A method of photo-nickel catalyzed butadiene sulfonyl arylation

Abstract

The present application relates to a method for butadiene sulfonyl arylation. Specifically, using simple substrates aryl iodide, butadiene and sodium sulfinate as starting materials, under the condition of photocatalyst / nickel catalyst / ligand / blue light promotion, the 1,4-addition sulfonyl arylation product can be obtained. The present application has the following advantages: simple and easily available raw materials, simple synthesis, environmental friendliness, mild conditions, high atom economy, and a series of sulfonylated products with high added value are obtained from bulk chemicals butadiene.

Description

Technical Field

[0001] This invention relates to a synthetic method for the sulfonyl arylation of butadiene. Specifically, using aryl iodine, butadiene, and sodium sulfite as raw materials, under the promotion of a photocatalyst / nickel catalyst / ligand / blue light, a sulfonyl arylation product of 1,4-addition of butadiene can be obtained. This invention has the following advantages: the raw materials are simple and readily available; aryl iodine, butadiene, and sodium sulfite are all commercially available and inexpensive; and it allows for the direct, highly selective introduction of aryl and sulfonyl groups in a single step, yielding a highly selective 1,4-addition E-type olefin structure. Background Technology

[0002] Sulfonyl functional groups are ubiquitous in various drugs, chemicals, and functional materials. They are also commonly considered a universal building block for carbon-carbon coupling, such as in the Julia-Kocieneski alkenylation reaction (Equation 1). Therefore, the efficient construction of sulfone compounds using simple, inexpensive, and readily available raw materials is of great significance. Butadiene, a bulk chemical, is inexpensive and readily available, with an annual production of over 10 million tons, making it an important raw material for organic synthesis. Sodium sulfinate is inexpensive and stable, and can generate sulfonyl radicals upon photoexcitation, making it a commercially available and suitable sulfonyl source.

[0003]

[0004] In recent years, the use of transition metals and photocatalysis in organic reactions has become an effective strategy, especially photo-nickel catalysis, which has developed into a mature catalytic system for constructing sulfone compounds. In 2019, Rueping's group reported the sulfonyl arylation of non-conjugated dienes using a photo-nickel catalytic system. In 2021, Lu's group reported the photo-nickel catalytic sulfonyl arylation of alkenes and alkynes. In 2022, Chu's group reported the photo-nickel catalytic sulfonyl alkenylation of alkynes. In 2023, Nevado's group reported the photo-nickel catalytic sulfonyl arylation of activated alkenes. However, most substrates have been limited to highly reactive activated alkenes, alkynes, alkenes and alkynes, and activated non-conjugated dienes; simple bulk chemicals such as butadiene have not yet been reported. Therefore, developing a simple, efficient, mild, and stereoselective sulfonyl arylation reaction for butadiene is particularly important. Conjugated dienes are a large-scale industrial chemical, inexpensive, readily available, and produced in high annual quantities. This patent develops a photocatalytic nickel-catalyzed reaction of butadiene, sodium sulfinate, and aryl iodine, which can directly and selectively introduce aryl and sulfonyl groups in one step, and obtain 1,4-addition E-type olefin structures with high selectivity. Summary of the Invention

[0005] The purpose of this invention is to develop a photocatalyst / nickel catalyst / ligand / blue light system using simple chemicals butadiene, sodium sulfite and aryl iodine as raw materials, which can yield 1,4-addition sulfonyl arylized E-type products.

[0006] This invention is achieved through the following technical solution:

[0007] Aryl iodine 1, butadiene 2a, and sodium sulfite 3 can be reacted with a photocatalyst, a nickel catalyst, ligands, and blue light to yield a 1,4-addition sulfonyl aryl product, as shown in the following reaction formula:

[0008]

[0009] The specific steps are as follows:

[0010] Under a nitrogen atmosphere, a photocatalyst, a nickel catalyst, a ligand, and sodium sulfite 3 were added sequentially. Then, a certain amount of solvent was added to dissolve them. Finally, butadiene 2a and aryl iodine 1 were added. The reaction was carried out under blue light irradiation at room temperature. The reaction system was monitored by TLC. After the reaction was completed, the solvent was evaporated and column chromatography (mobile phase: petroleum ether / ethyl acetate) was performed to obtain the target product 4.

[0011] The present invention has the following advantages:

[0012] The present invention has the following advantages: the raw materials are simple and readily available, the synthesis is simple, the environment is friendly, the conditions are mild, the stereoselectivity is high, and it has broad applicability, and can be applied to the synthesis of drugs and drug derivatives.

[0013] It has high atom economy and can generate a series of high-value-added sulfonylation products from butadiene, a bulk chemical. Detailed Implementation

[0014] The present invention will be described below with specific embodiments, but the scope of protection of the present invention is not limited to these examples. The aryl iodine, butadiene, and sodium sulfite used in the following examples are all known products and are commercially available.

[0015] 1. Photocatalytic reaction of aryl iodine, butadiene and sodium sulfite using nickel photocatalysis

[0016] In a 4.0 mL reaction flask, photocatalyst (2 mol% relative to aryl iodine 1), nickel catalyst (10 mol% relative to aryl iodine 1), ligand (10 mol% relative to aryl iodine 1), and sodium sulfite 3 (2.0 equiv. relative to aryl iodine 1) were added sequentially and dissolved in 1.0 mL acetonitrile and 0.2 mL dimethyl sulfoxide. Then, butadiene 2a (0.60 mmol) and aryl iodine 1 (0.20 mmol) were added. The reaction was carried out at room temperature under blue light (wavelength range 400 nm-480 nm) for 24 h. After the reaction was completed, trimethylbenzene was added as an internal standard, and the yield of target product 4 was detected by GC-FID.

[0017] The photocatalyst is [Ir(ppy)2(dtbbpy)]PF6;

[0018]

[0019] Table 1. Effects of ligands and Ni catalyst on the reaction

[0020]

[0021] As shown in Table 1, when the molar ratio of aryl iodine 1a, butadiene 2a, and sodium phenylsulfinate 3a is 1:3:2, and the reaction is carried out at room temperature under blue light irradiation with [Ir(ppy)2(dtbbpy)]PF6 as the photocatalyst (PC) and NiBr2 as the catalyst, the target product 4aa is obtained in 91% yield with an E / Z ratio of 14 / 1 (Example 1) when 2,2'-bipyridine is used as the ligand. When a methyl group is attached to the 4- or 5-position of the 2,2'-bipyridine ligand, the yield of product 4aa remains essentially unchanged, while the E / Z ratio decreases slightly (Examples 3-4). However, when a methyl group is attached to the 6-position of the 2,2'-bipyridine ligand, the yield of product 4aa drops significantly to 35%. The effect of different substituents at the 4-position of the 2,2'-bipyridine ligand on the reaction was further investigated. Electron-donating tert-butyl-substituted bipyridine ligands yielded 89% of the reaction with an E / Z ratio of 10 / 1 (Example 5), while electron-withdrawing ester-substituted bipyridine ligands yielded 66% of the reaction with an E / Z ratio of 16 / 1 (Example 6). Although the latter yielded a slightly lower yield, it offered better stereoselectivity control. The effect of other types of dinitrogen ligands on the reaction was also investigated. 1,10-o-phenanthroline ligands yielded moderate results, while terpyridine ligands completely inhibited the reaction (Examples 7-8). 4,4'-methyl dicarboxylate-2,2'-bipyridine was selected as the ligand to investigate the effect of different Ni catalysts on the reaction. Compared to NiBr2, the yield of 4aa product decreased significantly when NiCl2 or NiCl2(dppp) was used as a catalyst. However, the effect was similar to that of NiBr2 when NiCl2·DME was used as a catalyst (Examples 9-11). When NiBr2·DME was used as a catalyst, 84% yield of 4aa product was obtained with an E / Z ratio of 20 / 1 and good stereoselectivity control (Example 12). Therefore, the preferred ligand is methyl 4,4′-dicarboxylate-2,2′-bipyridine, and the preferred catalyst is NiBr2·DME.

[0022] 2. Substrate type

[0023] In a glove box, photocatalyst (2 mol% relative to aryl iodine 1), nickel catalyst (10 mol% relative to aryl iodine 1), ligand (10 mol% relative to aryl iodine 1), and sodium sulfite 3 (2.0 equiv. relative to aryl iodine 1) were added sequentially to a 4.0 mL reaction flask. The flask was dissolved in 1.0 mL acetonitrile and 0.2 mL dimethyl sulfoxide. Then, butadiene 2a (0.60 mmol) and aryl iodine 1 (0.20 mmol) were added. The reaction was carried out under blue light (wavelength range 400 nm-480 nm) at room temperature. The reaction system was monitored by TLC. After the reaction was completed, the solvent was evaporated and column chromatography (mobile phase: petroleum ether / ethyl acetate, volume ratio 1:1) was performed to obtain the target product 4.

[0024]

[0025] The photocatalyst is [Ir(ppy)2(dtbbpy)]PF6; the ligand is methyl 4,4'-dicarboxylate-2,2'-bipyridine; and the catalyst is NiBr2·DME.

[0026] The aryl iodine 1 and the product R1 are hydrogen, acetyl, formamido, or fluorine, respectively (the positions of which are shown in the product structures below).

[0027] Sodium sulfite 3 and R2 in the product are phenyl, p-methoxyphenyl, p-tert-butylphenyl or p-oxyphenylphenyl, respectively (the positions of which are shown in the product structures below).

[0028]

[0029] (E)-((4-Phenylbut-2-en-1-yl)sulfonyl)benzene(4aa): White solid, mp147-148℃.46.0mg, 84% yield, E / Z=20 / 1, R f =0.25(petroleum ether / ethylacetate 5 / 1). 1 H NMR(400MHz,Chloroform-d)δ=7.82–7.68(m,2H),7.57–7.49(m,1H),7.40(t,J=7.7Hz,2H),7.27–7.05(m,3H),7.04–6.8 9(m,2H),5.58(dt,J=15.1,6.8Hz,1H),5.40(dtt,J=15.1,7.4,1.5Hz,1H),3.70(d,J=7.3Hz,2H),3.24(d,J=6.7Hz,2H); 13 CNMR(101MHz,Chloroform-d)δ=139.95,138.87,138.22,133.61,129.02,128.51,128.49,126.35,117.53,59.98,38.88; HRMS calculated for C 16 H 17 O2S[M+H] + 273.0944, found 273.0948.

[0030]

[0031] (E)-1-Methoxy-4-((4-phenylbut-2-en-1-yl)sulfonyl)benzene(4ab):Whitesolid,m.p.105-106℃.48.5mg,80%yield,E / Z>20 / 1,R f =0.20(petroleumether / ethylacetate5 / 1). 1 H NMR(400 MHz,Chloroform-d)δ=7.77–7.68(m,2H),7.32–7.18(m,3H),7.09–6.99(m,2H),6.96–6.85(m,2H),5.65(dtt,J=15.3,6.7,1.1Hz,1H),5.49(dtt,J=15.1,7.4,1.4Hz,1H),3.85(s,3H),3.75(dd,J=7.4,1.0Hz,2H),3.33(d,J=6.7Hz,2H); 13 CNMR(101MHz,Chloroform-d)δ=163.65,139.65,138.99,130.66,129.75,128.52,128.48,126.32,117.91,114.16,60.24,55.65,38.91;HRMS calculated for C 17 H 19 O3S[M+H] + 303.1049,found303.1054.

[0032]

[0033] (E)-1-(Tert-butyl)-4-((4-phenylbut-2-en-1-yl)sulfonyl)benzene(4ac):Whitesolid,m.p.98-99℃.63.9mg,97%yield,E / Z=20 / 1,R f =0.25(petroleumether / ethyl acetate5 / 1). 1H NMR(400MHz,Chloroform-d)δ=7.73(d,J=8.6Hz,2H),7.46(d,J=8.6Hz,2H),7.34–7.23(m,2H),7.22–7.14(m,1H),7.11–7.01(m,2H),5.68(dtt,J=15.2,6.7,1.1Hz,1H),5.49(dtt,J=15.1,7.3,1.5Hz,1H),3.75(dd,J=7.4,1.1Hz,2H),3.34(d,J=6.8Hz,2H),1.32(s,9H); 13 C NMR(101MHz,Chloroform-d)δ=157.51,139.77,138.98,135.30,128.55,128.51,128.36,126.33,125.97,117.63,59.97,38.97,35.24,31.09;HRMScalculated for C 20 H 25 O2S[M+H] + 329.1570,found329.1572.

[0034]

[0035] (E)-1-Phenoxy-4-((4-phenylbut-2-en-1-yl)sulfonyl)benzene(4ad):Whitesolid,m.p.93-94℃.29.6mg,41%yield,E / Z=17 / 1,R f =0.25(petroleumether / ethyl acetate 5 / 1). 1 H NMR(400MHz,Chloroform-d)δ=7.78–7.68(m,2H),7.47–7.35(m,2H),7.31–7.21(m,3H),7.21–7.15(m,1H),7.10–7.01(m,4H),7.00–6.92(m,2H),5.69(dtt,J=15.2,6.7,1.2Hz,1H),5.49(dtt,J=15.2,7.4,1.5Hz,1H),3.76(dd,J=7.4,1.0Hz,2H),3.34(d,J=6.7Hz,2H); 13C NMR(101MHz,Chloroform-d)δ=162.43,154.90,139.88,138.91,131.63,130.79,130.24,128.53,128.51,126.39,125.15,120.44,117.73,117.35,60.16,38.93;HRMS calculated for C 22 H 21 O3S[M+H] + 365.1206,found365.1208.

[0036]

[0037] (E)-1-Methyl-4-((4-phenylbut-2-en-1-yl)sulfonyl)benzene(4ba):Whitesolid,m.p.67-68℃.52.4mg,91%yield,E / Z=20 / 1,R f =0.25(petroleumether / ethyl acetate5 / 1). 1 H NMR(400MHz,Chloroform-d)δ=7.69(d,J=8.3Hz,2H),7.31–7.23(m,4H),7.23–7.15(m,1H),7.07–6.98(m,2H),5.73–5.59(m,1H),5.53–5.43(m,1H),3.75(dd,J=7.3,1.1Hz,2H),3.32(d,J=6.7Hz,2H),2.43(s,3H). 13 C NMR(101MHz,Chloroform-d)δ=144.54,139.75,138.95,135.26,129.63,128.51,128.46,126.31,117.72,60.06,38.89,21.65;HRMS calculated for C 17 H 19 O2S[M+H] + 287.1100,found287.1099.

[0038]

[0039] (E)-1-(2-(4-Tosylbut-2-en-1-yl)phenyl)ethan-1-one(4bb):Yellow liquid,64.9mg,99%yield,E / Z>20 / 1,R f =0.25(petroleum ether / ethyl acetate3 / 1). 1 HNMR(400MHz,Chloroform-d)δ=7.69(dd,J=7.7,1.4Hz,1H),7.65(d,J=8.3Hz,2H),7.41(td,J=7.5,1.5Hz,1H),7.32(td,J=7.6,1.4Hz,1H),7.25–7.20(m,2H),7.13(dd,J=7.6,1.3Hz,1H),5.69(dtt,J=15.3,6.7,1.1Hz,1H),5.42(dtt,J=15.1,7.4,1.5Hz,1H),3.73(dd,J=7.5,1.1Hz,2H),3.59(dd,J=6.7,1.4Hz,2H),2.55(s,3H),2.40(s,3H); 13 C NMR(101MHz,Chloroform-d)δ=201.49,144.43,139.91,139.14,137.22,135.17,131.82,131.32,129.54,128.49,126.45,117.46,60.05,37.00,29.58,21.64;HRMS calculatedfor C 19 H 21 O3S[M+H] + 329.1206,found329.1214.

[0040]

[0041] (E)-2-(4-Tosylbut-2-en-1-yl)benzamide(4bc):Yellow solid,m.p.124-125℃.52.8mg,80%yield,E / Z>20 / 1,R f =0.20(petroleum ether / ethyl acetate3 / 1). 1HNMR(400MHz,Chloroform-d)δ=7.64(d,J=8.3Hz,2H),7.44(dd,J=7.5,1.5Hz,1H),7.34(td,J=7.6,1.5Hz,1H),7.28–7.21(m,3H),7.09(dd,J=7.7,1.2Hz,1H),6.26(s,1H),6.07(s,1H),5.82–5.71(m,1H),5.39(dtt,J=15.2,7.5,1.6Hz,1H),3.72(dd,J=7.4,1.1Hz,2H),3.56(dd,J=6.5,1.5Hz,2H),2.41(s,3H); 13 C NMR(101MHz,Chloroform-d)δ=171.97,144.64,140.07,137.12,135.30,135.28,130.50,130.40,129.70,128.35,127.36,126.56,117.64,59.96,36.27,21.66;HRMS calculated for C 18 H 20 NO3S[M+H] + 330.1158,found330.1167.

[0042]

[0043] (E)-1-Fluoro-2-(4-tosylbut-2-en-1-yl)benzene(4bd):White solid,m.p.93-94℃.60.0mg,99%yield,E / Z>20 / 1,R f =0.25(petroleum ether / ethyl acetate5 / 1). 1 HNMR(400MHz,Chloroform-d)δ=7.63–7.55(m,2H),7.20–7.08(m,3H),7.00–6.86(m,3H),5.53(dt,J=15.3,6.6Hz,1H),5.44–5.33(m,1H),3.66(dd,J=7.4,1.0Hz,2H),3.26(d,J=6.5Hz,2H),2.33(s,3H); 13CNMR(101MHz,Chloroform-d)δ=160.79(d,J=245.5Hz),144.55,138.16,135.01,130.58(d,J=4.6Hz),129.58,128.52,128.1 8(d,J=8.0Hz),125.87(d,J=15.9Hz),124.10(d,J=3.7Hz),118.16,115.26(d,J=21.8Hz),59.97,31.97(d,J=3.1Hz),21.66; 19 F NMR(376MHz,Chloroform-d)δ=-118.34; HRMS calculated forC 17 H 18 FO2S[M+H] + 305.1006, found 305.1007.

[0044] Application Example 1:

[0045] Oxidation of product 4ba yields compound 5, which contains a sulfonyl group. The specific procedure is as follows:

[0046]

[0047] Under air atmosphere, 4ba (57.3 mg, 0.20 mmol), BH3·H2O (0.60 mL, 1 M in THF, 0.60 mmol), and tetrahydrofuran (2.0 mL) were added sequentially to a 4.0 mL reaction flask for dissolution. The mixture was stirred at 0 °C for 4 h, then H2O2 (2.0 mL) was added, and stirring continued for another 4 h. After the reaction was complete, the product was extracted three times with dichloromethane, the organic phase was collected, washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4, filtered, and the solvent was evaporated under vacuum. Product 5 (30.3 mg, 50%) was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1). The structure of compound 5 was confirmed by NMR (1H, 1C, and high-resolution NMR).

[0048]

[0049] 4-Phenyl-1-tosylbutan-2-ol (6c): Colorless liquid, 30.3 mg, 50% yield, Rf = 0.25 (petroleum ether / ethyl acetate 10 / 1). 1H NMR(400MHz,Chloroform-d)δ=7.78(d,J=8.3Hz,2H),7.36(d,J=8.0Hz,2H),7.27–7.21(m,2H),7.20–7.14(m,1H),7.13–7.08(m,2H),4.19–4.09(m,1H),3.47(s,1H),3.23(dd,J=14.2,9.2Hz,1H),3.14(dd,J=14.2,2.0Hz,1H),2.75(ddd,J=14.9,9.6,5.7Hz,1H),2.65(ddd,J=13.7,9.3,6.6Hz,1H),1.86(dddd,J=13.8,9.4,8.2,5.7Hz,1H),1.78–1.68(m,1H); 13 C NMR(101MHz,Chloroform-d)δ=145.20,141.04,136.18,130.12,128.48,128.39,127.95,126.03,65.32,62.33,38.05,31.31,21.69;HRMS calculated for C 17 H 21 O3S[M+H]+305.1206,found305.1208.

Claims

1. A method for photocatalytic nickel-catalyzed butadiene sulfonyl arylation, characterized in that: Aryl iodine 1, butadiene 2a, and sodium sulfite 3 can be reacted with a photocatalyst, a nickel catalyst, ligands, and blue light to yield a 1,4-addition sulfonyl aryl product, as shown in the following reaction formula: The substituent R of the reactant aryl iodine 1 1 It can be one or more of the following substituents: hydrogen, methyl, phenyl, fluorine, chlorine, bromine, trifluoromethyl, formamido, methyl formate, etc., with the number being 1 to 5, preferably 1 to 2; R on sodium sulfite 3 2 It can be one or more of methyl, ethyl, cyclopropyl, phenyl, or substituted phenyl groups; the substituents on the substituted phenyl group are one or more of methyl, phenyl, fluorine, chlorine, bromine, trifluoromethyl, methyl formate, etc.

2. The method according to claim 1, characterized in that: The specific steps are as follows: Under a nitrogen atmosphere, a photocatalyst, a nickel catalyst, a ligand, sodium sulfite 3, a solvent, butadiene 2a, and aryl iodine 1 were added to a container, and the reaction was carried out under blue light irradiation at room temperature to obtain the target product 4.

3. The method according to claim 2, characterized in that: The reaction system was monitored by TLC. After the reaction was completed, the solvent was evaporated and column chromatography (mobile phase: petroleum ether / ethyl acetate) was performed to obtain the target product 4.

4. The method according to claim 1 or 2, characterized in that: The photocatalyst is [Ir(ppy)2(dtbbpy)]PF6; The nickel catalyst is NiBr2·DME (nickel bromide made from ethylene glycol dimethyl ether); The ligand is a bipyridine dinitrogen ligand, preferably methyl 4,4'-dicarboxylate-2,2'-bipyridine.

5. The method according to claim 1 or 2, characterized in that: The solvent used is a mixture of acetonitrile and dimethyl sulfoxide in a volume ratio of 1:1 to 9:1, preferably 5:

1.

6. The method according to claim 1 or 2, characterized in that: The molar ratio of substrate aryl iodine 1, butadiene 2a, and sodium sulfite 3 is 1:1 to 3:1 to 3, preferably 1:3:

2.

7. The method according to claim 1 or 2, characterized in that: The reaction is carried out at room temperature, and the reaction time is between 12 and 24 hours.

8. The method according to claim 1, 2, or 4, characterized in that: The molar ratio of substrate aryl iodine 1, photocatalyst, nickel catalyst, and ligand is 1:0.02-0.05:0.05-0.10:0.05-0.1, preferably 1:0.02:0.1:0.

1.

9. The method according to claim 1, 2, or 5, characterized in that: The substrate aryl iodine 1 is in a solvent at a concentration of 0.09–0.15 M, preferably 0.13 M.

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