Chiral allyl substituted spirocyclic tetronate derivatives, processes for their preparation and use

Abstract

The present application relates to a novel chiral allyl-substituted spirocyclic tetronate derivative with insecticidal and miticidal activity, and a preparation method and application thereof. Specifically, the present application provides a compound of formula (I), an optical isomer, a cis-trans isomer, or a pesticidally acceptable salt thereof. The compound of the present application has obvious insecticidal and miticidal activity, and can be used for developing a novel crop insecticide and miticide with low toxicity, high efficiency and environmental friendliness. (I)

Description

Technical Field

[0001] This invention belongs to the field of pesticide technology, specifically relating to a novel chiral allyl-substituted spirocyclic terfenidamide compound with insecticidal and acaricidal activities, its preparation method, and its application. Background Technology

[0002] The long-term use of existing pesticides has led to resistance in pests, diseases, and weeds, resulting in a significant increase in pesticide use and severe environmental damage. Therefore, there is a need to continuously discover new pesticides with novel mechanisms of action, such as those with higher activity in insecticidal, acaricidal, or herbicidal applications. Quaternary ketoacids, with their unique chemical structures, novel modes of action, outstanding control effects, and low resistance rates, have stood out among numerous insecticides and acaricides, becoming a hot topic in global insecticide and acaricide research and development. Introducing cyclopropane-containing fragments into the structure of quaternary ketoacids and conducting rational molecular design to generate new and more effective insecticides and acaricides, thereby solving the resistance problem of quaternary ketoacids and enabling their application in insecticides and acaricides, is the technical problem this invention aims to solve. Summary of the Invention

[0003] The main objective of this invention is to address the problems mentioned above by providing a novel chiral allyl-substituted spirocyclic terfenidamide derivative with a novel structure and excellent insecticidal and acaricidal activity.

[0004] To achieve the above objectives, a first aspect of the present invention provides a chiral allyl-substituted spirocyclic terfenidamide compound, its optical isomer, cis-trans isomer, or a pesticide-acceptable salt thereof, wherein the structural formula of the derivative is shown in formula (I):

[0005]

[0006] (I)

[0007] In the formula:

[0008] X represents O, S, CH-R 3 or NR 4 , where R 3 and R 4 Each is independently selected from: hydrogen, substituted or unsubstituted C. 1-8 Alkyl, substituted or unsubstituted C 2-8 alkenyl, substituted or unsubstituted C 2-8 Alkyne group, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 1-8 Alkoxy, substituted or unsubstituted C 1-8 alkylthio, substituted or unsubstituted C 6-10Aryl, substituted or unsubstituted 3-6 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from O, S, and N, substituted or unsubstituted 5-6 membered heteroaryl groups containing 1-3 heteroatoms selected from O, S, and N, substituted or unsubstituted C 3-6 cycloalkyl (C 1-4 Alkyl-, substituted or unsubstituted 3- to 6-membered heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from O, S and N (C 1-4 )alkyl-, substituted or unsubstituted phenyl (C 1-4 )alkyl-, substituted or unsubstituted 5-6 membered heteroaryl groups containing 1-3 heteroatoms selected from O, S and N (C 1-4 )alkyl-, substituted or unsubstituted C 1-4 Alkoxy (C 1-4 )alkyl, substituted or unsubstituted C 1-8 Alkyl CO-, substituted or unsubstituted C 1-8 Alkoxy CO-, substituted or unsubstituted C 1-8 Alkyl SO-, substituted or unsubstituted C 1-8 Alkyl SO2-, substituted or unsubstituted C 1-8 Alkoxy SO-, substituted or unsubstituted C 1-8 Alkoxy SO2-, substituted or unsubstituted C 3-6 Cycloalkyl CO-, benzoyl; wherein substitution refers to one or more H atoms on the group being independently substituted by a group selected from the group consisting of: hydrogen, halogen, CN, nitro, hydroxyl, cyano, amino, C 1-4 Alkyl, C 1-4 Halogenated alkyl, C=alkoxy or C 1-4 Halogenated alkoxy groups;

[0009] R 1 Selected from: hydrogen, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl groups containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur, substituted or unsubstituted benzyl, substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted, 3-8 membered heterocycloalkyl groups containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur; wherein substitution means that one or more H atoms on the group are independently substituted by groups selected from the group consisting of hydrogen, halogen, C 1-8 Alkyl, C 1-8 Haloalkyl, C 2-8 alkenyl, C 2-8 Haloalkenyl, C 2-8 alkynyl group, C 2-8 Halogenated alkynyl group, C 1-8 Alkoxy, C 1-8 Halogenated alkoxy groups, C 1-8 Alkylthio, C1-8 Haloalkylthio group, C 1-8 Alkyl sulfoxide, C 1-8 Alkyl sulfone, nitro, hydroxyl, cyano, amino, C 6-10 aryl or one or more selected from C 1-4 Alkyl, C 1-4 The C-substituents of alkyl halogens, halogens, and cyano groups 6-10 Aryl;

[0010] R 2 Selected from: substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl groups containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur, substituted or unsubstituted benzyl, substituted or unsubstituted C 1-8 Alkyl groups, substituted or unsubstituted C3-8 cycloalkyl groups, substituted or unsubstituted 3-8 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur; wherein, substitution means that one or more H atoms on the group are independently substituted by groups selected from the group consisting of: hydrogen, halogen, C 1-8 Alkyl, C 1-8 Haloalkyl, C 2-8 alkenyl, C 2-8 Haloalkenyl, C 2-8 alkynyl group, C 2-8 Halogenated alkynyl group, C 1-8 Alkoxy, C 1-8 Halogenated alkoxy groups, C 1-8 Alkylthio, C 1-8 Haloalkylthio group, C 1-8 Alkyl sulfoxide group, C 1-8 Alkyl sulfone, nitro, hydroxyl, cyano, amino, C 6-10 aryl or one or more selected from C 1-4 Alkyl, C 1-4 The C-substituents of alkyl halogens, halogens, and cyano groups 6-10 Aryl.

[0011] Preferably, X is selected from: O, S, CH-R 3 or NR 4 , where R 3 and R 4 Each of the following groups, independently selected from hydrogen, substituted or unsubstituted, is selected: C 1-8 Alkyl, C 3-8 Cycloalkyl, phenyl, benzyl, pyridyl, pyrazolyl, thiophenyl, furanyl or thiazolyl, biphenyl; substitution refers to one or more H atoms on a group being independently replaced by a substituent selected from the group consisting of: halogen, nitro, hydroxyl, cyano, amino, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4Halogenated alkoxy groups, C 1-4 Alkylthio, C 1-4 Haloalkylthio group, C 2-4 alkenyl, C 2-4 Haloalkenyl, C 2-4 alkynyl group, C 2-4 Halogenated alkynyl group.

[0012] Ideally, R 1 Selected from: hydrogen, substituted or unsubstituted groups of the following: C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 3-6 cycloalkyl, C 1-8 Alkoxy, C 1-8 Alkylthio, C 6-10 aryl, 3-6 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from O, S and N, C 3-6 cycloalkyl (C 1-4 )alkyl-, 3-6 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from O, S and N (C 1-4 )alkyl-, benzyl, C 1-4 Alkoxy (C 1-4 )alkyl, C 1-8 Alkyl CO-, C 1-8 Alkoxy CO-, C 1-8 Alkyl SO-, C 1-8 Alkyl SO2-, C 1-8 Alkyl groups SO-, C 1-8 Alkoxy SO2-, C 3-6 Cycloalkyl CO-, benzoyl; substitution refers to the independent substitution of one or more H atoms on a group by a group selected from the following groups: hydrogen, halogen, CN, nitro, hydroxyl, cyano, amino, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy or C 1-4 Halogenated alkoxy groups.

[0013] Preferably, R 2 Selected from the following groups, whether substituted or unsubstituted: C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 3-6 cycloalkyl, C 1-8 Alkoxy, C 1-8 Alkylthio, C 6-10 aryl, 3-6 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from O, S and N, C 3-6 cycloalkyl (C 1-4 )alkyl-, 3-6 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from O, S and N (C 1-4)alkyl-, benzyl, C 1-4 Alkoxy (C 1-4 )alkyl, C 1-8 Alkyl CO-, C 1-8 Alkoxy CO-, C 1-8 Alkyl SO-, C 1-8 Alkyl SO2-, C 1-8 Alkyl groups SO-, C 1-8 Alkoxy SO2-, C 3-6 Cycloalkyl CO-, benzoyl.

[0014] Preferably, X is selected from:

[0015] And / or,

[0016] R 1 Selected from:

[0017] And / or,

[0018] R 2 Selected from:

[0019] ;

[0020] Preferably, the chiral allyl-substituted spirocyclic terfenidamide derivative is selected from:

[0021]

[0022] A second aspect of the invention provides an agricultural composition comprising, by weight of 100%, (a) 0.001% to 99.99% by weight of the chiral allyl-substituted spirocyclic terfenidamide derivative, its optical isomers, cis-trans isomers, or pesticide-acceptable salts, or combinations thereof; and (b) a pesticide-acceptable carrier and / or excipient.

[0023] A third aspect of the invention provides the use of the chiral allyl-substituted spirocyclic terfenidamide derivative, its optical isomers, cis-trans isomers, or pesticide-acceptable salts, or the agricultural compositions thereof, as insecticides and acaricides for the control of agricultural plant diseases. Preferably, it is used to control alfalfa aphids, carmine spider mites, and diamondback moths.

[0024] A fourth aspect of the present invention provides an insecticidal and / or insect-repellent method comprising applying the chiral allyl-substituted spirocyclic terfenamide derivative, its optical isomer, cis-trans isomer or a pesticide-acceptable salt thereof, or the agricultural composition of the present invention, to an animal / plant that is suffering from or may be suffering from insect pests, the surrounding soil or environment.

[0025] The present invention also provides a method for controlling pests, which involves applying an effective acaricide dose (10-1000 mg / L, more preferably 50-200 mg / L) of the chiral allyl-substituted spirocyclic terfenidamide derivative of the present invention, its optical isomer, cis-trans isomer, or a pesticide-acceptable salt thereof, or the agricultural composition of the present invention, to the plant seeds and / or plant leaves and / or plant fruits or the location where the plant is growing or is expected to grow.

[0026] Preferred pests that can be used for control include (but are not limited to): (i) pests that can be used to kill and / or control at least one pest of the order Acari, order Homoptera, and order Lepidoptera and / or its nymphs and / or its eggs; (ii) pests that can be used to kill insects and / or mites; and (iii) compositions or preparations for the killing and / or control of mites, insects and / or their eggs.

[0027] In a fifth aspect, the present invention provides a composition comprising (i) a chiral allyl-substituted spirocyclic terfenidamide derivative, a geometric isomer thereof, a stereoisomer thereof, or a pesticide-acceptable salt thereof as an active ingredient; and (ii) a carrier and / or a surfactant.

[0028] Preferably, the content of the compound in the composition is 0.001-99.999 wt%.

[0029] Preferably, the composition is a pesticide composition; more preferably, it is an acaricide and insecticide composition.

[0030] In a sixth aspect, the present invention provides a method for killing mites and insects, comprising the steps of: contacting mites and insects with an effective amount of a spirocyclopropane quaternary keto acid derivative, its geometric isomer, stereoisomer, or a pesticide-acceptable salt or prodrug, or a composition as described herein.

[0031] A seventh aspect of the present invention provides a method for preparing the chiral allyl-substituted spirocyclic terfenidamide derivative, comprising the steps of:

[0032] (1) Synthesis of quaternary keto acid intermediates

[0033] (i) Synthesis of spirocyclic quaternary keto acid intermediates

[0034]

[0035] Compound A-2 undergoes amino protonation and carboxyl esterification with an acyl chloride reagent and methanol to transform into compound A-3. Under alkaline conditions, compound A-3 undergoes nucleophilic acylation with an α-haloester in the appropriate solvent to generate compound A-4. Compound A-4 is first heated under reflux in a strongly alkaline environment, followed by intramolecular cyclization under reflux in a neutral / weakly alkaline aqueous medium to obtain compound A-1.

[0036] In the formula, X is as defined above.

[0037] (ii) Synthesis of spirocyclic quaternary ketoacid intermediates containing benzyl protected amides

[0038]

[0039] This explanation only covers the synthesis in the second step; the other steps are similar.

[0040] Under alkaline conditions, compound A-3 is alkylated with BnBr in the corresponding solvent to generate compound B-2.

[0041] In the formula, X is as defined above.

[0042] (iii) Synthesis of spirocyclic quaternary keto acid intermediates containing methyl-protected amides

[0043]

[0044] This explanation only covers the synthesis in the second step; the other steps are similar.

[0045] Compound A-3 undergoes reductive amination with paraformaldehyde and sodium borohydride in the respective solvents to generate compound C-2.

[0046] In the formula, X is as defined above.

[0047] (2) Synthesis of allyl alcohol intermediate

[0048]

[0049] Under a nitrogen atmosphere, compound D-2 and compound D-3 undergo a Grignard reaction in their respective solvents to give compound D-1.

[0050] In the formula, R 2 As defined above.

[0051] (3) Synthesis of the target compound

[0052]

[0053] Under a nitrogen atmosphere, compound E and compound D-1 undergo asymmetric allyl alkylation in their respective solvents with the aid of an iridium catalyst and ligands to generate intermediate compound G; the obtained compound G then undergoes acetylation with acetic anhydride and pyridine in their respective solvents to give compound (I).

[0054] In the formula, X and R 1 R 2 As defined above.

[0055] In step (1), the solvent used is selected from one or more of the following with a water content of less than 10 ppm: acetonitrile, tetrahydrofuran, toluene, trifluorotoluene, 1,2-dichloroethane, dichloromethane, 1,4-dioxane, methyl tert-butyl ether, cyclopentyl methyl ether, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide and N,N-dimethylacetamide, or a combination thereof.

[0056] In step (1), one of the following acyl chloride reagents is selected: thionyl chloride, oxalyl chloride, phosphorus trichloride, and phosphorus pentachloride.

[0057] In step (1), the following bases are selected: piperidine, sodium carbonate, pyridine, trimethylamine, sodium hydride, calcium hydride, sodium hydroxide, cesium hydroxide, potassium hydroxide, sodium carbonate, lithium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, triethylamine, ammonia, sodium tert-butoxide, potassium tert-butoxide, lithium diisopropylamino, lithium diisopropylethylamine, lithium bis(trimethylsilyl)amino, DBU, TBD, DMAP, or combinations thereof.

[0058] In step (1), the reaction is carried out at -10 to 120°C, more preferably at 0 to 25°C.

[0059] In step (1), the reaction time is 1-24h, more preferably 15h.

[0060] In step (2), the solvent used is the same as in step (1).

[0061] In step (2), the reaction is carried out at -10 to 120°C, more preferably at 0 to 25°C.

[0062] In step (2), the reaction time is 1-24h, more preferably 2h.

[0063] In step (3), the iridium catalyst is selected from common ones such as [Ir(cod)Cl]2, [Ir(coe)2Cl]2, Ir(ppy)3, and [IrCl(cod)(NHC)].

[0064] In step (3), the molar amount of iridium catalyst is 2%-5%; the base used is the same as in step (1);

[0065] In step (3), the ligand is selected from one of the following phosphoramidite ligands L1 to L12, preferably L1;

[0066]

[0067] In step (3), the molar ratio of metal catalyst to ligand is 1%:4%, 2%:8%, or 4%:16%, preferably 4%:16%.

[0068] In step (3), the reaction is carried out at -20 to 35°C, more preferably at 0 to 25°C;

[0069] In step (3), the reaction time is 1-48 hours, more preferably 24 hours;

[0070] In step (3), the solvent used is the same as in step (1).

[0071] This invention, through extensive and in-depth research, screening, and testing, provides a novel chiral allyl-substituted spirocyclic terfenadine derivative with insecticidal and acaricidal activity, its preparation method, and applications. This invention modifies the structure of existing quaternary ketoacid compounds by introducing an allyl functional group at the methylene position, followed by esterification modification to regulate the lipophilicity of the molecule. A series of novel quaternary ketoacid compounds were designed and synthesized, achieving excellent insecticidal and acaricidal activity and expanding the insecticidal spectrum, with the potential for developing low-toxicity, highly efficient, and environmentally friendly new pesticides. Detailed Implementation

[0072] To provide a clearer understanding of the technical content of this invention, the following embodiments are provided in detail. However, it is important to note that these descriptions are merely for further illustrating the features and advantages of this invention, and not for limiting the scope of the claims.

[0073] Unless otherwise specified, the reagents and methods involved in the examples are all commonly used in the art.

[0074] the term

[0075] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0076] prefix "C" u-v " indicates that the following groups have u to v carbon atoms, such as "C 1-8 "Can be C1, C2, C3, C4, C5, C6, C7, or C8. For example, "C 1-8 "Alkyl" indicates that the alkyl group has 1 to 8 carbon atoms.

[0077] The term "multiple" refers to two or more, such as 2, 3, 4, 5 or 6.

[0078] The term "halogen" or "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0079] The term "alkyl" refers to a straight-chain or branched, unsubstituted alkyl group having 1-8 carbon atoms (i.e., C46-C56). 1-8 Alkyl groups, preferably hydrocarbon groups with 1-6 carbon atoms (i.e., C16, C26, C36, C46, ​​C56, C6 ... 1-6 Alkyl groups, more preferably hydrocarbon groups with 1-4 carbon atoms (i.e., C4 groups). 1-4 Alkyl). Examples of "alkyl" include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl and 3-methylpentyl, etc.

[0080] The term "alkylene" refers to a saturated divalent hydrocarbon group (i.e., C16-C26) having 1-8 carbon atoms, derived by removing two hydrogen atoms from a straight-chain or branched saturated hydrocarbon. 1-8 Alkylene group, preferably a hydrocarbon group with 1-4 carbon atoms (i.e., C464-C ... 1-4 Alkylene), more preferably 1-3 carbon atoms (i.e., C10-C2 ... 1-3 Alkylene). Examples of "alkylene" include, but are not limited to, methylene, ethylene, isopropylene, etc.

[0081] The term "alkenyl" refers to a group having 2-8 carbon atoms (i.e., C24-C24). 2-8 alkenyl), preferably 2-6 carbon atoms (i.e., C 2-6 Alkenyl) or 2-4 carbon atoms (i.e., C) 2-4 Alkenyl groups are straight-chain or branched hydrocarbon groups having 1-2 carbon-carbon double bonds. Examples of alkenyl groups include, but are not limited to, vinyl, propenyl, and butadienyl (including 1,2-butadienyl and 1,3-butadienyl).

[0082] The term "alkynyl" refers to a group having 2-8 carbon atoms (i.e., C24-C24). 2-8 (Alkyne group), preferably 2-6 carbon atoms (i.e., C10, C20, C30, C40, C50, C60, C60, C70, C6 ... 2-6 (alkynyl group) or 2-4 carbon atoms (i.e., C46) 2-4 Alkyne group, and has 1-2 carbon-carbon triple bonds in a straight / branched hydrocarbon group.

[0083] The term "cycloalkyl" refers to a non-aromatic, saturated, or partially unsaturated cyclic hydrocarbon group, which may be substituted by one or more substituents as described in this application, having 3-6 carbon atoms to form a monocyclic ring or 7-12 carbon atoms to form a bicyclic ring. As used herein, cycloalkyl groups have 3 to 8 cyclic carbon atoms (i.e., C64-C ... 3-8 cycloalkyl groups or 3 to 6 cyclic carbon atoms (i.e., C164-C ...3-6 Cycloalkyl. Examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, cycloheptyl, and cyclooctyl. Exemplary bridged bicyclic cycloalkyl groups include, but are not limited to, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, and bicyclo[3.2.2]nonane.

[0084] The terms “aromatic ring” and “aryl” refer to aromatic carbocyclic groups having a single ring (e.g., monocyclic) or multiple rings (e.g., bicyclic or tricyclic), including fused systems. As used herein, aryl groups have 6 to 10 ring carbon atoms (i.e., C64 ... 6-10 Aryl groups comprise bicyclic groups, wherein the bicyclic group includes an aromatic ring (such as benzo[a]carbon ring) that is fused to a saturated or partially unsaturated carbocyclic or heterocyclic structure. 3-6 Aromatic groups typically include, but are not limited to, the following groups: benzene, naphthalene, anthracene, biphenyl, 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthyl, 2,3-dihydrobenzofuranyl, etc. The term "aryl" includes structures with aryl rings fused to cycloalkyl or heterocycloalkyl groups.

[0085] The terms “heterocyclic,” “heterocyclic,” “heterocyclic group,” and “heterocyclic alkyl” refer to optionally substituted, fully saturated, or partially unsaturated non-aromatic cyclic groups, which can be 3-7 membered monocyclic, 7-11 membered bicyclic, or 10-15 membered tricyclic systems, having at least one heteroatom in at least one carbon-containing ring. Each ring of a heteroatom-containing heterocyclic group may have one, two, or three heteroatoms selected from oxygen, nitrogen, and sulfur. As described herein, heterocyclic groups have 3 to 10 ring atoms (i.e., 3-10 membered heterocyclic groups), 3 to 8 ring atoms (i.e., 3-8 membered heterocyclic groups), 3-8 membered heterocyclic groups, or 3 to 6 ring atoms (i.e., 3-6 membered heterocyclic groups), or 5 to 6 ring atoms (i.e., 5-6 membered heterocyclic groups). The "heterocyclic group" may be substituted by one or more of the substituents described in this application. Examples of "heterocyclic groups" include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, morpholino, thiomorpholino, piperazinyl, homopiperazinyl, propylene oxide, imidazoalkyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[4.1.0]heptyl, azabicyclo[2.2.2]hexyl, N-pyridylurea, pyrimidinoneyl, and 1,1-dioxo-thiomorpholinyl.

[0086] The term "heteroaryl" or "heteroary ring" refers to a heteroaryl system containing one or more heteroatoms selected from oxygen, nitrogen, and sulfur, including monocyclic, bicyclic, or polycyclic fused systems. The heteroaryl group may be substituted by one or more substituents as described herein. As used herein, a heteroaryl group may have 5 to 10 ring atoms (i.e., 5-10-membered heteroaryl), 5 to 8 ring atoms (i.e., 3-8-membered heteroaryl), or 5 to 6 ring atoms (i.e., 5-6-membered heteroaryl). The heteroaryl group may have 1 to 3 cyclic heteroatoms, 1 to 2 cyclic heteroatoms, or 1 cyclic heteroatomum, wherein the cyclic heteroatomum is independently selected from oxygen, nitrogen, and sulfur. Examples of "heteroaryl" include, but are not limited to, pyrrole, pyridyl, pyrazolyl, imidazolyl, pyrazinyl, imidazopyridyl, benzofuranyl, pyrimidinyl, triazolyl, tetrazolyl, furanyl, thiophenyl, thiazolyl, quinolinyl, isoquinolinyl, indolyl, etc.

[0087] "Oxygen group" refers to the -O- group; "acyloxy group" refers to the -C(=O)-O- group; "carbonyl group" refers to the -C(=O)- group; "nitro group" refers to the -NO2 group; "cyano group" refers to the -CN group; "hydroxyl group" refers to the -OH group; and "amino group" refers to the -NH2 group. The term "oxo-" represents a divalent group (=O). "Sulfanamide group" refers to the -SO2NH2 group. "Carboxyl group" refers to the -COOH group. "Benzoyl group" refers to the phenyl -CO- group.

[0088] The term "substituted" refers to the substitution of one or more hydrogen atoms in a specific group by any substituent mentioned in this specification, provided that the substitution does not exceed the normal valence of the specified group or atom, and the resulting compound is stable, i.e., a compound that can be isolated, characterized, and tested for bioactivity. Unless otherwise specified, "substituted" means that one or more (e.g., 2, 3, or 4) hydrogen atoms in a group are independently substituted by a group selected from the group consisting of: H, substituted or unsubstituted C atoms. 1-8 Alkyl, substituted or unsubstituted C 1-8 Alkoxy, substituted or unsubstituted C 1-8 Alkoxy-C 1-8 Alkyl, substituted or unsubstituted C 1-8 Alkoxy-carbonyl, substituted or unsubstituted allyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenoxycarbonyl, substituted or unsubstituted C 2-8 alkenyl-carbonyl, substituted or unsubstituted C 2-8 Alkynyl-carbonyl, substituted or unsubstituted C 3-8 cycloalkyl, substituted or unsubstituted C 3-8 The group may contain cycloalkyl-carbonyl, substituted or unsubstituted benzoyl, substituted or unsubstituted furanyl, or substituted or unsubstituted N,N-dimethylcarbonyl, wherein the substitution refers to one or more H atoms on the group being independently substituted by a substituent selected from the group consisting of halogen, halogenated or unsubstituted C.1-4 Alkyl, halogenated or unsubstituted C 2-4 alkenyl, halogenated or unsubstituted C 2-4 Alkyne, halogenated or unsubstituted C 1-4 Alkoxy and halogenated or unsubstituted C 1-4 Alkyl-carbonyl.

[0089] The terms “active substance of the present invention” or “active compound of the present invention” refer to compounds with the structure shown in general formula (I) or their optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof.

[0090] The term "pesticide-acceptable salt" means that the anion of the salt is known and acceptable in forming the pesticide-acceptable salt. Preferably, the salt is water-soluble. Suitable acid addition salts formed from compounds of formula (I) include salts formed from inorganic acids, such as hydrochlorides, phosphates, sulfates, and nitrates; and salts formed from organic acids, such as acetates, benzoates, etc.

[0091] Active ingredients

[0092] This invention provides a compound of formula (I), its optical isomer, cis-trans isomer, or a pesticide-acceptable salt thereof:

[0093] (I)

[0094] Among them, X and R 1 R 2 As defined above.

[0095] In another preferred embodiment, the compound is any of the compounds in the examples.

[0096] This invention aims to include salts of compounds. A "pesticide-acceptable salt" may have more than one charged atom, and the multiple charged atoms may have multiple equilibria. Any salt form, such as pharmaceutically acceptable salts of the compounds of this invention, including salts of inorganic or organic acids, is within the scope of this invention. Furthermore, various crystal forms of pharmaceutically acceptable salts of the compounds of this invention are also within the scope of this invention. Any prodrugs of the compounds of this invention are also within the scope of this invention.

[0097] As used herein, the term "pesticide-acceptable salt" refers to those salts that, within reasonable medical judgment, are suitable for contact with human and lower animal tissues without excessive toxicity, irritation, allergic reactions, etc., and that are proportionate to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pesticide-acceptable, non-toxic acid addition salts are salts formed by reacting an amino group with an inorganic acid (such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid) or with an organic acid (such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid) or by using other methods used in the art (such as ion exchange). Other pharmaceutically acceptable salts include, but are not limited to, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, hydrogen sulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, gluconate, glyceryl phosphate, gluconate, hemisulfate, heptaate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 3-phenylpropionate, phosphate, neopentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc.

[0098] A solvate is a combination or complex of one or more solvent molecules with a compound of the present invention. Examples of solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and ethanolamine. The compounds of the present invention can exist in a non-solventized form or in a solvated form with pharmaceutically acceptable solvents such as water and ethanol; therefore, the present invention includes both solvated and non-solventized forms.

[0099] Some compounds exist as tautomers. These tautomers exist in equilibrium with each other. For example, amide-containing compounds can exist in equilibrium with imine tautomers. Regardless of which tautomer is exhibited, and regardless of the equilibrium nature between the tautomers, those skilled in the art will understand that a compound comprises all or every tautomer of the compound. Therefore, amide-containing compounds should be understood as including their imine tautomers. Similarly, imine-containing compounds should be understood as including their amide tautomers.

[0100] The compounds of the present invention may contain an asymmetric center or a chiral center, and thus exist in various stereoisomeric forms. The compounds may be chiral, racemic, or may exist as compositions comprising one or more stereoisomers. The present invention includes enantiomers, diastereomers, racemic mixtures, enantiomer-rich mixtures, and diastereomer-rich mixtures. All stereoisomeric forms of the compounds of the present invention, including but not limited to diastereomers, enantiomers, and sterically hindered isomers, and mixtures thereof, such as racemic mixtures, will form part of the present invention. Additionally, the asymmetric carbon atom may be present in a substituent such as an alkyl group. All such isomers and mixtures thereof are intended to be included within the present invention. If a specific enantiomer of a compound of the present invention is desired, it can be prepared by asymmetric synthesis or by derivatization with a chiral auxiliary agent, wherein the resulting diastereomeric mixture is isolated and the auxiliary group is cleaved to provide a pure desired enantiomer. Alternatively, when the molecule contains a basic functional group such as an amino group or an acidic functional group such as a carboxyl group, it can form a diastereomeric salt with a suitable optically active acid or base. The diastereomer thus formed can then be resolved by fractional crystallization or chromatography known in the art, and the pure enantiomer can subsequently be recovered. Furthermore, the separation of enantiomers and diastereomers can be achieved using chromatography with a chiral stationary phase.

[0101] In this document, all stereoisomers are considered when the stereochemistry of any particular chiral atom is not determined. Furthermore, this invention relates to all geometric and positional isomers. The compounds of this invention can exist in various tautomeric forms, and all such forms are included within the scope of this invention. All stereoisomers of the compounds of this invention are contemplated to include mixtures or pure or substantially pure forms.

[0102] In this document, unless otherwise stated, the structures described herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. In addition to therapeutic uses, such compounds may be used, for example, as analytical tools or probes in bioassays. Any formula or structure given herein is also intended to represent both the unlabeled and isotopically labeled forms of the compounds. Isotopically labeled compounds have the structures described by the formulas given herein, except that one or more atoms are replaced by atoms having selected atomic masses or mass numbers. Examples of isotopes that may be incorporated into the compounds of this disclosure include, but are not limited to, isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as, but not limited to, 2 H (deuterium, D) 3 H (tritium) 11 C 13 C 14 C 15 N、 18 F, 31 P, 32 P, 35 S,36 Cl and 125 I. Various isotope-labeled compounds disclosed herein, for example, those doped with radioactive isotopes such as 3 H and 14 Compounds of C can be used in metabolic studies, reaction kinetic studies, detection or imaging techniques such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), including drug or substrate tissue distribution analysis or patient radiotherapy.

[0103] Insecticidal activity of the substance of the present invention

[0104] The active compounds of this invention are active ingredients with preventive and / or therapeutic value in the field of pest control, possessing a broad spectrum of biocidal activity and good tolerance to warm-blooded species, fish, and plants. These active ingredients act on all or individual developmental stages of animal pests, and their insecticidal or acaricidal activity can be directly expressed.

[0105] The active compounds of this invention can be used to combat and control infestations by insect pests (e.g., Lepidoptera, Homoptera) and other invertebrate pests (e.g., mites). Insects and mites are collectively referred to as pests below. Pests that can be combated and controlled by using these compounds include those related to crop cultivation.

[0106] The compounds provided by this invention possess significant insecticidal activity and can be used to control and eliminate a wide range of pests. In this specification, the pests that can be killed or controlled include, but are not limited to, the following: such as the carmine spider mite. "Mite control" refers to acaricidal activity at every stage of the mite life cycle (egg, larva, adult). Therefore, the technical solution of this invention also includes the use of the spirocyclopropane quaternary keto acid compounds of Formula I as acaricides in agriculture or other fields. The chiral allyl-substituted spirocyclopropane terfenamide derivatives of this invention are also suitable for controlling at least one of the Homoptera (such as alfalfa aphids) and Lepidoptera (such as diamondback moths) pests in agriculture or other fields.

[0107] Therefore, the technical solution of the present invention also includes the use of the novel chiral allyl-substituted spirocyclic terfenidamide derivative of formula (I) as an insecticide in agriculture or other fields.

[0108] Composition

[0109] Insecticide / acaricide compositions containing the "active substance of the present invention" can be prepared into insecticide compositions using conventional methods. These active compounds can be formulated into conventional formulations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with the active substance, microcapsules in polymers, seed coating formulations, and formulations for use with combustion devices, such as fumigation cylinders and fumigation discs, as well as ULV cold mist and warm mist formulations. These formulations can be produced using known methods, for example, by mixing the active compound with expanders, which are liquid, liquefied gaseous, or solid diluents or carriers, and surfactants, i.e., emulsifiers and / or dispersants and / or foaming agents, can be selected at will. Organic solvents can also be used as adjuvants, for example, when water is used as the expander.

[0110] Liquid solvents are generally suitable as diluents or carriers, such as: aromatic hydrocarbons, such as xylene, toluene, or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride, or dichloromethane; aliphatic hydrocarbons, such as cyclohexane or paraffins, such as mineral oil fractions; alcohols, such as ethanol or ethylene glycol and their ethers and esters; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, or cyclohexanone; or less commonly used polar solvents, such as dimethylformamide, dimethyl sulfoxide, and water.

[0111] A liquefied gas diluent or carrier refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants, halogenated hydrocarbons, and butane, propane, nitrogen, and carbon dioxide.

[0112] Solid carriers can be ground natural minerals such as kaolin, clay, talc, quartz, activated clay, montmorillonite, or diatomaceous earth; and ground synthetic minerals such as highly dispersed silica, alumina, and silicates. Solid carriers for granulation are crushed and graded natural zircon, such as calcite, marble, pumice, sepiolite, dolomite, inorganic and organic coarse powders synthesized into granules, and organic materials such as sawdust, coconut husks, corncobs, and tobacco stalks.

[0113] Nonionic and anionic emulsifiers can be used as emulsifiers and / or foam forming agents. Examples include polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, alkylaryl polyethylene glycol ethers, alkyl sulfonates / sulfates, aryl sulfonates, and albumin hydrolysates. Dispersants include lignin sulfite waste and methylcellulose.

[0114] Binders, such as carboxymethyl cellulose, and natural and synthetic polymers in the form of powders, granules, or emulsions, such as gum arabic, polyvinyl alcohol, and polyvinyl acetate, can be used in the formulation.

[0115] Coloring agents such as inorganic dyes, such as iron oxide, cobalt oxide and Prussian blue; organic dyes, such as azo dyes or metal phthalocyanine dyes; and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, aluminum and zinc, can be used.

[0116] The "active compound of the present invention" can be mixed with other active compounds and exist in their commercial formulations or in dosage forms prepared from these formulations. These other active compounds are insecticides (such as phosphate esters, carbamates, chlorinated hydrocarbons, and substances produced by microorganisms, such as abamectin), fungicides (methoxyacrylates, amides, triazoles, etc., fungicides, herbicides, growth controllers, etc.).

[0117] Furthermore, the "active compound of the present invention" can also be mixed with synergists in commercial formulations or in dosage forms prepared from these formulations. These synergists are compounds that enhance the activity of the active compound. Since the active compound itself is active, the synergist may not be necessary. These formulations typically contain 0.001 to 99.99% by weight, preferably 0.01 to 99.9% by weight, and more preferably 0.05 to 90% by weight of the "active compound of the present invention" in the total weight of the composition. The concentration of the active compound in the commercial formulation or dosage form can vary over a wide range. The concentration of the active compound in the dosage form can range from 0.0000001 to 100% (g / v), preferably between 0.0001 and 1% (g / v).

[0118] Tests have shown that the compound shown in formula (I), its optical isomers, cis-trans isomers, or its pesticide-acceptable salts have particularly good control effects on alfalfa aphids, carmine spider mites, and diamondback moths.

[0119] The main advantages of this invention include:

[0120] (1) This invention provides a novel chiral allyl-substituted spirocyclic terfenidamide derivative, its composition, uses and preparation method.

[0121] (2) The compounds of the present invention have significant insecticidal and acaricidal activities and have broadened the insecticidal spectrum, and are expected to develop new crop insecticides and acaricides that are low in toxicity, highly efficient and environmentally friendly.

[0122] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Percentages and parts are by weight unless otherwise stated.

[0123] Example 1

[0124] The preparation process of (S)-acetic acid-2-oxoylide-3-(1-phenylprop-2-enyl)-1-azaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0125]

Step 1

[0126]

[0127] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0128] Specifically, it includes the following steps:

[0129] Intermediate e-1: 1-azaspiro[4.5]decane-2,4-dione

[0130] (e-1)

[0131] 2.86 g (20 mmol) of 1-cyclohexylcarbamic acid was placed in a 100 mL round-bottom flask, and 40 mL of methanol was added. After adding 4.7 g (40 mmol) of SOCl2 dropwise in an ice bath at 0 °C, the reaction flask was brought to room temperature and two drops of DMF were added. After the reaction was complete, the solvent was removed by concentration under reduced pressure. The obtained solid product, the hydrochloride salt of the amino acid ester, could be directly used in the next step, with a yield of 99%.

[0132] 3.86 g (20 mmol) of methyl 1-cyclohexylcarbamate hydrochloride and 4.44 g (44 mmol) of triethylamine were dissolved in 40 mL of dichloromethane. 3.26 g (24 mmol) of methyl malonate chloride was added dropwise in an ice bath at 0 °C. The mixture was stirred overnight at room temperature, quenched with 20 mL of water, and extracted with dichloromethane. The combined organic phases were dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a yellow oily product. This was directly added to the next step.

[0133] The yellow oily product obtained in the previous step was dissolved in 40 mL of methanol, and 9.6 mL (48 mmol, 5.0 M / CH3OH) of a methanol solution of sodium methoxide was added dropwise. The mixture was stirred and refluxed overnight at 65 °C. After the reaction was complete, the methanol was removed by concentration under reduced pressure. The residue was diluted with 10 mL of water, acidified with 20 mL of concentrated hydrochloric acid, and extracted five times with 20 mL of dichloromethane. The organic phases were combined, dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a yellow oily product. 40 mL of acetonitrile and 1.5 mL (80 mmol) of distilled water were added to the obtained residue. The mixture was refluxed at 80 °C for 2 h and then concentrated under reduced pressure to remove the solvent. The crude product was pulped with isopropyl ether, filtered, and washed to obtain the quaternary keto acid intermediate e-1.

[0134]

Step Two

[0135]

[0136] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0137] Specifically, it includes the following steps:

[0138] Intermediate d-1: 1-Phenylon-2-Buten-1-ol

[0139] (d-1)

[0140] Under a nitrogen atmosphere, 10 mL of dry THF and 10.0 mmol of benzaldehyde were added to a pre-dried 50 mL Schlenk flask. While stirring in an ice bath at 0 °C, 20.0 mmol of vinyl magnesium bromide (1.0 M / THF) was added dropwise. The ice bath was removed, and the mixture was allowed to cool to room temperature. After the reaction was complete, the mixture was quenched dropwise with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic phases were dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the solvent. The residue was purified by column chromatography using silica gel and separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to give a colorless oily phenyl-substituted allyl alcohol d-1.

[0141]

Step 3

[0142]

[0143] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0144] Specifically, it includes the following steps:

[0145] Compound I-1: (S)-Acetyl-2-oxoylide-3-(1-phenylprop-2-enyl)-1-azaspiro[4.5]dec-3-en-4-yl ester

[0146] (S)-Ⅰ-1

[0147] Under a nitrogen atmosphere, [Ir(cod)Cl]₂ (0.004 mmol) and Carreira ligand (S)-L or (rac)-L (0.016 mmol) were added to a 10 mL Schlenk tube dried with a heat gun. The tube was purged and backfilled with nitrogen, and freshly distilled CH₂Cl₂ (3.0 mL) was added. The mixture was stirred at room temperature for 15 minutes, and the solution gradually turned deep red. Then, e⁻¹ (0.4 mmol) was added, and the reaction mixture immediately turned bright yellow. Subsequently, d⁻¹ (0.2 mmol) and trifluoroacetic acid (0.2 mmol) were added sequentially. The reaction mixture was stirred at room temperature until d⁻¹ was completely reacted (monitored by TLC). Separation using a preparative thin-layer chromatography plate (CH₂Cl₂ / MeOH = 20 / 1) yielded a pale red solid. This intermediate was directly added to the next reaction step without further detection. Intermediate g-1 was dissolved in dichloromethane (5.0 mL), and pyridine (0.4 mmol) and acetic anhydride (0.4 mmol) were added. The mixture was stirred at room temperature for 16 h. The reaction was quenched with 10 mL of water, and the mixture was extracted with dichloromethane (10 mL × 3). The combined organic phases were dried over 10 mL of saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the solvent. After removing the solvent under reduced pressure, the mixture was separated by preparative thin-layer chromatography (CH2Cl2 / MeOH = 20 / 1) using a triethylamine-treated column chromatography plate to give compound (S)-I-1 (white solid, 97% yield, 99% ee, mp: 167-168℃).

[0148] The final test results are as follows: 1H NMR (400 MHz, CDCl3) δ 7.38 (brs, 1H), 7.31 - 7.24(m, 4H), 7.22 - 7.17 (m, 1H), 6.24 (ddd, J = 17.2, 10.0, 7.2 Hz, 1H), 5.20(d, J = 10.0 Hz, 1H), 5.11 (d, J = 17.2, Hz, 1H), 4.46 (d, J = 7.2 Hz, 1H), 1.96 (s, 3H), 1.81 - 1.10 (m, 10H); HPLC (Chiralpak AD-H, n-hexane / ethanol =90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R = 9.194 min (minor), 10.492 min (major).

[0149] Example 2

[0150] The preparation process of (S)-acetic acid-3-[1-(4-chlorophenyl)prop-2-enyl]-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0151]

Step 1

[0152]

[0153] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0154]

Step Two

[0155]

[0156] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0157]

Step 3

[0158] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0159] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 95%, 99% ee, mp: 196-197℃. 1 H NMR (400 MHz, CDCl3) δ 7.80 (brs, 1H), 7.29 - 7.18 (m, 4H), 6.21 (ddd, J = 17.2, 10.0, 7.2 Hz, 1H), 5.19 (d, J = 10.0 Hz, 1H), 5.07 (d, J t R = 9.316 min (minor), 11.280 min (major).

[0160] Example 3

[0161] The preparation process of (S)-acetic acid-2-oxylidene-3-(1-phenylprop-2-enyl)-1-aza-8-oxaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0162]

Step 1

[0163]

[0164] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0165]

Step Two

[0166]

[0167] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0168]

Step 3

[0169]

[0170] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0171] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 82%, 99% ee, mp: 141-143℃. 1 H NMR (400 MHz, CDCl3)δ 8.71 (brs, 1H), 7.33 - 7.16 (m, 5H), 6.24 (ddd, J = 17.2, 10.0, 7.2 Hz, 1H), 5.21 (d, J = 10.0 Hz, 1H), 5.11 (d, J =17.2 Hz, 1H), 4.46 (d, J = 7.2 Hz, 1H), 3.98 - 3.96 (m, 2H), 3.67 - 3.54 (m2H), 2.00 (s, 3H), 2.07 - 1.94 (m, 2H), 1.43 - 1.32 (m, 2H); HPLC (ChiralpakAD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R =14.459 min (minor), 17.157 min (major).

[0172] Example 4

[0173] The preparation process of (R)-acetic acid-2-oxylidene-3-(1-phenylprop-2-enyl)-1-aza-8-oxaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0174]

Step 1

[0175]

[0176] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0177]

Step Two

[0178]

[0179] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0180]

Step 3

[0181]

[0182] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (R)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0183] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 80%, 96% ee, mp: 141-143℃. 1 H NMR (400 MHz, CDCl3)δ 8.71 (brs, 1H), 7.33 - 7.16 (m, 5H), 6.24 (ddd, J = 17.2, 10.0, 7.2 Hz, 1H), 5.21 (d, J = 10.0 Hz, 1H), 5.11 (d, J =17.2 Hz, 1H), 4.46 (d, J = 7.2 Hz, 1H), 3.98 - 3.96 (m, 2H), 3.67 - 3.54 (m2H), 2.00 (s, 3H), 2.07 - 1.94 (m, 2H), 1.43 - 1.32 (m, 2H); HPLC (ChiralpakAD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R =14.300 min (major), 17.154 min (minor).

[0184] Example 5

[0185] The preparation process of (S)-acetic acid-3-[1-(2,4-dichlorophenyl)prop-2-enyl]-2-oxo-1-aza-8-oxaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0186]

Step 1

[0187]

[0188] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0189]

Step Two

[0190]

[0191] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0192]

Step 3

[0193]

[0194] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, (PhO)2PO2H, nitrogen protection, room temperature, 24h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16h.

[0195] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 86%, 99% ee, mp: 120-123℃. 1 H NMR (400 MHz, CDCl3)δ 8.89 (brs, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.37 (s, 1H), 7.20 (d, J = 8.4 Hz, 1H), 6.18 (ddd, J = 17.2, 10.4, 6.8 Hz,1H), 5.25 (d, J = 10.4 Hz, 1H), 5.14 (d, J = 17.2 Hz, 1H), 4.75 (d, J = 6.8Hz, 1H), 3.99 - 3.90 (m, 2H), 3.67 - 3.55 (m, 2H), 2.04 (s, 3H), 2.03 - 1.93(m, 2H), 1.43 - 1.34 (m, 2H); HPLC (Chiralpak AD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R = 31.985 min (major), 34.038 min (minor).

[0196] Example 6

[0197] The preparation process of (S)-acetic acid-3-[1-(2,4-dimethylphenyl)prop-2-enyl]-2-oxo-1-aza-8-oxaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0198]

Step 1

[0199]

[0200] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0201]

Step Two

[0202]

[0203] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0204]

Step 3

[0205]

[0206] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0207] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 40%, 99% ee, mp: 112-120℃. 1H NMR (400 MHz, CDCl3)δ 8.48 (brs, 1H), 7.14 (d, J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.15 (ddd, J = 17.2, 10.0, 6.8 Hz,1H), 5.20 (d, J = 10.0 Hz, 1H), 5. 06 (d, J = 17.2 Hz, 1H), 4.59 (d, J = 6.8Hz, 1H), 3.98 - 3.89 (m, 2H), 3.68 - 3.54 (m, 2H), 2.28 (s, 3H), 2.21 (s, 3H), 2.06 - 1.91 (m, 2H), 1.85 (s, 3H), 1.42 - 1.23 (m, 2H); HPLC (ChiralpakAD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R =9.877 min (major), 11.688 min (minor).

[0208] Example 7

[0209] The preparation process of (R)-acetic acid-3-[1-(2,4-dimethylphenyl)prop-2-enyl]-2-oxo-1-aza-8-oxaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0210]

Step 1

[0211]

[0212] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0213]

Step Two

[0214]

[0215] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0216]

Step 3

[0217]

[0218] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (R)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0219] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 43%, 99% ee, mp: 112-120℃. 1 H NMR (400 MHz, CDCl3)δ 8.48 (brs, 1H), 7.14 (d, J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.15 (ddd, J = 17.2, 10.0, 6.8 Hz,1H), 5.20 (d, J = 10.0 Hz, 1H), 5. 06 (d, J = 17.2 Hz, 1H), 4.59 (d, J = 6.8Hz, 1H), 3.98 - 3.89 (m, 2H), 3.68 - 3.54 (m, 2H), 2.28 (s, 3H), 2.21 (s, 3H), 2.06 - 1.91 (m, 2H), 1.85 (s, 3H), 1.42 - 1.23 (m, 2H); HPLC (ChiralpakAD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R =9.824 min (major), 11.606 min (minor).

[0220] Example 8

[0221] The preparation process of (S)-acetic acid-3-[1-(4-fluorophenyl)prop-2-enyl]-2-oxylidene-1-aza-8-oxaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0222]

Step 1

[0223]

[0224] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0225]

Step Two

[0226]

[0227] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0228]

Step 3

[0229]

[0230] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, (PhO)2PO2H, nitrogen protection, room temperature, 24h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16h.

[0231] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: pale red solid, yield 45%, 99% ee, mp: 174-176℃. 1 H NMR (400 MHz, CDCl3)δ 8.65 (s, 1H), 7.27 - 7.22 (m, 2H), 7.02 -6.94 (m, 2H), 6.22 (ddd, J = 17.2, 10.0, 7.2 Hz, 1H), 5.20 (d, J = 10.0 Hz,1H), 5.07 (d, J = 17.2 Hz, 1H), 4.41 (d, J = 7.2 Hz, 1H), 3.99 - 3.91 (m,2H), 3.64 - 3.53 (m, 2H), 2.09 (s, 3H), 2.07 - 1.95 (m, 2H), 1.41 - 1.34 (m,2H); HPLC (Chiralpak AD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R =18.689 min (minor), 20.714 min (major).

[0232] Example 9

[0233] The preparation process of (S)-acetic acid-3-(but-3-en-2-yl)-2-oxylide-1-aza-8-oxaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0234]

Step 1

[0235]

[0236] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (c) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0237]

Step Two

[0238]

[0239] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0240]

Step 3

[0241]

[0242] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, (PhO)2PO2H, nitrogen protection, room temperature, 24h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16h.

[0243] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 15%, 99% ee, mp: 173-175℃. 1H NMR (400 MHz, CDCl3)δ 7.75 (brs, 1H), 6.01 (ddd, J = 16.8, 10.4,6.4 Hz, 1H), 5.08 (d, J = 6.4, 1H), 5.04 (d, J = 10.4 Hz, 1H), 4.03 - 3.96(m, 2H), 3.65 - 3.54 (m, 2H), 3.23 - 3.15 (m, 1H), 2.26 (s, 3H), 2.07 - 1.95(m, 2H), 1.38 (d, J = 13.6 Hz, 2H), 1.28 (d, J = 6.8 Hz, 3H); HPLC (ChiralpakAD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R =15.381 min (major), 16.683 min (minor).

[0244] Example 10

[0245] The preparation process of (S)-acetic acid-1-methyl-2-oxoylide-3-(1-phenylprop-2-enyl)-1-azaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0246]

Step 1

[0247]

[0248] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) Paraformaldehyde, NaBH3, MeOH, 60℃, 1h; (c) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (d) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0249] Specifically, it includes the following steps:

[0250] Intermediate e-3: N-methyl-4-propyl-succinimide

[0251] (e-3)

[0252] 2.86 g (20 mmol) of 1-cyclohexylcarbamic acid was placed in a 100 mL round-bottom flask, and 40 mL of methanol was added. After adding 4.7 g (40 mmol) of SOCl2 dropwise in an ice bath at 0 °C, the reaction flask was brought to room temperature and two drops of DMF were added. After the reaction was complete, the solvent was removed by concentration under reduced pressure. The obtained solid product, the hydrochloride salt of the amino acid ester, could be directly used in the next step, with a yield of 99%.

[0253] 3.14 g (20 mmol) of methyl 1-cyclohexylcarbamate hydrochloride was dissolved in 40 mL of methanol and refluxed at 60 °C for 0.5 h. 0.6 g (20 mmol) of paraformaldehyde was added, and the mixture was stirred under heating for another 0.5 h. After the solution cooled to room temperature, 1.51 g (40 mmol) of sodium borohydride was added. Once no more bubbles were generated, the mixture was refluxed at 60 °C for 15 min, quenched with 15 mL of water, and extracted three times with dichloromethane. The organic phases were combined, dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a colorless oil. Purification by column chromatography on silica gel (petroleum ether: ethyl acetate = 2:1) yielded the product methyl 1-(methylamino)cyclohexane-1-carbamate.

[0254] 3.86 g (20 mmol) of methyl 1-(methylamino)cyclohexane-1-carboxylate and 4.44 g (44 mmol) of triethylamine were dissolved in 40 mL of dichloromethane. 3.26 g (24 mmol) of methyl malonate chloride was added dropwise under ice bath conditions at 0 °C. The mixture was stirred overnight at room temperature, quenched with 20 mL of water, and extracted with dichloromethane. The combined organic phases were dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a yellow oily product. This was directly added to the next step.

[0255] The yellow oily product obtained in the previous step was dissolved in 40 mL of methanol, and 9.6 mL (48 mmol, 5.0 M / CH3OH) of a methanol solution of sodium methoxide was added dropwise. The mixture was stirred and refluxed overnight at 65 °C. After the reaction was complete, the methanol was removed by concentration under reduced pressure. The residue was diluted with 10 mL of water, acidified with 20 mL of concentrated hydrochloric acid, and extracted five times with 20 mL of dichloromethane. The organic phases were combined, dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a yellow oily product. 40 mL of acetonitrile and 1.5 mL (80 mmol) of distilled water were added to the residue. The mixture was refluxed at 80 °C for 2 h and then concentrated under reduced pressure to remove the solvent. The crude product was pulped with isopropyl ether, filtered, and washed to obtain the quaternary keto acid intermediate e-3.

[0256]

Step Two

[0257]

[0258] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0259]

Step 3

[0260]

[0261] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0262] The remaining specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: pale yellow solid, yield 73%, 20% ee, mp: 104-107℃. 1 H NMR (400 MHz, CDCl3) δ 7.32 - 7.25 (m, 4H), 7.23 - 7.18 (m,1H), 6.28 (ddd, J = 17.4, 10.0, 7.6 Hz, 1H), 5.21 (d, J = 10.0 Hz, 1H), HPLC (Chiralpak) AD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, λ = 220 nm) t R = 6.829 min (minor),8.799 min (major).

[0263] Example 11

[0264] The preparation process of (S)-acetic acid-1-benzyl-2-oxoylide-3-(1-phenylprop-2-enyl)-1-azaspiro[4.5]dec-3-en-4-yl ester is shown below:

[0265]

Step 1

[0266]

[0267] Reagents and conditions: (a) SOCl2, MeOH, 0℃-room temperature, 16h; (b) BnBr, DIPEA, acetonitrile, 80℃, 2h; (c) Triethylamine, methyl malonate chloride, CH2Cl2, 0℃-room temperature, 16h; (d) (i) Sodium methoxide, MeOH, 65℃, 16h; (ii) Water, acetonitrile, 80℃, 16h.

[0268] Specifically, it includes the following steps:

[0269] Intermediate e-4: N-benzyl-4-propyl-succinimide

[0270] (e-4)

[0271] 2.86 g (20 mmol) of 1-cyclohexylcarbamic acid was placed in a 100 mL round-bottom flask, and 40 mL of methanol was added. After adding 4.7 g (40 mmol) of SOCl2 dropwise in an ice bath at 0 °C, the reaction flask was brought to room temperature and two drops of DMF were added. After the reaction was complete, the solvent was removed by concentration under reduced pressure. The obtained solid product, the hydrochloride salt of the amino acid ester, could be directly used in the next step, with a yield of 99%.

[0272] 3.86 g (20 mmol) of methyl 1-cyclohexylcarbamate hydrochloride and 5.17 g (40 mmol) of DIPEA were dissolved in 40 mL of acetonitrile. 3.308 g (18 mmol) of benzyl bromide was added dropwise. The mixture was refluxed at 80 °C for 2 h, concentrated under reduced pressure to remove acetonitrile, and extracted three times with water and dichloromethane. The combined organic phases were dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a pale yellow oily product. This was directly used in the next step.

[0273] The pale yellow oily product from the previous step and 4.44 g (44 mmol) of triethylamine were dissolved in 40 mL of dichloromethane. 3.26 g (24 mmol) of methyl malonate chloride was added dropwise under ice bath conditions at 0 °C. The mixture was stirred overnight at room temperature, quenched with 20 mL of water, and extracted with dichloromethane. The combined organic phases were dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a yellow oily product. This was directly added to the next step.

[0274] The yellow oily product obtained in the previous step was dissolved in 40 mL of methanol, and 9.6 mL (48 mmol, 5.0 M / CH3OH) of a methanol solution of sodium methoxide was added dropwise. The mixture was stirred and refluxed overnight at 65 °C. After the reaction was complete, the methanol was removed by concentration under reduced pressure. The residue was diluted with 10 mL of water, acidified with 20 mL of concentrated hydrochloric acid, and extracted five times with 20 mL of dichloromethane. The organic phases were combined, dried over saturated brine and anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a yellow oily product. 40 mL of acetonitrile and 1.5 mL (80 mmol) of distilled water were added to the residue. The mixture was refluxed at 80 °C for 2 h and then concentrated under reduced pressure to remove the solvent. The crude product was pulped with isopropyl ether, filtered, and washed to obtain the quaternary keto acid intermediate e-4.

[0275]

Step Two

[0276]

[0277] Reagents and conditions for reaction: (d) THF, 0℃-room temperature, 2h.

[0278]

Step 3

[0279]

[0280] Reagents and conditions: (a) [Ir(cod)Cl]2, Carreira ligand (S)-L, CH2Cl2, trifluoroacetic acid, nitrogen protection, room temperature, 24 h; (b) acetic anhydride, pyridine, CH2Cl2, room temperature, 16 h.

[0281] The remaining specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white solid, yield 80%, 99% ee, mp: 90-93℃. 1 H NMR (400 MHz, CDCl3) δ 7.37 - 7.16 (m, 10H), 6.33 (ddd, J = 17.2,10.0, 7.6 Hz, 1H), 5.25 (d, J = 10.0 Hz, 1H), 5.17 (d, J = 17.2 Hz, 1H), 4.58(s, 2H), 4.51 (d, J = 7.6 Hz, 1H), 1.94 (s, 3H), 1.71 - 1.49 (m, 9H), 1.19 -1.08 (m, 1H); HPLC (Chiralpak IF, n-hexane / ethanol = 95 / 5, flow rate = 1.0mL / min, λ = 220 nm) t R=32.562 min (minor), 35.458 min (major).

[0282] Test Example: Insecticidal Activity Test of the Compounds of the Invention

[0283] Test Example 1: Insecticidal activity against alfalfa aphids

[0284] Aphids belong to the order Hemiptera and are pests with piercing-sucking mouthparts; they are common crop pests. Taking the alfalfa aphid as an example, the immersion method was used for testing.

[0285] Procedure: Accurately weigh the sample and add DMSO as a co-solvent to prepare a stock solution of 10,000 mg / L. Take a certain amount of the stock solution and dilute it with 0.1 mL / L Triton X-100 aqueous solution. Use spirotetramat or spirodiclofen of the same concentration as a positive control. Use DMSO of the same concentration as a blank control. Screening concentrations are 200 mg / L, 100 mg / L, and 50 mg / L.

[0286] Seven-day-old adult wingless aphids were selected and transferred to cultured broad bean leaves with stems to reproduce nymphs, with 4-5 adults on each leaf. After 24 hours, the adults were removed from the leaves, leaving 15-25 nymphs on each leaf. After another 24 hours, the broad bean leaves with nymphs were immersed in the pesticide solution for 10 seconds, then removed and placed on a culture rack. Each treatment concentration was used in triplicate, and the racks were covered with perforated transparent plastic cups. Mortality rates were recorded 5 days after treatment. The results are shown in Table 1 below.

[0287] Test Example 2: Insecticidal activity against Tetranychus carmineus

[0288] The carmine spider mite, belonging to the family Tetranychusidae in the order Ephemerales, is a common crop pest. Taking the carmine spider mite (Tetranychuscinnabarinus) as an example, the immersion method was used for testing.

[0289] Procedure: Accurately weigh the sample and add DMSO as a co-solvent to prepare a stock solution of 10,000 mg / L. Take a certain amount of the stock solution and dilute it with 0.1 mL / L Triton X-100 aqueous solution. Use spirotetramat or spirodiclofen of the same concentration as a positive control. Use DMSO of the same concentration as a blank control. Screening concentrations are 200 mg / L, 100 mg / L, and 50 mg / L.

[0290] Broad bean stems and leaves infested with adult mites and nymphs were transferred to cultured broad bean leaves with stems. Adult mites were removed after 24 hours, leaving 20-30 nymphs on each leaf. The broad bean leaves infested with nymphs were immersed in the pesticide solution for 10 seconds, then removed and placed on a culture rack. Three replicates were set up for each treatment concentration. Mortality rates were recorded 5 days after treatment. The results are shown in Table 1 below.

[0291] Table 1. Bioactivity of the compounds against alfalfa aphid and carmine spider mite (Tetranychus cinnabarinus)

[0292]

[0293] Table 2. LC50 of different enantiomers of II-1 and II-3 against Alfalfa Aphid 50 value (rac)-Ⅱ-1 0.178 Y=-4.609 + 2.047X 0.073-0.345 0.958 (S)-Ⅱ-1 0.094 Y=-4.484 + 2.275X 0.062-0.124 0.981 (R)-Ⅱ-1 0.174 Y=-3.988 + 1.780X 0.037-0.442 0.972 (rac)-Ⅱ-3 0.114 Y=-4.455 + 2.167X 0.098-0.130 0.987 (S)-Ⅱ-3 0.098 Y=-5.577 + 2.799X 0.067-0.129 0.998 (R)-Ⅱ-3 0.142 Y=-5.774 + 2.681X 0.054-0.278 0.950

[0294] The experimental results above show that some compounds in this invention exhibit good insecticidal activity against alfalfa aphids. Specifically, (rac)-II-1 and (rac)-II-3, at a concentration of 200 mg / L, achieved corrected mortality rates of 60% and 68% against alfalfa aphids, respectively. Further analysis using LC-MS (Table 2) demonstrates this activity. 50 Value analysis showed that the insecticidal activity of (S)-configuration enantiomers such as (S)-II-1 and (S)-II-3 was significantly better than that of their corresponding (R)-configurations and racemic mixtures. For example, the LC50 of (S)-II-1 was significantly higher. 50 The value was only 0.094 g / L, far lower than (rac)-II-1's 0.178 g / L and (R)-II-1's 0.174 g / L, indicating that optical configuration has a significant impact on the insecticidal activity of this type of compound. For Tetranychus carmine, most compounds only showed a 100% corrected mortality rate at high concentrations of 500 mg / L, with low or no activity at concentrations of 200 mg / L and below.

[0295] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0296] In this specification, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and variations can be made without departing from the spirit and scope of the invention. Therefore, this specification should be considered illustrative rather than restrictive.

Claims

1. A chiral allyl-substituted spirocyclic terfenidamide derivative, its optical isomer, cis-trans isomer, or a pesticide-acceptable salt thereof, characterized in that, The structural formula of the derivative is shown in formula (I): (I) In the formula: X represents O, S, CH-R 3 or NR 4 , where R 3 and R 4 Each is independently selected from: hydrogen, substituted or unsubstituted C. 1-8 Alkyl, substituted or unsubstituted C 2-8 alkenyl, substituted or unsubstituted C 2-8 Alkyne, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 1-8 Alkoxy, substituted or unsubstituted C 1-8 alkylthio, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 3-6 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from O, S, and N, substituted or unsubstituted 5-6 membered heteroaryl groups containing 1-3 heteroatoms selected from O, S, and N, substituted or unsubstituted C 3-6 cycloalkyl (C 1-4 Alkyl-, substituted or unsubstituted 3- to 6-membered heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from O, S, and N (C 1-4 )alkyl-, substituted or unsubstituted phenyl (C 1-4 ) alkyl-, substituted or unsubstituted 5-6 membered heteroaryl groups containing 1-3 heteroatoms selected from O, S and N (C 1-4 )alkyl-, substituted or unsubstituted C 1-4 Alkoxy (C 1-4 )alkyl, substituted or unsubstituted C 1-8 Alkyl CO-, substituted or unsubstituted C 1-8 Alkoxy CO-, substituted or unsubstituted C 1-8 Alkyl SO-, substituted or unsubstituted C 1-8 Alkyl SO2-, substituted or unsubstituted C 1-8 Alkoxy SO-, substituted or unsubstituted C 1-8 Alkoxy SO2-, substituted or unsubstituted C 3-6 Cycloalkyl CO-, benzoyl; wherein substitution refers to one or more H atoms on the group being independently substituted by a group selected from the group consisting of: hydrogen, halogen, CN, nitro, hydroxyl, cyano, amino, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy or C 1-4 Halogenated alkoxy groups; R 1 Selected from: hydrogen, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl groups containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur, substituted or unsubstituted benzyl, substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted, 3-8 membered heterocycloalkyl groups containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur; wherein substitution means that one or more H atoms on the group are independently substituted by groups selected from the group consisting of hydrogen, halogen, C 1-8 Alkyl, C 1-8 Haloalkyl, C 2-8 alkenyl, C 2-8 Haloalkenyl, C 2-8 alkynyl group, C 2-8 Halogenated alkynyl group, C 1-8 Alkoxy, C 1-8 Halogenated alkoxy groups, C 1-8 Alkylthio, C 1-8 Haloalkylthio group, C 1-8 Alkyl sulfoxide group, C 1-8 Alkyl sulfone, nitro, hydroxyl, cyano, amino, C 6-10 aryl or one or more selected from C 1-4 Alkyl, C 1-4 The C-substituents of alkyl halogens, halogens, and cyano groups 6-10 Aryl; R 2 Selected from: substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl groups containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur, substituted or unsubstituted benzyl, substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted, 3-8 membered heterocycloalkyl groups containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur; wherein substitution means that one or more H atoms on the group are independently substituted by groups selected from the group consisting of hydrogen, halogen, C 1-8 Alkyl, C 1-8 Haloalkyl, C 2-8 alkenyl, C 2-8 Haloalkenyl, C 2-8 alkynyl group, C 2-8 Halogenated alkynyl group, C 1-8 Alkoxy, C 1-8 Halogenated alkoxy groups, C 1-8 Alkylthio, C 1-8 Haloalkylthio group, C 1-8 Alkyl sulfoxide group, C 1-8 Alkyl sulfone, nitro, hydroxyl, cyano, amino, C 6-10 aryl or one or more selected from C 1-4 Alkyl, C 1-4 The C-substituents of alkyl halogens, halogens, and cyano groups 6-10 Aryl.

2. The chiral allyl-substituted spirocyclic terfenidamide derivative according to claim 1, characterized in that, X is selected from: O, S, CH-R 3 or NR 4 , where R 3 and R 4 Each is independently selected from: hydrogen, substituted or unsubstituted C. 1-8 Alkyl, substituted or unsubstituted C 2-8 alkenyl, substituted or unsubstituted C 2-8 Alkyne, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 1-8 Alkoxy, substituted or unsubstituted C 1-8 alkylthio, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 3-6 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from O, S, and N, substituted or unsubstituted 5-6 membered heteroaryl groups containing 1-3 heteroatoms selected from O, S, and N, substituted or unsubstituted C 3-6 cycloalkyl (C 1-4 Alkyl-, substituted or unsubstituted 3- to 6-membered heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from O, S, and N (C 1-4 )alkyl-, substituted or unsubstituted phenyl (C 1-4 ) alkyl-, substituted or unsubstituted 5-6 membered heteroaryl groups containing 1-3 heteroatoms selected from O, S and N (C 1-4 )alkyl-, substituted or unsubstituted C 1-4 Alkoxy (C 1-4 )alkyl, substituted or unsubstituted C 1-8 Alkyl CO-, substituted or unsubstituted C 1-8 Alkoxy CO-, substituted or unsubstituted C 1-8 Alkyl SO-, substituted or unsubstituted C1-8 alkyl SO2-, substituted or unsubstituted C 1-8 Alkoxy SO-, substituted or unsubstituted C1-8 alkoxy SO2-, substituted or unsubstituted C 3-6 Cycloalkyl CO-, benzoyl; wherein substitution refers to one or more H atoms on the group being independently substituted by a group selected from the group consisting of: hydrogen, halogen, CN, nitro, hydroxyl, cyano, amino, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy or C 1-4 Halogenated alkoxy groups.

3. The chiral allyl-substituted spirocyclic terfenidamide derivative according to claim 1, characterized in that, X is selected from: ; and / or, R 1 Selected from: and / or R 2 Selected from: 。 4. The chiral allyl-substituted spirocyclic terfenidamide derivative according to claim 1, characterized in that, The chiral allyl-substituted spirocyclic terfenidamide derivatives are selected from:

5. An agricultural composition, characterized in that, include: (a) 0.001% by weight to 99.99% by weight of any chiral allyl-substituted spirocyclic terfenidamide derivative, its optical isomer, cis-trans isomer, or pesticide-acceptable salt, or combination thereof, as described in any one of claims 1 to 4; and (b) Pesticide-acceptable carriers and / or excipients.

6. Use of the chiral allyl-substituted spirocyclic terfenidamide derivative, its optical isomer, cis-trans isomer, or pesticide-acceptable salt thereof, or the agricultural composition of claim 5, as an insecticide and acaricide for the control of agricultural plant diseases, according to any one of claims 1 to 4.

7. The use according to claim 6, characterized in that, Used to control alfalfa aphids, carmine spider mites, and diamondback moths.

8. A method for preparing a derivative according to any one of claims 1 to 4, characterized in that, The method includes the steps of reacting the compound of formula E and the compound of formula D-1 under conditions of solvent, acid catalyst, metal catalyst, and ligand to obtain the intermediate compound of formula G, and reacting the compound of formula G under conditions of acetic anhydride, pyridine, and solvent to obtain a chiral compound having the structure of general formula I. #imgpt38# 9. The preparation method according to claim 9, characterized in that, The reaction solvent is selected from one or more of the following: acetonitrile, tetrahydrofuran, toluene, trifluorotoluene, 1,2-dichloroethane, dichloromethane, 1,4-dioxane, methyl tert-butyl ether, cyclopentyl methyl ether, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide, with a water content of less than 10 ppm. The metal catalyst used in the reaction is an iridium complex; preferably, it is a 1,5-cyclooctadiene iridium chloride dimer. The ligand is selected from one of the phosphoramidite ligands L1 to L12: #imgpt39# Metal catalysts: The molar ratio of ligands is 1%:4%, 2%:8%, or 4%:16%; The acid catalyst is selected from one or more of the following: o-nitrobenzoic acid, m-nitrobenzoic acid, diphenyl phosphate, diphenylsulfonamide, trifluoroacetic acid, trichloroacetic acid, acetic acid, phosphoric acid, boron trifluoride diethyl ether complex, iron trifluoromethanesulfonate, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, cerium trifluoromethanesulfonate, neodymium trifluoromethanesulfonate, europium trifluoromethanesulfonate, dysprosium trifluoromethanesulfonate, lutetium trifluoromethanesulfonate, erbium trifluoromethanesulfonate, and gadolinium trifluoromethanesulfonate. The reaction temperature is -20 to 35℃; The reaction time is 1 to 48 hours.

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