A method for preparing propargyl sulfones by a multi-component coupling reaction using SO2 insertion

Abstract

The present invention provides a method for preparing propargyl sulfones by a multi-component coupling reaction with SO2 insertion. Using propargyl acetate, aryl iodide, and solid sulfur dioxide (SO2) reagent as raw materials, in the presence of a palladium catalyst, a ligand, a base, a reducing agent, and an additive are simultaneously added, and a multi-component coupling reaction with SO2 insertion is carried out in an organic solvent to obtain propargyl sulfones as shown in formula (III). This preparation method quickly obtains propargyl sulfones through a multi-component one-pot method, with good atom and step economy. This method avoids the use of extremely foul-smelling thioethers and toxic sulfur dioxide gas, and has good environmental friendliness. In addition, the reaction has good yields, good functional group tolerance, strong substrate generality, and strong versatility and practicability.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing propargyl sulfone by a multi-component coupling reaction with SO2 insertion. Background Art

[0002] Propargyl sulfone is an important synthon in organic synthesis. For example, the (3 + 2) cycloaddition reaction of propargyl sulfone with imine gives pyrroline derivatives; the copper-catalyzed hydrosilylation reaction of propargyl sulfone can effectively synthesize polysubstituted alkenylsilane compounds. In addition, propargyl sulfone is also the core skeleton of many drugs and bioactive molecules. In the following formula, A is a cathepsin inhibitor for the treatment of osteoporosis; B is a thyroid cancer regulator; C is a DNA molecular scissor for gene cleavage and editing.

[0003] Some drug examples containing the propargyl sulfone core skeleton are as follows:

[0004]

[0005] The traditional synthesis of propargyl sulfone mainly relies on the oxidation method of propargyl thioether (J. Am. Chem. Soc. 2015, 137, 6857 - 6865). Its route starts from propargyl alcohol and goes through esterification, thio-substitution, oxidation and other reaction processes to obtain the target molecule. The thio-substitution reaction as the key step is an S N 2 substitution reaction, so only primary and secondary propargyl alcohols can participate in the reaction, and the substrate scope is relatively limited. In addition, this method not only has a long reaction route, but also requires the use of strong bases and strong oxidants, and the reaction conditions are harsh.

[0006] In 2018, the research group of Professor Luoping Luo reported a reaction for the preparation of propargyl sulfone by a direct coupling method (Org. Lett. 2018, 20, 5353 - 5356). This reaction directly couples propargyl alcohol with arylsulfinic acid under metal-free catalytic conditions to obtain the target molecule, with mild reaction conditions and good generality. The disadvantage of this reaction is that the arylsulfinic acid used needs to be prepared through two-step reactions starting from sulfonyl chloride with a pungent odor, and the experimental operation is cumbersome. Summary of the Invention

[0007] To solve the problems existing in the prior art, the present invention provides a method for preparing propargyl sulfone by a multi-component coupling reaction with SO2 insertion. The reaction process of this preparation method uses a green and environmentally friendly solid SO2 (sulfur dioxide) reagent, and efficiently synthesizes propargyl sulfone through a transition metal-catalyzed three-component coupling reaction; the reaction has a high yield, a wide substrate range, good functional group tolerance, and strong practical value.

[0008] A method for preparing propargyl sulfone by a multi-component coupling reaction with SO2 insertion, comprising:

[0009] A multi-component coupling reaction of intermolecular SO2 (sulfur dioxide) insertion is carried out among propargyl acetate, aryl iodide, solid sulfur dioxide reagent, palladium catalyst, ligand, base, reducing agent and additive in an organic solvent. After the reaction is completed, the propargyl sulfone is obtained by post-treatment;

[0010] Among them, the structural formula of the propargyl acetate is shown in formula (I):

[0011]

[0012] The structural formula of the aryl iodide is shown in formula (II):

[0013]

[0014] The structural formula of the propargyl sulfone is shown in formula (III):

[0015]

[0016] In formulas (I) to (III), R 1 is one of H, alkyl, methoxy, halogen, aryl, trifluoromethyl; m = 1 to 5; when m ≠ 1, multiple Rs 1 are each independently selected from one of H, alkyl, methoxy, halogen, aryl, trifluoromethyl;

[0017] R 2 is one of H, alkyl, alkoxy, halogen, trifluoromethyl; n = 1 to 5; when n ≠ 1, multiple Rs 2 are each independently selected from one of H, alkyl, alkoxy, halogen, trifluoromethyl;

[0018] When there are two adjacent Rs 2 , the two Rs 2 and the C to which they are attached can form a 3- to 6-membered fused ring, and 1 to 2 carbon atoms in the fused ring are replaced by O.

[0019] Among them, (R 1 ) m , (R 2 ) n respectively represent one or more substituents on the benzene ring where R 1 , R 2 are located.

[0020] Preferably, R 1 is one of H, C1-C3 alkyl, methoxy, fluorine, chlorine, C6-C8 aryl, trifluoromethyl. More preferably, it is one of H, F.

[0021] Preferably, R 2It is one of H, C1-C3 alkyl, C1-C3 alkoxy, fluorine, chlorine, and trifluoromethyl. More preferably, it is one of H and methyl.

[0022] Preferably, when there are two adjacent Rs 2 the fused ring structure formed by two adjacent Rs 2 and the C to which they are attached is:

[0023]

[0024] Preferably, the solid sulfur dioxide reagent is at least one of 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) and sodium metabisulfite (Na2S2O5). More preferably, it is 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO).

[0025] Preferably, the molar ratio of propargyl acetate, aryl iodide, and solid sulfur dioxide reagent is 1:(1-5):(1-4). More preferably, the molar ratio of propargyl acetate, aryl iodide, and solid sulfur dioxide reagent is 1:(2.5-3.5):(1.5-2.5). Even more preferably, the molar ratio of propargyl acetate, aryl iodide, and solid sulfur dioxide reagent is 1:3:2.

[0026] Preferably, the organic solvent is at least one of dimethyl sulfoxide (DMSO) and N,N-dimethylformamide. More preferably, it is dimethyl sulfoxide (DMSO).

[0027] Preferably, the palladium catalyst is Pd2(dba)3 (tris(dibenzylideneacetone)dipalladium) (CAS: 51364-51-3).

[0028] Preferably, the amount of the palladium catalyst used is 2-8 mol% of the amount of propargyl acetate used. More preferably, it is 4-6 mol%. Even more preferably, it is 5 mol%.

[0029] Preferably, the ligand is one or more of triphenylphosphine (PPh3), tris(4-trifluoromethylphenyl)phosphine, and bis(2-diphenylphosphinophenyl)ether. More preferably, it is triphenylphosphine (PPh3).

[0030] Preferably, the amount of the ligand used is 10-30 mol% of the amount of propargyl acetate used. More preferably, it is 15-25 mol%. Even more preferably, it is 20 mol%.

[0031] Preferably, the base is one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, and sodium tert-butoxide. More preferably, it is sodium hydroxide.

[0032] Preferably, the molar ratio of the propargyl acetate to the base is 1:(1 - 4). More preferably, it is 1:(1.5 - 2.5). Even more preferably, it is 1:2.

[0033] Preferably, the reducing agent is at least one of zinc powder and manganese powder. More preferably, it is manganese powder.

[0034] Preferably, the molar ratio of the propargyl acetate to the reducing agent is 1:(1 - 5). More preferably, it is 1:(2 - 4). Even more preferably, it is 1:3.

[0035] Preferably, the additive is one or more of tetrabutylammonium iodide (TBAI), tetrabutylammonium bromide, tetrabutylammonium chloride, and pyridine. The additive is used as a phase transfer catalyst to promote dissolution and accelerate the reaction. More preferably, it is tetrabutylammonium iodide (TBAI).

[0036] Preferably, the molar ratio of the propargyl acetate to the additive is 1:(0.5 - 4). More preferably, it is 1:(1 - 2). Even more preferably, it is 1:1.5.

[0037] Preferably, the molar ratio of the propargyl acetate, aryl iodide, solid SO2 reagent, base, reducing agent, and additive is 1:3:2:2:3:1.5.

[0038] Preferably, the reaction temperature of the multi-component coupling reaction is 70 - 120 °C. More preferably, it is 70 - 90 °C. Even more preferably, it is 80 °C.

[0039] Preferably, the reaction time of the multi-component coupling reaction is 20 - 30 h. More preferably, it is 23 - 26 h.

[0040] Preferably, the multi-component coupling reaction with SO2 insertion is carried out under a nitrogen atmosphere.

[0041] Preferably, the post-treatment steps include:

[0042] Filter the reaction mixture through diatomaceous earth and wash it with ethyl acetate. After adding water, extract and separate the layers. The organic phase is concentrated under reduced pressure in vacuo, and the concentrate is purified by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent to obtain the propargyl sulfone.

[0043] Preferably, in the eluent, the volume ratio (v / v) of ethyl acetate to petroleum ether is 1:(10 - 20).

[0044] In the above preparation method, taking solid SO2 reagent as DABSO, palladium catalyst as Pd2(dba)3, ligand as PPh3, base as NaOH, reducing agent as Mn powder, additive as TBAI (tetrabutylammonium iodide), and solvent as DMSO (dimethyl sulfoxide) as examples, the reaction formula of the multi-component coupling reaction with SO2 insertion is specifically as follows:

[0045]

[0046] Taking R 1 and R 2 both being H as an example, the reaction mechanism of the above reaction is as follows:

[0047]

[0048] In the reaction, on the one hand, iodobenzene 2a undergoes an oxidative addition reaction with the zero-valent active Pd 0 (PPh3)2 species to obtain a metal intermediate IM1; the SO2 in-situ released by DABSO inserts between the C-Pd bond of IM1 to form an intermediate IM2; IM2 releases benzenesulfinate anion (PhSO2 - ) and divalent palladium; the divalent palladium is reduced to zero-valent Pd 0 (PPh3)2 species by manganese powder.

[0049] On the other hand, propargyl acetate 1a undergoes an oxidative addition reaction with Pd 0 (PPh3)2 species to obtain a metal intermediate IM3; IM4 formed by the reaction of IM3 with benzenesulfinate anion undergoes a reductive elimination reaction to obtain the propargyl sulfone product 3a and releases Pd 0 (PPh3)2 species, completing the reaction cycle.

[0050] The preparation method of propargyl sulfone of the present invention uses propargyl acetate, aryl iodide and solid sulfur dioxide (SO2) reagent as raw materials. In the presence of a palladium catalyst, a ligand, a base, a reducing agent and an additive are added simultaneously, and a multi-component coupling reaction with SO2 insertion is carried out in an organic solvent to obtain the propargyl sulfone shown in formula (III).

[0051] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0052] The method for preparing propargyl sulfones by multi-component coupling reaction with SO2 insertion of the present invention uses propargyl acetate, aryl iodide and solid sulfur dioxide (SO2) reagent as raw materials. Through the coupling reaction with SO2 insertion, propargyl sulfones can be rapidly obtained by a multi-component one-pot method, which has good atomic and step economy. This method avoids the use of extremely unpleasant thioethers and toxic sulfur dioxide gas, and has good environmental friendliness. In addition, the reaction has good yields, good functional group tolerance and strong substrate generality, and has strong versatility and practicality. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 1H NMR spectrum of the product prepared in Example 1; 1

[0054] Figure 2 13C NMR spectrum of the product prepared in Example 1; 13

[0055] Figure 3 1H NMR spectrum of the product prepared in Example 2; 1

[0056] Figure 4 13C NMR spectrum of the product prepared in Example 2; 13

[0057] Figure 5 1H NMR spectrum of the product prepared in Example 3; 1

[0058] Figure 6 13C NMR spectrum of the product prepared in Example 3; 13

[0059] Figure 7 1H NMR spectrum of the product prepared in Example 4; 1

[0060] Figure 8 13C NMR spectrum of the product prepared in Example 4; 13

[0061] Figure 9 19F NMR spectrum of the product prepared in Example 4. 19 DETAILED DESCRIPTION OF THE INVENTION

[0062]

[0063] In a reaction tube, propargyl acetate 1 (0.2 mmol, 1.0 equiv), aryl iodide 2 (0.6 mmol, 3.0 equiv), DABSO (96 mg, 0.4 mmol, 2.0 equiv), Pd2(dba)3 (9.2 mg, 5 mol%), PPh3 (10.5 mg, 20 mol%), NaOH (16 mg, 0.4 mmol, 2.0 equiv), Mn powder (33 mg, 0.6 mmol, 3.0 equiv) and TBAI (110.8 mg, 0.3 mmol, 1.5 equiv) were successively weighed and dissolved in 1.0 mL of DMSO; the mixture was reacted at 80 °C for 24 hours. After the reaction was completed, the reaction mixture was filtered through diatomaceous earth and washed with ethyl acetate. The organic phase was extracted with ethyl acetate and water and then concentrated under reduced pressure in vacuo. Using ethyl acetate / petroleum ether as the eluent, the concentrate was purified by silica gel column chromatography to obtain the corresponding product 3.

[0064] The present invention will be further described below in conjunction with specific embodiments.

[0065] Example 1

[0066]

[0067] In a reaction tube, propargyl acetate 1a (40.5 mg, 0.2 mmol, 1.0 equiv), iodobenzene 2a (67 μL, 0.6 mmol, 3.0 equiv), DABSO (96 mg, 0.4 mmol, 2.0 equiv), Pd2(dba)3 (9.2 mg, 5 mol%), PPh3 (10.5 mg, 20 mol%), NaOH (16 mg, 0.4 mmol, 2.0 equiv), Mn powder (33 mg, 0.6 mmol, 3.0 equiv) and TBAI (110.8 mg, 0.3 mmol, 1.5 equiv) were successively weighed and dissolved in 1.0 mL of DMSO; the mixture was reacted at 80 °C for 24 hours. After the reaction was completed, the reaction mixture was filtered through diatomaceous earth and washed with ethyl acetate. The organic phase was extracted with ethyl acetate and water and then concentrated under reduced pressure in vacuo. Using ethyl acetate / petroleum ether (v / v, 1:20) as the eluent, the concentrate was purified by silica gel column chromatography to obtain the corresponding product 3a with a yield of 84%.

[0068] For the synthesis of propargyl acetate 1a used in this example, refer to: Jiao, Z.; Shi, Q.; Zhou, J. S. Asymmetric Intermolecular Heck Reaction of Propargylic Acetates and Cycloalkenes to Access Fused Cyclobutenes. Angew. Chem. Int. Ed. 2017, 56, 14567 - 14571.

[0069] Nuclear magnetic resonance data of product 3a: 1 H NMR (600 MHz, CDCl3): δ = 8.04 - 8.02 (m, 2H), 7.69 - 7.66 (m, 1H), 7.57 - 7.53 (m, 2H), 7.35 - 7.28 (m, 5H), 1.70 (s, 6H) ppm.

[0070] 13 C NMR (151 MHz, CDCl3): δ = 135.1, 134.1, 131.8, 131.0, 128.9, 128.6, 128.4, 122.1, 87.5, 86.6, 59.6, 23.5 ppm.

[0071] Figure 1 1H NMR spectrum of product 3a prepared in Example 1 1 ;

[0072] Figure 2 13C NMR spectrum of product 3a prepared in Example 1 13 ;

[0073] Example 2

[0074]

[0075] In a reaction tube, propargyl acetate 1a (40.5 mg, 0.2 mmol, 1.0 equiv), p-methyl iodobenzene 2b (78 μL, 0.6 mmol, 3.0 equiv), DABSO (96 mg, 0.4 mmol, 2.0 equiv), Pd2(dba)3 (9.2 mg, 5 mol%), PPh3 (10.5 mg, 20 mol%), NaOH (16 mg, 0.4 mmol, 2.0 equiv), Mn powder (33 mg, 0.6 mmol, 3.0 equiv) and TBAI (110.8 mg, 0.3 mmol, 1.5 equiv) were successively weighed and dissolved in 1.0 mL of DMSO; the mixture was reacted at 80 °C for 24 hours. After the reaction was completed, the reaction mixture was filtered through diatomaceous earth and washed with ethyl acetate. The organic phase was extracted with ethyl acetate and water and then concentrated under reduced pressure in vacuo. Using ethyl acetate / petroleum ether (v / v, 1:20) as the eluent, the concentrate was purified by silica gel column chromatography to obtain the corresponding product 3b with a yield of 81%.

[0076] 1H NMR data of product 3b: 1 1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 8.0 Hz, 2H), 7.35 - 7.28 (m, 7H), 2.46 (s, 3H), 1.69 (s, 6H) ppm.

[0077] 13 13C NMR (101 MHz, CDCl3): δ = 145.1, 132.2, 131.8, 131.1, 129.3, 128.9, 128.5, 122.2, 87.7, 86.5, 59.5, 23.5, 21.8 ppm.

[0078] Figure 3 1H NMR spectrum of product 3b prepared in Example 2 1 ;

[0079] Figure 4 13C NMR spectrum of product 3b prepared in Example 2 13 ;

[0080] Example 3

[0081]

[0082] In a reaction tube, propargyl acetate 1a (40.5 mg, 0.2 mmol, 1.0 equiv), 1-iodo-3,4-methylenedioxybenzene 2c (79 μL, 0.6 mmol, 3.0 equiv), DABSO (96 mg, 0.4 mmol, 2.0 equiv), Pd2(dba)3 (9.2 mg, 5 mol%), PPh3 (10.5 mg, 20 mol%), NaOH (16 mg, 0.4 mmol, 2.0 equiv), Mn powder (33 mg, 0.6 mmol, 3.0 equiv) and TBAI (110.8 mg, 0.3 mmol, 1.5 equiv) were dissolved in 1.0 mL of DMSO; the mixture was reacted at 80 °C for 24 hours. After the reaction was completed, the reaction mixture was filtered through diatomaceous earth and washed with ethyl acetate. The organic phase was extracted with ethyl acetate and water and then concentrated under reduced pressure. Using ethyl acetate / petroleum ether (v / v, 1:10) as the eluent, the concentrate was purified by silica gel column chromatography to obtain the corresponding product 3c in a yield of 72%.

[0083] 1H NMR data of product 3c: 1 1H NMR (400 MHz, CDCl3): δ = 7.58 (dd, J = 8.0, 1.6 Hz, 1H), 7.44 (d, J = 1.6 Hz, 1H), 7.37 - 7.28 (m, 5H), 6.92 (d, J = 8.0 Hz, 1H), 6.10 (s, 2H), 1.69 (s, 6H) ppm.

[0084] 13 13C NMR (101 MHz, CDCl3): δ = 152.7, 148.0, 131.8, 128.9, 128.5, 128.3, 127.2, 122.1, 111.0, 108.1, 102.6, 87.7, 86.6, 59.8, 23.6 ppm.

[0085] Figure 5 1H NMR spectrum of the product 3c prepared in Example 3 1 ;

[0086] Figure 6 13C NMR spectrum of the product 3c prepared in Example 3 13 ;

[0087] Example 4

[0088]

[0089] In a reaction tube, propargyl acetate 1b (44 mg, 0.2 mmol, 1.0 equiv), iodobenzene 2a (67 μL, 0.6 mmol, 3.0 equiv), DABSO (96 mg, 0.4 mmol, 2.0 equiv), Pd2(dba)3 (9.2 mg, 5 mol%), PPh3 (10.5 mg, 20 mol%), NaOH (16 mg, 0.4 mmol, 2.0 equiv), Mn powder (33 mg, 0.6 mmol, 3.0 equiv) and TBAI (110.8 mg, 0.3 mmol, 1.5 equiv) were successively weighed and dissolved in 1.0 mL of DMSO; the mixture was reacted at 80 °C for 24 hours. After the reaction was completed, the reaction mixture was filtered through diatomaceous earth and washed with ethyl acetate, the organic layer was extracted with ethyl acetate and water and then concentrated under reduced pressure in vacuo. Using ethyl acetate / petroleum ether (v / v, 1:20) as the eluent, the concentrate was purified by silica gel column chromatography to obtain the corresponding product 3d in a yield of 78%.

[0090] The synthesis of propargyl acetate 1b used in this example was referenced from: Jiao, Z.; Shi, Q.; Zhou, J. S. Asymmetric Intermolecular Heck Reaction of Propargylic Acetates and Cycloalkenes to Access Fused Cyclobutenes. Angew. Chem. Int. Ed. 2017, 56, 14567 - 14571.

[0091] 1H NMR data of product 3d: 1 1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 7.2 Hz, 2H), 7.68 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7.6 Hz, 2H), 7.33 - 7.29 (m, 2H), 7.02 - 7.98 (m, 2H), 1.70 (s, 6H) ppm.

[0092] 13 13C NMR (101 MHz, CDCl3): δ = 162.9 (d, J C-F = 250.7 Hz), 135.2, 134.2, 133.8 (d, J C-F = 8.7 Hz), 131.1, 128.7, 118.2 (d, J C-F = 3.5 Hz), 115.8 (d, J C-F = 22.0 Hz), 87.3, 85.7, 59.6, 23.5 ppm.

[0093] 19 19F NMR (337 MHz, CDCl3): δ = -109.9 ppm.

[0094] Figure 7 1H NMR spectrum of the product 3d prepared in Example 4 1 1H NMR spectrum;

[0095] Figure 8 13C NMR spectrum of the product 3d prepared in Example 4 13 13C NMR spectrum;

[0096] Figure 9 19F NMR spectrum of the product 3d prepared in Example 4 19 19F NMR spectrum.

Claims

1. A method for preparing propargyl sulfones by a multicomponent coupling reaction using SO2 insertion, characterized in that, Comprising: A multi-component coupling reaction of intermolecular SO2 insertion is carried out among propargyl acetate, aryl iodide, solid sulfur dioxide reagent, palladium catalyst, ligand, base, reducing agent and additive in an organic solvent. After the reaction is completed, the propargyl sulfone is obtained through post-treatment. Among them, the structural formula of the propargyl acetate is as shown in formula (I): （I） The structural formula of the aryl iodide is as shown in formula (II): (II) The structural formula of the propargyl sulfone is as shown in formula (III): (III) In formulas (I) to (III), R 1 is one of H, alkyl, methoxy, halogen, aryl, and trifluoromethyl; m = 1 to 5; when m ≠ 1, multiple R 1 are each independently selected from one of H, alkyl, methoxy, halogen, aryl, and trifluoromethyl; R 2 is one of H, alkyl, alkoxy, halogen, and trifluoromethyl; n = 1 to 5; when n ≠ 1, multiple Rs 2 are each independently selected from one of H, alkyl, alkoxy, halogen, and trifluoromethyl; When there are two adjacent Rs 2 two Rs 2 and the C atoms connected thereto can form a 3- to 6-membered fused ring, and 1 to 2 carbon atoms in the fused ring are replaced by O; The ligand is one or more of triphenylphosphine, tris(4-trifluoromethylphenyl)phosphine, bis(2-diphenylphosphinophenyl)ether; The reducing agent is at least one of zinc powder and manganese powder; The additive is one or more of tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, pyridine; 2. The method for preparing propargyl sulfone by multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, R 1 is one of H, C1-C3 alkyl, methoxy, fluorine, chlorine, C6-C8 aryl, and trifluoromethyl; R 2 is one of H, C1-C3 alkyl, C1-C3 alkoxy, fluorine, chlorine, and trifluoromethyl.

3. The method for preparing propargyl sulfone by multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The solid sulfur dioxide reagent is at least one of 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct, sodium metabisulfite; The molar ratio of the propargyl acetate, aryl iodide, and solid sulfur dioxide reagent is 1:(1 - 5):(1 - 4); The organic solvent is at least one of dimethyl sulfoxide and N,N -dimethylformamide.

4. The method for preparing propargyl sulfone by a multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The palladium catalyst is Pd2(dba)3; The dosage of the palladium catalyst is 2 - 8 mol% of the dosage of the propargyl acetate.

5. The method for preparing propargyl sulfone by multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The dosage of the ligand is 10 - 30 mol% of the dosage of the propargyl acetate.

6. The method for preparing propargyl sulfones by a multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The base is one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium tert-butoxide; The molar ratio of the propargyl acetate to the base is 1:(1 - 4).

7. The method for preparing propargyl sulfone by a multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The molar ratio of the propargyl acetate to the reducing agent is 1:(1 - 5).

8. The method for preparing propargyl sulfone by a multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The molar ratio of the propargyl acetate to the additive is 1:(0.5 - 4).

9. The method for preparing propargyl sulfone by a multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The reaction temperature of the multi-component coupling reaction is 70 - 120 °C.

10. The method for preparing propargyl sulfone by multi-component coupling reaction using SO2 insertion according to claim 1, characterized in that, The post-treatment steps include: Filter the reaction mixture through diatomaceous earth and wash it with ethyl acetate. After adding water, extract and separate the layers. The organic phase is concentrated under reduced pressure in vacuo, and the concentrate is purified by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent to obtain the propargyl sulfone.

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