Asymmetric hydroarylation method of internal olefin

Abstract

The invention provides an efficient method for asymmetric hydroarylation of internal olefin. The method provided by the invention has the advantages of high yield, simple operation, mild reaction conditions, strong chiral control ability and wide substrate applicability, and has high academic and application values.

Description

Technical Field

[0001] The present invention relates to the field of organic chemistry, and in particular provides a method for hydrogen functionalization of unsaturated heterocycles and internal olefins. Background Art

[0002] Chiral saturated heterocyclic skeletons are widely present in natural products, active pharmaceutical ingredients, and biofunctional materials. In particular, structural units such as dihydrofuran and dihydropyrrole are often used as core drug structures or intermediates, and have extremely high synthetic value and research significance. Constructing multi-substituted, enantioenriched heterocyclic skeletons is one of the important challenges in the current field of organic synthesis. However, traditional methods usually rely on pre-designed substrate structures or multi-step reaction sequences, which limits the versatility and molecular diversity of the reactions. Therefore, developing a modular, concise, and highly stereoselective synthetic strategy has become a key goal of current research.

[0003] Asymmetric hydroarylation is an efficient method for constructing C–C bonds. It can directly convert simple alkenes into high-value-added chiral products with advantages such as high atom economy and mild conditions. In recent years, this type of reaction has been used to construct a variety of chiral heterocyclic structures. The application of strategies such as alkyl cross-coupling, C–H activation, and photocatalytic hydrogen atom transfer (HAT) has also significantly improved the complexity and selectivity of molecules. However, the application of internal alkenes, especially heterocyclic alkenes such as 2,3- or 2,5-dihydrofuran and dihydropyrrole, in asymmetric hydroarylation still faces the following key challenges: (1) In the absence of chelating directing groups or conjugated systems, it is difficult to precisely control the regioselectivity and enantioselectivity; (2) The structural stability of internal alkenes is poor, and undesirable olefin isomerization and protonation side reactions are prone to occur during the reaction, which seriously interferes with the stereo- and positional selectivity of the products; (3) At present, high enantioselective reactions often require the guidance of auxiliary groups, which increases the number of synthetic steps and affects the overall synthetic efficiency and atom economy. Given these challenges, there is an urgent need to develop a highly enantioselective and regioselective asymmetric hydroarylation reaction system for internal olefins that does not require an external directing group. This strategy is particularly suitable for heterocyclic structures such as 2,3- or 2,5-dihydrofuran and dihydropyrrole, allowing the construction of polysubstituted chiral heterocyclic products. This strategy has the potential to simplify synthetic routes, expand the structural space of heterocyclic molecules, and promote their widespread application in drug development and the construction of complex functional molecules. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art, such as the need to pre-introduce a directing functional group into the reaction substrate, the narrow substrate universality, and the limited range of functional group selection. Thus, a highly efficient method for the hydroarylation of internal olefins, including 2,5-dihydrofuran and 2,5-dihydropyrrole, is provided. The method of the present invention has the advantages of high yield, simple operation, mild reaction conditions, strong chirality control, and wide substrate applicability, and has high academic and application value.

[0005] The first aspect of the present invention provides a method for hydroarylation of internal olefins, characterized in that it comprises the steps of:

[0006]

[0007] or

[0008]

[0009] Under a protective gas atmosphere, compound IV, compound III, bis(1,5-cyclooctadiene)nickel and a solvent are mixed, and then compound I and compound II are added thereto in sequence. After that, the protective gas environment is removed and the reaction is carried out at room temperature to obtain a compound of formula A;

[0010] Among them, R 1 、R 2 Each independently selected from the following group: C 1-20 Alkyl, C 6-10 Aromatic ring, 1, 2 or 3 R 1-1 Substituted C 1-20 Alkyl, 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkyl, 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkenyl, -LR 1-1 ;

[0011] L is a chemical bond, -C 1-20 Alkylene-, -OC 1-20 Alkylene-, -C 1-20 Alkylene-O-, -C 1-20 Alkylene-S-, -CO-C 1-20 Alkylene-, -C 1-20 Alkylene-CO-, -NH-C 1-20 Alkylene-, -C 1-20 Alkylene-NH-;

[0012] R 1-1 、R 1-2 Each independently selected from the group consisting of halogen, -OSiR a R b Rc ;

[0013] R 3 Select from the following group: C 6-14 Aryl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, 5-16 membered heteroaryl, 1, 2 or 3 R 3-1 Substituted C 6-14 Aryl, substituted by 1, 2 or 3 R 3-2 Substituted C 3-20 Cycloalkenyl, substituted by 1, 2 or 3 R 3-3 substituted 5-16 membered heteroaryl;

[0014] R 3-1 、R 3-2 、R 3-3 Each independently selected from the group consisting of halogen, C 1-20 Alkyl, -OC 1-20 Alkyl, -C 1-20 Alkyl-O-, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, -C 1-6 Alkylene-5-16 membered heterocycloalkyl, -OC 1-6 Alkylene-C 6-10 Aryl, C 6-10 Aryl, 5-16 membered heteroaryl, -NR a R b 、-CO-OC 1-20 alkyl;

[0015] R a 、R b and R c Each independently selected from the following group: H, C 1-20 Alkyl or C 6-10 aromatic rings;

[0016] X is Cl, Br, I, OTs or OTf;

[0017] Z is N, O, S, P or Si;

[0018] R 4 Select from the following group: C 1-10 alkyl;

[0019] M is an alkali metal;

[0020] The 5-16 membered heteroaryl group is a 5-16 membered heteroaromatic ring having one, two or three heteroatoms selected from N, O and S and having one, two, three or four heteroatoms;

[0021] The 5-16 membered heterocycloalkyl group is a 5-16 membered heterocycloalkyl group having one, two or three heteroatoms selected from N, O and S and having one, two, three or four heteroatoms;

[0022] The structure of compound IV is:

[0023]

[0024] in,

[0025] R 9a 、R 9b 、R 9c and R 9d Each independently selected from: C 1-6 Alkyl, unsubstituted or replaced by R 9a-1 Substituted C 6-14 aryl;

[0026] R 9a-1 C 1-4 alkyl;

[0027] R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R 8c Each independently selected from: H or C 1-4 alkyl;

[0028] R 5 and R 6 are independently hydrogen, C 1-4 Alkyl, halogen, or C 6-10 Aryl; wherein R 5-1 and R 5-2 are each independently hydrogen or C 1-4 alkyl;

[0029] is a single bond or a double bond;

[0030] Or, R 5 、R 6 Together with the carbon atoms to which it is attached,

[0031] Y - It is a monovalent anion;

[0032] In another preferred embodiment, the R 1 、R 2 Each independently selected from the following group: C 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10Cycloalkenyl, substituted by 1, 2 or 3 R 1-2 Substituted C 3-10 Cycloalkyl, -LR 1-1 .

[0033] In another preferred embodiment, the R 1 、R 2 Each independently selected from the following group: C 1-10 Alkyl, C 3-10 Cycloalkyl, -LR 1 -1 .

[0034] In another preferred embodiment, the R 1 Select from the following group: C 1-10 Alkyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, substituted by 1, 2 or 3 R 1-2 Substituted C 3-10 Cycloalkyl, -LR 1-1 ; R 2 Independently C 1-10 alkyl.

[0035] In another preferred embodiment, the R 1 and R 2 In the C 1-20 Alkyl and 1, 2 or 3 R 1-1 Substituted C 1-20 C in the alkyl group 1-20 Alkyl is C 1-10 Alkyl; for example, C 1-6 Alkyl; another example is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; another example is methyl.

[0036] In another preferred embodiment, the L is a chemical bond, C 1-10 Alkylene, -C 1-10 Alkylene-O-, -C 1-10 Alkylene-CO-, -C 1-10 Alkylene-NH-.

[0037] In another preferred embodiment, the R 1-1 、R 1-2 Each independently selected from the group consisting of halogen, C 1-6 Alkyl, 5-16 membered heterocycloalkyl, C 6-10 Aromatic ring, 1, 2 or 3 R 1-1-1 Substituted C 6-10 Aromatic ring, 1, 2 or 3 R 1-1-1 Substituted 5-16 membered heterocycloalkyl.

[0038] In another preferred embodiment, the R 1-1-1 Selected from the group consisting of halogen, C 1-20 Alkyl, -OC 1-20 Alkyl, -C 1-20 Alkyl-O-, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, -C 1-6 Alkylene-5-16 membered heterocycloalkyl, -OC 1-6 Alkylene-C 6-10 Aryl, C 6-10 Aryl, 5-16 membered heteroaryl, -NR a R b 、-CO-OC 1-20 alkyl.

[0039] In another preferred embodiment, the R 1-1 In the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; another example is methyl.

[0040] In another preferred embodiment, the R 1-2 wherein the halogen is F, Cl, Br or I, for example, F.

[0041] In another preferred embodiment, the R 3 Select from the following group: C 6-10 Aryl, C 3-16 Cycloalkenyl, 5-16 membered heterocycloalkyl, 5-16 membered heteroaryl, 1, 2 or 3 R 3-1 Substituted C 6-10 Aryl.

[0042] In another preferred embodiment, R 3 Select from the following group: C 6-10 Aryl, C 3-12 Cycloalkenyl, 5-12 membered heterocycloalkyl, 5-12 membered heteroaryl, 1, 2 or 3 R 2-1 Substituted C 6-10 Aryl.

[0043] In another preferred embodiment, the R 3 Select from the following group: C 6-10 Aryl, substituted by 1, 2 or 3 R 3-1 Substituted C 6-10 Aryl.

[0044] In another preferred embodiment, the R 3 In the C 6-10 Aryl and said 1, 2 or 3 R 3-1 Substituted C 6-10 C in aromatic rings6-10 Aryl is substituted phenyl or naphthyl.

[0045] In another preferred embodiment, R 3-1 、R 3-2 、R 3-3 Each independently selected from the group consisting of halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Halogenated alkyl, -SC 1-6 Alkyl, 5-8 membered heterocycloalkyl, -C 1-3 Alkylene-5-8 membered heterocycloalkyl, -OC 1-3 Alkylene-C 6-10 Aromatic ring, C 6-10 Aromatic ring, -NR a R b ,-CO-OC 1-10 alkyl.

[0046] In another preferred embodiment, the compound III is a metal salt of an alcohol, and the metal salt of the alcohol is an alkali metal salt of a primary alcohol or a secondary alcohol.

[0047] In another preferred embodiment, the compound of formula III is not sodium tert-butoxide.

[0048] In another preferred embodiment, the R 4 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.

[0049] In another preferred embodiment, the M is Li, Na or K.

[0050] In another preferred embodiment, the R 4 OM is EtOLi, EtONa, EtOK, i PrOLi, i PrONa, i PrOK, preferably i PrONa.

[0051] In another preferred embodiment, the structure of compound IV is selected from the following group:

[0052]

[0053] In another preferred embodiment, the R 9a 、R 9b 、R 9c and R 9d Same or different.

[0054] In another preferred embodiment, the R 9a 、R 9b 、R 9cand R 9d Each independently is C 1-6 Alkyl, C 6-10 Aromatic ring, or 1 or 2 R 9a-1 Substituted C 6-10 Aromatic ring.

[0055] In another preferred embodiment, R 9a 、R 9b 、R 9c and R 9d Each independently is C 1-6 Alkyl, C 6-10 Aromatic rings,

[0056] In another preferred embodiment, R 9a 、R 9b 、R 9c and R 9d In the C 6-14 The aromatic ring and the R 9a-1 Alkyl substituted C 6-14 C in aromatic rings 6-14 The aromatic rings are independently C 6-10 An aromatic ring, such as a benzene ring or a naphthalene ring.

[0057] In another preferred embodiment, each of the R 9a-1 is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; another example is methyl or tert-butyl.

[0058] In another preferred embodiment, R 9a 、R 9b 、R 9c and R 9d Each is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0059] In another preferred embodiment, R 9a 、R 9b 、R 9c and R 9d Each independently selected from the following group: For example, R 9a 、R 9b 、R 9c and R 9d Same, for

[0060] In another preferred embodiment, R 7a 、R 7b 、R 7c 、R 8a 、R 8band R 8c Same or different.

[0061] In another preferred embodiment, R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R 8c Each is independently hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0062] In another preferred embodiment, R 7a 、R 7c 、R 8a and R 8c All are hydrogen, R 7b 、R 8b Each is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl. 5 and R 6 Each independently is C 6-10 Aryl, or R 5 and R 6 Together with the carbon atoms to which it is attached,

[0063] In another preferred embodiment, when R 9a 、R 9b 、R 9c and R 9d is unsubstituted or replaced by R 9a-1 Substituted C 6-14 When aryl, R 5 and R 6 Together with the carbon atoms to which it is attached,

[0064] In another preferred embodiment, when R 9a 、R 9b 、R 9c and R 9d C 1-6 When alkyl, R 5 and R 6 Each independently is C 6-10 Aryl.

[0065] In another preferred embodiment, Y - F - 、Cl - Br - , I - or BF4 - ; For example, Cl - or BF4 - .

[0066] In another preferred embodiment, the compound I is selected from the following group:

[0067]

[0068] In another preferred embodiment, the compound II is selected from the following group:

[0069] In another preferred embodiment, the compound IV is selected from the following group:

[0070] In another preferred embodiment, the compound A is selected from the following group:

[0071]

[0072] In another preferred embodiment, the ee value of the compound A is greater than 80%, preferably greater than 85%, preferably greater than 90%, for example, 91%, 92%, 93%, 94%, or 95%.

[0073] In another preferred example, the molar ratio of the compound I to the compound II is 10:1 to 1:10, preferably 8:1 to 1:5, for example 6:1, 4:1, 2:1, 1:1, 1:2, 1:5.

[0074] In another preferred example, the molar ratio of the compound I to the compound III is 10:1 to 1:10, preferably 5:1 to 1:5, for example 4:1, 2:1, 1:1, 1:2, 1:3, 1:5.

[0075] In another preferred example, the molar ratio of the compound I to bis(1,5-cyclooctadiene)nickel is 1:0.01-0.5, preferably 1:0.01-0.1, for example 60:1, 50:1, 30:1, 20:1, 10:1.

[0076] In another preferred embodiment, the molar ratio of the compound IV to bis(1,5-cyclooctadiene)nickel is 0.5-2:0.5-2, preferably 0.8-1.2:0.8-1.2, for example 1:1.

[0077] In another preferred embodiment, the solvent is an alkane solvent, an ether solvent, or a combination thereof.

[0078] In another preferred embodiment, the solvent is selected from the group consisting of n-hexane, n-heptane, cyclohexane, cycloheptane, tetrahydrofuran, 1,4-dioxane, or a combination thereof.

[0079] In another preferred embodiment, the reaction temperature is 10-60°C, preferably 20-50°C, for example 30°C.

[0080] In another preferred embodiment, the reaction time is 12-24 hours; for example, 24 hours.

[0081] In another preferred embodiment, the feeding process is carried out in a protective gas atmosphere, and the protective gas is selected from the following group: nitrogen, helium, argon, or a combination thereof.

[0082] In another preferred embodiment, the reaction is carried out under stirring.

[0083] In another preferred embodiment, the stirring speed is 100-1500 rpm.

[0084] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one.

[0085] the term

[0086] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which this invention belongs. Unless otherwise specified, the terms used in this invention have the following meanings:

[0087] In the present invention, the term "internal olefin" includes but is not limited to the structure shown in Compound I of the present invention.

[0088] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0089] The term "alkyl" refers to a group having a specified number of carbon atoms (e.g., C 1-20 ). The alkyl group preferably includes 1 to 20, or 1 to 10, or 1 to 8, or 1 to 6, or 1 to 4 carbon atoms, and the alkyl group includes but is not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl and n-hexyl.

[0090] The term "cycloalkyl" refers to a cycloalkyl group having the specified number of carbon atoms (e.g., C 3-20 ) and is composed only of carbon atoms. The cycloalkyl group preferably includes 3 to 20, or 3 to 12, or 3 to 10, or 3 to 8, or 3 to 6 carbon atoms. The cycloalkyl group may include a fused cycloalkyl group, a bridged cycloalkyl group, or a spirocycloalkyl group. Preferably, the cycloalkyl group includes but is not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0091] The term "aromatic ring" refers to a ring having a specified number of carbon atoms (e.g., C 6-14) is a cyclic hydrocarbon group consisting only of carbon atoms, which is monocyclic or polycyclic, and at least one of the groups is aromatic (in accordance with Huckel's rule). Aryl groups include but are not limited to phenyl, naphthyl and anthracenyl.

[0092] The term "heteroaromatic ring" refers to a cyclic hydrocarbon group having a specified number of carbon atoms (e.g., 5-16 members), a specified number of heteroatoms (e.g., 1, 2, or 3 members), and a specified heteroatom species (one or more of N, O, and S), which is monocyclic or polycyclic, and at least one ring is aromatic (in accordance with Huckel's rule). The heteroaromatic ring preferably includes a 3-20 membered, or 3-12 membered, or 3-10 membered, or 3-8 membered, or 3-6 membered heteroaromatic ring, and the heteroaromatic ring may include a fused ring, a bridged ring, or a spiro ring. Preferably, the heteroaromatic ring includes, but is not limited to, a furan ring, a pyrrole ring, a thiophene ring, a pyrazole ring, an imidazole ring, an oxazole ring, a thiazole ring, a pyridine ring, a pyrimidine ring, and an indole ring.

[0093] The term "heterocycloalkyl" refers to a group having the specified number of carbon atoms (e.g., C 3-20 ), a specified number of heteroatoms (e.g., 1, 2 or 3), and a specified type of heteroatoms (one or more of N, O and S). The heterocycloalkyl group preferably includes a 3- to 20-membered, or 3- to 12-membered, or 3- to 10-membered, or 3- to 8-membered, or 3- to 6-membered heterocycloalkane, and the heterocycloalkyl group may include a fused heterocycloalkyl group, a bridged heterocycloalkyl group or a spiroheterocycloalkyl group. Preferably, the heterocycloalkyl group includes but is not limited to the following.

[0094] The term "cycloalkenyl" means a cyclic hydrocarbon group having at least one double bond (such as a carbon-carbon double bond), and which may be connected to the rest of the molecule via a single bond via any suitable carbon atom; for example, the cycloalkenyl group preferably comprises 3 to 20, or 3 to 12, or 3 to 10, or 3 to 8, or 3 to 6 carbon atoms, and the cycloalkenyl group may include a fused cycloalkenyl group, a bridged cycloalkenyl group or a spirocycloalkenyl group, preferably, the C 3-20 Cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl.

[0095] Those skilled in the art will understand that, according to the conventions used in the art, the structural formula used in this application to describe a group means that the corresponding group R is connected to other fragments and groups in the compound through this site.

[0096] A "-" at the end of a group means that the group is attached to another fragment in the molecule through that site. For example, -OCH3 refers to a methoxy group, in which the oxygen atom is attached to the rest of the molecule.

[0097] When any variable (such as R Ar) appears multiple times in the definition of a compound, the definition of each position of the variable is independent of the definition of the other positions, and their meanings are independent of each other and do not affect each other. Therefore, if a group is replaced by 1, 2 or 3 R Ar group substituted, that is, the group may be replaced by up to 3 R Ar Replace, the position R Ar Definition and other positions R Ar In addition, combinations of substituents and / or variables are permissible only if such combinations result in stable compounds.

[0098] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention. DETAILED DESCRIPTION

[0099] The present invention provides a method for asymmetric hydrogen-hydrogen functionalization of internal olefins. In the method, only a compound of formula IV and Ni(cod)2 are used, without using other bases or nucleophilic reagents, such as sodium tert-butoxide in the prior art, to complete the asymmetric hydrogen arylation reaction of internal olefins with very high enantioselectivity. In addition, the present invention can change the configuration of the product by adjusting the configuration of the ligand to directly obtain a product with a high ee value.

[0100] Compared to existing technologies, this invention successfully suppresses olefin isomerization and enables asymmetric hydroarylation of internal olefins under mild conditions. In particular, when using 2,5-dihydrofuran and 2,5-dihydropyrrole, 3-arylated saturated heterocyclic products are exclusively obtained, whereas other technologies often undergo isomerization to yield 2-arylated asymmetric saturated heterocyclic products.

[0101] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which specific conditions are not specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0102] Example 1

[0103]

[0104] General Method A: In a nitrogen-filled glove box, compound IV-1 (9.4 mg, 0.02 mmol, 5 mol%), compound III sodium isopropoxide (50.1 mg, 0.61 mmol, 3.05 equiv), Ni(cod)2 (2.8 mg, 0.02 mmol, 5 mol%), and 2 mL of isopropanol were added to a 4 mL vial and stirred at room temperature for 30 minutes. Compound I (0.2 mmol) and compound II (0.4 mmol) were then added sequentially. The mixture was removed from the glove box and reacted at 40°C for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography.

[0105] Among them, the structural formula of compound IV-1 is:

[0106]

[0107] General Method B: In a nitrogen-filled glove box, compound IV-2 (8.2 mg, 0.02 mmol, 5 mol%), compound III sodium isopropoxide (50.1 mg, 0.61 mmol, 3.05 equiv), Ni(cod)2 (2.8 mg, 0.02 mmol, 5 mol%), and 2 mL of isopropanol were added to a 4 mL vial and stirred at room temperature for 30 minutes. Compound I (0.2 mmol) and compound II (0.4 mmol) were then added sequentially. The mixture was removed from the glove box and reacted at 40°C for 12 hours. After completion of the reaction, the product was directly isolated by column chromatography.

[0108] Among them, the structural formula of compound IV-2 is:

[0109]

[0110] The structural formula of the compound prepared in this example is:

[0111]

[0112] Compound 1-1: prepared according to general method B as a yellow liquid with a yield of 80%. 1H NMR (400 MHz, CDCl3) δ7.25–7.17 (m, 1H), 6.72–6.58 (m, 3H), 4.16 (t, J = 8.0 Hz, 1H), 4.12–4.05 (m, 1H), 3.97–3.89 (m, 1H), 3.78 (t, J = 8.1 Hz, 1H), 3.39 (p, J = 8.0 Hz, 1H), 2.97 (s, 6H), 2.42–2.31 (m, 1H), 2.12–2.00 (m, 1H). HPLC analysis (OD-H, 5% IPA in hexanes, 1 mL / min, 254 nm) found 92% ee:t R (minor)=6.1min,t R (major)=7.5min.

[0113] Compound 1-2: prepared according to general method B as a yellow liquid with a yield of 57%. 1 H NMR (400 MHz, CDCl3) δ7.19–7.09 (m, 4H), 4.17–4.11 (m, 1H), 4.10–4.03 (m, 1H), 3.96–3.88 (m, 1H), 3.70 (t, J = 8.1 Hz, 1H), 3.37 (p, J = 7.9 Hz, 1H), 2.40–2.29 (m, 4H), 2.06–1.93 (m, 1H). HPLC analysis (AD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 92% ee:t R (major)=5.0min,t R (minor)=5.2min.

[0114] Compound 1-3: prepared according to general method B as a white solid with a yield of 94%. 1 H NMR (400 MHz, CDCl3) δ7.64–7.55 (m, 4H), 7.49–7.43 (m, 2H), 7.39–7.33 (m, 3H), 4.20 (t, J = 8.0 Hz, 1H), 4.16–4.09 (m, 1H), 4.02–3.93 (m, 1H), 3.80 (t, J = 8.0 Hz, 1H), 3.47 (p, J = 7.8 Hz, 1H), 2.47–2.36 (m, 1H), 2.14–2.02 (m, 1H). HPLC analysis (OD-H, 2% IPA in hexanes, 1 mL / min, 280 nm) revealed 80% ee:t R (major)=9.4min,t R (minor)=9.9min.

[0115] Compound 1-4: prepared according to general method B as a yellow liquid with a yield of 92%. 1 H NMR (400 MHz, CDCl3) δ 7.24 (t, J = 7.9 Hz, 1H), 6.88–6.83 (m, 1H), 6.82–6.75 (m, 2H), 4.17–4.11 (m, 1H), 4.10–4.03 (m, 1H), 3.95–3.88 (m, 1H), 3.81 (s, 3H), 3.77–3.70 (m, 1H), 3.39 (p, J = 7.8 Hz, 1H), 2.41–2.30 (m, 1H), 2.07–1.96 (m, 1H). HPLC analysis (AD-H, 2% IPA in hexanes, 1 mL / min, 220 nm) found 90% ee:t R (major)=7.5min,t R (minor)=8.1min.

[0116] Compound 1-5: prepared according to general method B as an orange liquid with a yield of 85%. 1 H NMR (400 MHz, CDCl3) δ 6.80 (d, J = 8.2 Hz, 1H), 6.76 (d, J = 2.1 Hz, 1H), 6.74–6.70 (m, 1H), 4.27–4.21 (m, 4H), 4.13–4.07 (m, 1H), 4.07–4.00 (m, 1H), 3.89 (td, J = 8.2, 7.2 Hz, 1H), 3.65 (t, J = 8.1 Hz, 1H), 3.30 (p, J = 7.9 Hz, 1H), 2.36–2.26 (m, 1H), 2.01–1.90 (m, 1H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 254 nm) found 92% ee:t R (minor)=26.1min,t R (major) = 28.1 min.

[0117] Compound 1-6: prepared according to general method B as a yellow liquid with a yield of 83%. 1H NMR (400 MHz, CDCl3) δ7.18 (s, 4H), 4.13 (t, J = 8.0 Hz, 1H), 4.10–4.03 (m, 1H), 3.96–3.88 (m, 1H), 3.71 (t, J = 8.0 Hz, 1H), 3.60 (t, J = 7.0 Hz, 2H), 3.36 (s, 4H), 2.87 (t, J = 7.1 Hz, 2H), 2.40–2.30 (m, 1H), 2.05–1.94 (m, 1H). HPLC analysis (AD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 90% ee:t R (major)=7.7min,t R (minor)=8.1min.

[0118] Compound 1-7: prepared according to general method B as a pale yellow liquid with a yield of 54%. 1 H NMR (400 MHz, CDCl3) δ 7.24–7.17 (m, 2H), 7.03–6.96 (m, 2H), 4.15–4.09 (m, 1H), 4.09–4.03 (m, 1H), 3.91 (q, J = 7.9 Hz, 1H), 3.73–3.66 (m, 1H), 3.39 (p, J = 7.7 Hz, 1H), 2.41–2.31 (m, 1H), 2.03–1.90 (m, 1H). HPLC analysis (IG-H, 2% IPA in hexanes, 1 mL / min, 254 nm) revealed 80% ee:t R (major)=6.7min,t R (minor)=7.0min.

[0119] Compound 1-8: prepared according to general method B as a pale yellow liquid with a yield of 46%. 1 H NMR (400 MHz, CDCl3) δ7.32–7.26 (m, 1H), 7.24–7.17 (m, 1H), 7.13–7.08 (m, 1H), 7.06–6.99 (m, 1H), 4.14 (t, J = 7.8 Hz, 1H), 4.08–4.01 (m, 1H), 3.97–3.89 (m, 1H), 3.79–3.73 (m, 1H), 3.68 (p, J = 7.5 Hz, 1H), 2.41–2.30 (m, 1H), 2.10–1.97 (m, 1H). HPLC analysis (IC-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 80% ee:t R (minor)=6.0min,tR (major)=6.3min.

[0120] Compound 1-9: prepared according to general method B as a yellow liquid with a yield of 62%. 1 H NMR (400MHz, CDCl3) δ7.94–7.86(m,2H),7.47–7.41(m,1H),7.37(t,J=7.6Hz,1H),5.25(hept,J=6.3Hz,1H),4.16(t,J=8.0Hz,1H),4.12–4.05(m ,1H),3.97–3.89(m,1H),3.77–3.70(m,1H),3.46(p,J=7.8Hz,1H),2.45–2.32(m,1H),2.10–1.95(m,1H),1.37(d,J=6.3Hz,6H). HPLC analysis (AD-H, 2% IPA in hexanes, 1mL / min, 254nm) measured 84%ee:t R (major)=7.6min,t R (minor)=8.5min.

[0121] Compound 1-10: prepared according to general method B as a yellow liquid with a yield of 61%. 1 H NMR (400 MHz, CDCl3) δ 7.36–7.28 (m, 3H), 7.24–7.20 (m, 1H), 5.36 (s, 1H), 4.17–4.11 (m, 1H), 4.10–4.03 (m, 1H), 3.95–3.88 (m, 1H), 3.75–3.69 (m, 1H), 3.42 (t, J = 7.9 Hz, 1H), 3.33 (s, 6H), 2.44–2.28 (m, 1H), 2.09–1.95 (m, 1H). HPLC analysis (OD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 88% ee:t R (minor)=8.5min,t R (major)=8.9min.

[0122] Compound 1-11: prepared according to general method B as a red liquid with a yield of 99%. 1H NMR (400 MHz, CDCl3) δ7.23 (t, J = 7.8 Hz, 1H), 6.90–6.69 (m, 3H), 4.13 (t, J = 8.0 Hz, 1H), 4.10–4.03 (m, 1H), 3.95–3.81 (m, 5H), 3.75 (t, J = 7.9 Hz, 1H), 3.37 (p, J = 7.8 Hz, 1H), 3.23–3.10 (m, 4H), 2.43–2.28 (m, 1H), 2.10–1.96 (m, 1H). HPLC analysis (OD-H, 5% IPA in hexanes, 0.6 mL / min, 254 nm) found 90% ee:t R (minor)=16.3min,t R (major)=16.9min.

[0123] Compound 1-12: prepared according to general method B as a yellow liquid with a yield of 45%. 1 H NMR (400 MHz, CDCl3) δ 7.62–7.57 (m, 1H), 7.51–7.43 (m, 2H), 7.34–7.27 (m, 1H), 7.27–7.21 (m, 1H), 4.24–4.15 (m, 1H), 4.11–4.02 (m, 1H), 4.00–3.91 (m, 1H), 3.89–3.81 (m, 1H), 3.58 (p, J = 7.5 Hz, 1H), 2.45–2.34 (m, 1H), 2.17–2.05 (m, 1H). HPLC analysis (OD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 81% ee:t R (minor)=8.3min,t R (major)=8.6min.

[0124] Compound 1-13: prepared according to general method B as a white solid with a yield of 49%. 1H NMR (400MHz, CDCl3) δ7.98–7.92(m,1H),7.86–7.81(m,1H),7.57(d,J=8.2H z,1H),7.51(d,J=8.5Hz,1H),7.49–7.43(m,1H),7.38–7.31(m,2H),4.22(t ,J=8.0Hz,1H),4.19–4.11(m,1H),4.02–3.93(m,1H),3.88–3.81(m,1H),3. 58(p,J=7.7Hz,1H),2.52–2.40(m,1H),2.17–2.03(m,1H).HPLC analysis (OJ-H,5% IPAin hexanes, 1 mL / min, 254 nm) with an ee:t of 92%. R (minor)=19.6min,t R (major)=20.8min.

[0125] Compound 1-14: prepared according to general method B as a pale yellow liquid with a yield of 92%. 1 H NMR (400 MHz, CDCl3) δ 7.27–7.23 (m, 2H), 7.21–7.14 (m, 2H), 5.99 (td, J = 7.2, 1.6 Hz, 1H), 4.03–3.92 (m, 2H), 3.91–3.81 (m, 1H), 3.58 (t, J = 7.9 Hz, 1H), 3.40–3.27 (m, 1H), 2.52 (t, J = 7.1 Hz, 2H), 2.20–2.01 (m, 3H), 1.94–1.73 (m, 3H). HPLC analysis (AD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 60% ee:t R (minor)=4.5min,t R (major) = 4.9 min.

[0126] Compound 1-15: prepared according to general method B as a yellow liquid with a yield of 75%. 1H NMR (400MHz, CDCl3) δ7.45(d,J=8.1Hz,2H),7.23(d,J=8.1Hz,2H),7.10–6. 95(m,2H),6.66(d,J=2.3Hz,2H),6.42–6.36(m,1H),4.13(t,J=8.0Hz,1H), 4.10–4.03(m,1H),3.95–3.88(m,1H),3.82(s,6H),3.73(t,J=8.0Hz,1H),3 .40(p,J=7.8Hz,1H),2.42–2.29(m,1H),2.07–1.94(m,1H).HPLC analysis (AD-H,5% IPAin hexanes, 1 mL / min, 254 nm) with 90% ee:t R (minor)=27.7min,t R (major) = 29.2 min.

[0127] Compound 2-1: prepared according to general method B as a yellow solid with a yield of 92%. 1 H NMR (400 MHz, CDCl3) δ 7.20 (t, J = 7.8 Hz, 1H), 6.69–6.57 (m, 3H), 3.92–3.72 (m, 1H), 3.71–3.52 (m, 1H), 3.48–3.24 (m, 3H), 2.96 (s, 6H), 2.31–2.19 (m, 1H), 2.09–1.94 (m, 1H), 1.50 (d, J = 6.4 Hz, 9H). HPLC analysis (OD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) revealed 90% ee:t R (major)=10.3min,t R (minor)=12.6min.

[0128] Compound 2-2: prepared according to general method A as a yellow liquid with a yield of 75%. 1 H NMR (400 MHz, CDCl3) δ7.47–7.28 (m, 5H), 7.25–7.17 (m, 1H), 6.70–6.55 (m, 3H), 5.27–5.12 (m, 2H), 3.99–3.85 (m, 1H), 3.80–3.64 (m, 1H), 3.56–3.30 (m, 3H), 2.96 (s, 6H), 2.36–2.23 (m, 1H), 2.12–1.97 (m, 1H). HPLC analysis (OJ-H, 10% IPA in hexanes, 1 mL / min, 254 nm) found 98% ee:tR (major)=15.3min,t R (minor)=19.1min.

[0129] Compound 2-3: prepared according to general method A as an orange liquid with a yield of 89%. 1 H NMR (400 MHz, CDCl3) δ 7.37–7.27 (m, 3H), 6.80–6.71 (m, 4H), 6.71–6.66 (m, 2H), 3.83–3.76 (m, 1H), 3.64–3.43 (m, 4H), 3.03 (s, 6H), 2.53–2.44 (m, 1H), 2.30–2.19 (m, 1H). HPLC analysis (OJ-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 98% ee:t R (minor)=23.6min,t R (major) = 27.1 min.

[0130] Compound 2-4: prepared according to general method A as a red liquid with a yield of 65%. 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J = 8.1 Hz, 1H), 6.95–6.88 (m, 2H), 6.75–6.66 (m, 3H), 6.63–6.56 (m, 2H), 3.81 (s, 3H), 3.74–3.68 (m, 1H), 3.56–3.36 (m, 4H), 2.99 (s, 6H), 2.49–2.38 (m, 1H), 2.26–2.13 (m, 1H). HPLC analysis (AD-H, 2% IPA in hexanes, 1 mL / min, 254 nm) found 98% ee:t R (minor)=7.9min,t R (major) = 9.5 min.

[0131] Compound 2-5: prepared according to general method B as an orange liquid with a yield of 87%. 1H NMR (400 MHz, CDCl3) δ 7.40–7.31 (m, 2H), 7.30–7.22 (m, 1H), 7.22–7.10 (m, 3H), 6.89–6.76 (m, 3H), 4.08–3.94 (m, 1H), 3.88–3.72 (m, 4H), 3.68–3.37 (m, 3H), 2.41–2.25 (m, 1H), 2.17–2.00 (m, 1H). HPLC analysis (IB-H, 5% IPA in hexanes, 1 mL / min, 254 nm) found 94% ee:t R (major)=21.2min,t R (minor)=23.0min.

[0132] Compound 2-6: prepared according to general method A as a pale yellow liquid with a yield of 79%. 1 H NMR (400 MHz, CDCl3) δ 7.23 (t, J = 7.9 Hz, 1H), 7.18–7.12 (m, 2H), 7.10–7.03 (m, 1H), 6.93–6.87 (m, 1H), 6.81–6.76 (m, 1H), 6.76–6.71 (m, 1H), 6.71–6.68 (m, 1H), 4.13 (t, J = 6.7 Hz, 1H), 3.80 (s, 3H), 3.01–2.81 (m, 2H), 2.25–2.15 (m, 1H), 1.99–1.87 (m, 2H), 1.85–1.74 (m, 1H). HPLC analysis (OD-H, 0.5% IPA in hexanes, 1 mL / min, 220 nm) found 98% ee:t R (minor)=7.7min,t R (major) = 9.2 min.

[0133] Compound 2-7: Prepared according to general method A as a yellow liquid with a yield of 96%. 1 H NMR (400 MHz, CDCl3) δ 7.15–7.11 (m, 2H), 7.08–7.01 (m, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.61–6.56 (m, 2H), 5.92 (s, 2H), 4.09–4.01 (m, 1H), 2.97–2.78 (m, 2H), 2.21–2.09 (m, 1H), 1.97–1.69 (m, 3H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 254 nm) found 92% ee:t R(major)=8.3min,t R (minor)=9.0min.

[0134] Compound 2-8: prepared according to general method A as a colorless liquid with a yield of 83%. 1 H NMR (400 MHz, CDCl3) δ 7.20–7.12 (m, 4H), 7.10–7.02 (m, 3H), 6.90 (d, J = 7.7 Hz, 1H), 4.13 (t, J = 6.7 Hz, 1H), 3.02–2.83 (m, 2H), 2.38 (s, 3H), 2.25–2.14 (m, 1H), 2.01–1.86 (m, 2H), 1.86–1.73 (m, 1H). HPLC analysis (OD-H, hexanes, 1 mL / min, 254 nm) found 83% ee:t R (major)=7.2min,t R (minor)=9.5min.

[0135] Compound 2-9: Prepared according to general method A as a yellow liquid with a yield of 94%. 1 H NMR (400 MHz, CDCl3) δ 7.20 (t, J = 7.9 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.78–6.64 (m, 4H), 6.41 (d, J = 2.7 Hz, 1H), 4.06 (t, J = 6.7 Hz, 1H), 3.78 (s, 3H), 3.66 (s, 3H), 2.94–2.70 (m, 2H), 2.23–2.08 (m, 1H), 1.96–1.82 (m, 2H), 1.80–1.67 (m, 1H). HPLC analysis (OJ-H, 0.5% IPA in hexanes, 1 mL / min, 220 nm) found 90% ee:t R (minor)=8.2min,t R (major)=10.6min.

[0136] Compound 2-10: prepared according to general method A as a pale yellow liquid with a yield of 87%. 1H NMR (400 MHz, CDCl3) δ7.22 (t, J = 7.9 Hz, 1H), 7.10–7.04 (m, 1H), 6.85–6.74 (m, 2H), 6.69 (d, J = 7.7 Hz, 1H), 6.66–6.62 (m, 1H), 6.59–6.52 (m, 1H), 4.04 (t, J = 6.9 Hz, 1H), 3.78 (s, 3H), 2.92–2.73 (m, 2H), 2.21–2.09 (m, 1H), 1.98–1.67 (m, 3H). HPLC analysis (OD-H, 0.5% IPA in hexanes, 1 mL / min, 254 nm) found 96% ee:t R (minor)=5.6min,t R (major)=6.9min.

[0137] Compound 2-11: prepared according to general method A as a pale yellow solid with a yield of 88%. 1 H NMR (400 MHz, CDCl3) δ 7.23 (t, J = 7.9 Hz, 1H), 7.12–7.04 (m, 2H), 6.88–6.84 (m, 1H), 6.81–6.76 (m, 1H), 6.72–6.67 (m, 1H), 6.66–6.63 (m, 1H), 4.05 (t, J = 6.8 Hz, 1H), 3.79 (s, 3H), 2.93–2.74 (m, 2H), 2.21–2.09 (m, 1H), 1.97–1.81 (m, 2H), 1.80–1.67 (m, 1H). HPLC analysis (OD-H, 0.5% IPA in hexanes, 1 mL / min, 254 nm) found 98% ee:t R (minor)=8.4min,t R (major)=13.1min.

[0138] Compound 2-12: prepared according to general method A as a white solid with a yield of 69%. 1 H NMR (400MHz, CDCl3) δ7.23–7.16(m,1H),6.98(d,J=8.3Hz,1H),6.78–6.73(m,1H),6.72–6.68(m,1H),6.67–6.60(m,2H),6 .36–6.30(m,1H),4.03(t,J=6.8Hz,1H),3.81–3.74(m,3H),2.92–2.68(m,2H),2.23–2.08(m,1H),1.94–1.80(m,2H),1.79

[0139] –1.66 (m, 1H), 0.96–0.83 (m, 9H), 0.06 (s, 6H). HPLC analysis (OD-H, 0.5% IPA in hexanes, 1 mL / min, 220 nm) revealed 97% ee:t R (minor)=5.2min,t R (major) = 6.1 min.

[0140] Compound 2-13: prepared according to general method A as an orange liquid with a yield of 43%. 1 H NMR (400 MHz, CDCl3) δ7.31 (d, J = 7.3 Hz, 1H), 7.22–7.12 (m, 3H), 7.04 (d, J = 7.4 Hz, 1H), 6.67–6.61 (m, 2H), 6.57 (d, J = 7.5 Hz, 1H), 4.31 (t, J = 8.4 Hz, 1H), 3.12–3.03 (m, 1H), 3.01–2.96 (m, 1H), 2.94 (s, 6H), 2.65–2.54 (m, 1H), 2.18–2.05 (m, 1H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 254 nm) found 92% ee:t R (major)=7.4min,t R (minor)=8.4min.

[0141] Compound 2-14: prepared according to general method A as a brown liquid with a yield of 23%. 1 H NMR (400 MHz, CDCl3) δ 7.21 (t, J = 7.9 Hz, 1H), 7.19–7.15 (m, 1H), 7.12–7.06 (m, 1H), 6.97–6.88 (m, 2H), 6.78–6.74 (m, 1H), 6.69–6.65 (m, 1H), 6.65–6.62 (m, 1H), 4.19 (t, J = 5.1 Hz, 1H), 3.76 (s, 3H), 2.98–2.84 (m, 2H), 2.38–2.27 (m, 2H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 254 nm) found 99% ee:t R (major)=15.0min,t R (minor)=26.6min.

[0142] Compound 2-15: prepared according to general method A as a yellow liquid with a yield of 88%. 1H NMR (400 MHz, CDCl3) δ 7.21 (t, J = 7.9 Hz, 1H), 7.14–7.08 (m, 1H), 6.88–6.82 (m, 2H), 6.82–6.74 (m, 2H), 6.72 (d, J = 7.6 Hz, 1H), 6.70–6.67 (m, 1H), 4.21–4.11 (m, 3H), 3.76 (s, 3H), 2.35–2.25 (m, 1H), 2.15–2.04 (m, 1H). HPLC analysis (OJ-H, 1% IPA in hexanes, 1 mL / min, 220 nm) found 99% ee:t R (major)=12.8min,t R (minor)=17.9min.

[0143] Compound 2-16: prepared according to general method B as a colorless liquid with a yield of 49%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.24–7.13 (m, 3H), 6.87–6.75 (m, 4H), 6.75–6.69 (m, 1H), 3.81–3.75 (m, 6H), 3.73 (t, J = 7.8 Hz, 1H), 2.11–1.97 (m, 2H), 0.91 (t, J = 7.3 Hz, 3H). HPLC analysis (OD-H, 1% IPA in hexanes, 1 mL / min, 220 nm) found 84% ee:t R (major)=7.1min,t R (minor)=7.7min.

[0144] Compound 2-17: prepared according to general method A as a colorless liquid with a yield of 87%. 1 H NMR (400 MHz, CDCl3) δ7.19 (t, J = 8.0 Hz, 1H), 6.68–6.56 (m, 3H), 2.97 (s, 6H), 2.77–2.69 (m, 1H), 2.43–2.33 (m, 2H), 1.83–1.53 (m, 5H), 1.42–1.17 (m, 3H). HPLC analysis (OJ-H, 0.5% IPA in hexanes, 1 mL / min, 254 nm) revealed 90% ee:t R (minor)=6.6min,t R (major) = 9.1 min.

[0145] The positive progress effect of the present invention is:

[0146] (1) The present invention is used in asymmetric hydroarylation reactions of internal olefins, including 2,5-dihydrofuran and 2,5-dihydropyrrole, with high efficiency, regio- and stereoselectivity. This is of great significance for the efficient and precise synthesis of chiral heterocyclic products and the hydroarylation of bulk chemical products.

[0147] (2) The yield of the alkyl aromatics and chiral heterocyclic compounds prepared by the method of the present invention is high, the reaction regioselectivity is high, and most of them are above 98 / 2. The reaction enantioselectivity is high, and most of them have ee values ​​exceeding 90%.

[0148] (3) The method of the present invention has a wide range of substrate applicability and is very suitable for various types of olefins. The synthesized alkyl aromatic compounds and chiral heterocyclic compounds have various structures.

[0149] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A method for hydroarylation of internal olefins, characterized in that: Including steps: or Under a protective gas atmosphere, compound IV, compound III, bis(1,5-cyclooctadiene)nickel and a solvent are mixed, and then compound I and compound II are added thereto in sequence. After that, the protective gas environment is removed and the reaction is carried out at room temperature to obtain a compound of formula A; Among them, R 1 、R 2 Each independently selected from the following group: C 1-20 Alkyl, C 6-10 Aromatic ring, 1, 2 or 3 R 1-1 Substituted C 1-20 Alkyl, 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkyl, 1, 2 or 3 R 1-2 Substituted C 3-20 Cycloalkenyl, -LR 1-1 ; L is a chemical bond, -C 1-20 Alkylene-, -OC 1-20 Alkylene-, -C 1-20 Alkylene-O-, -C 1-20 Alkylene-S-, -CO-C 1-20 Alkylene-, -C 1-20 Alkylene-CO-, -NH-C 1-20 Alkylene-, -C 1-20 Alkylene-NH-; R 1-1 、R 1-2 Each independently selected from the group consisting of halogen, -OSiR a R b R c ; R 3 Select from the following group: C 6-14 Aryl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, 5-16 membered heteroaryl, 1, 2 or 3 R 3-1 Substituted C 6-14 Aryl, substituted by 1, 2 or 3 R 3-2 Substituted C 3-20 Cycloalkenyl, substituted by 1, 2 or 3 R 3-3 substituted 5-16 membered heteroaryl; R 3-1 、R 3-2 、R 3-3 Each independently selected from the group consisting of halogen, C 1-20 Alkyl, -OC 1-20 Alkyl, -C 1-20 Alkyl-O-, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 5-16 membered heterocycloalkyl, -C 1-6 Alkylene-5-16 membered heterocycloalkyl, -OC 1-6 Alkylene-C 6-10 Aryl, C 6-10 Aryl, 5-16 membered heteroaryl, -NR a R b 、-CO-OC 1-20 alkyl; R a 、R b and R c Each independently selected from the following group: H, C 1-20 Alkyl or C 6-10 aromatic rings; X is Cl, Br, I, OTs or OTf; Z is N, O, S, P or Si; R 4 Select from the following group: C 1-10 alkyl; M is an alkali metal; The 5-16 membered heteroaryl group is a 5-16 membered heteroaromatic ring having one, two or three heteroatoms selected from N, O and S and having one, two, three or four heteroatoms; The 5-16 membered heterocycloalkyl group is a 5-16 membered heterocycloalkyl group having one, two or three heteroatoms selected from N, O and S and having one, two, three or four heteroatoms; The structure of compound IV is: in, R 9a 、R 9b 、R 9c and R 9d Each independently selected from: C 1-6 Alkyl, unsubstituted or replaced by R 9a-1 Substituted C 6-14 aryl; R 9a-1 C 1-4 alkyl; R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R 8c Each independently selected from: H or C 1-4 alkyl; R 5 and R 6 are independently hydrogen, C 1-4 Alkyl, halogen, or C 6-10 Aryl; wherein R 5-1 and R 5-2 are each independently hydrogen or C 1-4 alkyl; is a single bond or a double bond; Or, R 5 、R 6 Together with the carbon atoms to which it is attached, Y - It is a monovalent anion.

2. The method according to claim 1, characterized in that The compound III is a metal salt of an alcohol, and the metal salt of the alcohol is an alkali metal salt of a primary alcohol and a secondary alcohol.

3. The method according to claim 1, characterized in that The structure of the compound IV is selected from the following group:

4. The method according to claim 1, wherein The compound I is selected from the following group:

5. The method according to claim 1, wherein The compound II is selected from the following group:

6. The method according to claim 1, characterized in that The compound IV is selected from the following group:

7. The method according to claim 1, characterized in that The compound A is selected from the following group:

8. The method according to claim 1, characterized in that The solvent is an alkane solvent, an ether solvent, or a combination thereof.

9. The method according to claim 1, characterized in that The solvent is selected from the group consisting of n-hexane, n-heptane, cyclohexane, cycloheptane, tetrahydrofuran, 1,4-dioxane, or a combination thereof.

10. The method according to claim 1, characterized in that The feeding process is carried out in a protective gas atmosphere, and the protective gas is selected from the following group: nitrogen, helium, argon, or a combination thereof.

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