Method for photocatalytic synthesis of N, O-spiroketal amine derivative

Abstract

The invention discloses a method for photocatalytic synthesis of N, O-spiroketal amine derivatives, and belongs to the technical field of organic synthesis. Aiming at the problems of harsh conditions, small substrate range and the like of the existing synthesis method, the invention provides the method for photocatalytic synthesis of the N, O-spiroketal amine derivative, and the method comprises the following steps: mixing a 1-alkenyloxy ring compound, a 1-azido vinyl ring compound, a photocatalyst, alkali and an organic solvent, and carrying out photocatalytic reaction to obtain the N, O-spiroketal amine derivative. The 1, 1, 2-trifunctional reaction of the N-alkenyloxy onium salt and the vinyl azide is successfully realized through a strategy of efficiently constructing an N, O-spiroketal amine skeleton under the catalysis of photooxidation reduction, and the method is simple and convenient to operate and high in yield. The method is mild in reaction condition, stable in process condition, high in product yield, easy in product purification, wide in substrate range, good in functional group tolerance, low in production cost and suitable for large-scale production.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for photocatalytic synthesis of N,O-spiroketalamine derivatives. Background Art

[0002] N,O-spiroketalamine and its derivatives constitute a common substructure in many bioactive compounds and are the core of natural or synthetic products with important biological activities. The skeletonal azo-oxa-spirobicyclic structural motif is a specific spiroheterocyclic unit embedded in natural and synthetic bioactive molecules and has potential pharmaceutical activities. For example, active molecules such as the calcium channel inhibitor Lycoplanine A of lycopodium alkaloids, the glycosidase inhibitor spironucleoside, the herbicide Hydantocidine, the bacteriostatic agent Armeniaspirol A, the human colon cancer cell inhibitor Marineosins, and the anti-proliferative agent Penicitrinine A of various tumor cells (Org. Lett. 2017, 19, 4668 - 4671; Chem. Eur. J. 1999, 5, 2866 - 2876; Eur. J. Org. Chem. 1999, 1999, 1269 - 1274; Tetrahedron. 1995, 51, 6669 - 6678; J. Nat. Prod. 2019, 82, 318 - 323; Org. Biomol. Chem. 2013, 11, 2936 - 2938; Mar Drugs. 2015, 13, 4733 - 4753). In addition, the N,O-spiroketalamine skeleton has a unique three-dimensional rigid conformation. Its spirocyclic scaffold can effectively fill three-dimensional space without additional linking modules and has the ability to regulate the physicochemical properties and pharmacokinetic properties of drug molecules. Its structural general formula is as follows.

[0003]

[0004] The classical construction methods of the N,O-spiroketalamine skeleton structure can be mainly divided into two types, namely: (1) Monocyclization of cyclic substrates to construct the spirocyclic skeleton, such as synthesizing the N,O-spiroketalamine skeleton through amidoallylation of imide derivatives, constructing the N,O-spiroketalamine skeleton through an asymmetric catalytic cyclopropanation-rearrangement (CP-RA) strategy, synthesizing N,O-spiroketalamine and spiroketal derivatives through a [3 + 2] cycloaddition reaction of exocyclic enamine / enol ether catalyzed by chiral copper with 1,4-benzoquinone ester, through metal Ir and Synthesis of N,O-spiroacetalamine derivatives by acid co-catalyzed asymmetric [4+2] cycloaddition of cyclic enamides with 2-(1-hydroxyallyl)phenols, etc. (Org. Lett. 2015, 17, 5846-5849; Angew. Chem. Int. Ed. 2020, 59, 18964-18969; Chem. Eur. J. 2024, 30, e202401062; Chem. Commun. 2024, 60, 1448-1451); (2) Construction of spirocyclic skeletons by linear substrate bicyclization, such as construction of N,O-spiroacetalamine skeletons through highly efficient asymmetric cascade reactions of keto esters with alkynols and alkynamides, construction of spirocyclic skeletons through highly efficient asymmetric cascade reactions of racemic 2-(1-hydroxyallyl)phenols with alkynols / alkynamides by gold and iridium tandem catalytic systems, synthesis of N,O-spiroacetalamine derivatives by metal-free, visible light-driven, thiol-assisted amide radical addition / cyclization reactions of 2-acylaminoalkynols with oxygen as the only terminal oxidant, etc. (Angew. Chem. Int. Ed. 2016, 55, 6075-6078; Angew. Chem. Int. Ed. 2022, 61, e202203661; Org. Lett. 2024, 26, 298-303).

[0005] However, for the catalytic synthesis of N,O-spiroacetalamines with multiple substitutions and complex structures, the synthetic routes are limited. Most of the existing synthetic methods have problems such as harsh reaction conditions, multi-step catalytic processes, expensive metal catalysts, limited substrate structures, and single reaction modes. Therefore, there is an urgent need to develop a novel, general, and effective catalytic method to prepare N,O-spiroacetalamine derivatives with complex and diverse structures from simple and readily available linear substrates under mild and environmentally friendly conditions. Summary of the Invention

[0006] The object of the present invention is to provide a method for synthesizing N,O-spiroacetalamine derivatives with simple operation, mild conditions, high reaction efficiency, wide substrate scope, and good functional group tolerance in view of the problems existing in the existing methods for preparing N,O-spiroacetalamine derivatives.

[0007] To achieve the above object, the present invention provides a method for photocatalytic synthesis of N,O-spiroacetalamine derivatives, which comprises the following steps: mixing a 1-alkenyloxycyclic compound represented by formula I, a 1-azidoethenylcyclic compound represented by formula II, a photocatalyst, a base, and an organic solvent, and carrying out a 1,1,2-trifunctionalization reaction of unactivated alkenes under visible light irradiation and inert gas protection. After the reaction is completed, through post-treatment, an N,O-spiroacetalamine derivative represented by formula III is obtained;

[0008]

[0009] Wherein,

[0010] Ring A is selected from a substituted or unsubstituted pyridyl group, a substituted or unsubstituted quinolinyl group, a substituted or unsubstituted isoquinolinyl group (the N in the pyridyl group, quinolinyl group, or isoquinolinyl group of Ring A is positively charged and forms an onium salt with TSO - );

[0011] In Ring A, the substituents of the substituted pyridyl group, substituted quinolinyl group, and substituted isoquinolinyl group are selected from C1-C4 alkyl groups;

[0012] R 1 is selected from hydrogen, C1-C4 alkyl groups;

[0013] R 2 and R 3 are independently selected from C1-C4 alkyl groups, or R 2 and R 3 form a 3- to 8-membered alkyl ring with the adjacent carbon atom;

[0014] n is selected from 0, 1, 2, or 3;

[0015] Ring B is selected from a 6- to 10-membered aryl group or a 5- to 6-membered heteroaryl group;

[0016] In Ring B, the 5- to 6-membered heteroaryl group contains one heteroatom selected from N, S, and O;

[0017] R 4 is selected from hydrogen, halogen, cyano, C1-C 10 halogen-substituted or unsubstituted alkyl, C1-C 10 halogen-substituted or unsubstituted alkoxy, C1-C4 halogen-substituted or unsubstituted alkoxycarbonyl, C2-C4 alkenyl, substituted or unsubstituted 6- to 10-membered aryl, substituted or unsubstituted 5- to 6-membered heteroaryl;

[0018] R 4 In the 5- to 6-membered heteroaryl group, the heteroatom is selected from N, S, and O;

[0019] R 4 In the substituted 6- to 10-membered aryl group and the substituted 5- to 6-membered heteroaryl group, the substituents are selected from halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 alkoxycarbonyl.

[0020] Among them, in the above synthesis method, in Ring A, the substituents of the substituted pyridyl group, substituted quinolinyl group, and substituted isoquinolinyl group are selected from methyl, ethyl, n-propyl, or n-butyl.

[0021] Preferably, in the above synthesis method, Ring A is selected from

[0022] Among them, in the above synthesis method, R 1 is selected from hydrogen, methyl, ethyl, n-propyl or n-butyl.

[0023] Preferably, in the above synthesis method, R 1 is selected from hydrogen, methyl or ethyl.

[0024] Among them, in the above synthesis method, R 2 , R 3 are independently selected from methyl, ethyl, n-propyl or n-butyl, or R 2 and R 3 form a 4- to 6-membered alkyl ring with the connected carbon atom.

[0025] Preferably, in the above synthesis method, R 2 , R 3 are independently selected from methyl or ethyl, or R 2 and R 3 form a 4- to 6-membered alkyl ring with the connected carbon atom.

[0026] Among them, in the above synthesis method, n is selected from 0, 1, 2 or 3.

[0027] Preferably, in the above synthesis method, n is selected from 1 or 2.

[0028] Among them, in the above synthesis method, the formula I is selected from:

[0029]

[0030] Among them, in the above synthesis method, ring B is selected from phenyl, pyridyl, thienyl or furyl.

[0031] Among them, in the above synthesis method, R 4 is selected from hydrogen, fluorine, chlorine, bromine, cyano, C1-C6 fluorine-substituted or unsubstituted alkyl, C1-C6 fluorine-substituted or unsubstituted alkoxy, C1-C4 fluorine-substituted or unsubstituted alkoxycarbonyl, C2-C4 alkenyl, substituted or unsubstituted 6-membered aryl, substituted or unsubstituted 5- to 6-membered heteroaryl; in R 4 , the 5- to 6-membered heteroaryl is selected from pyridyl, thienyl or furyl; in R 4 , the substituents of the substituted 6-membered aryl and the substituted 5- to 6-membered heteroaryl are selected from fluorine, chlorine, bromine, methyl, fluoromethyl, ethyl, fluoroethyl, methoxy, fluoromethoxy, methoxycarbonyl or fluoromethoxycarbonyl.

[0032] Preferably, in the above synthesis method, R 4Selected from hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, ethyl, fluoroethyl, propyl, butyl, pentyl, methoxy, fluoromethoxy, methoxycarbonyl, fluoromethoxycarbonyl, vinyl, phenyl, fluorophenyl, pyridyl, fluoropyridyl, thienyl, fluorothienyl, furyl or fluorofuryl.

[0033] Among them, in the above synthesis method, the formula II is selected from:

[0034] Among them, in the above synthesis method, the formula III is selected from:

[0035]

[0036] Among them, in the above synthesis method, the photocatalyst is selected from fac-Ir(ppy)3, Ir(p-F-ppy)3, [Ir(dtppy)(ppy)2]PF6, Eosin Y or PTH.

[0037] Preferably, in the above synthesis method, the photocatalyst is fac-Ir(ppy)3.

[0038] Among them, in the above synthesis method, the base is selected from at least one of alkali metal carbonates, alkaline earth metal carbonates, alkali metal bicarbonates, alkaline earth metal bicarbonates, alkali metal hydroxides, alkaline earth metal hydroxides or organic amines.

[0039] Preferably, in the above synthesis method, the base is selected from at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide, triethylamine or N,N-diisopropylethylamine.

[0040] More preferably, in the above synthesis method, the base is selected from at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium hydroxide, sodium hydroxide or lithium hydroxide.

[0041] Most preferably, in the above synthesis method, the base is potassium carbonate or sodium carbonate.

[0042] Among them, in the above synthesis method, the organic solvent is selected from at least one of N,N-dimethylformamide, 1,4-dioxane, ether, ethyl acetate, methanol, ethanol, acetone, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide or acetonitrile.

[0043] Preferably, in the above synthesis method, the organic solvent is selected from at least one of 1,4-dioxane, ethanol or dimethyl sulfoxide.

[0044] More preferably, in the above synthesis method, the organic solvent is 1,4-dioxane.

[0045] Among them, in the above synthesis method, the molar ratio of the 1-alkenyloxycyclic compound shown in Formula I, the 1-azidoethenylcyclic compound shown in Formula II, the photocatalyst and the base is 1:1-2:0.005-0.03:0.5-2.

[0046] Preferably, in the above synthesis method, the molar ratio of the 1-alkenyloxycyclic compound shown in Formula I, the 1-azidoethenylcyclic compound shown in Formula II, the photocatalyst and the base is 1:1-2:0.01-0.02:0.5-1.

[0047] More preferably, in the above synthesis method, the molar ratio of the 1-alkenyloxycyclic compound shown in Formula I, the 1-azidoethenylcyclic compound shown in Formula II, the photocatalyst and the base is 1:2:0.02:1.

[0048] Among them, in the above synthesis method, the amount of the organic solvent used is 1-15 mL / mmol of Formula I.

[0049] Preferably, in the above synthesis method, the amount of the organic solvent used is 5-10 mL / mmol of Formula I.

[0050] Among them, in the above synthesis method, the light source used for the visible light irradiation is selected from a blue light source, a green light source, an ultraviolet light source or a white light source.

[0051] Preferably, in the above synthesis method, the light source used for the visible light irradiation is a blue light source.

[0052] Among them, in the above synthesis method, the wavelength used for the visible light irradiation is 455-465 nm.

[0053] Among them, in the above synthesis method, the temperature of the reaction is 0-80 °C.

[0054] Preferably, in the above synthesis method, the temperature of the reaction is 20-30 °C.

[0055] Among them, in the above synthesis method, the time of the reaction is 1-6 hours.

[0056] Preferably, in the above synthesis method, the time of the reaction is 2-3 hours.

[0057] In the present invention, after the reaction is completed, the post-treatment is a conventional operation in the art, namely: quenching the reaction with an appropriate amount of water and extracting with an appropriate amount of an appropriate organic solvent (such as ethyl acetate, dichloromethane, etc.), then washing the organic layer with saturated brine and drying it over Na2SO4, removing the solvent under reduced pressure, and subjecting the obtained residue to column chromatography separation using an organic solvent with an appropriate polarity according to the polarity of the product to obtain the target product.

[0058] The structural formula of the compound of formula III in the present invention can also be drawn as Among them, the three bold bonds represent the three newly formed bonds, indicating the 1,1,2-trifunctionalization of the alkene.

[0059] Advantages of the present invention:

[0060] In the present invention, N-alkenyloxycyclic compound oxonium salts and azido vinyl cyclic compounds are used as raw materials, and through a highly efficient strategy for constructing N,O-spiroacetalamine skeletons by photoredox catalysis, the 1,1,2-trifunctionalization reaction of N-alkenyloxy oxonium salts and vinyl azides is successfully achieved. The obtained compounds are confirmed by nuclear magnetic resonance spectroscopy, breaking through the structural limitations of N,O-spiroacetalamine derivatives in nature, and providing a new route for the industrial production of compounds containing the N,O-spiroacetalamine core skeleton; in the present invention, by optimizing the reaction conditions, screening catalysts, bases, organic solvents, etc., the product yield is ensured; the method of the present invention is easy to operate, has mild reaction conditions, stable process conditions, easy product purification, wide substrate scope, good functional group tolerance, low production cost, and is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 1H NMR spectrum of compound 3aa 1 H spectrum.

[0062] Figure 2 13C NMR spectrum of compound 3aa 13 C spectrum. DETAILED DESCRIPTION OF THE INVENTION

[0063] The following will explain the solution of the present invention in conjunction with the examples. Those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention. For those not specified in the examples regarding specific techniques or conditions, they shall be carried out according to the techniques or conditions described in the literature in the art or according to the product specifications.

[0064] Example 1: Preparation of 9,9-dimethyl-7-(p-tolyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3aa)

[0065]

[0066] Under argon atmosphere, N-alkenyloxypyridinium salt 2a (0.3 mmol, R1 is H, R2 and R3 are both methyl, n = 1), K2CO3 (0.3 mmol), fac-Ir(ppy)3 (2 mol%), 1-(1-azidoethylene)-4-methylbenzene 1a (0.6 mmol) and dry 1,4-dioxane (3 mL) were successively added to a dry Schlenk tube (10 mL) equipped with a magnetic stir bar, and irradiated with a blue LED light source (wavelength 455 - 465 nm). The reaction was carried out at 25 °C for 3 hours. After the reaction was completed, 6 mL of water was added to the system to quench the reaction, and ethyl acetate was added in small portions for extraction. After collecting the organic phase, it was washed successively with saturated brine and dried over anhydrous sodium sulfate. Finally, the solvent was removed by distillation under reduced pressure to obtain a brownish-yellow crude product, which was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 15:1) to obtain the target product 3aa. The obtained product was a yellow liquid with a yield of 81%. From Figure 1 and Figure 2 it can be seen that the product characterization is as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J = 7.8 Hz, 2H), 7.18 (d, J = 7.8 Hz, 2H), 4.17–4.10 (m, 1H), 3.90–3.81 (m, 1H), 2.91 (d, J = 16.1 Hz, 1H), 2.68 (d, J = 16.1 Hz, 1H), 2.36 (s, 3H), 2.33–2.25 (m, 1H), 2.01–1.93 (m, 3H), 1.15 (s, 3H), 1.04 (s, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 173.0, 140.9, 132.2, 129.0, 127.7, 112.7, 68.5, 49.5, 43.1, 31.9, 25.6, 25.5, 22.2, 21.5; HRMS(ESI) calcd for C 16 H 21 NO [M+H] + : 244.1696, found: 244.1698.

[0067]

[0068] The screening results of other reaction parameters are shown in Table 1 below.

[0069] Table 1 Screening Results of Reaction Parameters

[0070] Number Single-factor condition change Yield (%) 1 Example 1 81 2 <![CDATA[Replacement of fac-Ir(ppy)3 with Ir(p-F-ppy)3]]> 44 3 <![CDATA[[Ir(dtppy)(ppy)2]PF6 replaces fac-Ir(ppy)3]]> 33 4 <![CDATA[10-phenyl-10H-phenothiazine (PTH) replacing fac-Ir(ppy)3]]> 42 5 <![CDATA[Replacement of fac-Ir(ppy)3 with Eosin Y]]> 50 6 <![CDATA[Replacement of fac-Ir(ppy)3 with 3DPA2FBN]]> trace 7 Replace 1,4-dioxane with dichloromethane 38 8 Replace 1,4-dioxane with tetrahydrofuran 41 9 Replace 1,4-dioxane with acetonitrile 21 10 Replace 1,4-dioxane with dimethyl sulfoxide 60 11 Replace 1,4-dioxane with methanol 45 12 Replace 1,4-dioxane with ethanol 64 13 Replace potassium carbonate with cesium carbonate 68 15 Replace potassium carbonate with lithium hydroxide 63 16 Replace potassium carbonate with potassium tert-butoxide trace 17 Replace potassium carbonate with triethylamine 40 18 Replace potassium carbonate with N,N-diisopropylethylamine 28 19 <![CDATA[Replace 0.02 equivalent of fac-Ir(ppy)3 with 0.01 equivalent of fac-Ir(ppy)3]]> 72 20 Replace 1.0 equivalent of potassium carbonate with 0.5 equivalent of potassium carbonate 60 21 Replace 3 hours with 1 hour 61 22 Replace 3 hours with 2 hours 73 23 No light irradiation 17 24 No photocatalyst 13

[0071] Example 2: Preparation of 9,9-dimethyl-7-phenyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ba)

[0072]

[0073] Referring to Example 1, replacing 1-(1-azidoethenyl)-4-methylbenzene with (1-azidoethenyl)benzene, the resulting product was a yellow liquid with a yield of 65%. Product characterization: 1 H NMR (400 MHz, Chloroform-d) δ 7.85–7.81 (m, 2H), 7.42–7.36 (m, 3H), 4.16–4.10 (m, 1H), 3.89–3.82 (m, 1H), 2.93 (d, J = 16.2 Hz, 1H), 2.70 (dd, J = 16.2, 0.8 Hz, 1H), 2.34–2.25 (m, 1H), 2.01–1.93 (m, 3H), 1.15 (s, 3H), 1.04 (s, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 173.2, 134.9, 130.8, 128.4, 127.8, 112.7, 68.6, 49.4, 43.1, 31.9, 25.6, 25.5, 22.2; HRMS (ESI) calcd for C 15 H 19 NO [M+H] + : 230.1539, found: 230.1536.

[0074] Example 3: Preparation of 7-(4-ethylphenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ca)

[0075]

[0076] Referring to Example 1, replacing 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-4-ethylbenzene, the resulting product was a yellow liquid with a yield of 53%. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.78–7.73 (m, 2H), 7.23–7.19 (m, 2H), 4.16–4.10 (m, 1H), 3.88–3.81 (m, 1H), 2.92 (d, J = 16.1 Hz, 1H), 2.71 (d, J = 4.5 Hz, 1H), 2.69–2.61 (m, 2H), 2.33–2.25 (m, 1H), 1.99–1.94 (m, 3H), 1.22 (t, J = 7.6 Hz, 3H), 1.15 (s, 3H), 1.03 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 173.1, 147.3, 132.3, 127.88, 127.85, 112.7, 68.5, 49.4, 43.1, 31.9, 28.8, 25.6, 25.5, 22.2, 15.5; HRMS (ESI) calcd for C 17 H 23 NO [M+H] + : 258.1852, found: 258.1861.

[0077] Example 4: Preparation of 9,9-dimethyl-7-(4-propylphenyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3da)

[0078]

[0079] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-4-propylbenzene. The resulting product is a yellow liquid with a yield of 64%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.75 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 4.16–4.10 (m, 1H), 3.89–3.82 (m, 1H), 2.91 (d, J = 16.1 Hz, 1H), 2.68 (d, J = 16.1 Hz, 1H), 2.59 (t, J = 7.6 Hz, 2H), 2.32–2.25 (m, 1H), 1.99–1.93 (m, 3H), 1.67–1.58 (m, 2H), 1.15 (s, 3H), 1.04 (s, 3H), 0.91 (t, J = 7.4 Hz, 3H); 13¹³C NMR (101 MHz, Chloroform-d) δ 173.0, 145.7, 132.5, 128.5, 127.7, 112.7, 68.5, 49.5, 43.1, 37.9, 31.9, 25.6, 25.5, 24.4, 22.2, 13.8; HRMS (ESI) calcd for C 18 H 25 NO [M+H] + : 272.2009, found: 272.2015。

[0080] Example 5: Preparation of 7-(4-butylphenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ea)

[0081]

[0082] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 1-(1-azidoethenyl)-4-butylbenzene. The resulting product was a yellow liquid with a yield of 57%. Product characterization: 1 ¹H NMR (400 MHz, Chloroform-d) δ 7.77–7.73 (m, 2H), 7.21–7.17 (m, 2H), 4.16–4.11 (m, 1H), 3.90–3.82 (m, 1H), 2.92 (d, J = 16.1 Hz, 1H), 2.69 (d, J = 16.2 Hz, 1H), 2.65–2.59 (m, 2H), 2.33–2.25 (m, 1H), 2.00–1.94 (m, 3H), 1.63–1.54 (m, 2H), 1.37–1.29 (m, 2H), 1.15 (s, 3H), 1.04 (s, 3H), 0.91 (t, J = 7.3 Hz, 3H); 13 ¹³C NMR (101 MHz, Chloroform-d) δ 173.0, 145.9, 132.4, 128.4, 127.7, 112.7, 68.5, 49.4, 43.1, 35.6, 33.5, 31.9, 25.6, 25.5, 22.3, 22.2, 14.0; HRMS (ESI) calcd for C 19 H 27 NO [M+H] + : 286.2165, found: 286.2170。

[0083] Example 6: Preparation of 9,9-dimethyl-7-(4-pentylphenyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3fa)

[0084]

[0085] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 1-(1-azidoethenyl)-4-pentylbenzene, and the resulting product was a yellow liquid with a yield of 64%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.76–7.74(m,2H),7.19(d,J=8.0Hz,2H),4.16–4.11(m,1H),3.89–3.83(m,1H),2.92(d,J=16.1Hz,1H),2.69(d,J=16.1Hz,1H),2.62(t,J=7.7Hz,2H),2.33–2.25(m,1H),2.00–1.94(m,3H),1.65–1.57(m,2H),1.34–1.26(m,4H),1.15(s,3H),1.04(s,3H),0.88(t,J=6.8Hz,3H); 13 CNMR(101MHz,Chloroform-d)δ173.1,146.0,132.4,128.4,127.7,112.7,68.5,49.5,43.1,35.9,31.9,31.4,31.0,25.6,25.5,22.5,22.2,14.1;HRMS(ESI)calcd for C 20 H 29 NO[M+H] + :300.2322,found:300.2333。

[0086] Example 7: Preparation of 7-([1,1'-biphenyl]-4-yl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ga)

[0087]

[0088] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 4-(1-azidoethenyl)-1,1'-biphenyl, and the resulting product was a white solid with a melting point of 77.6 - 78.8 °C and a yield of 40%. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.95–7.89 (m, 2H), 7.66–7.61 (m, 4H), 7.49–7.43 (m, 2H), 7.40–7.34 (m, 1H), 4.20–4.14 (m, 1H), 3.93–3.86 (m, 1H), 2.98 (d, J = 16.2 Hz, 1H), 2.75 (d, J = 16.2 Hz, 1H), 2.37–2.28 (m, 1H), 2.04–1.98 (m, 3H), 1.19 (s, 3H), 1.08 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.8, 143.4, 140.4, 133.8, 128.9, 128.3, 127.8, 127.2, 127.0, 112.8, 68.6, 49.5, 43.2, 31.9, 25.63, 25.56, 22.2; HRMS(ESI) calcd for C 21 19 23 14 + NO [M+H]+: 306.1852, found: 306.1860.

[0089] Example 8: Preparation of 7-(4-methoxyphenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ha)

[0090]

[0091] Referring to Example 1, replacing 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-4-methoxybenzene, the obtained product was a white solid with a melting point of 83.4 - 84.8 °C and a yield of 62%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.80–7.72 (m, 2H), 6.88–6.82 (m, 2H), 4.13–4.07 (m, 1H), 3.84–3.79 (m, 1H), 3.77 (s, 3H), 2.86 (d, J = 16.1 Hz, 1H), 2.64 (d, J = 16.1 Hz, 1H), 2.30–2.21 (m, 1H), 1.96–1.90 (m, 3H), 1.12 (s, 3H), 1.00 (s, 3H); 1313C NMR (101 MHz, Chloroform-d) δ 172.4, 161.7, 129.4, 127.6, 113.6, 112.7, 68.5, 55.3, 49.3, 43.1, 31.9, 25.61, 25.58, 22.1; HRMS (ESI) calcd for C 16 H 21 NO2 [M+H] + : 260.1645, found: 260.1645。

[0092] Example 9: Preparation of 7-(4-fluorophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ia)

[0093]

[0094] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 1-(1-azidoethenyl)-4-fluorobenzene, and the resulting product was a yellow liquid with a yield of 66%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.86–7.80 (m, 2H), 7.09–7.03 (m, 2H), 4.15–4.09 (m, 1H), 3.89–3.82 (m, 1H), 2.91 (d, J = 16.2 Hz, 1H), 2.68 (d, J = 16.2 Hz, 1H), 2.33–2.24 (m, 1H), 2.01–1.93 (m, 3H), 1.15 (s, 3H), 1.04 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.0, 164.4 (d, J = 250.8 Hz), 131.1 (d, J = 3.1 Hz), 129.8 (d, J = 8.6 Hz), 115.4 (d, J = 21.6 Hz), 112.8, 68.6, 49.5, 43.2, 31.8, 25.59, 25.58, 22.1; 19 19F NMR (376 MHz, Chloroform-d) δ -109.61; HRMS (ESI) calcd for C 15 H 18 FNO [M+H] + : 248.1445, found: 248.1444。

[0095] Example 10: Preparation of 7-(4-chlorophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ja)

[0096]

[0097] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 1-(1-azidoethenyl)-4-chlorobenzene, and the resulting product was a yellow liquid with a yield of 59%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.76(d,J=8.6Hz,2H),7.34(d,J=8.6Hz,2H),4.15–4.09(m,1H),3.89–3.82(m,1H),2.90(d,J=16.2Hz,1H),2.66(d,J=16.2Hz,1H),2.32–2.23(m,1H),2.01–1.93(m,3H),1.14(s,3H),1.03(s,3H); 13 C NMR(101MHz,Chloroform-d)δ172.1,136.8,133.3,129.1,128.6,112.8,68.6,49.4,43.2,31.8,25.6(2C),22.1;HRMS(ESI)calcd for C 15 H 18 ClNO[M+H] + :264.1150,found:264.1152.

[0098] Example 11: Preparation of 7-(4-bromophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ka)

[0099]

[0100] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 1-(1-azidoethenyl)-4-bromobenzene, and the resulting product was a white solid with a melting point of 62.6 - 64.3 °C and a yield of 61%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.68(d,J=8.5Hz,2H),7.49(d,J=8.5Hz,2H),4.13–4.07(m,1H),3.87–3.81(m,1H),2.88(d,J=16.2Hz,1H),2.64(d,J=16.2Hz,1H),2.30–2.23(m,1H),1.98–1.92(m,3H),1.13(s,3H),1.02(s,3H); 1313C NMR(101MHz,Chloroform-d)δ172.1,133.7,131.5,129.3,125.3,112.8,68.6,49.3,43.2,31.8,25.6(2C),22.1;HRMS(ESI)calcd for C 15 H 18 BrNO[M+H] + :308.0645,found:308.0652。

[0101] Example 12: Preparation of 9,9-Dimethyl-7-(4-(trifluoromethyl)phenyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3la)

[0102]

[0103] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-4-(trifluoromethyl)benzene. The resulting product is a yellow liquid with a yield of 43%. Product characterization: 1 1H NMR(400MHz,Chloroform-d)δ7.94(d,J = 8.1Hz,2H),7.64(d,J = 8.1Hz,2H),4.16–4.10(m,1H),3.91–3.85(m,1H),2.95(d,J = 16.3Hz,1H),2.71(d,J = 16.2Hz,1H),2.35–2.25(m,1H),2.02–1.95(m,3H),1.16(s,3H),1.05(s,3H); 13 13C NMR(101MHz,Chloroform-d)δ172.0,138.1,132.3(q,J = 32.4Hz),128.0,125.3(q,J = 3.8Hz),123.9(q,J = 272.3Hz),112.8,68.7,49.5,43.2,31.8,25.52,25.48,22.1; 19 19F NMR(376MHz,Chloroform-d)δ - 62.79; HRMS(ESI)calcd for C 16 H 18 F3NO[M+H] + :298.1413,found:298.1420。

[0104] Example 13: Preparation of 4-(9,9-Dimethyl-1-oxa-6-azaspiro[4.4]non-6-en-7-yl)benzonitrile (3ma)

[0105]

[0106] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 4-(1-azidoethenyl)benzonitrile. The resulting product is a yellow liquid with a yield of 58%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.99–7.79(m,2H),7.70–7.42(m,2H),4.10–4.04(m,1H),3.86–3.80(m,1H),2.88(d,J=16.3Hz,1H),2.65(d,J=16.4Hz,1H),2.28–2.20(m,1H),1.97–1.90(m,3H),1.11(s,3H),1.00(s,3H); 13 C NMR(101MHz,Chloroform-d)δ171.6,138.8,132.1,128.3,118.5,113.9,112.8,68.7,49.3,43.2,31.8,25.48,25.47,22.0;HRMS(ESI)calcd for C 16 H 18 N2O[M+H] + :255.1492,found:255.1503.

[0107] Example 14: Preparation of methyl 4-(9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-en-7-yl)benzoate (3na)

[0108]

[0109] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with methyl 4-(1-azidoethenyl)benzoate. The resulting product is a white solid with a melting point of 46.5 - 47.7 °C and a yield of 30%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ8.02(d,J=8.2Hz,2H),7.87(d,J=8.3Hz,2H),4.13–4.08(m,1H),3.89(s,3H),3.88–3.82(m,1H),2.93(d,J=16.3Hz,1H),2.69(d,J=16.2Hz,1H),2.31–2.23(m,1H),2.00–1.93(m,3H),1.14(s,3H),1.03(s,3H); 1313C NMR(101MHz,Chloroform-d)δ172.4,166.6,138.9,131.8,129.6,127.7,112.8,68.7,52.3,49.5,43.2,31.8,25.53,25.51,22.1;HRMS(ESI)calcd for C 17 H 21 NO3[M+H] + :288.1954,found:288.1954。

[0110] Example 15: Preparation of 7-(3-methoxyphenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3oa)

[0111]

[0112] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-3-methoxybenzene. The resulting product is a yellow liquid with a yield of 58%. Product characterization: 1 1H NMR(400MHz,Chloroform-d)δ7.44–7.43(m,1H),7.35–7.32(m,1H),7.31–7.23(m,1H),6.99–6.92(m,1H),4.15–4.10(m,1H),3.89–3.84(m,1H),3.82(s,3H),2.90(d,J = 16.2Hz,1H),2.68(d,J = 16.2Hz,1H),2.33–2.24(m,1H),1.98–1.94(m,3H),1.14(s,3H),1.04(s,3H); 13 13C NMR(101MHz,Chloroform-d)δ172.9,159.6,136.3,129.3,120.5,117.2,112.7,112.1,68.6,55.4,49.6,43.2,31.9,25.6,25.4,22.2;HRMS(ESI)calcd for C 16 H 21 NO2[M+H] + :260.1645,found:260.1642。

[0113] Example 16: Preparation of 9,9-dimethyl-7-(m-tolyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3pa)

[0114]

[0115] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 1-(1-azidoethenyl)-3-methylbenzene, and the resulting product was a yellow liquid with a yield of 58%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.74–7.70(m,1H),7.61–7.54(m,1H),7.30–7.22(m,2H),4.17–4.11(m,1H),3.90–3.83(m,1H),2.93(d,J=16.2Hz,1H),2.71(d,J=16.2Hz,1H),2.37(s,3H),2.33–2.26(m,1H),2.01–1.96(m,3H),1.16(s,3H),1.05(s,3H); 13 C NMR(101MHz,Chloroform-d)δ173.4,138.0,134.8,131.6,128.24,128.18,125.0,112.7,68.6,49.5,43.1,31.9,25.6,25.5,22.2,21.4;HRMS(ESI)calcd for C 16 H 21 NO[M+H] + :244.1696,found:244.1700。

[0116] Example 17: Preparation of 7-(3-fluorophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3qa)

[0117]

[0118] Referring to Example 1, 1-(1-azidoethenyl)-4-methylbenzene was replaced with 1-(1-azidoethenyl)-3-fluorobenzene, and the resulting product was a yellow liquid with a yield of 46%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.59–7.54(m,2H),7.37–7.31(m,1H),7.13–7.08(m,1H),4.15–4.09(m,1H),3.89–3.83(m,1H),2.91(d,J=16.3Hz,1H),2.67(d,J=16.2Hz,1H),2.32–2.24(m,1H),1.99–1.94(m,3H),1.15(s,3H),1.04(s,3H); 1313C NMR (101 MHz, Chloroform-d) δ 172.1 (d, J = 2.7 Hz), 162.7 (d, J = 246.1 Hz), 137.1 (d, J = 7.4 Hz), 129.9 (d, J = 8.0 Hz), 123.5 (d, J = 2.9 Hz), 117.6 (d, J = 21.4 Hz), 114.5 (d, J = 22.2 Hz), 112.7, 68.7, 49.5, 43.2, 31.8, 25.5 (2C), 22.1; 19 19F NMR (376 MHz, Chloroform-d) δ -112.98; HRMS (ESI) calcd for C 15 H 18 FNO [M+H] + : 248.1445, found: 248.1448.

[0119] Example 18: Preparation of 7-(3-chlorophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ra)

[0120]

[0121] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-3-chlorobenzene. The resulting product is a yellow liquid with a yield of 52%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.87–7.84 (m, 1H), 7.70–7.66 (m, 1H), 7.42–7.37 (m, 1H), 7.35–7.30 (m, 1H), 4.17–4.10 (m, 1H), 3.91–3.84 (m, 1H), 2.92 (d, J = 16.2 Hz, 1H), 2.68 (d, J = 16.3 Hz, 1H), 2.34–2.26 (m, 1H), 2.01–1.95 (m, 3H), 1.16 (s, 3H), 1.05 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.0, 136.7, 134.5, 130.7, 129.6, 127.8, 125.9, 112.8, 68.7, 49.4, 43.2, 31.8, 25.54, 25.53, 22.1; HRMS (ESI) calcd for C 15 H 18 ClNO [M+H] + : 264.1150, found: 264.1159.

[0122] Example 19: Preparation of 7-(3-bromophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3sa)

[0123]

[0124] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-3-bromobenzene. The resulting product is a white solid with a melting point of 104.8 - 106.2 °C and a yield of 51%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ8.02–7.99(m,1H),7.72–7.68(m,1H),7.54–7.50(m,1H),7.26–7.21(m,1H),4.14–4.08(m,1H),3.88–3.82(m,1H),2.88(d,J=16.3Hz,1H),2.65(d,J=16.2Hz,1H),2.32–2.23(m,1H),1.98–1.93(m,3H),1.13(s,3H),1.02(s,3H); 13 C NMR(101MHz,Chloroform-d)δ171.9,136.9,133.6,130.6,129.9,126.4,122.7,112.7,68.7,49.4,43.2,31.8,25.5(2C),22.1;HRMS(ESI)calcd for C 15 H 18 BrNO[M+H] + :308.0645,found:308.0653。

[0125] Example 20: Preparation of 9,9-dimethyl-7-(o-tolyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3ta)

[0126]

[0127] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-2-methylbenzene. The resulting product is a yellow liquid with a yield of 60%. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.39–7.36 (m, 1H), 7.27–7.23 (m, 1H), 7.21–7.16 (m, 2H), 4.16–4.09 (m, 1H), 3.93–3.85 (m, 1H), 2.96 (d, J=16.3 Hz, 1H), 2.63 (d, J=16.3 Hz, 1H), 2.49 (s, 3H), 2.35–2.25 (m, 1H), 2.04–1.93 (m, 3H), 1.17 (s, 3H), 1.07 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 175.7, 136.8, 135.5, 131.1, 129.2, 128.4, 125.6, 112.9, 68.4, 53.1, 42.9, 31.8, 25.6, 25.3, 21.8, 21.1; HRMS(ESI) calcd for C 16 H 21 NO[M + H] + : 244.1696, found: 244.1697。

[0128] Example 21: Preparation of 7-(2-fluorophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ua)

[0129]

[0130] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-2-fluorobenzene. The resulting product is a yellow liquid with a yield of 64%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.99–7.93 (m, 1H), 7.40–7.33 (m, 1H), 7.18–7.12 (m, 1H), 7.08–7.00 (m, 1H), 4.16–4.08 (m, 1H), 3.91–3.83 (m, 1H), 3.01 (dd, J=16.9, 3.2 Hz, 1H), 2.77 (dd, J=16.9, 3.4 Hz, 1H), 2.35–2.22 (m, 1H), 2.00–1.94 (m, 3H), 1.14 (s, 3H), 1.04 (s, 3H); 1313C NMR (101 MHz, Chloroform-d) δ 170.8 (d, J = 2.1 Hz), 161.7 (d, J = 252.5 Hz), 132.1 (d, J = 8.6 Hz), 130.1 (d, J = 3.4 Hz), 124.2 (d, J = 3.4 Hz), 123.2 (d, J = 11.8 Hz), 116.1 (d, J = 22.5 Hz), 111.7, 68.6, 52.7 (d, J = 6.1 Hz), 43.0 (d, J = 1.9 Hz), 31.7, 25.5, 25.3, 22.0; 19 19F NMR (376 MHz, Chloroform-d) δ -113.0; HRMS (ESI) calcd for C 15 H 18 FNO [M+H] + : 248.1445, found: 248.1443.

[0131] Example 22: Preparation of 7-(2-chlorophenyl)-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3va)

[0132]

[0133] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-2-chlorobenzene. The resulting product is a yellow liquid with a yield of 44%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.59–7.55 (m, 1H), 7.37–7.33 (m, 1H), 7.31–7.25 (m, 2H), 4.18–4.11 (m, 1H), 3.92–3.86 (m, 1H), 3.00 (dd, J = 16.7, 2.4 Hz, 1H), 2.82 (dd, J = 16.6, 1.3 Hz, 1H), 2.33–2.23 (m, 1H), 2.04–1.94 (m, 3H), 1.16 (s, 3H), 1.09 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 174.7, 135.6, 132.4, 130.5, 130.1, 130.0, 126.8, 112.1, 68.6, 52.9, 43.7, 31.6, 25.2, 25.2, 21.9; HRMS (ESI) calcd for C 15 H 18 ClNO [M+H] + : 264.1150, found: 264.1150.

[0134] Example 23: Preparation of 9,9-dimethyl-7-(thiophen-2-yl)-1-oxa-6-azaspiro[4.4]non-6-ene (3wa)

[0135]

[0136] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with 2-(1-azidoethenyl)thiophene. The resulting product is a yellow liquid with a yield of 32%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.43–7.41(m,1H),7.36–7.34(m,1H),7.08–7.01(m,1H),4.16–4.06(m,1H),3.88–3.78(m,1H),2.93(d,J=16.0Hz,1H),2.68(d,J=16.0Hz,1H),2.33–2.22(m,1H),2.04–1.88(m,3H),1.15(s,3H),1.04(s,3H); 13 C NMR(101MHz,Chloroform-d)δ167.7,139.9,129.8,129.6,127.4,112.8,68.6,50.1,43.4,31.7,25.6(2C),22.0;HRMS(ESI)calcd for C 13 H 17 NOS[M+H] + :236.1104,found:236.1101。

[0137] Example 24: Preparation of isopropyl 2-(4-(4-(9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-en-7-yl)benzo[b]thiophen-1-yl)phenoxy)-2-methylpropanoate (3xa)

[0138]

[0139] Referring to Example 1, replace 1-(1-azidoethenyl)-4-methylbenzene with isopropyl 2-(4-(1-(4-(1-azidoethenyl)phenyl)ethenyl)phenoxy)-2-methylpropanoate. The resulting product is a yellow liquid with a yield of 54%. Product characterization: 1HNMR(400MHz,Chloroform-d)δ7.90–7.86(m,2H),7.73–7.67(m,4H),6.84–6.77(m,2H),5.07–4.99(m,1H),4.13–4.06(m,1H),3.87–3.79(m,1H),2.92(d,J=16.3Hz,1H),2.69(d,J=16.3Hz,1H),2.31–2.21(m,1H),1.98–1.92(m,3H),1.61(s,6H),1.16–1.12(m,9H),1.02(s,3H); 13 C NMR(101MHz,Chloroform-d)δ194.9,173.0,172.4,159.7,139.8,137.9,132.0,130.3,129.7,127.5,117.1,112.8,79.3,69.3,68.6,49.5,43.2,31.8,25.50,25.49,25.3(2C),22.1,21.5(2C);HRMS(ESI)calcd for C 29 H 35 NO5[M+H] + :278.2588,found:278.2571。

[0140] Example 25: Preparation of 2,9,9-Trimethyl-7-(p-tolyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3ad)

[0141]

[0142] Referring to Example 1, replace the N-(6-methyl-5-vinyloxy)pyridinium salt with the N-(2,6-dimethylhept-5-vinyloxy)pyridinium salt (R1, R2, and R3 are all methyl, n = 1). The resulting product is a yellow liquid with a yield of 74% and a dr of 1:1. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.77–7.67 (m, 2H), 7.17 (d, J = 7.8 Hz, 2H), 4.49–4.40 (m, 0.5H), 4.13–4.06 (m, 0.5H), 2.93–2.80 (m, 1H), 2.65 (d, J = 16.5 Hz, 1H), 2.40–2.31 (m, 3.5H), 2.07–1.90 (m, 3H), 1.54–1.50 (m, 0.5H), 1.32 (d, J = 6.1 Hz, 1.5H), 1.22 (d, J = 6.2 Hz, 1.5H), 1.17 (s, 1.5H), 1.13 (s, 1.5H), 1.06 (s, 1.5H), 0.99 (s, 1.5H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.8, 172.1, 140.8, 140.7, 132.4, 132.3, 129.01, 128.98, 127.8, 127.7, 112.95, 112.86, 76.6, 75.1, 49.4, 49.3, 43.15, 43.05, 33.5, 32.9, 32.5, 31.5, 25.9, 25.0, 23.0, 22.2, 21.7, 21.6, 21.5 (2C); HRMS (ESI) calcd for C 17 H 23 NO [M+H] + : 258.1852, found: 258.1851。

[0143] Example 26: Preparation of 7-([1,1'-biphenyl]-4-yl)-2,9,9-trimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3gd)

[0144]

[0145] Referring to Example 1, replace the N-(6-methyl-5-vinyloxy)pyridinium salt with the N-(2,6-dimethylhept-5-vinyloxy)pyridinium salt (R1, R2, and R3 are all methyl, n = 1), and replace 1-(1-azidoethylene)-4-methylbenzene with 4-(1-azidoethylene)-1,1'-biphenyl. The obtained product is a yellow solid, with a melting point of 89.3 - 91.5 °C, a yield of 56%, and a dr of 1.3:1. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.92–7.89 (m, 2H), 7.62–7.59 (m, 4H), 7.45–7.41 (m, 2H), 7.37–7.32 (m, 1H), 4.50–4.44 (m, 0.55H), 4.16–4.09 (m, 0.45H), 2.94 (dd, J=18.4, 16.1 Hz, 1H), 2.71 (dd, J=16.2, 1.7 Hz, 1H), 2.40–2.35 (m, 0.5H), 2.11–1.92 (m, 3H), 1.57–1.51 (m, 0.5H), 1.34 (d, J=6.0 Hz, 1.35H), 1.24 (d, J=6.2 Hz, 1.65H), 1.19 (s, 1.35H), 1.15 (s, 1.65H), 1.08 (s, 1.65H), 1.01 (s, 1.35H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.7, 172.0, 143.35, 143.32, 140.5, 140.4, 134.0, 133.9, 128.9, 128.3, 128.2, 127.8, 127.7, 127.2, 127.03, 127.00, 113.1, 113.0, 76.8, 75.3, 49.5, 49.3, 43.3, 43.2, 33.6, 32.9, 32.5, 31.5, 25.9, 25.0, 23.0, 22.2, 21.72, 21.66; HRMS (ESI) calcd for C 22 H 25 NO [M+H] + : 320.2010, found: 320.2017。

[0146] Example 27: Preparation of 7-(3-chlorophenyl)-2,9,9-trimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3rd)

[0147]

[0148] Referring to Example 1, replace N-(6-methyl-5-vinyloxy)pyridinium salt with N-(2,6-dimethylhept-5-vinyloxy)pyridinium salt (R1, R2, and R3 are all methyl, n = 1), and replace 1-(1-azidoethylene)-4-methylbenzene with 1-(1-azidoethylene)-3-chlorobenzene. The resulting product is a yellow liquid with a yield of 54% and a dr of 1:1. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.87–7.82 (m, 1H), 7.70–7.65 (m, 1H), 7.40–7.36 (m, 1H), 7.33–7.28 (m, 1H), 4.47–4.40 (m, 0.5H), 4.14–4.08 (m, 0.5H), 2.89 (dd, J=19.0, 16.2 Hz, 1H), 2.65 (dd, J=16.2, 5.5 Hz, 1H), 2.39–2.32 (m, 0.5H), 2.09–1.89 (m, 3H), 1.58–1.51 (m, 0.5H), 1.31 (d, J=6.0 Hz, 1.5H), 1.22 (d, J=6.1 Hz, 1.5H), 1.17 (s, 1.5H), 1.12 (s, 1.5H), 1.06 (s, 1.5H), 0.99 (s, 1.5H); 13 13C NMR (101 MHz, Chloroform-d) δ 171.9, 171.3, 136.9, 136.7, 134.5, 134.4, 130.60, 130.57, 129.62, 129.59, 127.8, 127.7, 126.0, 125.8, 113.0, 112.9, 76.9, 75.3, 49.4, 49.3, 43.3, 43.2, 33.5, 32.8, 32.4, 31.4, 25.8, 25.0, 22.8, 22.1, 21.7, 21.5; HRMS (ESI) calcd for C 16 H 20 ClNO [M+H] + : 278.1306, found: 278.1298.

[0149] Example 28: Preparation of 2-Ethyl-9,9-dimethyl-7-(p-tolyl)-1-oxa-6-azaspiro[4.4]non-6-ene (3ae)

[0150]

[0151] Referring to Example 1, replace the N-(6-methyl-5-enyloxy)pyridinium salt with N-(2-methyl-6-ethylhept-5-enyloxy)pyridinium salt (R1 is ethyl, R2 and R3 are methyl, n = 1). The resulting product is a yellow liquid with a yield of 44% and a dr of 1.3:1. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 4.26–4.20 (m, 0.55H), 3.92–3.86 (m, 0.45H), 2.90 (dd, J = 16.1, 7.6 Hz, 1H), 2.67 (dd, J = 16.1, 2.4 Hz, 1H), 2.37 (s, 3H), 2.35–2.29 (m, 0.55H), 2.05–1.89 (m, 3H), 1.78–1.71 (m, 0.45H), 1.64–1.45 (m, 2H), 1.18 (s, 1.35H), 1.14 (s, 1.65H), 1.06 (s, 1.65H), 1.00 (s, 1.35H), 0.96–0.88 (m, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.9, 172.2, 140.84, 140.79, 132.5, 132.3, 129.01, 129.00, 127.8, 127.7, 112.8, 112.5, 82.1, 80.4, 49.40, 49.35, 43.13, 43.08, 32.5, 31.4, 31.0, 30.0, 29.3, 29.0, 25.9, 25.1, 22.9, 21.6, 21.5 (2C), 10.2, 10.1; HRMS (ESI) calcd for C 18 H 25 NO [M+H] + : 272.2010, found: 272.2015.

[0152] Example 29: Preparation of 2-Ethyl-9,9-dimethyl-7-phenyl-1-oxa-6-azaspiro[4.4]non-6-ene (3be)

[0153]

[0154] Referring to Example 1, replace N-(6-methyl-5-vinyloxy)pyridinium salt with N-(2-methyl-6-ethylhept-5-vinyloxy)pyridinium salt (R1 is ethyl, R2 and R3 are methyl, n = 1), and replace 1-(1-azidoethylene)-4-methylbenzene with (1-azidoethylene)benzene. The obtained product is a yellow liquid with a yield of 57% and a dr of 1:1. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.86–7.82 (m, 2H), 7.42–7.36 (m, 3H), 4.27–4.21 (m, 0.5H), 3.93–3.87 (m, 0.5H), 2.92 (dd, J=16.2, 6.7 Hz, 1H), 2.69 (dd, J=16.2, 2.4 Hz, 1H), 2.39–2.33 (m, 0.5H), 2.05–1.89 (m, 3H), 1.78–1.71 (m, 0.5H), 1.65–1.44 (m, 2H), 1.18 (s, 1.5H), 1.15 (s, 1.5H), 1.07 (s, 1.5H), 1.01 (s, 1.5H), 0.98–0.89 (m, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.9, 172.3, 135.2, 135.0, 130.62, 130.58, 128.31, 128.30, 127.8, 127.7, 112.8, 112.5, 82.1, 80.4, 49.43, 49.38, 43.15, 43.10, 32.5, 31.4, 31.0, 30.0, 29.4, 29.0, 25.9, 25.1, 22.9, 21.6, 10.2, 10.1; HRMS (ESI) calcd for C 17 H 23 NO [M+H] + : 258.1852, found: 258.1849。

[0155] Example 30: Preparation of 7-(4-Bromophenyl)-2-ethyl-9,9-dimethyl-1-oxa-6-azaspiro[4.4]non-6-ene (3ke)

[0156]

[0157] Referring to Example 1, replace the N-(6-methyl-5-vinyloxy)pyridinium salt with the N-(2-methyl-6-ethylhept-5-vinyloxy)pyridinium salt (R1 is ethyl, R2 and R3 are methyl, n = 1), and replace 1-(1-azidoethylene)-4-methylbenzene with 1-(1-azidoethylene)-4-bromobenzene. The resulting product is a yellow liquid with a yield of 40% and a dr of 1:1. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.69 (dd, J = 8.6, 1.2 Hz, 2H), 7.50 (dd, J = 8.7, 0.7 Hz, 2H), 4.24–4.19 (m, 0.5H), 3.91–3.86 (m, 0.5H), 2.88 (dd, J = 16.2, 9.4 Hz, 1H), 2.64 (dd, J = 16.2, 6.1 Hz, 1H), 2.37–2.31 (m, 0.5H), 2.05–1.88 (m, 3H), 1.76–1.70 (m, 0.5H), 1.65–1.44 (m, 2H), 1.17 (s, 1.5H), 1.13 (s, 1.5H), 1.05 (s, 1.5H), 0.99 (s, 1.5H), 0.91 (dt, J = 15.1, 7.4 Hz, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.0, 171.4, 134.0, 133.9, 131.52, 131.51, 129.4, 129.3, 125.2, 125.1, 112.9, 112.6, 82.2, 80.6, 49.3, 49.2, 43.3, 43.2, 32.5, 31.3, 31.0, 29.9, 29.3, 29.0, 25.9, 25.1, 22.8, 21.6, 10.13, 10.09; HRMS (ESI) calcd for 17 C 22 H + BrNO [M+H]

[0158] Example 31: Preparation of 11-(p-tolyl)-6-oxa-10-azaspiro[3.0.4 5 .3 4 dodec-10-ene (3af)

[0159]

[0160] Referring to Example 1, replace N-(6-methyl-5-vinyloxy) pyridinium salt with N-(4-cyclobutylbutoxy) pyridinium salt (R1 is H, R2 and R3 form cyclobutane with the connected carbon atoms, n = 1), the obtained product is a white solid, melting point 85.6 - 87.4 °C, yield 68%. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.69–7.66 (m, 2H), 7.19 (d, J = 7.9 Hz, 2H), 3.78–3.71 (m, 1H), 3.61–3.54 (m, 1H), 3.31 (d, J = 17.4 Hz, 1H), 2.91 (d, J = 17.4 Hz, 1H), 2.36 (s, 3H), 2.02–1.91 (m, 4H), 1.83–1.71 (m, 3H), 1.63–1.58 (m, 1H), 1.53–1.45 (m, 2H); 13 13C NMR (101 MHz, Chloroform-d) δ 169.4, 140.8, 132.0, 129.1, 127.5, 88.1, 79.7, 61.0, 44.4, 39.8, 37.4, 30.9, 22.5, 21.5, 19.9; HRMS (ESI) calcd for C 17 H 21 NO[M + H] + : 256.1696, found: 256.1688.

[0161] Example 32: Preparation of 11-(4-pentylphenyl)-6-oxa-10-azaspiro[3.0.4 5 .3 4 dodec-10-ene (3ff)

[0162]

[0163] Referring to Example 1, replace N-(6-methyl-5-vinyloxy) pyridinium salt with N-(4-cyclobutylbutoxy) pyridinium salt (R1 is H, R2 and R3 form cyclobutane with the adjacent carbon atoms, n = 1), and replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-4-pentylbenzene. The obtained product is a white solid, with a melting point of 47.8 - 49.2 °C and a yield of 57%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.72–7.68 (m, 2H), 7.21–7.17 (m, 2H), 3.76–3.70 (m, 1H), 3.59–3.53 (m, 1H), 3.31 (d, J = 17.4 Hz, 1H), 2.91 (d, J = 17.5 Hz, 1H), 2.63–2.57 (m, 2H), 2.03–1.91 (m, 4H), 1.82–1.71 (m, 3H), 1.63–1.56 (m, 3H), 1.52–1.45 (m, 2H), 1.33–1.26 (m, 4H), 0.86 (t, J = 6.8 Hz, 3H);13 C NMR (101 MHz, Chloroform-d) δ 169.4, 145.8, 132.2, 128.5, 127.5, 88.1, 79.7, 61.0, 44.4, 39.8, 37.4, 35.8, 31.4, 31.0, 30.9, 22.53, 22.51, 19.9, 14.1; HRMS (ESI) calcd for C 21 H 29 NO[M + H] + : 312.2322, found: 312.2319。

[0164] Example 33: Preparation of 11-(3-fluorophenyl)-6-oxa-10-azaspiro[3.0.4 5 .3 4 dodec-10-ene (3qf)

[0165]

[0166] Referring to Example 1, replace N-(6-methyl-5-vinyloxy)pyridinium salt with N-(4-cyclobutylbutoxy)pyridinium salt (R1 is H, R2 and R3 form a cyclobutane with the adjacent carbon atoms, n = 1), and replace 1-(1-azidoethylene)-4-toluene with 1-(1-azidoethylene)-3-fluorobenzene. The obtained product is a yellow liquid with a yield of 50%. Product characterization: 1 H NMR (400 MHz, Chloroform-d) δ 7.53–7.47 (m, 2H), 7.37–7.29 (m, 1H), 7.12–7.05 (m, 1H), 3.77–3.70 (m, 1H), 3.59–3.52 (m, 1H), 3.28 (d, J = 17.5 Hz, 1H), 2.89 (d, J = 17.2 Hz, 1H), 2.03–1.91 (m, 4H), 1.81–1.70 (m, 3H), 1.63–1.56 (m, 1H), 1.52–1.44 (m, 2H); 13 C NMR (101 MHz, Chloroform-d) δ 168.5 (d, J = 2.6 Hz), 162.8 (d, J = 246.4 Hz), 136.9 (d, J = 7.3 Hz), 130.0 (d, J = 8.0 Hz), 123.3 (d, J = 2.9 Hz), 117.5, 114.0, 88.2, 80.0, 61.0, 44.6, 39.5, 37.3, 30.8, 22.5, 19.8; 19FNMR (376 MHz, Chloroform-d) δ -112.8 (d, J = 2.8 Hz); HRMS (ESI) calcd for C 16 H 18 FNO[M + H] + : 260.1445, found: 260.1439。

[0167] Example 34: Preparation of 12-(p-tolyl)-1-oxa-13-azaspiro[4.0.4 6 .3 5 tridec-12-ene (3ag)

[0168]

[0169] Referring to Example 1, replace the N-(6-methyl-5-vinyloxy) pyridinium salt with N-(4-cyclopentylbutoxy) pyridinium salt (R1 is H, R2 and R3 form a cyclopentane with the connected carbon atoms, n = 1). The resulting product is a yellow liquid with a yield of 60%. Product characterization: 1 H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H), 4.18–4.12 (m, 1H), 3.95–3.89 (m, 1H), 2.92 (d, J = 16.0 Hz, 1H), 2.72 (d, J = 16.0 Hz, 1H), 2.36 (s, 3H), 2.31–2.25 (m, 1H), 2.00–1.93 (m, 3H), 1.90–1.84 (m, 1H), 1.73–1.62 (m, 5H), 1.56–1.50 (m, 1H), 1.45–1.39 (m, 1H); 13 C NMR (101 MHz, Chloroform-d) δ 172.4, 140.9, 132.2, 129.0, 127.7, 112.2, 68.6, 55.5, 48.1, 35.3, 33.2, 32.7, 25.7, 24.5, 24.2, 21.5; HRMS (ESI) calcd for C 18 H 23 NO[M + H] + : 270.1852, found: 270.1842。

[0170] Example 35: Preparation of 12-(4-propylphenyl)-1-oxa-13-azaspiro[4.0.4 6 .3 5 tridec-12-ene (3dg)

[0171]

[0172] Referring to Example 1, replace N-(6-methyl-5-vinyloxy)pyridinium salt with N-(4-cyclopentylbutoxy)pyridinium salt (R1 is H, R2 and R3 form a cyclopentane with the connected carbon atoms, n = 1), and replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-4-propylbenzene. The obtained product is a yellow liquid with a yield of 58%. Product characterization: 1 H NMR(400MHz,Chloroform-d)δ7.75(d,J=8.2Hz,2H),7.19(d,J=8.0Hz,2H),4.20–4.12(m,1H),3.96–3.89(m,1H),2.93(d,J=16.0Hz,1H),2.72(d,J=16.0Hz,1H),2.64–2.55(m,2H),2.31–2.25(m,1H),2.01–1.93(m,3H),1.90–1.84(m,1H),1.71–1.60(m,7H),1.56–1.50(m,1H),1.46–1.40(m,1H),0.92(t,J=7.4Hz,3H); 13 C NMR(101MHz,Chloroform-d)δ172.5,145.7,132.4,128.5,127.7,112.2,68.6,55.5,48.1,37.9,35.3,33.2,32.7,25.7,24.5,24.4,24.2,13.8;HRMS(ESI)calcd for C 20 H 27 NO[M+H] + :298.2165,found:298.2163。

[0173] Example 36: Preparation of 13-(p-tolyl)-1-oxa-14-azaspiro[4.0.5 6 .3 5 tetradec-13-ene(3ah)

[0174]

[0175] Referring to Example 1, replace N-(6-methyl-5-vinyloxy)pyridinium salt with N-(4-cyclohexylbutoxy)pyridinium salt (R1 is H, R2 and R3 form a cyclohexane with the connected carbon atoms, n = 1). The obtained product is a yellow liquid with a yield of 61%. Product characterization: 11H NMR (400 MHz, Chloroform-d) δ 7.76 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 4.16–4.10 (m, 1H), 3.88–3.81 (m, 1H), 2.87 (d, J = 3.3 Hz, 2H), 2.37 (s, 3H), 2.34–2.27 (m, 1H), 2.00–1.91 (m, 3H), 1.75–1.67 (m, 4H), 1.40–1.25 (m, 6H); 13 13C NMR (101 MHz, Chloroform-d) δ 172.7, 140.9, 132.3, 129.0, 127.8, 113.4, 68.3, 47.2, 43.8, 32.7, 31.8, 30.4, 26.3, 25.4, 23.9, 23.7, 21.5; HRMS (ESI) calcd for C 19 H 25 NO [M+H] + : 284.2010, found: 284.2009.

[0176] Example 37: Preparation of 13-(4-methoxyphenyl)-1-oxa-14-azaspiro[4.0.5 6 .3 5 tetradec-13-ene (3hh)

[0177]

[0178] Referring to Example 1, replace the N-(6-methyl-5-vinyloxy) pyridinium salt with N-(4-cyclohexylbutoxy) pyridinium salt (R1 is H, R2 and R3 form a cyclohexane with the adjacent carbon atoms, n = 1), and replace 1-(1-azidoethenyl)-4-methylbenzene with 1-(1-azidoethenyl)-4-methoxybenzene. The obtained product is a yellow liquid with a yield of 63%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.47–7.44 (m, 1H), 7.40–7.36 (m, 1H), 7.29 (m, 1H), 6.96 (dd, J = 8.2, 2.6 Hz, 1H), 4.16–4.10 (m, 1H), 3.88–3.81 (m, 4H), 2.92–2.80 (m, 2H), 2.34–2.25 (m, 1H), 1.99–1.89 (m, 3H), 1.74–1.64 (m, 4H), 1.38–1.17 (m, 6H); 1313C NMR (101 MHz, Chloroform-d) δ 172.5, 159.6, 136.5, 129.3, 120.4, 117.1, 113.4, 112.2, 68.3, 55.4, 47.2, 43.9, 32.7, 31.8, 30.4, 26.2, 25.4, 23.9, 23.7; HRMS (ESI) calcd for C 19 H 25 NO2 [M+H] + : 300.1958, found: 300.1961。

[0179] Example 38: Preparation of 4,4-dimethyl-2-(p-tolyl)-6-oxa-1-azaspiro[4.5]dec-1-ene (3ai)

[0180]

[0181] Referring to Example 1, replace N-(6-methyl-5-vinyloxy) pyridinium salt with N-(7-methyl-6-vinyloxy) pyridinium salt (R1 is H, R2 and R3 are methyl, n = 2), the obtained product is a yellow liquid with a yield of 32%. Product characterization: 1 1H NMR (400 MHz, Chloroform-d) δ 7.78 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 7.9 Hz, 2H), 4.23–4.14 (m, 1H), 3.73–3.66 (m, 1H), 2.91 (d, J = 16.2 Hz, 1H), 2.68 (d, J = 16.2 Hz, 1H), 2.39 (s, 3H), 2.22–2.14 (m, 1H), 1.80–1.74 (m, 1H), 1.69–1.60 (m, 4H), 1.10 (s, 3H), 0.99 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 173.4, 140.9, 132.6, 129.1, 127.7, 102.5, 63.4, 49.5, 44.8, 30.0, 26.1, 24.5, 22.2, 21.5, 20.5; HRMS (ESI) calcd for C 17 H 23 NO [M+H] + : 258.1852, found: 258.1853。

Claims

1. A method for photocatalytic synthesis of N,O-spiroacetalamine derivatives, characterized in that: Comprising the following steps: Mix the 1-alkenyloxycyclic compound shown in Formula I, the 1-azidoethenylcyclic compound shown in Formula II, a photocatalyst, a base, and an organic solvent, and carry out the 1,1,2-trifunctionalization reaction of unactivated alkenes under visible light irradiation and inert gas protection. After the reaction is completed, through post-treatment, an N,O-spiroketalamine derivative shown in Formula III is obtained; Wherein, Ring A is selected from a substituted or unsubstituted pyridyl group, a substituted or unsubstituted quinolinyl group, a substituted or unsubstituted isoquinolinyl group; In Ring A, the substituents of the substituted pyridyl group, the substituted quinolinyl group, and the substituted isoquinolinyl group are selected from C1-C4 alkyl groups; R 1 selected from hydrogen, C1-C4 alkyl; R 2 、R 3 are independently selected from C1-C4 alkyl, or R 2 and R 3 form a 3- to 8-membered alkyl ring with the adjacent carbon atom; n is selected from 0, 1, 2, or 3; Ring B is selected from a 6- to 10-membered aryl group or a 5- to 6-membered heteroaryl group; In Ring B, the 5- to 6-membered heteroaryl group contains one heteroatom, and the heteroatom is selected from N, S, or O; R 4 selected from hydrogen, halogen, cyano, C1-C 10 halogen-substituted or unsubstituted alkyl, C1-C 10 halogen-substituted or unsubstituted alkoxy, C1-C4 halogen-substituted or unsubstituted alkoxycarbonyl, C2-C4 alkenyl, substituted or unsubstituted 6- to 10-membered aryl, substituted or unsubstituted 5- to 6-membered heteroaryl; R 4 In which, the 5- to 6-membered heteroaryl contains one heteroatom selected from N, S, and O; R 4 Among them, the substituents of the substituted 6- to 10-membered aryl group and the substituted 5- to 6-membered heteroaryl group are selected from halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy or C1-C4 alkoxycarbonyl.

2. The method for photocatalytic synthesis of an N,O-spiroketalamine derivative according to claim 1, wherein: In Ring A, the substituents of the substituted pyridyl group, the substituted quinolinyl group, and the substituted isoquinolinyl group are selected from a methyl group, an ethyl group, a n-propyl group, or a n-butyl group; Preferably, ring A is selected from 3. The method for photocatalytic synthesis of N,O-spiroacetalamine derivatives according to claim 1, characterized in that: At least one of the following is satisfied: R 1 is selected from hydrogen, methyl, ethyl, n-propyl or n-butyl; preferably, R 1 is selected from hydrogen, methyl or ethyl; R 2 and R 3 are independently selected from methyl, ethyl, n-propyl or n-butyl, or R 2 and R 3 form a 4- to 6-membered alkyl ring with the adjacent carbon atom; preferably, R 2 and R 3 are independently selected from methyl or ethyl, or R 2 and R 3 form a 4- to 6-membered alkyl ring with the adjacent carbon atom; n is selected from 0, 1, 2, or 3; preferably, n is selected from 1 or 2.

4. The method for photocatalytic synthesis of an N,O-spiroketalamine derivative according to claim 1, wherein: The formula I is selected from:

5. The method for photocatalytic synthesis of an N,O-spiroketalamine derivative according to claim 1, wherein: Ring B is selected from a phenyl group, a pyridyl group, a thiophenyl group, or a furyl group; Preferably, ring B is selected from 6. The method for photocatalytic synthesis of an N,O-spiroketalamine derivative according to claim 1, wherein: R 4 selected from hydrogen, fluorine, chlorine, bromine, cyano, C1-C6 fluorine-substituted or unsubstituted alkyl, C1-C6 fluorine-substituted or unsubstituted alkoxy, C1-C4 fluorine-substituted or unsubstituted alkoxycarbonyl, C2-C4 alkenyl, substituted or unsubstituted 6-membered aryl, substituted or unsubstituted 5-6-membered heteroaryl; R 4 in which, the 5-6-membered heteroaryl is selected from pyridyl, thienyl or furyl; R 4 in which, the substituents of the substituted 6-membered aryl and the substituted 5-6-membered heteroaryl are selected from fluorine, chlorine, bromine, methyl, fluoromethyl, ethyl, fluoroethyl, methoxy, fluoromethoxy, methoxycarbonyl or fluoromethoxycarbonyl; Preferably, R 4 is selected from hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, ethyl, fluoroethyl, propyl, butyl, pentyl, methoxy, fluoromethoxy, methoxycarbonyl, fluoromethoxycarbonyl, vinyl, phenyl, fluorophenyl, pyridyl, fluoropyridyl, thienyl, fluorothienyl, furyl or fluorofuryl; More preferably, the formula II is selected from:

7. The method for photocatalytic synthesis of an N,O-spiroketalamine derivative according to claim 1, wherein: The formula III is selected from:

8. The method for photocatalytic synthesis of N,O-spiroacetalamine derivatives according to any one of claims 1 to 7, characterized in that: At least one of the following is satisfied: The photocatalyst is selected from fac-Ir(ppy)3, Ir(p-F-ppy)3, [Ir(dtppy)(ppy)2]PF6, Eosin Y, or PTH; preferably fac-Ir(ppy)3; The base is selected from at least one of alkali metal carbonates, alkaline earth metal carbonates, alkali metal bicarbonates, alkaline earth metal bicarbonates, alkali metal hydroxides, alkaline earth metal hydroxides, or organic amines; preferably at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide, triethylamine, or N,N-diisopropylethylamine; more preferably at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium hydroxide, sodium hydroxide, or lithium hydroxide; most preferably potassium carbonate or sodium carbonate; The organic solvent is selected from at least one of N,N-dimethylformamide, 1,4-dioxane, diethyl ether, ethyl acetate, methanol, ethanol, acetone, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, or acetonitrile; preferably at least one of 1,4-dioxane, ethanol, or dimethyl sulfoxide; more preferably 1,4-dioxane.

9. The method for photocatalytic synthesis of N,O-spiroacetalamine derivatives according to any one of claims 1 to 7, characterized in that: At least one of the following is satisfied: The molar ratio of the 1-alkenyloxycyclic compound represented by Formula I, the 1-azidovinylcyclic compound represented by Formula II, the photocatalyst, and the base is 1:1-2:0.005-0.03:0.5-2; preferably 1:1-2:0.01-0.02:0.5-1; more preferably 1:2:0.02:1; The amount of the organic solvent used is 1-15 mL / mmol of Formula I; preferably 5-10 mL / mmol of Formula I.

10. The method for photocatalytic synthesis of N,O-spiroacetalamine derivatives according to any one of claims 1 to 7, characterized in that: At least one of the following is satisfied: The light source used for the visible light irradiation is selected from a blue light source, a green light source, an ultraviolet light source, or a white light source; preferably a blue light source; The wavelength used for the visible light irradiation is 455-465 nm; The temperature of the reaction is 0-80 °C; preferably 20-30 °C; The time of the reaction is 1-6 hours; preferably 2-3 hours.

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