A method for ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation

Abstract

The invention discloses a method for the ring-opening acrylate of tertiary alcohol by iron-catalyzed oxidation, the method comprising the following steps: in a solvent, using (E)-3-benzenesulfonyl methyl acrylate as a reagent, 1-aryl tertiary alcohol as a ring-opening substrate, peroxide as an oxidant, iron as a catalyst, amino acids and derivatives thereof as ligands, catalyzing the C-C single bond cleavage ring-opening acrylate reaction of tertiary alcohol by oxidation, and generating distal acrylate compounds. The method of the invention has the advantages of wide source of catalysts, low cost and environmental protection; wide source of oxidants, low cost; mild reaction conditions, high selectivity; good reaction of non-strained tertiary alcohols; good compatibility of substrate functional groups and wide application range of substrates; and realizing efficient distal functionalization strategy to synthesize acrylate compounds. Under optimized reaction conditions, the yield of the target product after separation can reach 82%.

Description

Technical Field

[0001] This invention belongs to the fields of catalytic synthesis technology and fine chemical synthesis, and relates to a method for iron-catalyzed oxidation of cyclic tertiary alcohols into ring-opening acrylates. Background Art

[0002] Carbon-carbon (CC) σ bonds form the basic framework of organic molecules. Direct functionalization of carbon-carbon bonds is one of the most efficient and economical transformations in synthetic chemistry. Cleavage and recombination of carbon-carbon (CC) bonds are an important technology in industrial crude oil refining, and controlled selective CC bond cleavage under mild reaction conditions has special applications in fine chemical production and laboratory reaction innovation. In the past few decades, transition metal-mediated carbon-carbon bond activation has developed rapidly. In contrast, radical-promoted CC bond cleavage has received relatively less attention. As a complement to transition metal catalysis, controlled radical reactions have become a powerful tool for activating CC bonds. Cyclic tertiary alcohols are favorable precursors for the synthesis of distally substituted alkyl ketones and polycyclic aromatic hydrocarbons (PAHs). Using a ring-opening strategy, direct functionalization of cyclic tertiary alcohols can form CC bonds. Since ring strain significantly promotes the cleavage of cyclic CC bonds, strain energy-driven CC bond activation mainly depends on three- and four-membered rings. Functionalization of CC bonds in unstrained molecules (such as 5- and 6-membered rings) remains challenging. Therefore, the activation of C-C bonds in unstressed rings is of great significance.

[0003] Several challenges remain in current ring-opening reactions of cyclic tertiary alcohols, such as harsh reaction conditions, poor functional group tolerance leading to substrate limitations (X.Wu, C.Zhu*, Chin.J.Chem., 2019, 37, 171-182.), the use of noble metal catalysis, high solvent toxicity, poor atom economy (X.Wu, C.Zhu*, Chin.J.Chem., 2019, 37, 171-182.), applicability only to the oxidative ring-opening of strained cyclic tertiary alcohols, and the difficulty and high cost of preparing the oxidant DMP (Dies Martin periodoyl alkyl ether) (X.Wu, C.Zhu*Chem.Rec., 2018, 18, 587-598.). These factors severely limit the large-scale application of this method. Summary of the Invention

[0004] Objective of the Invention: To address the problems existing in the prior art, this invention provides a method for iron-catalyzed oxidation of cyclic tertiary alcohols to achieve ring-opening acrylate synthesis. This method utilizes a suitable oxidant catalyzed by iron to oxidize cyclic tertiary alcohols, thereby synthesizing distal acrylate compounds. This invention not only provides an economical and applicable new method for the synthesis of acrylate compounds but also solves a series of problems associated with existing non-strained cyclic tertiary alcohol ring-opening reactions, such as demanding reaction conditions, low reaction yields, and the need for noble metal catalysts.

[0005] The method of this invention requires only one reaction step, does not require the participation of acids or bases, and has the advantages of having a wide range of catalyst sources, being inexpensive and environmentally friendly; having inexpensive and low-toxicity oxidants; having a wide range of and stable substrate sources; having mild reaction conditions and good selectivity; having good compatibility of substrate functional groups and a wide range of substrate applicability; being compatible with both strained and non-strained tertiary alcohols, and being able to effectively achieve the ring-opening synthesis of acrylate compounds with distal functionalization from non-strained tertiary alcohols.

[0006] Technical solution: In order to achieve the above objectives, the present invention provides a method for iron-catalyzed oxidation of cyclic tertiary alcohols to open ring-opening acrylates, comprising the following steps: in a solvent, using (E)-3-benzenesulfonyl acrylate as a reagent, 1-aryl cyclic tertiary alcohol as a ring-opening substrate, peroxide as an oxidant, iron as a catalyst, and amino acid or its derivative as a ligand, the method catalyzes the oxidation of cyclic tertiary alcohols to open ring-opening acrylates by C / C bond cleavage, thereby generating acrylate compounds with distally functionalized groups;

[0007] The general formula for the reaction is as follows:

[0008]

[0009] In the formula: R1 represents an alkyl or halogen; R2 represents an alkyl group; n = 3, 4, 5, 6, 7; m = 1, 2, 3, 4, 5.

[0010] In this context, R1 represents a substituent on the aryl group of the cyclotertiary alcohol, R1 is a monosubstituted hydrogen atom on the aromatic ring, and R1 is an alkyl group or a halogen.

[0011] Wherein, R1 represents an alkyl group that is methyl, ethyl, isopropyl, or tert-butyl; and R2 represents an alkyl group that is methyl or n-pentyl.

[0012] Preferably, the alkyl group is generally methyl.

[0013] The iron is selected from ferrous trifluoromethanesulfonate, ferric trifluoromethanesulfonate, ferrous chloride, ferrous acetylacetone, ferric acetylacetone, ferrous 2,2,6,6-tetramethyl-3,5-heptadecyl iron, ferrous 2,2,6,6-tetramethyl-3,5-heptadecyl iron, ferrous 1,3-diphenylpropanedione, ferrous 1,3-diphenylpropanedione, ferrous benzoylacetone, ferric benzoylacetone, ferrous ferric ferric cyanide, ferric ferric cyanide, ferrous acetate, ferrous sulfate, ferrous ammonium sulfate, ferric sulfate, ferrous oxalate, ferric oxalate, ferrous fluoride, ferrous fluoride, ferrous bromide, ferric bromide, ferrous iodide, ferric iodide, ferric chloride, ferric perchlorate (III) hydrate, 1,1'-bis(diphenylphosphine)ferrocene, ferrous phthalocyanine, ferric nitrate, iron oxide, or iron(III) oxide.

[0014] The ligand is selected from S-acetamidomethyl-N-tert-butoxycarbonyl-L-cysteine, N-acetyl-L-cysteine, N,N'-bis(tert-butoxycarbonyl)-L-cysteine, L-serine, D-cysteine, aspartic acid, D-arginine, isoserine, L-threonine, L-tyrosine, BOC-L-proline, BOC-glycine-glycine-glycine, 2-allyl-N-FMOC-L-glycine, BOC-D-phenylalanine, L-cysteine, D-serine, β-thiovaline, D-proline, D-valine, L-proline, L-phenylalanine, N-BOC-N'-triphenylmethyl-L-histidine, L-tryptophan, N-BOC-L-leucine, L-histidine, BOC-L-glutamic acid, L-cysteine, or L-homocysteine.

[0015] The oxidant is selected from potassium persulfate, ammonium persulfate, sodium persulfate, tert-butyl hydroperoxide, hydrogen peroxide, peracetic acid, m-chloroperoxybenzoic acid, benzoyl peroxide, tert-butyl peroxide, di-tert-butyl peroxide, potassium persulfate, diisopropylbenzene peroxide, 2-butanone peroxide, or bis(trimethylsilyl)peroxide.

[0016] Wherein, the solvent is an organic solvent, water, or an aqueous solution of an organic solvent, wherein the organic solvent is selected from methanol, ethanol, ethylene glycol, n-propanol, isopropanol, 1,3-propanediol, glycerol, n-butanol, isobutanol, tert-butanol, trifluoroethanol, 2-methyl-2-butanol, 3-methoxybutanol, sec-butanol, tert-amyl alcohol, 4-methyl-2-pentanol, isoamyl alcohol, 2-pentanol, 3-pentanol, cyclopentanol, n-pentanol, polyethylene glycol 200-10000, acetonitrile, benzonitrile, toluene, acetone, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dicarboxamide, N,N-diacetamide, ethyl acetate, 1,4-dioxane, or tetrahydrofuran; when the solvent is an aqueous solution of an organic solvent, the volume ratio of the organic solvent to water is 1:(0.1-5).

[0017] The molar ratio of the (E)-3-benzenesulfonyl acrylate reagent, 1-arylcyclotertiary alcohol, peroxide, amino acid or its derivative, and iron catalyst is 1:(2-50):(2-50):(0.002-20):(0.001-10).

[0018] The reaction is carried out at a temperature of 25–150°C for a duration of 0.25–48 hours.

[0019] The method of this invention utilizes iron as a catalyst, which is characterized by its high natural abundance, low cost, and low toxicity. Specific amino acid ligands are used to coordinate with the iron catalyst, forming a highly active catalytic species. This catalytic species, in conjunction with the oxidant and solvent, enables the formation of alkyl radicals from cyclic tertiary alcohols to attack (E)-3-benzenesulfonyl acrylate reagents, exhibiting high activity and selectivity. Furthermore, the method of this invention uses mild reagents and a mild environment, overcoming the problem of harsh reaction conditions; it also solves the difficulty of opening unstrained rings; the reaction directly attacks (E)-3-benzenesulfonyl acrylate reagents without pre-functionalization; iron is used as the catalyst, eliminating the need for precious metals, and the effect is significant. The method of this invention has the advantages of widely available, inexpensive, and environmentally friendly catalysts; widely available and inexpensive oxidants; mild reaction conditions and high selectivity; good reaction of unstrained cyclic tertiary alcohols; good substrate functional group compatibility and a wide range of substrate applications; and it achieves an efficient distal functionalization strategy for the synthesis of acrylate compounds. Under optimized reaction conditions, the yield of the target product after separation can reach 82%.

[0020] This invention first oxidizes low-valent iron to high-valent iron using an oxidant, generating a corresponding anionic radical. This anionic radical then abstracts a hydrogen ion from a 1-arylcyclotertiary alcohol, providing an alkoxy radical. This alkoxy radical is generated through C / C bond cleavage. The alkyl radical interacts with (E)-3-benzenesulfonyl methyl acrylate to form a distally functionalized acrylate compound. Finally, the benzenesulfonyl radical loses electrons to gain a benzenesulfonyl cation, while the high-valent iron gains electrons and reverts to low-valent iron, thus completing the catalytic cycle. This invention introduces amino acids or their derivatives to coordinate with the iron catalyst. Practical application has demonstrated excellent results. By introducing amino acids or their derivatives to coordinate with the iron catalyst, a highly active catalytic species is formed, thus overcoming the limitations of existing methods that are only applicable to the oxidative ring-opening of strained cyclotertiary alcohols and suffer from poor functional group tolerance leading to substrate limitations.

[0021] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0022] (1) This invention provides a method for iron-catalyzed ring-opening esterification of cyclic tertiary alcohols by amino acid and its derivative ligands. This method requires only one step, does not require the participation of acid or base, and has the unique advantages of inexpensive, widely available and environmentally friendly catalysts, ligands and oxidants. The reaction conditions are mild and highly selective. The substrates are widely available, stable and easy to handle. The substrate functional groups are compatible and the substrates have a wide range of applications. Experimental results show that the reaction is applicable to non-strained cyclic tertiary alcohols, while there is no good method in the prior art to form highly active catalyst species.

[0023] (2) The method for ring-opening acrylate of cyclotertiary alcohols provided by the present invention is simple, easy and safe. It can directly obtain acrylate compounds with distal functional groups in one step. Under optimized reaction conditions, the yield of the target product after separation can reach 82%. It is a general, efficient, economical and environmentally friendly method for ring-opening acrylate of cyclotertiary alcohols.

[0024] (3) The reason why the method of the present invention can use ideal iron as a catalyst is that it uses amino acid ligands to coordinate with iron catalysts to form highly active catalytic species, so that the reaction can carry out the ring-opening esterification reaction of cyclic tertiary alcohols under very mild conditions, and can achieve ideal catalytic effect, especially for substrates with non-strained rings (especially 5-7 membered rings).

[0025] (4) The distal carbonyl acrylate compounds synthesized by the method of the present invention can be used as drugs or bioactive molecules, and are also important organic intermediates, which are widely used in the synthesis of pharmaceutical intermediates and high value-added fine chemicals. Detailed Implementation

[0026] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0027] Unless otherwise specified, the experimental methods described in the examples are conventional methods; unless otherwise specified, the reagents and materials can be obtained commercially or simply prepared using the methods described below.

[0028] The specific structures of the substrates and products in the embodiments are shown in Table 1.

[0029] Substrate 1a is (E)-3-benzenesulfonyl acrylate (synthesis can be found in compound 5c in the following literature: Stereoselective synthesis of substituted arylsulfonylated 1,3-butadienes and 2-propenoates by sulfonylation of acetylenic ester, Journal of Sulfur Chemistry, 2013, Vol.34, No.5, 532–538).

[0030] Synthesis method of 2b-2be:

[0031]

[0032] Wherein, R3 represents an alkyl group or a halogen, and the alkyl group is methyl, ethyl, isopropyl, or tert-butyl; R4 represents an alkyl group that is methyl or n-pentyl. n = 1, 2, 3, 4, and the above structure corresponds to the raw materials in Table 1.

[0033] In a nitrogen atmosphere, magnesium and anhydrous lithium chloride were added sequentially to a 25 mL reaction flask, followed by the dropwise addition of aryl bromide. After the addition of aryl bromide, heating was initiated using a blower (for approximately 5 minutes). Heating was stopped when tetrahydrofuran (THF) was refluxed or bubbles were produced in the reaction solution, and a large amount of heat was released from the reaction flask. The reaction was allowed to proceed at room temperature until the temperature dropped to room temperature and the magnesium shavings were observed to be almost completely consumed before the corresponding ketone was added. The reaction was then carried out at room temperature for 2 hours. TLC analysis revealed weak fluorescence with tailing (PE:EA from 40:1 to 20:1). The reaction solution was stirred for 2 hours, and quenched by adding saturated ammonium chloride solution (4 mL). After further stirring, the mixture was extracted with ethyl acetate (3 × 20 mL).

[0034]

[0035] In a nitrogen atmosphere, magnesium and anhydrous lithium chloride were added sequentially to a 25 mL reaction flask, followed by the dropwise addition of bromobenzene. After the addition of bromobenzene, the mixture was heated with a blower (for approximately 5 minutes) until tetrahydrofuran (THF) was refluxed or bubbles were produced in the reaction solution, and a large amount of heat was released from the reaction flask. Heating was then stopped, and the reaction was allowed to proceed at room temperature until the temperature dropped to room temperature and the magnesium scraps were observed to be almost completely consumed. Then, tricyclic [5,2,1,0(2,6)]dec-8-one was added. The reaction was then carried out at room temperature for 2 hours. TLC analysis revealed weak fluorescence with tailing (PE:EA from 40:1 to 20:1). The reaction solution was stirred for 2 hours, and quenched by adding saturated ammonium chloride solution (4 mL). After further stirring, the mixture was extracted with ethyl acetate (3 × 20 mL).

[0036]

[0037] In a nitrogen atmosphere, magnesium and anhydrous lithium chloride were added sequentially to a 25 mL reaction flask, followed by the dropwise addition of bromobenzene. After the addition of bromobenzene, the mixture was heated with a blower (for approximately 5 minutes) until tetrahydrofuran (THF) was refluxed or bubbles were produced in the reaction solution, and a large amount of heat was released from the reaction flask. Heating was then stopped, and the reaction was allowed to proceed at room temperature until the temperature dropped to room temperature and the magnesium scraps were observed to be almost completely consumed before adding 1-tetrahydronaphthone. The reaction was then carried out at room temperature for 2 hours. TLC analysis revealed weak fluorescence with tailing (PE:EA from 40:1 to 20:1). The reaction solution was stirred for 2 hours, and quenched by adding saturated ammonium chloride solution (4 mL). After further stirring, the mixture was extracted with ethyl acetate (3 × 20 mL).

[0038]

[0039] In a nitrogen atmosphere, add 2-3 mL of tetrahydrofuran to a 25 mL reaction flask. Over 5 min, add 6 mmol of MeMgBr (3 M) containing tetrahydrofuran to 4 mmol of isopropyl titanate containing tetrahydrofuran. The solution turns yellow; cool to 0 °C, then add 4 mmol of methyl benzoate. React at 0 °C for 30-40 min, then add 6 mmol of EtMgBr (1 M), heat to room temperature, and stir for 1 h. After the reaction is complete, dilute the reaction solution with 16 mL of 10% H₂SO₄ at 0 °C, then extract with ethyl acetate (3 × 20 mL).

[0040] Example 1

[0041] Synthesis of compound 1

[0042] In a nitrogen atmosphere, ferric trifluoromethanesulfonate (0.05 mmol), L-cysteine ​​(0.2 mmol), substrate 1a (0.5 mmol), ethanol (2.0 mL), substrate 2b (1 mmol), and sodium persulfate (4 mmol) were added sequentially to a 25 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was refluxed at 70 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 1 in 79% yield.

[0043] Example 2

[0044] Synthesis of compound 2

[0045] In a 25 mL reaction flask, 0.15 mmol of acetylacetone iron, 0.2 mmol of S-acetamidomethyl-N-tert-butoxycarbonyl-L-cysteine, 0.5 mmol of substrate 1a, 2.0 mL of isopropanol, 1.5 mmol of substrate 2c, and 2 mmol of peracetic acid were added sequentially. After thorough mixing at room temperature, the reaction mixture was refluxed at 80 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:1) yielded product 2 in 72% yield.

[0046] Example 3

[0047] Synthesis of compound 3

[0048] In a 25 mL reaction flask, ferrous acetylacetone (0.02 mmol), L-phenylalanine (0.32 mmol), substrate 1a (0.5 mmol), tert-butanol (2.0 mL), substrate 2d (3 mmol), and di-tert-butyl peroxide (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was refluxed at 25 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:2) yielded product 3 in 71% yield.

[0049] 1 H NMR (400MHz, CDCl3): δ7.73(d,J=7.8Hz,1H),7.63(ddd,J=9.5,2.3,1.7Hz,1H ),7.44(td,J=8.0,5.6Hz,1H),7.28-7.23(m,1H),6.96(dt,J=15.5,7.0Hz,1H) ,5.82(d,J=15.6Hz,1H),3.72(s,3H),2.94(t,J=7.3Hz,2H),2.22(ddd,J=14.5 ,7.3,1.3Hz,2H),1.78-1.71(m,2H),1.55-1.48(m,2H),1.44-1.37ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ198.9 (d, J = 2Hz, 1C), 167.1, 162.8 (d, J = 248Hz, 1C), 149.3, 139.0 (d, J = 6Hz, 1C), 130.2 (d, J = 8Hz ,1C),123.7(d,J=3Hz,1C),121.0,120.0(d,J=22Hz,1C),114.7(d,J=22Hz,1C),51.4,38.5,32.0,28.7,27.8,23.8ppm; 19 F NMR (300MHz, CDCl3): δ-111.9ppm; HRMS (ESI)calcd.for C 16 H 19 FO3H + [M+H + ]m / z 279.1391, found 279.1382; IR(KBr,cm -1 ):ν max 3359,2927,2854,1725,1689,1657,1590,1484,1441,1269,1246,1201,1174,1039,981,876,789,682.

[0050] Example 4

[0051] Synthesis of compound 4

[0052] In a 25 mL reaction flask, ferrous acetate (0.005 mmol), L-proline (1.0 mmol), substrate 1a (0.5 mmol), n-butanol (1.5 mL), and water (2.5 mL), substrate 2e (2 mmol), and hydrogen peroxide (2.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 12 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 40:1) to give product 4 in 65% yield.

[0053] 1 H NMR (400MHz, CDCl3): δ7.98(dd,J=8.8,5.5Hz,2H),7.13(t,J=8.6Hz,2H),6.96(dt,J=15.5,7.0Hz,1H),5.82(d,J=15.6Hz,1H) ,3.72(s,3H),2.94(t,J=7.3Hz,2H),2.22(dd,J=13.7,6.6Hz,2H),1.78-1.70(m,2H),1.55-1.48(m,2H),1.44-1.37ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ198.6, 167.1, 165.6 (d, J = 253Hz, 1C), 149.3, 133.4 (d, J = 3Hz, 1C), 130.6(d,J=9Hz,1C),121.0,115.6(d,J=22Hz,1C),51.4,38.3,32.0,28.8,27.8,23.9ppm; 19 F NMR (300MHz, CDCl3): δ-105.6ppm; HRMS (ESI)calcd.for C 16 H 19 FO3H + [M+H + ]m / z 279.1391, found 279.1381; IR(KBr,cm -1 ):ν max 3353,2923,2852,1723,1684,1597,1506,1437,1411,1270,1231,1200,1156,981,843.

[0054] Example 5

[0055] Synthesis of compound 5

[0056] In a 25 mL reaction flask, ferric bromide (0.1 mmol), isoserine (0.3 mmol), substrate 1a (0.5 mmol), acetone (1.5 mL), and water (0.5 mL), substrate 2f (1.5 mmol), and tert-butyl hydroperoxide (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 100 °C for 2 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with diethyl ether (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, the mixture was separated by column chromatography (petroleum ether: ethyl acetate V / V = 20:1) to give product 5 in 68% yield.

[0057] Example 6

[0058] Synthesis of Compound 6

[0059] In a 25 mL reaction flask, ferric chloride (0.08 mmol), L-threonine (0.4 mmol), substrate 1a (0.5 mmol), n-pentanol (2.0 mL), 2 g (1 mmol), and tert-butyl hydroperoxide (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 40:1) yielded product 6 in 65% yield.

[0060] Example 7

[0061] Synthesis of Compound 7

[0062] In a 25 mL reaction flask under normal nitrogen pressure, ferric nitrate (0.5 mmol), L-tyrosine (0.18 mmol), substrate 1a (0.5 mmol), acetonitrile (2.0 mL), substrate 2h (1.5 mmol), and m-chloroperoxybenzoic acid (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 25 °C for 24 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 40:3) yielded product 7, with a yield of 79%.

[0063] Example 8

[0064] Synthesis of Compound 8

[0065] In a 25 mL reaction flask, ferric fluoride (0.05 mmol), β-thiovaline (0.04 mmol), substrate 1a (0.5 mmol), acetonitrile (1.5 mL), and water (1.5 mL), substrate 2i (1 mmol), and potassium persulfate (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 5 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, the mixture was separated by column chromatography (petroleum ether:ethyl acetate V / V = 20:3) to give product 8 in 65% yield.

[0066] Example 9

[0067] Synthesis of Compound 9

[0068] In a 25 mL reaction flask, 0.2 mmol of ferrous benzoylacetone, 0.02 mmol of N-acetyl-L-cysteine, 0.5 mmol of substrate 1a, 2.0 mL of dichloromethane, 3.5 mmol of substrate 2j, and 2.5 mmol of benzoyl peroxide were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 70 °C for 2 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:1) yielded product 9 in 71% yield.

[0069] Example 10

[0070] Synthesis of Compound 10

[0071] In a 25 mL reaction flask under normal nitrogen pressure, ferrous bromide (0.1 mmol), D-proline (0.3 mmol), substrate 1a (0.5 mmol), N,N-diformamide (1.5 mL), and water (0.5 mL), substrate 2k (2 mmol), and sodium persulfate (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 8 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The combined organic phases were washed with water (5 mL × 3), and the organic phase was collected. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (petroleum ether: diethyl ether V / V = 20:3) to give product 10 in 66% yield.

[0072] 1H NMR (400MHz, CDCl3): δ7.95(d,J=7.2Hz,0.6H),7.81(d,J=8.6Hz,1.4H),7.60( d,J=8.6Hz,1.4H),7.46(t,J=7.6Hz,0.6H),6.99-6.92(m,1H),5.82(d,J=15.6 Hz,1H),3.72(s,3H),2.97(t,J=7.3Hz,1H),2.93(t,J=7.3Hz,1H),2.22(dd,J= 14.3,7.1Hz,2H),1.77-1.70(m,2H),1.55-1.47(m,2H),1.43-1.37ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ199.1,167.1,149.3,131.9,129.5,128.6,128.0,121.0,51.4,38.3,32.0,28.7,27.8,23.8ppm; HRMS(ESI)calcd.for C 16 H 19 BrO3H + [M+H + ]m / z 339.0591, found 339.0586; IR(KBr,cm -1 ):ν max 3357,2927,2853,1722,1686,1659,1586,1435,1270,1200,1176,1071,1038,1009,981,814,736,701.

[0073] Example 11

[0074] Synthesis of Compound 11

[0075] In a 25 mL reaction flask under normal nitrogen pressure, ferric iodide (0.05 mmol), aspartic acid (0.1 mmol), substrate 1a (0.5 mmol), 1,3-propanediol (4.0 mL), substrate 2l (1 mmol), and potassium persulfate (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 25 °C for 48 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The combined organic phases were washed with water (5 mL × 3), and the organic phase was collected. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (petroleum ether: diethyl ether V / V = 10:1) to give product 11 in 78% yield.

[0076] 1H NMR (400MHz, CDCl3): δ7.60(d,J=7.6Hz,1H),7.36(t,J=6.8Hz,1H),7.25(t,J=7.5Hz,2H),6.96(dt,J=15.6,7.0Hz,1H),5.82(dt,J=15.6,1 .5Hz,1H),3.72(s,3H),2.88(t,J=7.3Hz,2H),2.48(s,3H),2.24-2.19(m,2H),1.75-1.68(m,2H),1.54-1.47(m,2H),1.42-1.35ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ204.5,167.1,149.4,138.1,137.8,131.9,131.1,128.2, 125.6,121.0,51.4,41.4,32.0,28.7,27.8,24.1,21.2ppm; HRMS(ESI)calcd.for C 17 H 22 O3H + [M+H + ]m / z275.1642, found 275.1633; IR(KBr,cm -1 ):ν max 3359,3190,2924,2853,1723,1684,1602,1435,1270,1198,1039,980,857,735.

[0077] Example 12

[0078] Synthesis of Compound 12

[0079] In a 25 mL reaction flask, ferrous fluoride (0.02 mmol), BOC-glycine-glycine-glycine (0.2 mmol), substrate 1a (0.5 mmol), dichloromethane (2.0 mL), substrate 2m (1 mmol), and 2-butanone peroxide (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 25 °C for 12 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:3) yielded product 12 in 82% yield.

[0080] 1H NMR (400MHz, CDCl3): δ7.76-7.73(m,2H),7.38-7.26(m,2H),7.00-6.93(m,1H),5.82(d,J=15.6Hz,1H),3.72(s,3H),2.95 (t,J=7.3Hz,2H),2.41(s,3H),2.22(dd,J=13.9,7.0Hz,2H),1.78-1.70(m,2H),1.55-1.48(m,2H),1.44-1.37ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ200.5,167.1,149.4,138.3,137.0,133.7,128.5,128.4, 125.2,121.0,51.4,38.4,32.0,28.8,27.9,24.0,21.4ppm; HRMS(ESI)calcd.for C 17 H 22 O3H + [M+H + ]m / z275.1642, found 275.1631; IR(KBr,cm -1 ):ν max 2930,2858,1727,1686,1460,1271,1124,1073,1040,743.

[0081] Example 13

[0082] Synthesis of Compound 13

[0083] In a 25 mL reaction flask, ferrous ferricyanide (0.001 mmol), L-serine (0.1 mmol), substrate 1a (0.5 mmol), dimethyl sulfoxide (2.0 mL), substrate 2n (1 mmol), and dicumyl peroxide (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether: diethyl ether V / V = 10:7) yielded product 13 in 79% yield.

[0084] 1H NMR (400MHz, CDCl3): δ7.85(d,J=8.1Hz,2H),7.25(d,J=7.5Hz,2H),6.96(dt,J=15.5,7.0Hz,1H),5.82(d,J=15.6Hz,1H),3.72(s, 3H),2.94(t,J=7.3Hz,2H),2.41(s,3H),2.22(dd,J=13.6,6.6Hz,2H),1.77-1.70(m,2H),1.55-1.47(m,2H),1.44-1.36ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ199.9,167.1,149.4,143.7,134.5,129.2,128.1,121.0,51.4,38.3,32.0,28.8,27.9,24.1,21.6ppm; HRMS(ESI)calcd.for C 17 H 22 O3H + [M+H + ]m / z275.1642, found 275.1640; IR(KBr,cm -1 ):ν max 3359,2926,2854,1725,1683,1609,1435,1270,1180,1036,978,810,719.

[0085] Example 14

[0086] Synthesis of Compound 14

[0087] In a 25 mL reaction flask, ferric ferricyanide (0.05 mmol), BOC-L-proline (0.002 mmol), substrate 1a (0.5 mmol), acetonitrile (1.0 mL), and water (1.0 mL) were added sequentially. Substrate 2o (1.5 mmol) and ammonium persulfate (1.5 mmol) were then added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 2 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, the mixture was separated by column chromatography (petroleum ether:ethyl acetate V / V = 20:1) to give product 14 in 80% yield.

[0088] Example 15

[0089] Synthesis of Compound 15

[0090] In a 25 mL reaction flask under normal nitrogen pressure, ferrous phthalocyanine (0.02 mmol), L-histidine (0.15 mmol), substrate 1a (0.5 mmol), 1,2-dichloroethane (2.0 mL), substrate 2p (2.5 mmol), and benzoyl tert-butyl peroxide (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 70 °C for 6 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether:ethyl acetate V / V = 40:1) to give product 15 in 69% yield.

[0091] Example 16

[0092] Synthesis of Compound 16

[0093] In a 25 mL reaction flask, ferrous trifluoromethanesulfonate (0.05 mmol), L-cysteine ​​(0.04 mmol), substrate 1a (0.5 mmol), ethyl acetate (2.0 mL), substrate 2q (1.5 mmol), and potassium persulfate (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 90 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 40:7) yielded product 16 in 76% yield.

[0094] Example 17

[0095] Synthesis of Compound 17

[0096] In a 25 mL reaction flask, 0.04 mmol of 1,3-diphenylpropanedione, 0.1 mmol of BOC-D-phenylalanine, 0.5 mmol of substrate 1a, 2.0 mL of N,N-diacetamide, 1.5 mmol of substrate 2r, and 1.5 mmol of hydrogen peroxide were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 90 °C for 6 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 17 in 62% yield.

[0097] Example 18

[0098] Synthesis of Compound 18

[0099] In a 25 mL reaction flask, ferrous oxalate (0.1 mmol), D-valine (0.15 mmol), substrate 1a (0.5 mmol), 1,4-dioxane (2.0 mL), substrate 2s (1 mmol), and hydrogen peroxide (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 10 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:3) yielded product 18 in 59% yield.

[0100] Example 19

[0101] Synthesis of Compound 19

[0102] In a 25 mL reaction flask, ferrous sulfate (0.05 mmol), BOC-L-proline (0.1 mmol), substrate 1a (0.5 mmol), toluene (2.0 mL), substrate 2t (1.5 mmol), and sodium persulfate (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 12 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:5) yielded product 19, with a yield of 49%.

[0103] Example 20

[0104] Synthesis of Compound 20

[0105] In a 25 mL reaction flask, ferrous 1,3-diphenylpropanedione (0.08 mmol), BOC-L-glutamic acid (0.4 mmol), substrate 1a (0.5 mmol), tetrahydrofuran (1.0 mL), and water (1.0 mL) were added sequentially. Substrate 2u (2 mmol) and m-chloroperoxybenzoic acid (1 mmol) were then added. After thorough mixing at room temperature, the reaction mixture was reacted at 120 °C for 2 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with diethyl ether (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, column chromatography (petroleum ether:ethyl acetate V / V = 20:3) was performed to obtain product 20 in 69% yield.

[0106] 1H NMR (400MHz, CDCl3): δ7.95(d,J=7.1Hz,2H),7.55(t,J=7.4Hz,2H),7.46(t,J=7.6Hz,2H),6.86(dd,J=15.7,8.0Hz,1H),5.78(dd,J=1 5.7,1.0Hz,1H),3.72(s,3H),2.96(t,J=7.3,2H),2.35-2.29(m,1H),1.76-1.68(m,2H),1.45-1.34(m,4H),1.05ppm(d,J=6.7Hz,3H); 13 C NMR (100MHz, CDCl3): δ200.2,167.3,154.7,137.0,133.0,128.5,128.0,119.3,51.4,38.4,36.4,35.8,26.9,24.2,19.4ppm; HRMS(ESI)calcd.for C 17 H 22 O3H + [M+H + ]m / z 275.1642, found275.1631; IR(KBr,cm -1 ):ν max 3358,2928,2852,1722,1686,1657,1448,1435,1354,1274,1199,986,753,692.

[0107] Example 21

[0108] Synthesis of Compound 21

[0109] In a 25 mL reaction flask, ferrous chloride (0.05 mmol), BOC-D-phenylalanine (0.03 mmol), substrate 1a (0.5 mmol), sec-butanol (2.0 mL), substrate 2v (1 mmol), and potassium persulfate (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 24 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 21 in 56% yield.

[0110] 1H NMR (400MHz, CDCl3): δ7.95(d,J=7.3Hz,2H),7.56(t,J=7.3Hz,1H),7.46(t,J=7.6Hz,2H),6.97(dt,J=15.4,7.0Hz,1H),5.83(d,J =15.6Hz,1H),3.72(s,3H),3.00-2.94(m,2H),2.28-2.20(m,2H),1.84-1.77(m,1H),1.61-1.48(m,4H),0.95ppm(d,J=5.9Hz,3H); 13 C NMR (100MHz, CDCl3): δ200.5,167.1,149.6,136.9,133.0,128.6,128.0,120.9,51.4,36.1,35.0,32.1,30.9,29.7,19.2ppm; HRMS(ESI)calcd.for C 17 H 22 O3H + [M+H + ]m / z 275.1642, found 275.1635; IR(KBr,cm -1 ):ν max 3353,2921,2851,1723,1685,1658,1449,1272,1211,1177,986,741,691.

[0111] Example 22

[0112] Synthesis of Compound 22

[0113] In a 25 mL reaction flask, 0.1 mmol of ferrous ammonium sulfate, 0.4 mmol of N,N'-bis(tert-butyloxycarbonyl)-L-cysteine, 0.5 mmol of substrate 1a, 2.0 mL of ethylene glycol, 1.5 mmol of substrate 2w, and 1 mmol of di-tert-butyl peroxide were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 70 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:1) yielded product 22 in 68% yield.

[0114] 1H NMR (400MHz, CDCl3): δ7.94(d,J=7.2Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.6Hz,2H),6.9 6(dt,J=15.6,6.9Hz,1H),5.81(d,J=15.6Hz,1H),3.72(s,3H),2.92(dd,J=16.1,5.9Hz,1.33H) ,2.78(dd,J=16.0,7.7Hz,0.67H),2.25-2.16(m,2H),1.82-1.74(m,0.67H),1.71-1.63(m,1.33 H),1.55-1.47(m,1.5H),1.45-1.38(m,1.5H),0.96(d,J=6.7Hz,2H),0.93ppm(d,J=6.7Hz,1H); 13 C NMR (100MHz, CDCl3): δ200.1,167.1,149.4,137.3,132.9,128.6,128.0,121.0,51.4,45.8,36.5,32.3,29.5,25.5,19.9ppm; HRMS(ESI)calcd.for C 17 H 22 O3H + [M+H + ]m / z 275.1642, found 275.1637; IR(KBr,cm -1 ):ν max 2925,1724,1686,1449,1437,1318,1272,1210,1179,1039,980,751,691.

[0115] Example 23

[0116] Synthesis of Compound 23

[0117] In a 25 mL reaction flask, ferric perchlorate(III) hydrate (0.05 mmol), L-tryptophan (0.5 mmol), substrate 1a (0.5 mmol), glycerol (2.0 mL), substrate 2x (1.5 mmol), and 2-butanone peroxide (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 110 °C for 2 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 23 in 60% yield.

[0118] Example 24

[0119] Synthesis of Compound 24

[0120] In a 25 mL reaction flask, ferric oxide (0.2 mmol), L-homocysteine ​​(0.1 mmol), substrate 1a (0.5 mmol), cyclopentanol (2.0 mL), substrate 2y (1.5 mmol), and 2-butanone peroxide (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 6 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The combined organic phases were washed with water (5 mL × 3), and the organic phase was collected. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 10:4) to give product 24 in 65% yield.

[0121] 1 H NMR (400MHz, CDCl3): δ7.95 (d, J = 7.2Hz, 2H), 7.57 (t, J = 7.4Hz, 1H), 7.47 (t, J = 7.6Hz, 2H), 7.04 (dt, J = 15. 6,6.8Hz,1H),5.90(d,J=15.7Hz,1H),3.72(s,3H),3.15(t,J=7.3Hz,2H),2.66ppm(qd,J=7.2,1.4Hz,2H); 13 C NMR (100MHz, CDCl3): δ198.1,166.9,147.7,136.5,133.3,128.7,127.9,121.7,51.5,36.6,26.3ppm; HRMS(ESI)calcd.forC 13 H 14 O3H + [M+H + ]m / z 219.1016,found219.1009; IR(KBr,cm -1 ):ν max 3350,2950,2921,2850,1718,1683,1655,1447,1435,1373,1267,1010,971,863,744,701,688,568.

[0122] Example 25

[0123] Synthesis of Compound 25

[0124] Benzoyl acetone iron (0.05 mmol), N-BOC-L-leucine (0.1 mmol), substrate 1a (0.5 mmol), tert-amyl alcohol (1.5 mL), and water (0.5 mL) were added sequentially to a 25 mL reaction flask in air. Substrate 2z (1 mmol) and hydrogen peroxide (2 mmol) were then added. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 24 h. At the end of the reaction, ammonia (0.5 mL, 25%) was added, and the mixture was stirred for 1 h. Immediately afterwards, 5 mL of water was added, and the mixture was extracted with diethyl ether (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 10:3) to give product 25 in 61% yield.

[0125] 1 H NMR (400MHz, CDCl3): δ7.94(d,J=7.1Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.6Hz,2H),6.98(dt,J=15.6,6.9Hz,1H),5 .86(dt,J=15.7,1.5Hz,1H),3.72(s,3H),3.00(t,J=7.2Hz,2H),2.31(ddd,J=8.4,7.4,1.5Hz,2H),1.96-1.89ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ199.5,166.9,148.5,136.8,133.1,128.6,127.9,121.6,51.4,37.4,31.5,22.3ppm; HRMS(ESI)calcd.for C 14 H 16 O3H + [M+H + ]m / z 233.1172, found 233.1166; IR(KBr,cm -1 ):ν max 3504,2948,1723,1679,1597,1447,1321,1276,1202,1041,978,755,737,692,657,568.

[0126] Example 26

[0127] Synthesis of Compound 26

[0128] In a 25 mL reaction flask, ferric oxalate (0.05 mmol), 2-allyl-N-FMOC-L-glycine (0.08 mmol), substrate 1a (0.5 mmol), tert-amyl alcohol (2.0 mL), substrate 2ba (1 mmol), and bis(trimethylsilyl)peroxide (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 40 °C for 6 h. Upon completion of the reaction, direct chromatography (petroleum ether:diethyl ether V / V = 10:3) yielded product 26 in 71% yield.

[0129] 1 H NMR (400MHz, CDCl3): δ7.95(d,J=7.1Hz,2H),7.56(t,J=7.4Hz,1H),7.46(t,J=7.5Hz,2H),6.97(dt,J=15.6,7.0Hz,1H),5.84(dt,J =15.6,1.5Hz,1H),3.72(s,3H),2.99(t,J=7.2Hz,2H),2.27(ddd,J=14.7,7.3,1.5Hz,2H),1.82-1.74(m,2H),1.60-1.52ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ199.9,167.1,149.0,136.9,133.0,128.6,128.0,121.2,51.4,38.2,32.1,27.7,23.7ppm; HRMS(ESI)calcd.for C 15 H 18 O3NH4 + [M+NH4 + ]m / z 264.1594, found 264.1588; IR(KBr,cm -1 ):ν max 3357,2925,2852,1723,1687,1656,1449,1272,1200,1037,978,752,692.

[0130] Example 27

[0131] Synthesis of Compound 27

[0132] In a 25 mL reaction flask, ferrous 2,2,6,6-tetramethyl-3,5-heptadecane (0.05 mmol), D-serine (0.1 mmol), substrate 1a (0.5 mmol), isobutanol (1.5 mL), and water (0.5 mL), substrate 2bb (3 mmol), and ammonium persulfate (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 70 °C for 6 h. At the end of the reaction, ammonia (0.5 mL, 25%) was added, and the mixture was stirred for 1 h. Immediately afterwards, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 10:5) to give product 27 in 81% yield.

[0133] Example 28

[0134] Synthesis of Compound 28

[0135] In a 25 mL reaction flask, ferrous iodide (0.05 mmol), D-arginine (0.1 mmol), substrate 1a (0.5 mmol), benzonitrile (2 mL), substrate 2bc (1 mmol), and di-tert-butyl peroxide (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 4 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 28 in 60% yield.

[0136] Example 29

[0137] Synthesis of Compound 29

[0138] In a 25 mL reaction flask, 1,1'-bis(diphenylphosphine)ferrocene (0.02 mmol), L-cysteine ​​(0.1 mmol), substrate 1a (0.5 mmol), N,N-dicarboxamide (1.5 mL), and water (0.5 mL), substrate 2bd (1 mmol), and sodium persulfate (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 25 °C for 48 h. At the end of the reaction, ammonia (0.5 mL, 25%) was added, and the mixture was stirred for 1 h. Immediately afterwards, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, column chromatography (petroleum ether:ethyl acetate V / V = 20:3) was performed to obtain product 29, with a yield of 46%. The low yield in this example may be due to the presence of an additional benzylic site, indicating competition between benzylic oxidation and ring-opening processes.

[0139] 1H NMR (400MHz, CDCl3): δ7.79(d,J=7.1Hz,2H),7.59(t,J=7.4Hz,1H),7.46(t, J=7.7Hz,2H),7.42(dd,J=7.3,1.4Hz,1H),7.35(d,J=4.3Hz,1H),7.32-7.28( m,2H),6.88(dt,J=15.6,6.9Hz,1H),5.76(dt,J=15.6,1.5Hz,1H),3.70(s,3H ),2.68(t,J=7.7Hz,2H),2.16(dd,J=13.6,6.8Hz,2H),1.76-1.68ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ198.6,167.0,148.9,140.8,138.4,137.8,133.2,130.3,130.2 ,130.1,128.7,128.4,125.4,121.2,51.4,32.8,31.8,29.9ppm; HRMS(ESI)calcd.for C 20 H 20 O3H + [M+H + ]m / z 309.1485, found 309.1478; IR(KBr,cm -1 ):ν max 3358,2923,2851,1725,1662,1448,1270,1196,929,761,705,641.

[0140] Example 30

[0141] Synthesis of Compound 30

[0142] In a 25 mL reaction flask, 0.1 mmol of 2,2,6,6-tetramethyl-3,5-heptadecyl iron, 0.2 mmol of N-BOC-N'-triphenylmethyl-L-histidine, 0.5 mmol of substrate 1a, 2.0 mL of ethanol, 1 mmol of substrate 2be, and 1 mmol of tert-butyl hydroperoxide were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 12 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 40:7) yielded product 30 in 62% yield.

[0143] The structural formulas of the raw materials and products in Examples 1-30 and the corresponding experimental results are shown in Table 1 below:

[0144]

[0145] Table 1

[0146]

[0147]

[0148]

[0149]

[0150] Example 31

[0151] Example 31 uses the same method as Example 12, except that the molar ratio of (E)-3-benzenesulfonyl acrylate reagent, cyclotertiary alcohol compound, peroxide, amino acid derivative, and iron catalyst is 1:2:2:0.002:0.001.

[0152] Example 32

[0153] Example 32 uses the same method as Example 12, except that the molar ratio of (E)-3-benzenesulfonyl acrylate reagent, cyclotertiary alcohol compound, peroxide, amino acid derivative, and iron catalyst is 1:50:50:20:10.

[0154] Example 33

[0155] Example 33 uses the same method as Example 12, except that the molar ratio of (E)-3-benzenesulfonyl acrylate reagent, cyclotertiary alcohol compound, peroxide, amino acid derivative, and iron catalyst is 1:30:30:20:10.

[0156] Example 34

[0157] Example 34 uses the same method as Example 12, except that the solvent is entirely water and the total volume remains unchanged.

[0158] Comparative Example 1

[0159] The method of Comparative Example 1 is the same as that of Example 12, except that no iron catalyst is added and the yield of the target product is 0.

[0160] Comparative Example 2

[0161] Comparative Example 2 uses the same method as Example 12, except that no amino acid ligands are added, which greatly reduces the reaction yield to less than 30%.

[0162] Comparative Example 3

[0163] Comparative Example 3 uses the same method as Example 12, except that no oxidant is added and the yield of the target product is 0.

[0164] Comparative Example 4

[0165] Comparative Example 4 followed the same method as Example 12, except that it used a non-amino acid ligand, 1,10-phenanthroline, resulting in a yield of only 6%. Furthermore, other phosphorus-containing ligands, such as ethyldiphenylphosphine or diethylphenylphosphine, or nitrogen-containing ligands, such as neocopper reagent, also yielded poor results and very low yields.

[0166] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the invention. Theoretically, various iron catalysts in this invention can coordinate with amino acid ligands to form highly active iron catalyst species, thereby facilitating the smooth progress of the reaction. Amino acid ligands are promoters for the ring-opening acrylate reaction of cyclic tertiary alcohols, utilizing their ability to coordinate with iron. Theoretically, various amino acids and their derivatives all possess coordination functions and should achieve similar effects. Various peroxides are oxidizing agents. The reaction on cyclic tertiary alcohols involves the activation of carbon-carbon bonds, while the various substituents on the aromatic ring affect the electron cloud density within the ring and the steric hindrance during the reaction. That is, the modification of substituents only affects the reaction to a certain extent and does not play a decisive role in the occurrence of the reaction. Anyone skilled in the art will readily understand that, without departing from the scope of the technical solution of this invention, variations or modifications can be made to obtain corresponding embodiments. For example, the substituents can be replaced, changed, or modified within the scope of this invention to achieve the method of this invention. Any modifications, alterations, or equivalent changes made to the above embodiments based on the present invention without departing from the spirit of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for the ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation, characterized in that: The method comprises the following steps: in a solvent, using (E)-3-benzenesulfonyl methyl acrylate as a reagent, 1-aryl tertiary cyclic alcohol as a ring-opening substrate, peroxide as an oxidant, iron as a catalyst, and amino acid or its derivative as a ligand, catalyzing the CC single bond cleavage of the tertiary cyclic alcohol to form a ring-opening acrylate esterification reaction, thereby generating a remote functionalized acrylate compound; The general reaction formula is as follows: ； Wherein: R1 represents H or alkyl or halogen; R2 represents H or alkyl; n = 3,4,5,6,7; m = 1,2,3,4,5; Wherein, the iron is selected from ferrous trifluoromethanesulfonate, ferrous trifluoromethanesulfonate, ferrous chloride, ferrous acetylacetonate, ferrous acetylacetonate, ferrous 2,2,6,6-tetramethyl-3,5-heptanedione, ferrous 2,2,6,6-tetramethyl-3,5-heptanedione, ferrous 1,3-diphenylpropanedione, ferrous benzoylacetonate, ferrous benzoylacetonate, ferrous ferrocyanide, ferrous ferrocyanide, ferrous acetate, ferrous sulfate, ammonium ferrous sulfate, ferrous sulfate, ferrous oxalate, ferrous oxalate, ferrous fluoride, ferrous fluoride, ferrous bromide, ferrous bromide, ferrous iodide, ferric chloride, iron (III) perchlorate hydrate, 1,1'-bis(diphenylphosphino)ferrocene, ferrous phthalocyanine, ferric nitrate, ferric oxide or ferric oxide; wherein, the ligand is selected from S-acetamido methyl-N-tert-butyloxycarbonyl-L-cysteine, N-acetyl-L-cysteine, N,N'-bis(tert-butyloxycarbonyl)-L-cystine, L-serine, D-cystine, aspartic acid, D-arginine, isoserine, L-threonine, L-tyrosine, BOC-L-proline, BOC-glycine-glycine-glycine, 2-allyl-N-FMOC-L-glycine, BOC-D-phenylalanine, L-cysteine, D-serine, β-thiovaline, D-proline, D-valine, L-proline, L-phenylalanine, N-BOC-N'-trityl-L-histidine, L-tryptophan, N-BOC-L-leucine, L-histidine, BOC-L-glutamate, L-cystine or L-homocysteine.

2. The method for ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation according to claim 1, characterized in that: R1 represents a substituent on the aromatic group in the tertiary cyclic alcohol, R1 replaces the hydrogen on the aromatic ring, and R1 is an alkyl group or a halogen.

3. The method for ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation according to claim 2, characterized in that: The alkyl group represented by R1 is methyl, ethyl, isopropyl or tert-butyl; the alkyl group represented by R2 is methyl or n-pentyl.

4. The method for ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation according to claim 1, characterized in that: The oxidant is selected from potassium persulfate, ammonium persulfate, sodium persulfate, tert-butyl hydroperoxide, hydrogen peroxide, peracetic acid, m-chloroperbenzoic acid, benzoyl peroxide, tert-butyl benzoyl peroxide, di-tert-butyl peroxide, potassium monopersulfate, diisopropylbenzene peroxide, 2-methyl ethyl peroxide or bis(trimethylsilyl)peroxide.

5. The method for ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation according to claim 1, characterized in that: The solvent is an organic solvent, water or an aqueous solution of an organic solvent, and the organic solvent is selected from methanol, ethanol, ethylene glycol, n-propanol, isopropanol, 1,3-propylene glycol, glycerol, n-butanol, isobutanol, tert-butanol, trifluoroethanol, 2-methyl-2-butanol, 3-methoxybutanol, sec-butanol, tert-amyl alcohol, 4-methyl-2-pentanol, isopentanol, 2-pentanol, 3-pentanol, cyclopentanol, n-pentanol, polyethylene glycol 200-10000, acetonitrile, benzonitrile, toluene, acetone, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, N,N-diformamide, N,N-diacetamide, ethyl acetate, 1,4-dioxane or tetrahydrofuran; when the solvent is an aqueous solution of an organic solvent, the volume ratio of the organic solvent to water is 1:(0.1-5).

6. The method for ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation according to claim 1, characterized in that: The molar ratio of the (E)-3-benzenesulfonyl methyl acrylate reagent, 1-aryl tertiary alcohol, peroxide, amino acid or its derivative, and iron catalyst is 1:(2-50):(2-50):(0.002-20):(0.001-10).

7. The method for ring-opening acrylic esterification of tertiary cyclic alcohols by iron-catalyzed oxidation according to claim 1, characterized in that: The reaction temperature is 25 to 150° C. and the reaction time is 0.25 to 48 hours.

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