A method for preparing a β-lactam compound

Abstract

The present invention provides a method for preparing a β-lactam compound, comprising the following steps: a) Using the compound shown in Formula I, CO, and the imine shown in Formula II as raw materials, reacting in a solvent under the action of a transition metal catalyst, a ligand, an oxidant, and an organic base to obtain the β-lactam compound shown in Formula III. Compared with the prior art, the preparation method provided by the present invention uses bulk chemicals olefins or alkyl aromatics as the main raw materials, and can efficiently synthesize β-lactam compounds in one step. The raw materials are cheap, easily available, and stable. At the same time, it has good substrate adaptability, can prepare β-lactam compounds with diverse structures, and the by-product is tert-butanol, which has little environmental pollution and is easy to recycle and reuse.

Description

Technical Field

[0001] The present invention relates to the technical field of organic chemistry, and more particularly, to a method for preparing β-lactam compounds. Background Art

[0002] β-Lactam, as a special pharmacophore, widely exists in a variety of drugs and bioactive natural products, such as penicillin, cephalosporin, faropenem, etc. At the same time, β-lactam is also an important synthon in organic synthesis and is often used to synthesize heterocycles and amino acids. Due to the wide applications of such compounds, chemists have developed various methods for synthesizing β-lactam compounds, and the most common method among them is the Staudinger reaction (Tetrahedron 2008, 64, 10465-10496). In this reaction, acyl chloride is usually used as a raw material, and ketene is generated in situ under the action of a base and then reacts with imine to form the product β-lactam. However, acyl chloride is a compound with relatively high toxicity and high reactivity, sensitive to water, and liable to deterioration, and it often needs to be prepared on-site by using an acid and an equivalent amount of an activating reagent. Whether it is in-situ preparation or direct use of acyl chloride, an equivalent amount of by-products will be generated throughout the process of synthesizing β-lactam compounds, which is not environmentally friendly. Another common method is the Kinugasa reaction (Angew. Chem. Int. Ed. 2004, 43, 2198-2200). Since this method requires the use of hard-to-obtain nitrones as raw materials, its application is limited to a certain extent.

[0003] In addition to the above two common methods, there are also some methods that use zinc reagents (Chem. Rev. 1989, 89, 1447 - 1465.), diazo compounds (Curr. Org. Chem. 2016, 20, 29 - 40.), β - amino acids (Tetrahedron Lett. 1988, 29, 2203 - 2205.), aziridines (Eur. J. Org. Chem. 2017, 5943 - 5960.), sterically hindered secondary amines (Science 2016, 354, 851 - 857.), allyl halides (Tetrahedron 2004, 60, 6895 - 6900.), allyl phosphates (Tetrahedron Lett. 1993, 34, 6553 - 6556.), benzyl halides (Tetrahedron Letters 2012, 53, 1613 - 1616.), etc. as raw materials. Although these methods have their respective advantages, however, environmental unfriendliness and cumbersome synthetic steps of the substrates have always been inherent drawbacks of these reactions. Recent studies have shown that dienes and electron - deficient alkenes containing electron - withdrawing groups such as cyano, ester, and phosphate groups can also be used as raw materials to synthesize β - lactam compounds (CN112939835A). In contrast, unactivated alkenes and alkyl aromatics are inexpensive and readily available bulk chemicals and are ideal synthetic building blocks in chemical synthesis. Directly using unactivated alkenes or alkyl aromatics to synthesize structurally diverse β - lactam compounds is of great significance and has good application prospects. Summary of the Invention

[0004] In view of this, the object of the present invention is to provide a method for preparing β - lactam compounds. The preparation method provided by the present invention can achieve the efficient synthesis of β - lactam compounds using bulk chemicals alkenes or alkyl aromatics as raw materials. At the same time, it has good substrate adaptability, can prepare structurally diverse β - lactam compounds, and the by - product is tert - butanol, which has little environmental pollution and is easy to recycle and reuse.

[0005] The present invention provides a method for preparing β - lactam compounds, comprising the following steps:

[0006] a) Using the compound shown in Formula I, CO, and the imine shown in Formula II as raw materials, reacting in a solvent under the action of a transition metal catalyst, a ligand, an oxidant, and an organic base to obtain the β - lactam compound shown in Formula III;

[0007] The compound shown in Formula I includes the compounds shown in Formula I - 1 to I - 4:

[0008]

[0009] The imine shown in Formula II:

[0010]

[0011] The β-lactam compounds represented by formula III include compounds represented by formulas III-1 to III-3:

[0012]

[0013]

[0014] Among them, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 R is independently selected from hydrogen, aliphatic groups of C1 to C40, and aromatic groups of C4 to C60; 7 R is selected from hydrogen, a C1-C40 fatty group; 8 , R 9 Independently selected from aliphatic groups within C1 to C40 and aromatic groups within C4 to C60.

[0015] Preferably, the pressure of CO in step a) is 1 atm to 60 atm.

[0016] Preferably, in step a), the molar ratio of the compound shown in formula I to the imine shown in formula II is 10:1.

[0017] Preferably, the transition metal catalyst in step a) is selected from compounds containing palladium and / or compounds containing nickel;

[0018] The compound containing palladium element is selected from one or more of palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium trifluoroacetate, tri-tert-butylphosphine palladium, tetrakistriphenylphosphine palladium, triphenylphosphine palladium chloride, bisacetonitrile palladium chloride, and allyl palladium chloride;

[0019] The nickel-containing compound is selected from one or more of nickel chloride, nickel bromide, nickel iodide, nickel acetate, nickel trifluoroacetate, and bis-(1,5-cyclooctadiene) nickel;

[0020] The amount of the transition metal catalyst used is 0.01% to 10% of the molar amount of the imine shown in formula II.

[0021] Preferably, the ligand in step a) is a phosphine ligand containing phosphorus;

[0022] The phosphorus element-containing phosphine ligand is selected from one or more of (±)-2,2'-bis-(diphenylphosphino)-1,1'-binaphthalene, (±)-2,2'-bis-(diphenylphosphino)-6,6'-dimethoxy-1,1'-biphenyl, bis(2-diphenylphosphinophenyl) ether, and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene;

[0023] The dosage of the ligand is 0.02% to 20% of the molar amount of the imine shown in Formula II.

[0024] Preferably, in step a), the oxidant is selected from one or more of benzoyl peroxide, tert-butyl perbenzoate, methyl ethyl ketone peroxide, di-tert-butyl peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, diisopropylbenzene peroxide, and 1,1-di-tert-butylperoxycyclohexane;

[0025] The dosage of the oxidant is 100% to 300% of the molar amount of the imine shown in Formula II.

[0026] Preferably, in step a), the organic base is selected from one or more of triethylamine, N,N-diisopropylethylamine, 2,2,6,6-tetramethylpiperidine, 1,2,2,6,6-pentamethylpiperidine, pyridine, 3,5-dimethylpyridine, 2,4,6-trimethylpyridine, triethylenediamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, and N,N-dicyclohexylmethylamine;

[0027] The dosage of the organic base is 10% to 50% of the molar amount of the imine shown in Formula II.

[0028] Preferably, in step a), the solvent is selected from one or more of benzene, chlorobenzene, fluorobenzene, toluene, benzotrifluoride, xylene, mesitylene, acetonitrile, and benzonitrile.

[0029] Preferably, step a) is specifically as follows:

[0030] a1) Add the compound shown in Formula I, the imine shown in Formula II, the transition metal catalyst, the ligand, the oxidant, the organic base, and the solvent into a reaction kettle. After replacing with CO 2 to 4 times, charge CO for reaction to obtain a reaction mixture;

[0031] a2) Cool the reaction kettle to room temperature, release CO, and subject the reaction mixture to column chromatography to recover the unreacted raw materials and obtain the β-lactam compound shown in Formula III.

[0032] Preferably, the temperature of the reaction in step a) is 60°C to 160°C, and the time is 6 h to 30 h.

[0033] The present invention provides a method for preparing a β-lactam compound, comprising the following steps: a) Using the compound shown in Formula I, CO, and the imine shown in Formula II as raw materials, reacting in a solvent under the action of a transition metal catalyst, a ligand, an oxidant, and an organic base to obtain the β-lactam compound shown in Formula III; the compound shown in Formula I includes the compounds shown in Formula I-1 to I-4:

[0034]

[0035] The imine shown in Formula II:

[0036]

[0037] The β-lactam compound shown in Formula III includes the compounds shown in Formula III-1 to III-3:

[0038]

[0039] Wherein, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 are independently selected from hydrogen, a C1-C40 aliphatic group, and an aromatic group within C4-C60; R 7 is selected from hydrogen and a C1-C40 aliphatic group; R 8 、R 9 are independently selected from a C1-C40 aliphatic group and an aromatic group within C4-C60. Compared with the prior art, the preparation method provided by the present invention uses bulk chemicals olefins or alkyl aromatics as the main raw materials, and can efficiently synthesize β-lactam compounds in one step. The raw materials are cheap, easily available, and stable. At the same time, it has good substrate adaptability, can prepare β-lactam compounds with diverse structures, and the by-product is tert-butanol, which has little environmental pollution and is easy to recycle and reuse. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 1H NMR (400 MHz, CDCl3) spectrum of β-lactam 3 obtained in Example 1 of the present invention; 1 1H NMR (400 MHz, CDCl3) spectrum of β-lactam 3 obtained in Example 1 of the present invention;

[0041] Figure 2 13C NMR (101 MHz, CDCl3) spectrum of β-lactam 3 obtained in Example 1 of the present invention; 13 13C NMR (101 MHz, CDCl3) spectrum of β-lactam 3 obtained in Example 1 of the present invention;

[0042] Figure 3 1H NMR (400 MHz, CDCl3) spectrum of β-lactam 9 obtained in Example 12 of the present invention; 1 1H NMR (400 MHz, CDCl3) spectrum of β-lactam 9 obtained in Example 12 of the present invention;

[0043] Figure 4 For the β-lactam 9 obtained in Example 12 of the present invention 13 13C NMR (101 MHz, CDCl3) spectrum;

[0044] Figure 5 For the β-lactam 14 obtained in Example 17 of the present invention 1 1H NMR (400 MHz, CDCl3) spectrum;

[0045] Figure 6 For the β-lactam 14 obtained in Example 17 of the present invention 13 13C NMR (101 MHz, CDCl3) spectrum;

[0046] Figure 7 For the β-lactam 15 obtained in Example 18 of the present invention 1 1H NMR (400 MHz, CDCl3) spectrum;

[0047] Figure 8 For the β-lactam 15 obtained in Example 18 of the present invention 13 13C NMR (101 MHz, CDCl3) spectrum. Detailed implementation manners

[0048] Next, in combination with the embodiments of the present invention, the technical solutions of the present invention will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0049] The present invention provides a method for preparing a β-lactam compound, comprising the following steps:

[0050] a) Using the compound shown in Formula I, CO, and the imine shown in Formula II as raw materials, reacting in a solvent under the action of a transition metal catalyst, a ligand, an oxidant, and an organic base to obtain the β-lactam compound shown in Formula III;

[0051] The compound shown in Formula I includes the compounds shown in Formula I-1 to I-4:

[0052]

[0053] The imine shown in Formula II:

[0054]

[0055] The β-lactam compounds represented by Formula III include the compounds represented by Formula III-1 to III-3:

[0056]

[0057] Among them, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are independently selected from hydrogen, a C1-C40 aliphatic group, and an aromatic group within C4-C60; R 7 is selected from hydrogen and a C1-C40 aliphatic group; R 8 , R 9 are independently selected from a C1-C40 aliphatic group and an aromatic group within C4-C60.

[0058] In the present invention, the compound represented by Formula I, CO, and the imine represented by Formula II are used as raw materials, and under the action of a transition metal catalyst, a ligand, an oxidant, and an organic base, a reaction is carried out in a solvent to obtain the β-lactam compound represented by Formula III. There are no special restrictions on the sources of the compound represented by Formula I, CO, the imine represented by Formula II, the transition metal catalyst, the ligand, the oxidant, the organic base, and the solvent in the present invention, and commercially available products well-known to those skilled in the art can be used.

[0059] In the present invention, the compound represented by Formula I is an olefin compound or an alkylaromatic compound, including the compounds represented by Formula I-1 to I-4:

[0060]

[0061] Among them, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are independently selected from hydrogen, a C1-C40 aliphatic group, and an aromatic group within C4-C60; R 7 is selected from hydrogen and a C1-C40 aliphatic group;

[0062] In Formula I-4 is preferably an aromatic group within C4-C60;

[0063] In a preferred embodiment of the present invention, the olefin in Formula I-2 and Formula I-3 is a cyclic olefin.

[0064] In the present invention, the compound represented by Formula I is preferably mesitylene, m-fluorotoluene, 2-methylnaphthalene, 2,5-dimethylthiophene, or toluene.

[0065] In the present invention, the pressure of the CO is preferably 1 atm to 60 atm, more preferably 20 atm to 40 atm.

[0066] In the present invention, the imine represented by Formula II:

[0067]

[0068] wherein, R 8 and R 9 independently selected from aliphatic groups having 1 to 40 carbon atoms and aromatic groups within 4 to 60 carbon atoms.

[0069] In the present invention, the imine represented by Formula II is preferably

[0070] In the present invention, the molar ratio of the compound represented by I to the imine represented by Formula II is preferably (1 to 40):1, more preferably (10 to 38):1.

[0071] In the present invention, the transition metal catalyst is preferably selected from palladium element-containing compounds and / or nickel element-containing compounds; wherein, the palladium element-containing compounds are preferably selected from one or more of palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium trifluoroacetate, palladium tri-tert-butylphosphine, tetrakis(triphenylphosphine)palladium, palladium chloride triphenylphosphine, dichloro(phenyl cyanide)palladium, allyl palladium chloride; the nickel element-containing compounds are preferably selected from one or more of nickel chloride, nickel bromide, nickel iodide, nickel acetate, nickel trifluoroacetate, bis(1,5-cyclooctadiene)nickel. In a preferred embodiment of the present invention, the transition metal catalyst is preferably palladium acetate, dichloro(phenyl cyanide)palladium or nickel iodide.

[0072] In the present invention, the amount of the transition metal catalyst used is preferably 0.01% to 10% of the molar amount of the imine represented by Formula II, more preferably 1% to 8%.

[0073] In the present invention, the ligand is preferably a phosphorus element-containing phosphine ligand; the phosphorus element-containing phosphine ligand is preferably selected from one or more of (±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (BINAP), (±)-2,2'-bis(diphenylphosphino)-6,6'-dimethoxy-1,1'-biphenyl (MeO-BIPHEP), bis(2-diphenylphosphinophenyl) ether (DPE-phos), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), more preferably 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, bis(2-diphenylphosphinophenyl) ether or n-butylbis(1-adamantyl)phosphine.

[0074] In the present invention, the dosage of the ligand is preferably 0.02% to 20% of the molar amount of the imine shown in Formula II, more preferably 5% to 15%.

[0075] In the present invention, the oxidant is preferably selected from one or more of benzoyl peroxide, tert-butyl perbenzoate, methyl ethyl ketone peroxide, di-tert-butyl peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, dicumyl peroxide, 1,1-di-tert-butylperoxycyclohexane, and more preferably tert-butyl perbenzoate, 1,1-di-tert-butylperoxycyclohexane or di-tert-butyl peroxide.

[0076] In the present invention, the dosage of the oxidant is preferably 100% to 300% of the molar amount of the imine shown in Formula II, more preferably 150% to 250%.

[0077] In the present invention, the organic base is preferably selected from one or more of triethylamine, N,N-diisopropylethylamine, 2,2,6,6-tetramethylpiperidine, 1,2,2,6,6-pentamethylpiperidine, pyridine, 3,5-dimethylpyridine, 2,4,6-trimethylpyridine, triethylenediamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, N,N-dicyclohexylmethylamine, and more preferably triethylenediamine, 1,2,2,6,6-pentamethylpiperidine or 3,5-dimethylpyridine.

[0078] In the present invention, the dosage of the organic base is preferably 10% to 50% of the molar amount of the imine shown in Formula II, more preferably 20% to 40%.

[0079] In the present invention, the solvent is preferably selected from one or more of benzene, chlorobenzene, fluorobenzene, toluene, benzotrifluoride, xylene, mesitylene, acetonitrile, benzonitrile, and more preferably chlorobenzene, acetonitrile or toluene.

[0080] In the present invention, the dosage of the solvent is preferably 0.1 mL to 1 mL, more preferably 0.4 mL to 0.6 mL.

[0081] In the present invention, step a) is preferably specifically:

[0082] a1) Adding the compound shown in Formula I, the imine shown in Formula II, the transition metal catalyst, the ligand, the oxidant, the organic base, and the solvent into a reaction kettle, replacing with CO 2 to 4 times, and then charging CO for reaction to obtain a reaction mixture;

[0083] a2) Cooling the reaction kettle to room temperature, discharging CO, subjecting the reaction mixture to column chromatography, recovering the unreacted raw materials, and obtaining the β-lactam compound shown in Formula III;

[0084] More preferably:

[0085] a1) Add the compound shown in Formula I, the imine shown in Formula II, a transition metal catalyst, a ligand, an oxidant, an organic base, and a solvent into a reaction kettle. After replacing with CO three times, charge CO and carry out the reaction to obtain a reaction mixture;

[0086] a2) Cool the reaction kettle to room temperature, release CO, subject the reaction mixture to column chromatography, recover the unreacted raw materials, and obtain the β-lactam compound shown in Formula III.

[0087] In the present invention, the temperature of the reaction is preferably 60 °C to 160 °C, more preferably 100 °C to 140 °C; the reaction time is preferably 6 h to 30 h, more preferably 12 h to 24 h; the reaction process is preferably carried out under stirring.

[0088] The present invention provides a method for preparing a β-lactam compound, comprising the following steps: a) Using the compound shown in Formula I, CO, and the imine shown in Formula II as raw materials, reacting in a solvent under the action of a transition metal catalyst, a ligand, an oxidant, and an organic base to obtain the β-lactam compound shown in Formula III; the compound shown in Formula I includes the compounds shown in Formula I-1 to I-4:

[0089]

[0090] The imine shown in Formula II:

[0091]

[0092] The β-lactam compound shown in Formula III includes the compounds shown in Formula III-1 to III-3:

[0093]

[0094]

[0095] Wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are independently selected from hydrogen, a C1-C40 aliphatic group, and an aromatic group within C4-C60; R 7 is selected from hydrogen and a C1-C40 aliphatic group; R 8 , R 9An independent aliphatic group selected from C1 to C40 and an aromatic group within C4 to C60. Compared with the prior art, the preparation method provided by the present invention uses bulk chemical olefins or alkyl aromatics as the main raw materials, and can efficiently synthesize β-lactam compounds in one step. The raw materials are cheap, easy to obtain and stable. At the same time, it has good substrate adaptability, can prepare β-lactam compounds with diverse structures, and the by-product is tert-butanol, which has little environmental pollution and is easy to recycle and reuse.

[0096] To further illustrate the present invention, the following detailed description is provided through the following examples. The raw materials used in the following examples of the present invention are all commercially available products.

[0097] Example 1: Preparation of β-lactam 3

[0098]

[0099] Add olefin 1a (5 mmol, 871.5 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (oxidant1) (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) into an autoclave. After replacing with carbon monoxide three times, charge 30 atm of carbon monoxide and stir at 100 °C for 24 hours. After the reaction is completed, cool the autoclave to room temperature, release carbon monoxide, and the reaction system can be recovered as the reacted olefin by column chromatography and the product 3 is obtained with a yield of 89% and a d.r. > 20:1.

[0100] 1 H NMR (400 MHz, Chloroform-d) δ 7.39–7.31 (m, 6H), 7.30–7.24 (m, 4H), 7.22–7.17 (m, 4H), 6.47 (d, J = 15.8 Hz, 1H), 6.10 (dd, J = 15.8, 8.4 Hz, 1H), 4.08 (d, J = 2.1 Hz, 1H), 3.86 (dt, J = 14.1, 7.1 Hz, 1H), 3.68 (dd, J = 8.4, 2.9 Hz, 1H), 3.07 (dt, J = 14.1, 7.1 Hz, 1H), 2.88 (dh, J = 28.0, 7.2 Hz, 2H), 1.32 (s, 9H).

[0101] 1313C NMR (101 MHz, CDCl3) δ 168.6, 151.1, 138.5, 137.5, 133.8, 133.8, 129.1, 128.9, 128.8, 128.7, 126.8, 126.5, 126.2, 125.6, 121.7, 63.8, 62.5, 41.8, 34.7, 34.2, 31.4.

[0102] HRMS (ESI) calcd. for C 29 H 32 ON + [M + H] + : 410.2478, found: 410.2489.

[0103] Example 2: Preparation of β-lactam 3

[0104]

[0105] Alkene 1a (5 mmol, 871.5 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(OAc)2 (0.025 mmol, 5.6 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After displacing with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the unreacted alkene and obtain product 3 in a yield of 79% and a d.r. > 20:1.

[0106] Example 3: Preparation of β-lactam 3

[0107]

[0108] Olefin 1a (5 mmol, 871.5 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), bis(2-diphenylphosphinophenyl) ether (0.05 mmol, 26.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After three replacements with carbon monoxide, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 3 in 81% yield with a d.r. > 20:1.

[0109] Example 4: Preparation of β-lactam 3

[0110]

[0111] Olefin 1a (5 mmol, 871.5 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), tert-butyl perbenzoate (1 mmol, 194.2 mg), and acetonitrile (0.5 mL) were added to an autoclave. After three replacements with carbon monoxide, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 3 in 78% yield with a d.r. > 20:1.

[0112] Example 5: Preparation of β-lactam 3

[0113]

[0114] Olefin 1a (5 mmol, 871.5 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), triethylenediamine (0.2 mmol, 22.4 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After purging with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 3 in a yield of 76% and a d.r. > 20:1.

[0115] Example 6: Preparation of β-lactam 3

[0116]

[0117] Olefin 1a (5 mmol, 871.5 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and chlorobenzene (0.5 mL) were added to an autoclave. After purging with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 3 in a yield of 73% and a d.r. > 20:1.

[0118] Example 7: Preparation of β-lactam 4

[0119]

[0120] Olefin 1a (5 mmol, 871.5 mg), imine 2b (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After purging with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and the carbon monoxide was released. The reaction system was subjected to column chromatography to recover the unreacted olefin and obtain product 4 in 87% yield with a d.r. > 20:1.

[0121] 1 H NMR (400 MHz, CDCl3) δ 7.36–7.26 (m, 9H), 7.25–7.22 (m, 1H), 7.20–7.17 (m, 2H), 7.16–7.13 (m, 1H), 6.58 (d, J = 15.8 Hz, 1H), 6.25 (dd, J = 15.8, 8.6 Hz, 1H), 4.99 (d, J = 14.9 Hz, 1H), 4.51 (d, J = 2.3 Hz, 1H), 3.87 (d, J = 14.9 Hz, 1H), 3.74–3.71 (m, 1H), 2.13 (s, 3H), 1.30 (s, 9H).

[0122] 13 C NMR (101 MHz, CDCl3) δ 168.6, 151.1, 136.0, 135.7, 135.6, 134.1, 133.8, 130.9, 129.0, 128.6, 128.0, 127.9, 126.8, 126.3, 125.6, 124.7, 121.9, 63.6, 57.6, 44.9, 34.7, 31.4, 19.4.

[0123] HRMS (ESI) calcd. for C 29 H 32 ON + [M + H] + : 410.2478, found: 410.2487.

[0124] Example 8: Preparation of β-lactam 5

[0125]

[0126] Olefin 1a (5 mmol, 871.5 mg), imine 2c (0.5 mmol, 80.6 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After three replacements with carbon monoxide, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 5 in 83% yield with a d.r. > 20:1.

[0127] 1 H NMR (400 MHz, CDCl3) δ 7.43–7.38 (m, 2H), 7.37–7.30 (m, 7H), 6.59 (dd, J = 15.8, 1.1 Hz, 1H), 6.29 (dd, J = 15.8, 8.2 Hz, 1H), 4.39 (d, J = 2.2 Hz, 1H), 3.77–3.74 (m, 1H), 3.53 (dt, J = 14.0, 7.6 Hz, 1H), 2.90–2.83 (m, 1H), 1.52–1.44 (m, 2H), 1.38–1.32 (m, 2H), 1.31 (s, 9H), 0.89 (t, J = 7.3 Hz, 3H).

[0128] 13 C NMR (101 MHz, CDCl3) δ 168.5, 151.1, 137.8, 133.9, 133.8, 129.1, 128.7, 126.5, 126.2, 125.6, 121.9, 63.7, 62.2, 40.4, 34.7, 31.4, 29.8, 20.3, 13.7.

[0129] HRMS (ESI) calcd. for C 25 H 32 ON + [M+H] + : 362.2478, found: 362.2490.

[0130] Example 9: Preparation of β-lactam 6

[0131]

[0132] Olefin 1b (5 mmol, 591.0 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After purging with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the unreacted olefin and obtain product 6 in 87% yield with a d.r. > 20:1.

[0133] 1 H NMR (400 MHz, Chloroform-d) δ 7.39–7.34 (m, 3H), 7.33–7.27 (m, 6H), 7.26–7.22 (m, 2H), 7.21–7.16 (m, 4H), 6.49 (dd, J = 15.8, 1.1 Hz, 1H), 6.14 (dd, J = 15.9, 8.3 Hz, 1H), 4.10 (d, J = 2.2 Hz, 1H), 3.85 (dt, J = 14.1, 6.8 Hz, 1H), 3.69 (dd, J = 8.3, 2.8 Hz, 1H), 3.14–3.02 (m, 1H), 2.88 (dq, J = 25.5, 6.8 Hz, 2H).

[0134] 13 C NMR (101 MHz, CDCl3) δ 168.4, 138.5, 137.5, 136.6, 134.1, 129.1, 128.9, 128.8, 128.7, 128.7, 127.9, 126.8, 126.6, 126.5, 122.6, 63.7, 62.5, 41.8, 34.2.

[0135] HRMS (ESI) calcd. for C 25 H 24 ON + [M+H] + : 354.1852, found: 354.1861.

[0136] Example 10: Preparation of β-lactam 7

[0137]

[0138] Olefin 1c (5 mmol, 551.0 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After three replacements with carbon monoxide, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, carbon monoxide was released, and the reaction system was subjected to column chromatography to recover the unreacted olefin and obtain product 7 in a yield of 76% and a d.r. > 20:1.

[0139] 1 H NMR (500 MHz, Chloroform-d) δ 7.38–7.31 (m, 3H), 7.29–7.25 (m, 2H), 7.24–7.19 (m, 1H), 7.19–7.12 (m, 4H), 5.15 (d, J = 9.0 Hz, 1H), 3.96 (d, J = 2.1 Hz, 1H), 3.81–3.76 (m, 1H), 3.74 (dd, J = 9.0, 2.1 Hz, 1H), 3.04 (dt, J = 14.3, 7.4 Hz, 1H), 2.89–2.78 (m, 2H), 2.14–2.06 (m, 2H), 2.00–1.88 (m, 2H), 1.62–1.54 (m, 1H), 1.52–1.42 (m, 4H), 1.39–1.31 (m, 1H).

[0140] 13 C NMR (126 MHz, CDCl3) δ 169.8, 146.0, 138.5, 137.9, 128.9, 128.8, 128.6, 128.4, 126.6, 126.3, 114.2, 63.1, 59.3, 41.8, 36.9, 34.2, 29.6, 28.4, 27.8, 26.6.

[0141] HRMS (ESI) calcd. for C 24 H 28 ON + [M+H] + : 346.2165, found: 346.2162.

[0142] Example 11: Preparation of β-lactam 8

[0143]

[0144] Olefin 1d (5 mmol, 801.5 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After purging with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and the carbon monoxide was released. The reaction system was subjected to column chromatography to recover the unreacted olefin and obtain product 8 in a yield of 78% and a d.r. > 20:1.

[0145] 1 H NMR (400 MHz, Chloroform-d) δ 7.40–7.34 (m, 3H), 7.34–7.32 (m, 4H), 7.30–7.27 (m, 2H), 7.26–7.25 (m, 1H), 7.25–7.22 (m, 2H), 7.21–7.19 (m, 1H), 7.17–7.16 (m, 1H), 7.15–7.13 (m, 1H), 5.66 (d, J = 9.4 Hz, 1H), 4.04 (d, J = 2.1 Hz, 1H), 3.89 (dd, J = 9.4, 2.1 Hz, 1H), 3.82 (ddd, J = 14.1, 7.8, 6.4 Hz, 1H), 3.10–3.03 (m, 1H), 2.98–2.79 (m, 2H), 2.30 (t, J = 7.7 Hz, 2H), 1.34–1.27 (m, 1H), 1.22–1.11 (m, 1H), 0.68 (t, J = 7.3 Hz, 3H).

[0146] 13 C NMR (101 MHz, CDCl3) δ 169.1, 145.8, 142.2, 138.6, 137.7, 129.1, 128.9, 128.8, 128.7, 128.4, 127.4, 126.8, 126.6, 126.6, 121.3, 63.1, 60.6, 42.0, 34.3, 32.5, 22.2, 13.9.

[0147] HRMS (ESI) calcd. for C 28 H 30 ON + [M+H]+ : 396.2322, found: 396.2327.

[0148] Example 12: Preparation of β-lactam 9

[0149]

[0150] Olefin 1e (5 mmol, 421.0 mg), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), 1,1-di-tert-butylperoxycyclohexane (80% in mineral oil, 1 mmol, 325.5 mg), and acetonitrile (0.5 mL) were added to an autoclave. After three replacements with carbon monoxide, 30 atm of carbon monoxide was charged, and the mixture was stirred at 100 °C for 24 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the unreacted olefin and obtain product 9 in a yield of 78% and a d.r. > 20:1.

[0151] 1 H NMR (400 MHz, Chloroform-d) δ 7.39–7.32 (m, 3H), 7.31–7.26 (m, 2H), 7.24–7.16 (m, 5H), 4.09 (d, J = 2.1 Hz, 1H), 4.01 (d, J = 2.2 Hz, 1H), 3.91 (dt, J = 14.4, 7.4 Hz, 1H), 3.05 (dt, J = 14.1, 7.1 Hz, 1H), 2.96–2.77 (m, 2H), 1.65 (s, 3H), 1.56 (s, 3H), 1.44 (s, 3H).

[0152] 13 C NMR (101 MHz, CDCl3) δ 169.8, 138.5, 138.1, 131.0, 129.1, 128.8, 128.7, 128.5, 126.7, 126.5, 120.3, 64.2, 60.1, 41.2, 34.3, 21.0, 20.7, 14.1.

[0153] HRMS (ESI) calcd. for C 22 H 26 ON + [M + H] + : 320.2009, found: 320.2019.

[0154] Example 13: Preparation of β-lactam 10

[0155]

[0156] Add toluene 1f (2 mL), imine 2d (0.5 mmol, 97.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), di-tert-butyl peroxide (1 mmol, 146.2 mg), and acetonitrile (0.5 mL) into an autoclave. After displacing with carbon monoxide three times, charge 30 atm of carbon monoxide and stir at 130 °C for 12 hours. After the reaction is completed, cool the autoclave to room temperature, release carbon monoxide, and the reaction system can be recovered as the reacted alkene by column chromatography to obtain product 10 with a yield of 75% and d.r. > 20:1.

[0157] 1 H NMR (400 MHz, Chloroform-d) δ 7.44–7.29 (m, 10H), 7.27–7.24 (m, 2H), 7.07 (d, J = 8.1 Hz, 2H), 4.93 (d, J = 2.5 Hz, 1H), 4.26 (d, J = 2.5 Hz, 1H), 2.27 (s, 3H).

[0158] 13 C NMR (101 MHz, CDCl3) δ 165.5, 137.7, 135.2, 135.0, 133.8, 129.7, 129.4, 129.1, 128.7, 128.0, 127.6, 126.0, 117.3, 65.2, 63.8, 21.0.

[0159] HRMS (ESI) calcd. for C 22 H 20 ON + [M+H] + : 314.1539, found: 314.1543.

[0160] Example 14: Preparation of β-lactam 11

[0161]

[0162] Add 1 g (2 mL) of mesitylene, 2a (0.5 mmol, 104.7 mg) of imine, Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), di-tert-butyl peroxide (1 mmol, 146.2 mg), and acetonitrile (0.5 mL) into an autoclave. After displacing with carbon monoxide three times, charge 30 atm of carbon monoxide, and stir at 130 °C for 12 hours. After the reaction is completed, cool the autoclave to room temperature, release carbon monoxide, and the reaction system can be recovered by column chromatography to obtain the reacted olefin and product 11 with a yield of 97% and a d.r. > 20:1.

[0163] 1 H NMR (400 MHz, Chloroform-d) δ 7.41–7.33 (m, 3H), 7.32–7.24 (m, 3H), 7.23–7.18 (m, 4H), 6.88 (s, 1H), 6.67 (s, 2H), 4.24 (d, J = 2.2 Hz, 1H), 4.04–3.89 (m, 2H), 3.12 (dt, J = 13.8, 6.8 Hz, 1H), 2.93 (dt, J = 13.7, 6.8 Hz, 1H), 2.84 (dt, J = 14.4, 7.3 Hz, 1H), 2.26 (s, 6H).

[0164] 13 C NMR (101 MHz, CDCl3) δ 168.7, 138.5, 138.4, 137.7, 134.8, 129.4, 129.2, 128.8, 128.8, 128.7, 126.8, 126.6, 125.3, 65.4, 64.2, 41.3, 34.1, 21.4.

[0165] HRMS (ESI) calcd. for C 25 H 26 ON + [M+H] + : 356.2009, found: 356.2021.

[0166] Example 15: Preparation of β-lactam 12

[0167]

[0168] 1h (2 mL) of m-fluorotoluene, imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), di-tert-butyl peroxide (1 mmol, 146.2 mg), and acetonitrile (0.5 mL) were added to an autoclave. After purging with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 130 °C for 12 h. After the reaction was completed, the autoclave was cooled to room temperature, and the carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 12 in a yield of 85% and a d.r. > 20:1.

[0169] 1 H NMR (400 MHz, Chloroform-d) δ 7.42–7.34 (m, 3H), 7.32–7.18 (m, 8H), 6.98–6.91 (m, 1H), 6.81–6.78 (m, 1H), 6.73 (dt, J=9.7, 2.1 Hz, 1H), 4.20 (d, J=2.2 Hz, 1H), 4.04 (d, J=2.2 Hz, 1H), 3.98 (dt, J=14.4, 7.3 Hz, 1H), 3.12 (dt, J=13.8, 6.7 Hz, 1H), 2.95 (dt, J=13.6, 6.7 Hz, 1H), 2.84 (dt, J=14.0, 7.2 Hz, 1H).

[0170] 13 C NMR (101 MHz, Chloroform-d) δ 167.7, 163.1 (d, J=246.7 Hz), 138.2, 137.3 (d, J=7.6 Hz), 137.2, 130.4 (d, J=8.4 Hz), 129.3, 129.0, 128.9, 128.8, 127.0, 126.5, 123.3 (d, J=3.0 Hz), 114.7 (d, J=19.2 Hz), 114.5 (d, J=20.6 Hz), 64.7 (d, J=2.2 Hz), 64.0, 41.3, 34.1. 19 F NMR (376 MHz, CDCl3) δ -112.5.

[0171] HRMS (ESI) calcd. for C 23 H 21 FON + [M+H] + : 346.1602, found: 346.1615.

[0172] Example 16: Preparation of β-lactam 13

[0173]

[0174] 2-Methylnaphthalene 1i (10 mmol, 1.42 g), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), di-tert-butyl peroxide (1 mmol, 146.2 mg), and acetonitrile (0.5 mL) were added to an autoclave. After three replacements with carbon monoxide, 30 atm of carbon monoxide was charged, and the mixture was stirred at 130 °C for 12 h. After the reaction was completed, the autoclave was cooled to room temperature, and carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 13 in a yield of 79% and a d.r. > 20:1.

[0175] 1 H NMR (400 MHz, Chloroform-d) δ 7.81–7.73 (m, 3H), 7.55 (d, J = 1.7 Hz, 1H), 7.48–7.44 (m, 2H), 7.43–7.35 (m, 3H), 7.32–7.20 (m, 7H), 7.06 (dd, J = 8.5, 1.8 Hz, 1H), 4.31 (d, J = 2.2 Hz, 1H), 4.23 (d, J = 2.2 Hz, 1H), 4.03 (dt, J = 14.4, 7.4 Hz, 1H), 3.15 (dt, J = 13.8, 6.7 Hz, 1H), 2.96 (dt, J = 13.6, 6.7 Hz, 1H), 2.86 (dt, J = 14.4, 7.4 Hz, 1H).

[0176] 13 C NMR (101 MHz, CDCl3) δ 168.4, 138.3, 137.5, 133.5, 132.8, 132.4, 129.3, 128.9, 128.8, 128.8, 128.7, 127.9, 127.7, 126.8, 126.6, 126.4, 126.1, 125.2, 65.5, 64.2, 41.3, 34.1.

[0177] HRMS (ESI) calcd. for C 27 H 24 FON + [M+H] +: 378.1852, found: 378.1866.

[0178] Example 17: Preparation of β-lactam 14

[0179]

[0180] Add 2,5-dimethylthiophene 1j (2 mL), imine 2a (0.5 mmol, 104.7 mg), Pd(CH3CN)2Cl2 (0.025 mmol, 6.5 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.05 mmol, 28.9 mg), pentamethylpiperidine (0.2 mmol, 31.1 mg), di-tert-butyl peroxide (1 mmol, 146.2 mg), and acetonitrile (0.5 mL) into an autoclave. After purging with carbon monoxide three times, charge 30 atm of carbon monoxide and stir at 130 °C for 12 hours. After the reaction is completed, cool the autoclave to room temperature, release the carbon monoxide, and the reaction system can be recovered as the reacted olefin and the product 14 by column chromatography, with a yield of 82% and d.r. > 20:1.

[0181] 1 H NMR (400 MHz, Chloroform-d) δ 7.41–7.32 (m, 3H), 7.30–7.22 (m, 3H), 7.21–7.12 (m, 4H), 6.61–6.58 (m, 2H), 4.26 (d, J = 2.2 Hz, 1H), 4.18 (d, J = 2.2 Hz, 1H), 3.90 (dt, J = 14.2, 7.2 Hz, 1H), 3.09 (dt, J = 14.1, 7.1 Hz, 1H), 2.94–2.81 (m, 2H), 2.44 (s, 3H).

[0182] 13 C NMR (101 MHz, CDCl3) δ 167.6, 139.7, 138.3, 137.1, 134.3, 129.2, 128.8, 128.8, 126.7, 126.5, 125.6, 125.3, 65.1, 60.6, 41.8, 34.3, 15.4.

[0183] HRMS (ESI) calcd. for C 22 H 22 SON + [M+H] + : 348.1417, found: 348.1423.

[0184] Example 18: Preparation of β-lactam 15

[0185]

[0186] Toluene 1f (2 mL), imine 2e (0.5 mmol, 97.7 mg), NiI2 (0.025 mmol, 7.8 mg), n-butyldi(1-adamantyl)phosphine (0.05 mmol, 17.9 mg), 3,5-dimethylpyridine (0.1 mmol, 10.7 mg), and di-tert-butyl peroxide (1 mmol, 146.2 mg) were added to an autoclave. After purging with carbon monoxide three times, 30 atm of carbon monoxide was charged, and the mixture was stirred at 140 °C for 12 h. After the reaction was completed, the autoclave was cooled to room temperature, and the carbon monoxide was released. The reaction system was subjected to column chromatography to recover the reacted olefin and obtain product 15 in a yield of 54% and a d.r. > 20:1.

[0187] 1 H NMR (400 MHz, CDCl3) δ 7.39–7.32 (m, 3H), 7.31–7.21 (m, 8H), 7.20–7.16 (m, 4H), 4.96 (d, J = 14.9 Hz, 1H), 4.33 (d, J = 2.3 Hz, 1H), 4.18 (d, J = 2.3 Hz, 1H), 3.80 (d, J = 14.9 Hz, 1H).

[0188] 13 C NMR (101 MHz, CDCl3) δ 168.2, 137.1, 135.5, 134.9, 129.1, 128.9, 128.8, 128.6, 128.5, 127.7, 127.6, 127.3, 126.5, 65.1, 63.0, 44.5.

[0189] HRMS (ESI) calcd. for C 22 H 19 NNaO + [M+Na] + : 336.1359, found: 336.1363.

[0190] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the broadest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a β-lactam compound, comprising the following steps: a) Using the compound shown in Formula I, CO, and the imine shown in Formula II as raw materials, reacting in a solvent under the action of a transition metal catalyst, a ligand, an oxidant, and an organic base to obtain the β-lactam compound shown in Formula III; The compound shown in Formula I is the compound shown in Formulas I-1 to I-4: Formula I-1; Formula I-2; Formula I-3; Formula I-4; The imine shown in Formula II: Formula II; The β-lactam compound shown in Formula III is the compound shown in Formulas III-1 to III-3: Formula III-1; Formula III-2; Formula III-3; Among them, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are independently selected from hydrogen, a C1-C40 aliphatic group, and an aromatic group within C4-C60; R 7 is selected from hydrogen and a C1-C40 aliphatic group; R 8 , R 9 are independently selected from a C1-C40 aliphatic group and an aromatic group within C4-C60; is an aromatic group within C4 to C60; The transition metal catalyst is selected from compounds containing palladium elements and / or compounds containing nickel elements; The compounds containing palladium elements are selected from one or more of palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium trifluoroacetate, palladium tri-tert-butylphosphine, tetrakis(triphenylphosphine)palladium, triphenylphosphine palladium chloride, bis(acetonitrile)palladium chloride, allyl palladium chloride; The compounds containing nickel elements are selected from one or more of nickel chloride, nickel bromide, nickel iodide, nickel acetate, nickel trifluoroacetate, bis(1,5-cyclooctadiene)nickel; The ligand is a phosphorus-containing phosphine ligand; The phosphorus-containing phosphine ligands are selected from one or more of (±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene, (±)-2,2'-bis(diphenylphosphino)-6,6'-dimethoxy-1,1'-biphenyl, bis(2-diphenylphosphinophenyl)ether, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; The oxidant is selected from one or more of benzoyl peroxide, tert-butyl peroxybenzoate, methyl ethyl ketone peroxide, di-tert-butyl peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, diisopropylbenzene peroxide, 1,1-di-tert-butylperoxycyclohexane.

2. The preparation method according to claim 1, characterized in that, In step a), the pressure of CO is 1 atm to 60 atm.

3. The preparation method according to claim 1, wherein In step a), the molar ratio of the compound shown in I to the imine shown in Formula II is 10:

1.

4. The preparation method according to claim 1, characterized in that, In step a), the dosage of the transition metal catalyst is 0.01% to 10% of the molar amount of the imine shown in Formula II.

5. The preparation method according to claim 1, characterized in that, In step a), the dosage of the ligand is 0.02% to 20% of the molar amount of the imine shown in Formula II.

6. The preparation method according to claim 1, wherein In step a), the dosage of the oxidant is 100% to 300% of the molar amount of the imine shown in Formula II.

7. The preparation method according to claim 1, wherein The organic base in step a) is selected from one or more of triethylamine, N,N-diisopropylethylamine, 2,2,6,6-tetramethylpiperidine, 1,2,2,6,6-pentamethylpiperidine, pyridine, 3,5-dimethylpyridine, 2,4,6-trimethylpyridine, triethylenediamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, N,N-dicyclohexylmethylamine; The dosage of the organic base is 10% to 50% of the molar amount of the imine shown in Formula II.

8. The preparation method according to claim 1, wherein The solvent in step a) is selected from one or more of benzene, chlorobenzene, fluorobenzene, toluene, trifluorotoluene, xylene, mesitylene, acetonitrile, benzonitrile.

9. The preparation method according to claim 1, characterized in that, Step a) is specifically: a1) Add the compound shown in Formula I, the imine shown in Formula II, a transition metal catalyst, a ligand, an oxidant, an organic base, and a solvent into a reaction kettle. After replacing with CO 2 to 4 times, charge CO and carry out the reaction to obtain a reaction mixture; a2) Cool the reaction kettle to room temperature, release CO, subject the reaction mixture to column chromatography, recover the unreacted raw materials, and obtain the β-lactam compound shown in Formula III.

10. The preparation method according to claim 1, characterized in that, In step a), the temperature of the reaction is 60 °C to 160 °C, and the time is 6 h to 30 h.

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