of MBH adducts using sodium sulfinates, see:
    • 9a Kabalka GW, Venkataiah B, Dong G. Tetrahedron Lett. 2003; 44: 4673
    • 9b Chandrasekhar S, Saritha B, Jagadeshwer V, Narsihmulu C, Vijay D, Sarma GD, Jagadeesh B. Tetrahedron Lett. 2006; 47: 2981
    • 9c Wang Q, Sheng SR, Lin SY, Guo L, Wei MH, Huang X. Chin. J. Chem. 2007; 25: 1027
    • 9d Khamri S, Turki T, Amri H. J. Soc. Chim. Tunisie 2008; 10: 149
    • 9e Karnakar K, Shankar J, Murthy SN, Nageswar YV. D. Helv. Chim. Acta 2011; 94: 875
    • 9f Jiang L, Li Y.-G, Zhou J.-F, Chuan Y.-M, Li H.-L, Yuan M.-L. Molecules 2015; 20: 8213

      For sulfonylation of MBH adducts using other sulfonyl agents, see:
    • 10a Reddy LR, Hu B, Prashad M, Prasad K. Angew. Chem. Int. Ed. 2009; 48: 172
    • 10b Li H.-H, Dong D.-J, Jin Y.-H, Tian S.-K. J. Org. Chem. 2009; 74: 9501
    • 10c Garima, Srivastava VP, Yadav LD. S. Tetrahedron Lett. 2011; 52: 4622
    • 10d Li X, Xu X, Tang Y. Org. Biomol. Chem. 2013; 11: 1739
    • 10e Xie P, Wang J, Liu Y, Fan J, Wo X, Fu W, Sun Z, Loh T.-P. Nat. Commun. 2018; 9: 1321

      For selected reviews on MBH reaction, see:
    • 11a Basavaiah D, Tilak RN. New J. Chem. 2018; 42: 14036
    • 11b Kaur K, Namboothiri IN. N. Chimia 2012; 66: 913
    • 11c Basavaiah D, Reddy BS, Badsara BS. Chem. Rev. 2010; 110: 5447
    • 11d Declerck V, Martinez J, Lamaty F. Chem. Rev. 2009; 109: 1
    • 11e Singh V, Batra S. Tetrahedron 2008; 64: 4511
    • 11f Basavaiah D, Rao KV, Reddy RJ. Chem. Soc. Rev. 2007; 36: 1581
    • 12a Reddy RJ, Kumar JJ, Kumari AH, Krishna GR. Adv. Synth. Catal. 2020; 362: 1317
    • 12b Reddy RJ, Waheed M, Krishna GR. Org. Biomol. Chem. 2020; 18: 3243
    • 12c Reddy RJ, Waheed M, Kumar JJ. RSC Adv. 2018; 8: 40446
    • 12d Reddy RJ, Waheed M, Karthik T, Shankar A. New J. Chem. 2018; 42: 980
    • 12e Reddy RJ, Kumari AH. RSC Adv. 2021; 11: 9130
    • 12f Reddy RJ, Kumari AH, Kumar J. J. Org. Biomol. Chem. 2021; DOI: 10.1039/D1OB00111F.

      For reviews of thiyl radicals in organic synthesis, see:
    • 13a Subramanian H, Moorthy R, Sibi MP. Angew. Chem. Int. Ed. 2014; 53: 13660
    • 13b Dénès F, Pichowicz M, Povie G, Renaud P. Chem. Rev. 2014; 114: 2587

      The mixture of Z/E isomers of allyl sulfones was based on the corresponding MBH allyl bromides, see:
    • 14a Basavaiah D, Reddy KR, Kumaragurubaran N. Nat. Protoc. 2007; 2: 2665
    • 14b Basavaiah D. J. Sci. Res. Banaras Hindu Univ. 2019; 63: 169

      In the 1H NMR spectra of aryl substituted products, the vinylic proton cis- to the ester group appears around δ = 7.90 ppm and around δ = 6.85 ppm for the Z- and E-isomers, respectively. Similarly, the vinylic proton of the major Z-isomer appears at around δ = 7.09 ppm and a minor peak for the E-isomer appears at around δ = 6.08 ppm for alkyl substituted products. See:
    • 15a Basavaiah D, Muthukumaran K, Sreenivasulu B. Synthesis 2000; 545
    • 15b Manson PH, Esmile ND. Tetrahedron 1994; 41: 12001
    • 15c Shanmugam P, Singh PR. Synlett 2001; 1314 ; see also ref. 9a
    • 16a Poshkus AC, Herweh JE, Magnotta FA. J. Org. Chem. 1963; 28: 2766
    • 16b Kirihara M, Naito S, Nishimura Y, Ishizuka Y, Iwai T, Takeuchi H, Ogata T, Hanai H, Kinoshita Y, Kishida M, Yamazaki K, Noguchi T, Yamashoji S. Tetrahedron 2014; 70: 2464
    • 16c Silva-Cuevas C, Perez-Arrieta C, Polindara-García LA, Lujan-Montelongo JA. Tetrahedron Lett. 2017; 58: 2244

Zoom Image
Figure 1 Representative biologically active allyl sulfones
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Scheme 1 Allyl sulfonylation of MBH adducts using various sulfonyl reagents
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Scheme 2 Substrate scope for the synthesis of allyl sulfones via radical sulfonylation of MBH bromides with thiosulfonates. Reagents and conditions (performed on a 0.5 mmol scale of thiosulfonate): 1 (1.0 equiv), MBH bromide 2 (1.5 equiv), Cs2CO3 (1.0 equiv) in MeCN (2.5 mL) at 80 °C. Isolated yields are given. Z/E ratio based on 1H NMR analysis.
Zoom Image
Scheme 3 Substrate scope for the synthesis of allyl sulfones via radical sulfonylation of MBH acetates with thiosulfonates. Reagents and conditions (performed on a 0.5 mmol scale of thiosulfonates): 1 (1.0 equiv), MBH acetate 4 (1.5 equiv), Cs2CO3 (1.0 equiv) in MeCN (2.5 mL) at 80 °C. Isolated yield are given. Z/E ratio based on 1H NMR analysis.
Zoom Image
Scheme 4 Study of other allyl bromides 2o/p and gram-scale synthesis
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Scheme 5 Control experiments and a plausible mechanism