A method for the synthesis of chiral allyl alcohol compounds by cobalt photocatalysis

Abstract

The application belongs to the technical field of organic synthesis, and provides a method for synthesizing a chiral allyl alcohol compound by synergistic catalysis of light and cobalt. The method comprises the following steps: mixing a cobalt catalyst, a chiral ligand, an aldehyde with a structure shown in formula 1, an alkenyl halide with a structure shown in formula 2, a photo-redox catalyst, a halogen atom transfer reagent and a solvent, and performing an asymmetric radical addition reaction under irradiation of visible light or near-visible light to obtain a chiral allyl alcohol compound with a structure shown in formula 3; and a reaction formula is as follows. The method provided by the application can efficiently and highly selectively convert various aldehydes into chiral allyl alcohol compounds.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for synthesizing chiral allyl alcohol compounds by photocobalt synergistic catalysis. Background Technology

[0002] Allyl alcohols hold an irreplaceable strategic position in organic synthesis, medicinal chemistry, and the construction of bioactive molecules. They are key synthons in constructing complex molecular skeletons such as terpenes, polyketides, and alkaloids, and also serve as the core pharmacophores and key structural frameworks for many important drug molecules. The synergistic reactivity of nucleophilic hydroxyl groups and electrophilic alkenes in their molecules endows them with extremely high structural tunability and unique regio and stereoselectivity. They can efficiently construct CO, CC, and CN bonds through transformations such as oxidation, reduction, cyclization, rearrangement, and 1,2-addition (e.g., hydroformylation), and are widely involved in various key reactions, including Sharpless asymmetric epoxidation and Tsuji-Trost palladium-catalyzed coupling. Sharpless epoxidation, utilizing chiral tartrate ligands to precisely control absolute configuration, has become the gold standard for obtaining highly enantioselective chiral epoxides, while the Tsuji-Trost reaction provides a highly atom-economical route for the total synthesis of natural products and the late-stage modification of drug molecules. In the field of medicinal chemistry, allyl alcohol skeletons are widely found in antiepileptic drugs such as slipantor, calcipotriol for treating psoriasis, antifungal drugs such as terbinafine, antimalarial drugs such as artemisinin, antitumor drugs such as paclitaxel, and macrolide antibiotics. They are not only the starting point for constructing chiral centers, but their unique olefin-hydroxyl combination also directly determines the specific binding of drugs to targets (such as hydrogen bonds and spatial matching), and profoundly affects the solubility, metabolic stability, and distribution of molecules. In addition, their inherent antibacterial and anti-inflammatory biological activities make them an important structural unit for lead compound optimization. Furthermore, given the central role of chiral allyl alcohols in asymmetric catalysis and biosynthesis, and the important application of olefin tautomerism in the synthesis of ortho-allyl alcohols with high enantioselectivity, developing rapid and efficient methods for obtaining enantiomeric enrichment of allyl alcohols has become a research hotspot. In recent years, the rise of green chemistry technologies such as photocatalysis, electrosynthesis, and enzyme catalysis has brought new breakthroughs to the efficient and highly selective synthesis of allyl alcohols, further expanding their application prospects in sustainable chemistry. In summary, developing efficient and highly selective methods for synthesizing chiral allyl alcohol compounds has significant scientific importance and enormous industrial value.

[0003] The main strategies for synthesizing allyl alcohols currently include: the Barbier reaction, the Nozaki-Hiyama-Kishi (NHK) reaction, the cobalt-catalyzed NHK reaction, the asymmetric NHK reaction without metal reducing agents, and the electrochemical NHK reaction. The Barbier reaction involves the formation of an alkenyl metal intermediate through two single-electron transfers in the presence of magnesium catalysis, catalyzed by magnesium. This intermediate then undergoes nucleophilic addition with an aldehyde to generate a racemic allyl alcohol. This method is suitable for the synthesis of racemic allyl alcohols, requires stoichiometric amounts of metal, and has poor tolerance to functional groups. The NHK reaction is one of the most practical and reliable C / C bond formation reactions in organic synthesis. It achieves efficient coupling of aldehydes and allyl halides under mild conditions to generate higher allyl alcohols. In terms of substrates, it reacts with carbonyl compounds (aldehydes and ketones), preferentially reacting with aldehydes when both are present, and is also tolerant of ester and cyano functional groups. This method is also applicable to the synthesis of racemic allyl alcohols, but requires stoichiometric amounts of chromium and exhibits poor substrate tolerance. Cobalt-catalyzed NHK reactions provide a general approach to cobalt catalysis, enabling the rapid construction of highly diverse enantiomeric allyl alcohols with 1,1-, 1,2-disubstituted and trisubstituted alkenes and axial chiral centers. This method is primarily suitable for aromatic aldehyde substrates, with enantioselectivity generally below 92%. It performs poorly with aliphatic aldehydes, achieving only moderate enantioselectivity (≤82% ee). Asymmetric NHK reactions without metal reducing agents: Using catalysts such as hensyl ester (HE) and N,N-diisopropylethylamine (DIPEA) instead of stoichiometric metal reducing agents, chiral enols can be synthesized from alkenyl halides and aromatic aldehydes. However, this method is only suitable for aromatic aldehydes as substrates and shows almost no reaction with aliphatic aldehyde substrates. The electrochemical NHK reaction utilizes electric current as a reducing agent, avoiding the use of traditional chemical reducing agents. This not only reduces waste generation at the source but also provides new possibilities for the green transformation of chemical synthesis. Although this method is applicable to aliphatic aldehyde substrates, its enantioselectivity is moderate (ee ≤ 60%). In summary, the mainstream strategy for synthesizing allyl alcohols currently involves nucleophilic addition of aldehydes to olefin metal intermediates. However, the applicability of this type of asymmetric nucleophilic addition strategy is very limited—generally only effective for aromatic aldehyde substrates. For aliphatic aldehydes, the reaction is often difficult to occur, and even if it does occur, the yield is extremely low and the enantioselectivity is poor. Summary of the Invention

[0004] In view of this, the object of the present invention is to provide a method for the photo-cobalt co-catalyzed synthesis of chiral allyl alcohol compounds. Under visible or near-visible light irradiation, an excited-state photo-redox catalyst oxidizes a halogen atom transfer reagent via a single-electron transfer process. Subsequently, the halogen atom transfer reagent is deprotonated to generate an alkyl radical, which then undergoes a halogen atom transfer process with an alkenyl halide to generate an alkenyl radical; a structurally defined transition state d... 7 Co electronic configuration II L The species can act as Lewis acids, forming a chelate transition state through monodentate coordination with an aldehyde, followed by radical addition with an alkenyl radical intermediate to generate a chiral allyl cobalt complex, which then dissociates to release the chiral allyl alcohol product. The method provided by this invention can efficiently and selectively convert aliphatic aldehydes into chiral allyl alcohol compounds.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for the photo-cobalt co-catalyzed synthesis of chiral allyl alcohol compounds. A cobalt catalyst, a chiral ligand, an aldehyde with the structure shown in Formula 1, an alkenyl halide with the structure shown in Formula 2, a photoredox catalyst, a halogen atom transfer reagent, and a solvent are mixed and subjected to an asymmetric radical addition reaction under visible or near-visible light irradiation to obtain a chiral allyl alcohol compound with the structure shown in Formula 3. Formula 1, Equation 2, Formula 3; In Equation 1, R 1 Selected from alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl; In Equation 2, R 2 R 3 and R 4 The same or different, independently selected from hydrogen, alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl, halogen, nitro, cyano, carboxyl, ester, acyl, acyloxy, alkoxy, sulfonyl, amino, substituted amino, amide; the aryl group is selected from benzene, naphthalene, anthracene, phenanthrene, fluorene, pyridine, quinoline, isoquinoline, indole, pyrrole, pyrazine, pyrimidine, furan, benzofuran, benzothiazole, benzothiophene, carbazole; X is selected from halogens bromine and iodine.

[0006] The method of this invention uses an excited-state photo-redox catalyst under visible or near-visible light irradiation to oxidize a halogen atom transfer reagent via a single-electron transfer process. Subsequently, the halogen atom transfer reagent is deprotonated to generate an alkyl radical, which then undergoes a halogen atom transfer process with an alkenyl halide to generate an alkenyl radical. This process results in a structurally defined transition state d. 7Co electronic configuration II L The species can act as Lewis acids, forming a chelate transition state through monodentate coordination with aldehydes, followed by radical addition with an alkenyl radical intermediate to generate a chiral allyl cobalt complex, which then dissociates to release the chiral allyl alcohol product.

[0007] The chemical reaction formula for this method is as follows: The significant advantages of this invention are: the preparation method for aldehydes or alcohols yields high efficiency, produces few byproducts, has a wide range of applicable substrates, and exhibits good functional group compatibility. The preparation method utilizes inexpensive and readily available reagents, is simple to operate, and is easy to scale up, making it suitable for industrial production and market application. Attached Figure Description

[0008] Figure 1 The high-performance liquid chromatogram of racemic compound 3 is shown. Figure 2 The high-performance liquid chromatogram of white solid 3 is shown. Figure 3 The high-performance liquid chromatogram of racemic compound 9 is shown. Figure 4 The high-performance liquid chromatogram of white solid 9 is shown. Figure 5 The high-performance liquid chromatogram of racemic compound 27 is shown. Figure 6 The high-performance liquid chromatogram of white solid 27 is shown. Figure 7 The high-performance liquid chromatogram of racemic compound 41 is shown. Figure 8 The image shows the high-performance liquid chromatography (HPLC) spectrum of white solid 41. Detailed Implementation

[0009] Terminology definition: In this invention, the term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0010] In this invention, the term "alkyl" refers to a straight-chain or branched saturated hydrocarbon group having a specified number of carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and similar alkyl groups.

[0011] In this invention, the term "alkenyl" refers to a straight-chain or branched hydrocarbon group having one or more carbon-carbon double bonds and no carbon-carbon triple bonds. The one or more carbon-carbon double bonds can be internal (e.g., in 2-butenyl) or terminal (e.g., in 1-butenyl).

[0012] In this invention, the term "alkynyl" refers to a straight-chain or branched hydrocarbon group with one or more carbon-carbon triple bonds and optionally one or more carbon-carbon double bonds.

[0013] The term "heterocyclic group" includes "heterocyclic alkyl" and "heterocyclic alkenyl". "Heterocyclic alkyl" refers to a stable, saturated monocyclic or polycyclic (e.g., bicyclic, tricyclic, or more bridging rings, fused rings, or spirocyclic systems) cyclic group consisting of a carbon atom and 1, 2, 3, 4, 5, or 6 heteroatoms selected from N, O, and S. "Heterocyclic alkenyl" refers to a stable, partially unsaturated monocyclic or polycyclic (e.g., bicyclic, tricyclic, or more bridging rings, fused rings, or spirocyclic systems) non-aromatic cyclic group consisting of a carbon atom and 1, 2, 3, 4, 5, or 6 heteroatoms selected from N, O, and S, having at least one double bond.

[0014] In this invention, the term "alkoxy" refers to a cyclic or acyclic alkyl group connected by an oxygen bridge.

[0015] In this invention, "aryl" refers to a group having 6-14 atoms and zero heteroatoms, a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 shared p electrons in a cyclic array) ("C6-C14 aryl").

[0016] In this invention, "heteroaryl" refers to a group having a carbon atom and 1-4 heteroatoms (each heteroatom independently selected from one or more of nitrogen, oxygen, and sulfur, with the number of heteroatoms being 1, 2, 3, or 4) in a 5-10 member monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 shared p electrons in a cyclic array). In heteroaryl groups containing one or more nitrogen atoms, the linking point can be a carbon or nitrogen atom, provided the valence allows.

[0017] This invention provides a method for the photocobalt co-catalyzed synthesis of chiral allyl alcohol compounds, comprising the following steps: A cobalt catalyst, a chiral ligand, an aldehyde with the structure shown in Formula 1, an alkenyl halide with the structure shown in Formula 2, a photoredox catalyst, a halogen atom transfer reagent, and a solvent are mixed and subjected to an asymmetric radical addition reaction under visible or near-visible light irradiation to obtain a chiral allyl alcohol compound with the structure shown in Formula 3. Formula 1, Equation 2, Formula 3; In Equation 1, R 1 Selected from alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl; In Equation 2, R2 R 3 and R 4 The same or different, independently selected from hydrogen, alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl, halogen, nitro, cyano, carboxyl, ester, acyl, acyloxy, alkoxy, sulfonyl, amino, substituted amino, amide; the aryl group is selected from benzene, naphthalene, anthracene, phenanthrene, fluorene, pyridine, quinoline, isoquinoline, indole, pyrrole, pyrazine, pyrimidine, furan, benzofuran, benzothiazole, benzothiophene, carbazole; X is selected from halogens bromine and iodine.

[0018] Where: R 1 Selected from alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl; R 2 R 3 and R 4 Whether the groups are the same or different, they are selected from hydrogen, alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl, halogen, nitro, cyano, carboxyl, ester, acyl, acyloxy, alkoxy, sulfonyl, amino, substituted amino, and amide; the aryl groups are selected from benzene, naphthalene, anthracene, phenanthrene, fluorene, pyridine, quinoline, isoquinoline, indole, pyrrole, pyrazine, pyrimidine, furan, benzofuran, benzothiazole, benzothiophene, and carbazole; X is selected from halogens bromine and iodine.

[0019] In this invention, the aldehyde with the structure shown in Formula 1 preferably has the following structure: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0020] In this invention, the preferred specific structure of the alkenyl halide with the structure shown in Formula 2 is as follows: , , , , , , , , , , , , , , , , , , , , or .

[0021] In this invention, the cobalt catalyst is preferably selected from any one of the following three categories: inorganic cobalt salts, small molecule organic cobalt complexes, and macrocyclic conjugated cobalt complexes.

[0022] In this invention, the inorganic cobalt salt is preferably selected from cobalt iodide, cobalt chloride, cobalt bromide, cobalt fluoride, cobalt perchlorate, cobalt phosphate, cobalt nitrate, cobalt sulfate, cobalt fluoroborate, cobalt oxalate (II), cobalt trifluoromethanesulfonate, cobalt trifluoride, cobalt iodate (II, CAS13455-28-2), cobalt sulfide (II), cobalt thiocyanate (II), pentaammonia complex cobalt chloride (III, CAS 13859-51-3), and cobalt tetrafluoroborate (II) hexahydrate.

[0023] In this invention, the small molecule organocobalt complex is preferably selected from cobalt acetylacetonate (II, CAS 14024-48-7), cobalt acetate, cobalt carbonate, cobalt octacarbonyl, N,N'-disalicylic acid ethylenediamine cobalt (II), cobalt acetylacetonate (III, CAS 21679-46-9), cobalt cyclopentadiene, cobalt naphthenate (CAS 61789-51-3), cobalt isooctanoate (CAS 13586-82-8), bis(triphenylphosphine)cobalt chloride, cobalt neodecanoate (II, CAS 27253-31-2), bis(2,4-pentanedione)cobalt(II) dihydrate (CAS 123334-29-2), chloro(pyridine)bis(dimethylglyoxime)cobalt (III, CAS 23295-32-1), cyclohexanediamine bis(di-tert-butylsalicylic acid)cobalt ... 188264-84-8), bis(hexafluoroacetylacetone)cobalt(II) hydrate (CAS 19648-83-0), bis(trifluoro-2,4-pentanedione)cobalt(II) (CAS 16092-38-9), cobalt gluconate(II), bis(N,N'-diisopropylacetamidine)cobalt(II), tris(2,2,6,6-tetramethyl-3,5-heptadecanedione)cobalt(III).

[0024] In this invention, the macrocyclic conjugated cobalt complex is preferably selected from meso-tetraphenylporphyrin cobalt (CAS 14172-90-8), cobalt phthalocyanine (CAS 3317-67-7), octahydroxycobalt phthalocyanine (CAS 1395198-61-4), tetratert-butylcobalt phthalocyanine (CAS129551-41-3), and 2,3-naphthylcyanocobalt (CAS 26603-20-3).

[0025] In this invention, the chiral ligand is preferably selected from either substituted or unsubstituted chiral phosphine ligands or chiral P,N,N-type tridentate ligands.

[0026] In this invention, the substituted or unsubstituted chiral phosphine ligands are preferably monophosphine or bisphosphine compounds having an R or S configuration, specifically preferably selected from (2R,4R)-(+)-2,4-bis(diphenylphosphine)pentane, (((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene))bis(diphenylphosphine), (1R,2R)-(-)-1,2-bis(diphenylphosphinemethyl)cyclohexane, (S,S) -(-)-1,2-bis(tert-butylmethylphosphino)benzene, (-)-1,2-bis((2R,5R)-2,5-dimethylphosphine), 1,1'-(3R)-3,3'(2H,2'H)-spirobis[benzofuran]-4,4'-diylbis[1,1-diphenylphosphine] (CAS2305757-36-0), (1R,2R)-N,N'-bis(2-diphenylphosphinobenzoyl)-1,2-cyclohexanediamine (CAS 138517-61-0), (R)-2,2'-bis(diphenylphosphine)-1,1'-binaphthyl, (R)-N,N'-bis(diphenylphosphine)binaphthylamine, (R)-4,12-bis(diphenylphosphine)[2.2]p-cycloarane, 1,1'-(1R)-[1,1'-binaphthyl]-2,2'-diylbis[di(4-methylphenyl)phosphine](CAS99646-28-3), 1,1'-[(5aR,8aR,14aR)-5a,6,7,8,8a,9-hexahydro-5H-benzopyran[3,2-d]oxanthracene-1,13-diyl]bis[1,1-diphenylphosphine](CAS 1360823-43-3), 1,1'-[(5aR,8aR,14aR)-5a,6,7,8,8a,9-hexahydro-5H-benzopyran[3,2-d]oxanthracene-1,13-diyl]bis[1,1-di(4-methylphenyl)phosphine](CAS1429939-32-1), (4R)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydro-4-isopropyloxazole, (4S)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydro-4-phenyloxazole, (4S)-4-tert-butyl-2-[2-(diphenylphosphine)phenyl]-4,5-dihydrooxazole, (4S)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydrooxazole, (4S)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydrooxazole, [(2S,4S)-1-Boc-4-diphenylphosphine-2-(diphenylphosphinemethyl)pyrrolidine, (3R,4R)-3,4-bis(diphenylphosphine)-1-(phenylmethyl)pyrrolidine, [(R)-2'-methoxy[1,1'-binaphthyl]-2-yl]diphenylphosphine, (S)-2'-(diphenylphosphine)-[1,1'-binaphthyl]-2-phenol, 1,1'-[(1R)-2,2',3,3'-tetrahydro-1,1'-spirobis[1H-indene]-7,7'-diyl]bis[1,1-bis(4-methylphenyl)phosphine] (CAS528521-87-1), 1,1'-[(4R)-[4,4'-di-1,3-benzodioxane]-5,5'-diyl]bis[1,1-diphenylphosphine] (CAS 244261-66-3), 1,1'-[(4R)-2,2,2',2'-tetrafluoro[4,4'-di-1,3-methylenedioxyphenyl]-5,5'-diyl]bis[1,1-diphenylphosphine] (CAS 503538-69-0), 1,1'-(4R)-[4,4'-di-1,3-benzodioxane]-5,5'-diylbis[1,1-bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine] (CAS 566940-03-2), (2R,2'R,3R,3'R)-3,3'-di-tert-butyl-2,2',3,3'-tetrahydro-2,2'-bis-1,3-benzoxoxophosphazene (CAS1610785-35-7), 1,1'-(1S)-[1,1'-binaphthyl]-2,2'-bis[1,1-dicyclohexylphosphine], [S(R)]-N-[(S)-2-(diphenylphosphine)phenylmethyl]-2-tert-butylsulfinamide (CAS 1616688-62-0), [S(R)]-N-[(S)-(3,5-bis-tert-butyl-4-methoxyphenyl)[2-(diphenylphosphine)phenyl]methyl]-2-tert-butylsulfinamide (CAS 1616688-63-1), [S(R)]-N-[(1S)-1-[2-(diphenylphosphine)phenyl]-2,2-dimethylpropyl]-2-tert-butylsulfinamide, [S(R)]-N-[(S)-[6-(diphenylphosphine)benzo[d][1,3]-dioxolane-5-yl]benzylmethyl]-2-tert-butylsulfinamide (CAS2565792-39-2), [S(R)]-N-[(1S)-1-[(diphenylphosphine)methyl]-2-methylpropyl]-2-tert-butylsulfinamide (CAS 1803239-46-4), [S(R)]-N-[(R)-5-(diphenylphosphine)-9,9-dimethyl-9H-oxanthracenemethyl]-2-tert-butylsulfinamide (CAS 2160535-56-6), [S(R)]-N-[(1R)-1-[2-(di-tert-butylphosphine)phenyl]benzyl]-2-tert-butylsulfinamide (CAS 2565792-40-5), (3S)-4,4'-diphenylphosphine-2,2',6,6'-tetramethoxy-3,3'-dipyridine, (S)-4-(tert-butyl)-2-[2'-(diphenylphosphine)-2-(1,1'-biphenyl)]-4,5-dihydrooxazole, (4R,5S)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydro-4,5-diphenyl-oxazole.

[0027] In this invention, the chiral P,N,N type tridentate ligand is a substituted tridentate phosphine-nitrogen compound having an R configuration or an S configuration, selected from (4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-(tert-butyl)-4,5-dihydrooxazole), (4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-phenylphosphinebis(4-cyclohexyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-phenylphosphinebis(4-methyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-phenylphosphinebis(4-benzyl) -2-Benzen-4,5-dihydrooxazole), (4S,4'S)-2,2'-phenylphosphinebis(4-phenyl-2-benzen-4,5-dihydrooxazole), (4S,4'S,5S,5'S)-2,2'-phenylphosphinebis(4,5-diphenyl-2-benzen-4,5-dihydrooxazole), (4S,4'S)-2,2'-(p-methoxyphenyl)phosphinebis(4-isopropyl-2-benzen-4,5-dihydrooxazole), (4S,4'S)-2,2'-(4-dimethylamino)phenylphosphinebis(4-isopropyl-2-benzen-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxyphenyl)phosphinebis(4-isopropyl-2-benzen-4,5-dihydrooxazole) (CAS) 2368937-57-7), (4S,4'S)-2,2'-(4-fluorobenzyl)phosphine bis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxybenzyl)phosphine bis(4-phenyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxybenzyl)phosphine bis(4-benzyl-2-benzyl-4,5-dihydrooxazole) (CAS 2368937-58-8), (4S,4'S)-2,2'-methylphosphine bis(4-methyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxyphenyl)phosphine bis(4-methyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(phenylacetylene)phosphine bis(4-cyclohexyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'- (Phenylacetylene)phosphinebis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(tert-butylacetylene)phosphinebis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(triisopropylsilylacetylene)phosphinebis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(phenylacetylene)phosphinebis(4-phenyl-2-benzyl-4,5-dihydrooxazole).

[0028] In this invention, the photo-oxidation-reduction catalyst is preferably selected from any one of the following three categories: organic photocatalysts, iridium-based photocomplexes, and ruthenium-based photocomplexes.

[0029] In this invention, the organic photocatalyst is preferably selected from 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, 2,4,5,6-tetra(diphenylamino)-isophthalonitrile, 5,6-bis(5-methoxythiophene-2-yl)pyrazine-2,3-dicarboxynitrile, 9-trimethyl-10-phenylacridine tetrafluoroborate, 3,6-di-tert-butyl-9-m-methyl-10-phenylacridine tetrafluoroborate, eosin B, eosin Y, and thioxanthone-9-one.

[0030] In this invention, the iridium-based photocomplex is selected from bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate), 4,4'-di-tert-butyl-2,2'-bipyridine di[5-methyl-2-(4-methyl-2-pyridyl)phenyl]iridium hexafluorophosphate, [2,2'-bi(4-tert-butylpyridine)]bis[2-(2,4-difluorophenyl)pyridine]iridium(III) hexafluorophosphate, bis[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(tetra-tert-butylpyridine)]iridium di(hexafluorophosphate), and [5,5'-bis(trifluoromethyl)-2,2'-bipyridine]bis[3,5-difluoro-2-(5-trifluoromethyl-2-pyridyl)phenyl] Iridium hexafluorophosphate, bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2,2'-bipyridine]iridium di(hexafluorophosphate), (2,2'-bipyridine)bis[2-(2,4-difluorophenyl)pyridine]iridium(III) hexafluorophosphate, (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, tri(2-phenylpyridine)iridium, bis[2-(3-tert-butylphenyl)-4-tert-butylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium(III) hexafluorophosphate, 4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridinebis[3,5-difluoro-2-(5-fluoro-2-pyridyl)phenyl]iridium hexafluorophosphate (CAS 2042201-18-1), [2,2'-bi(4-tert-butylpyridine)]bis[2-(4-fluorophenyl)pyridine]iridium(III) hexafluorophosphate (CAS 1449110-90-0), (2,2'-bipyridine)bis[2-(4-fluorophenyl)pyridine]iridium(III) hexafluorophosphate (CAS 1580547-45-0), tri[2-(2,4-difluorophenyl)pyridine]iridium(III) (CAS 391665-84-2), [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine]bis[3-fluoro-5-(trifluoromethyl)-2-(5-trifluoromethyl-2-pyridyl)phenyl]iridium (CAS 2222402-20-0), tri[2-(4-tert-butyl-2-pyridyl)-3,5-difluorophenyl]iridium (CAS 1380203-57-5).

[0031] In this invention, the ruthenium-based photocomplex is selected from tris(2,2'-bipyridine)ruthenium di(hexafluorophosphate) (CAS 60804-74-2), cis-bis(2,2'-dipyridyl)ruthenium(II) dihydrate (CAS 15746-57-3), carbonyl chloride tris(triphenylphosphine)ruthenium(II) (CAS 16971-33-8), Grubbs second-generation catalyst (CAS 246047-72-3), tris(1,10-phenanthroline)ruthenium(II) bis(hexafluorophosphate) (CAS 60804-75-3), bis(1,10-phenanthroline)(2,2'-bipyridine)ruthenium(II) dichloride, (2,2'-bipyridine)bis(1,10-phenanthroline)ruthenium(2+) bis(hexafluorophosphate) (CAS 60804-74-2), cis-bis(2,2'-dipyridine)ruthenium(II) dihydrate (CAS 60804-74-2), cis-bis(2,2'-dipyridine)ruthenium(II) bis(hexafluorophosphate) ... 60828-39-9), Tris(acetonitrile)cyclopentadiene ruthenium hexafluorophosphate (CAS 80049-61-2).

[0032] In this invention, the halogen atom transfer reagent is preferably an amine compound, specifically selected from N-methyldicyclohexylamine, triethylamine, tripropylamine, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane, quinine ring, 1,8-diazabicyclo[5.4.0]undec-7-ene, tetramethylguanidine, tetramethylethylenediamine, N-methylmorpholine, N,N-dimethylpropylamine, tri-n-pentylamine, triisopentylamine, N,N,N',N'',N''-pentamethyldiethylenetriamine, N,N-diethylaniline, N,N-diethylethylenediamine, diisopropylamine, N,N,N',N'-tetramethyl-1,8-naphthyldiamine, tetra(dimethylamino)ethylene, N,N-diethyltrimethylsilylamine, triethylenediamine, triethanolamine, triethanolamine The following are all of the following: amine, dicyclohexylamine, dibenzylamine, N,N-dimethylethanolamine, N,N,N',N'-tetramethyl-1,3-propanediamine, N,N-dimethylaniline, N,N,N'-trimethylethylenediamine, N,N'-dimethyltrifluoroacetamide, N,N-diethylbenzamide, triethylamineborane, N,N-diethylhydroxylamine, N,N'-dicyclohexylcarbodiimide, 4-(4-methylpiperazine)aniline, ethylenediaminetetraacetic acid, methyldibenzylamine, tetramethylmethanediamine, methimazole, 4-dimethylaminopyridine, 7-diethylamino-4-methylcoumarin, tropine, N-methylpiperazine, 1,3-dimethyl-2-imidazolinone, 6-amino-3-methylpurine, hypozoxytriacetic acid, and 1-methyl-4-piperidinol.

[0033] In this invention, the solvent is preferably selected from one or more mixed solvents formed from alkane solvents, aromatic solvents, ether solvents, nitrile solvents, alcohol solvents, amide solvents, sulfoxide solvents, water, and pyridine.

[0034] In this invention, the alkane solvent is preferably selected from any one of nitromethane, butyl acetate, carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloroethane, ethyl acetate, n-hexane, cyclohexane, heptane, n-pentane, and petroleum ether. In this invention, the aromatic solvent is preferably selected from any one of benzene, toluene, xylene, trimethylbenzene, trifluorotoluene, and chlorobenzene. In this invention, the ether solvent is preferably selected from any one of tetrahydrofuran, diethyl ether, isopropyl ether, ethylene glycol dimethyl ether, 1,4-dioxane, and methyl tert-butyl ether. In this invention, the nitrile solvent is preferably acetonitrile. In this invention, the alcohol solvent is preferably selected from any one of methanol, ethanol, trifluoroethanol, hexafluoroisopropanol, isopropanol, n-propanol, n-butanol, isobutanol, and tert-butanol. In this invention, the amide solvent is preferably selected from any one of N,N-dimethylformamide and N,N-dimethylacetamide. In this invention, the sulfoxide solvent is preferably dimethyl sulfoxide. In one specific embodiment of this invention, the solvent is preferably a mixture of an ether solvent and an aromatic solvent, such as diethyl ether and chlorobenzene, wherein the volume ratio of diethyl ether to chlorobenzene is preferably 1:1.

[0035] In this invention, the aldehyde preferably includes one or more of aliphatic aldehydes, aromatic aldehydes, α,β-unsaturated aldehydes, and naturally occurring aldehydes. In this invention, the aliphatic aldehyde preferably includes primary, secondary, or tertiary aliphatic aldehydes.

[0036] In this invention, the molar ratio of the aldehyde to the alkenyl halide is preferably (0.1~5.0):1, more preferably (1.2~2.0):1, and can specifically be 0.1:1, 0.5:1, 1:1, 1.2:1, 1.5:1, 2.0:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1 or 5:1.

[0037] In this invention, the molar ratio of the halogen atom transfer reagent to the alkenyl halide compound is preferably (0.5~8.0):1, more preferably (2.5~4.0):1, and can specifically be 0.5:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1 or 8:1.

[0038] In this invention, the molar ratio of the photo-oxidation-reduction catalyst to the alkenyl halide compound is preferably (0.001~0.5):1, more preferably (0.01~0.05):1, and specifically can be 0.001:1, 0.005:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.1:1, 0.2:1, 0.3:1, 0.4:1 or 0.5:1.

[0039] In this invention, the molar ratio of the cobalt catalyst to the alkenyl halide compound is (0.001~0.5):1, more preferably (0.05~0.1):1, and specifically can be 0.001:1, 0.005:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.1:1, 0.2:1, 0.3:1, 0.4:1 or 0.5:1.

[0040] In this invention, the molar ratio of the chiral ligand to the alkenyl halide compound is (0.001~0.5):1, more preferably (0.06~0.12):1, and specifically can be 0.001:1, 0.005:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.1:1, 0.11:1, 0.12:1, 0.15:1, 0.2:1, 0.3:1, 0.4:1 or 0.5:1.

[0041] In this invention, the amount of solvent used is not specifically limited, as long as it does not affect the reaction.

[0042] In this invention, the preferred specific steps for mixing the cobalt catalyst, chiral ligand, aldehyde with the structure shown in Formula 1, alkenyl halide with the structure shown in Formula 2, photo-redox catalyst, halogen atom transfer reagent, and solvent are as follows: the cobalt catalyst and chiral ligand are dissolved in the solvent and stirred until homogeneous, and then the aldehyde with the structure shown in Formula 1, the alkenyl halide with the structure shown in Formula 2, the photo-redox catalyst, and the halogen atom transfer reagent are added.

[0043] In this invention, the wavelength of the visible or near-visible light is preferably 350-600 nm. Specifically, the wavelength of the visible or near-visible light is preferably a single wavelength or a mixture of wavelengths; the single wavelength is preferably 350-600 nm, more preferably 395-515 nm, and can specifically be 400 nm, 405 nm, 410 nm, 415 nm, 435 nm, 450 nm, 455 nm, 470 nm, or 475 nm; the range of the mixture of wavelengths is preferably 400-550 nm. In one specific embodiment of this invention, the visible light is preferably blue light, the wavelength of the blue light is preferably 455 nm, and the power is preferably 18 W.

[0044] In this invention, the visible light or near-visible light source is preferably an LED lamp, an incandescent lamp, or an energy-saving lamp.

[0045] In this invention, the temperature of the asymmetric free radical addition reaction is preferably -70℃ to 80℃, more preferably -60℃ to 0℃, and specifically can be -60℃, -40℃, -20℃, 0℃, 25℃, or 50℃. In this invention, the temperature of the asymmetric free radical addition reaction is preferably controlled by a cold trap. In this invention, the asymmetric radical addition reaction is preferably monitored, with the disappearance or cessation of reaction of the olefin halide as the endpoint. In this invention, the monitoring methods are preferably TLC, HPLC, or HNMR.

[0046] After the asymmetric free radical addition reaction is completed, the present invention preferably further includes the following post-processing step: concentrating the reaction solution and then performing column chromatography to obtain the chiral allyl alcohol product. The present invention does not specifically limit the concentration operation; any concentration operation well known to those skilled in the art can be used. In the present invention, the eluent used for column chromatography preferably includes ethyl acetate (EA) and petroleum ether (PE), and the volume ratio of ethyl acetate to petroleum ether is preferably 1:8 to 1:30. Specifically, 1:8, 1:10, 1:15, 1:20, 1:25, or 1:30 are preferred.

[0047] The following examples illustrate the method for synthesizing chiral allyl alcohols using photocobalt synergistic catalysis provided by the present invention, but these examples should not be construed as limiting the scope of protection of the present invention.

[0048] The following examples further illustrate the present invention in detail, but the scope of protection of the present invention is not limited to the content described. Unless otherwise specified, the reagents and methods used in the examples are all conventional reagents and methods. The present invention introduces chiral induction into a hole-catalyzed system to achieve asymmetric hole-catalyzed radical addition of olefin radicals to aliphatic aldehydes, thereby efficiently constructing chiral allyl alcohol compounds.

[0049] Example 1 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 8, V / V) to obtain a white solid 3 (yield 99%, ee 97%).

[0050] The high performance liquid chromatogram of racemic compound 3 ( Figure 1 Using the information (Table 1) as a control, the obtained white solid 3 was tested, specifically as follows: A CHIRALCEL® OD-3 chiral column was used, with a mobile phase of hexane / isopropanol at a volume ratio of 70:30, a flow rate of 0.6 mL / min, and a detection wavelength of 254 nm. The resulting high-performance liquid chromatography (HPLC) chromatogram is shown below. Figure 2 As shown in Table 2, the high performance liquid chromatography information is as follows.

[0051] Table 1. High-performance liquid chromatography information of racemic compound 3

[0052] Table 2 High Performance Liquid Chromatography Information for White Solid 3

[0053] from Figure 2 As shown in Table 2, the retention time of the main enantiomer was 15.117 min, the retention time of the minor enantiomer was 25.826 min, and the enantiomer excess value of the product was 97%.

[0054] Example 2 Under a nitrogen atmosphere, a cobalt catalyst (cobalt acetylacetonate, cobalt bromide, or cobalt phthalocyanine, with a molar ratio of 0.05:1 between the three cobalt catalysts and the alkenyl halide) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), with a molar ratio of 0.06:1 between the cobalt catalyst and the alkenyl halide) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorine). The mixture was stirred at room temperature and homogenized with benzene. Then, aldehyde 4 (0.15 mmol), alkenyl halide 2 (0.10 mmol), photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, with a molar ratio of 0.02:1 to the alkenyl halide) and halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition, the reactants were placed at -60°C and irradiated with an 18W 455nm LED lamp 8 cm away from the reaction apparatus for 48 hours. The mixture was directly concentrated and purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain colorless liquid 5 (the yield was 80% and ee was 96% when cobalt bromide was used as the cobalt catalyst; the yield was 68% and ee was 96% when cobalt acetylacetone was used as the cobalt catalyst; and the yield was 70% and ee was 90% when cobalt phthalocyanine was used as the cobalt catalyst).

[0055] Example 3 Under a nitrogen atmosphere, a cobalt catalyst (cobalt chloride, with a molar ratio of 0.05:1 to an alkenyl halide) and chiral ligands ((2R,4R)-(+)-2,4-bis(diphenylphosphine)pentane, (4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole) or [S(R)]-N-[(S)-(3,5-bis-tert-butyl-4-methoxyphenyl)[2-(diphenylphosphine)phenyl]methyl]-2-tert-butylsulfinamide, are reacted with an alkenyl halide... The aldehyde 6 (0.15 mmol), alkenyl halide 2 (0.10 mmol), photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile to alkenyl halide (0.02:1 molar ratio), and halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to 18 W at 455 nm. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 30, V / V) to obtain a colorless liquid 7. The yield was 50% and the ee was 68% when (2R,4R)-(+)-2,4-bis(diphenylphosphine)pentane was used as the chiral ligand; the yield was 82% and the ee was 94% when (4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole) was used as the chiral ligand; and the yield was 98% and the ee was 20% when [S(R)]-N-[(S)-(3,5-bis-tert-butyl-4-methoxyphenyl)[2-(diphenylphosphine)phenyl]methyl]-2-tert-butylsulfinamide was used as the chiral ligand.

[0056] Example 4 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (2.0 mL acetonitrile, 2.0 mL chlorobenzene, 2.0 mL methanol, 2.0 mL...). The mixture was stirred at room temperature in N,N-dimethylformamide or a 1.0 mL diethyl ether-1.0 mL chlorobenzene mixture. Aldehyde 8 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, with a molar ratio of 0.02:1 to the alkenyl halide), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were then added. After the addition was complete, the reactants were placed at -60°C and irradiated with an 18 W 455 nm LED lamp 8 cm away from the reaction apparatus for 48 hours. The mixture was then directly concentrated and purified by column chromatography (EA / PE = 0.15 mmol / L). 1 / 15, V / V) yielded a white solid 9 (yield of 99% and ee of 60% when acetonitrile was used as solvent; yield of 95% and ee of 81% when chlorobenzene was used as solvent; yield of 40% and ee of 66% when methanol was used as solvent; yield of 95% and ee of 81% when N,N-dimethylformamide was used as solvent; and yield of 91% and ee of 96% when 1.0 mL of diethyl ether and 1.0 mL of chlorobenzene were used as a mixed solvent).

[0057] High performance liquid chromatography of racemic compound 9 (HPLC) Figure 3 Using the information (Table 3) as a control, the obtained white solid 9 was tested, specifically as follows: A CHIRALCEL® OD-3 chiral column was used, with a mobile phase of hexane / isopropanol at a volume ratio of 70:30, a flow rate of 0.6 mL / min, and a detection wavelength of 254 nm. The resulting high-performance liquid chromatography (HPLC) chromatogram is shown below. Figure 4 As shown in Table 4, the high performance liquid chromatography information is as follows.

[0058] Table 3. High-performance liquid chromatography information for racemic compound 9.

[0059] Table 4. High-performance liquid chromatography information for white solid 9.

[0060] from Figure 4 As shown in Table 4, the retention time of the main enantiomer was 11.062 min, the retention time of the minor enantiomer was 16.955 min, and the enantiomer excess value of the product was 96%.

[0061] Example 5 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide of 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide of 0.06:1) were dissolved in a solvent (2.0 mL diethyl ether, 2.0 mL dimethyl sulfoxide, or 1.0 mL diethyl ether-1.0 mL chlorobenzene mixture). The mixture was stirred at room temperature in a solvent, and then aldehyde 10 (0.15 mmol), alkenyl halide 2 (0.10 mmol), photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, with a molar ratio of 0.02:1 to the alkenyl halide) and halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition, the reactants were placed at -60°C and irradiated with an 18W 455nm LED lamp 8 cm away from the reaction apparatus for 48 hours. The mixture was directly concentrated and purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain colorless liquid 11 (yield of 30% and ee of 79% when using dimethyl sulfoxide as solvent; yield of 20% and ee of 22% when using dimethyl sulfoxide as solvent; yield of 66% and ee of 94% when using 1.0 mL of dimethyl ether and 1.0 mL of chlorobenzene as a mixed solvent).

[0062] Example 6 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL diethyl ether and 1.0 mL chlorobenzene) and stirred at room temperature. Then, aldehyde 12 (0.15 mmol), alkenyl halide 2 (0.10 mmol), and a photoredox catalyst (5,6-bis(5-methoxythiophene-2-yl)pyrazine) were added. 2,3-Dicarbaonitrile, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile or bis[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate), with a photoredox catalyst to alkenyl halide molar ratio of 0.02:1 and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol), were added. After addition, the reactants were placed at -60°C and the reaction was carried out under a 18W 390nm light source (when the photoredox catalyst was 5,6-bis(5-methoxythiophen-2-yl)pyrazine-2,3-dicarbaonitrile). A 455nm LED lamp (18W) was used when the photoredox catalyst was 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile; a 420nm LED lamp (18W) was used when the photoredox catalyst was di[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate) salt). The reaction was irradiated at a distance of 8 cm from the reaction apparatus for 48 hours, followed by direct concentration and column chromatography purification (EA / PE = 1). 1 / 15, V / V) yielded a white solid 13 (yield 84% and ee 90% when using 5,6-bis(5-methoxythiophene-2-yl)pyrazine-2,3-dicarboxynitrile as a photoredox catalyst; yield 99% and ee 92% when using 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile as a photoredox catalyst; and yield 91% and ee 88% when using bis[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate) as a photoredox catalyst).

[0063] Example 7 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL diethyl ether and 1.0 mL chlorobenzene) and stirred at room temperature. Then, aldehyde 14 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (eosin Y, molar ratio to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition, the reactants were placed at -60°C and irradiated with an 18W 390nm LED lamp 8 cm away from the reaction apparatus for 48 hours. The mixture was then directly concentrated and purified by column chromatography (EA / PE = 0.05:1). 1 / 25, V / V) yielded a colorless liquid 15 (yield 77%, ee 95%).

[0064] Example 8 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL diethyl ether and 1.0 mL chlorobenzene) and stirred at room temperature until homogeneous. Then, aldehyde 1 was added. 6 (0.15 mmol), alkenyl halide 2 (0.10 mmol), photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile to alkenyl halide 0.02:1), and halogen atom transfer reagent (triethylamine, methyl dibenzylamine, or N-methyldicyclohexylamine, 0.35 mmol) were added. After addition, the reactants were placed at -60°C and irradiated with an 18W 455nm LED lamp 8 cm away from the reaction apparatus for 48 hours. The mixture was directly concentrated and purified by column chromatography (EA / PE = 1 / 30, V / V) to give colorless liquid 17 (yield of 80% and ee of 98% when triethylamine was used as the halogen atom transfer reagent; yield of 64% and ee of 98% when methyl dibenzylamine was used as the halogen atom transfer reagent; and yield of 83% and ee of 98% when N-methyldicyclohexylamine was used as the halogen atom transfer reagent).

[0065] Example 9 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 18 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18W 455nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain a colorless liquid 19 (yield 99%, ee 96%).

[0066] Example 10 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 20 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain colorless liquid 21 (yield 95%, ee 92%).

[0067] Example 11 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 22 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 30, V / V) to obtain a colorless liquid 23 (yield 70%, ee 96%).

[0068] Example 12 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 24 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 10, V / V) to obtain a white solid 25 (yield 58%, ee 90%).

[0069] Example 13 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL diethyl ether and 1.0 mL chlorobenzene) and stirred at room temperature until homogeneous. Then, aldehyde 26 (0.1 mL) was added. The reaction mixture consisted of 5 mmol of alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, with a molar ratio of 0.02:1 to the alkenyl halide), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol). After addition, the reactants were placed at temperatures (50 °C, 25 °C, 0 °C, -20 °C, -60 °C) and subjected to a photoredox reaction at 18 W and 455 nm. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain a white solid 27 (yield of 52% and ee of 86% at 50℃; 97% and ee of 86% at 25℃; 97% and ee of 90% at 0℃; 99% and ee of 92% at -20℃; and 99% and ee of 99% at -60℃).

[0070] High performance liquid chromatography of racemic compound 27 (HPLC) Figure 5 Using the information (Table 5) as a control, the white solid 27 obtained at -60℃ was tested, specifically as follows: A CHIRALCEL® OD-3 chiral column was used, with a mobile phase of hexane / isopropanol at a volume ratio of 85:15, a flow rate of 0.6 mL / min, and a detection wavelength of 254 nm. The resulting high-performance liquid chromatography (HPLC) chromatogram is shown below. Figure 6 As shown in Table 6, the high-performance liquid chromatography information is as follows.

[0071] Table 5. High-performance liquid chromatography information for racemic compound 27

[0072] Table 6. High Performance Liquid Chromatography Information for White Solid 27

[0073] from Figure 6 As shown in Table 6, the retention time of the main enantiomer was 15.432 min, the retention time of the minor enantiomer was 19.172 min, and the enantiomer excess value of the product was 99%.

[0074] Example 14 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 28 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain a colorless liquid 29 (yield 68%, ee 96%).

[0075] Example 15 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 30 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 25, V / V) to obtain a colorless liquid 31 (yield 68%, ee 99%, dr = 1:1).

[0076] Example 16 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 32 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain a white solid 33 (yield 90%, ee 99%).

[0077] Example 17 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 34 (0.15 mmol), alkenyl halide 2 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain a white solid 35 (yield 86%, ee 98%).

[0078] Example 18 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 36 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 10, V / V) to obtain a white solid 37 (yield 99%, ee 96%).

[0079] Example 19 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 38 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 7, V / V) to obtain a white solid 39 (yield 98%, ee 96%).

[0080] Example 20 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 40 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 5, V / V) to obtain a white solid 41 (yield 84%, ee 95%).

[0081] The high performance liquid chromatogram of racemic compound 41 ( Figure 7 Using the information (Table 7) as a control, the obtained white solid 41 was tested, specifically as follows: A CHIRALCEL® OD-3 chiral column was used, with a mobile phase of hexane / isopropanol at a volume ratio of 85:15, a flow rate of 0.6 mL / min, and a detection wavelength of 254 nm. The resulting high-performance liquid chromatography (HPLC) chromatogram is shown below. Figure 8 As shown in Table 8, the high performance liquid chromatography information is as follows.

[0082] Table 7. High-performance liquid chromatography information for racemic compound 41

[0083] Table 8 High Performance Liquid Chromatography Information for White Solid 41

[0084] from Figure 8 As shown in Table 8, the retention time of the main enantiomer was 15.021 min, the retention time of the secondary enantiomer was 19.952 min, and the enantiomer excess value of the product was 95%.

[0085] Example 21 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 42 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 10, V / V) to obtain a white solid 43 (yield 91%, ee 98%).

[0086] Example 22 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 44 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE=1 / 2, V / V) to obtain a white solid 45 (yield 50%, ee 98%).

[0087] Example 23 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 46 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 10, V / V) to obtain a white solid 47 (yield 99%, ee 90%).

[0088] Example 24 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 1 (0.15 mmol), alkenyl halide 48 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 8, V / V) to obtain a white solid 49 (yield 77%, ee 94%).

[0089] Example 25 As an antiepileptic drug, Stiripentol (50) can inhibit the activity of various cytochrome P450s, whereas in previous strategies, this process required two steps for racemic synthesis. Using the cobalt hole-catalyzed radical reaction of this invention, (-)-Stiripentol-(50) can be obtained in a single step (75% yield, 94% ee), demonstrating the extremely high efficiency of this method. The preparative formula for Stiripentol (50) prepared using the method provided by this invention is shown below: Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 22 (0.15 mmol), alkenyl halide 42 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain a colorless liquid 50 (yield 75%, ee 94%).

[0090] Example 26 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 51 (0.15 mmol), alkenyl halide 52 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to oxidation at 18 W 455 nm. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain a white solid 53 (yield 95%, ee 99%).

[0091] Example 27 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 54 (0.15 mmol), alkenyl halide 52 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain 54 (yield of 88%, ee of 97%).

[0092] Example 28 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 54 (0.15 mmol), alkenyl halide 56 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 10, V / V) to obtain 57 (yield of 60%, ee of 78%).

[0093] Example 29 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 58 (0.15 mmol), alkenyl halide 59 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction device for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain 60 (yield of 53%, ee of 84%).

[0094] Example 30 Under a nitrogen atmosphere, cobalt (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL diethyl ether and 1.0 mL chlorobenzene) and stirred at room temperature. Then, aldehyde 61 (0.15 mmol), alkenyl halide 62 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 30, V / V) to obtain 63 (yield of 72%, ee of 92%).

[0095] Example 31 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 64 (0.15 mmol), alkenyl halide 65 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction device for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain 66 (yield of 85%, ee of 96%).

[0096] Example 32 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 67 (0.15 mmol), alkenyl halide 68 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction device for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 10, V / V) to obtain 69 (yield of 65%, ee of 90%).

[0097] Example 33 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 70 (0.15 mmol), alkenyl halide 71 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain 72 (yield of 75%, ee of 88%).

[0098] Example 34 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 73 (0.15 mmol), alkenyl halide 74 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain 75 (yield of 72%, ee of 86%).

[0099] Example 35 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 76 (0.15 mmol), alkenyl halide 77 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 25, V / V) to obtain 78 (yield of 80%, ee of 94%).

[0100] Example 36 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 79 (0.15 mmol), alkenyl halide 80 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction device for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 25, V / V) to obtain 81 (yield of 62%, ee of 86%).

[0101] Example 37 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL diethyl ether and 1.0 mL chlorobenzene) and stirred at room temperature. Then, aldehyde 82 (0.15 mmol), alkenyl halide 83 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain 84 (yield 70%, ee 80%).

[0102] Example 38 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 85 (0.15 mmol), alkenyl halide 86 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction device for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 20, V / V) to obtain 87 (yield of 80%, ee of 92%).

[0103] Example 39 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 88 (0.15 mmol), alkenyl halide 89 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction apparatus for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE = 1 / 15, V / V) to obtain 90 (yield of 94%, ee of 99%).

[0104] Example 40 Under a nitrogen atmosphere, a cobalt catalyst (cobalt iodide, molar ratio of cobalt to alkenyl halide 0.05:1) and a chiral ligand ((4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), molar ratio of cobalt to alkenyl halide 0.06:1) were dissolved in a solvent (1.0 mL of diethyl ether and 1.0 mL of chlorobenzene) and stirred at room temperature. Then, aldehyde 91 (0.15 mmol), alkenyl halide 92 (0.10 mmol), a photoredox catalyst (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, molar ratio of cobalt to alkenyl halide 0.02:1), and a halogen atom transfer reagent (N-methyldicyclohexylamine, 0.35 mmol) were added. After the addition was complete, the reactants were placed at -60°C and subjected to a 18 W 455 nm reaction. The reaction was irradiated with an LED lamp 8 cm away from the reaction device for 48 hours. After direct concentration, the product was purified by column chromatography (EA / PE=1 / 25, V / V) to obtain 93 (yield of 78%, ee of 94%).

[0105] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing chiral allyl alcohol compounds using a cobalt-photocatalyst, characterized in that, Includes the following steps: A cobalt catalyst, a chiral ligand, an aldehyde with the structure shown in Formula 1, an alkenyl halide with the structure shown in Formula 2, a photoredox catalyst, a halogen atom transfer reagent, and a solvent are mixed and subjected to an asymmetric radical addition reaction under visible or near-visible light irradiation to obtain a chiral allyl alcohol compound with the structure shown in Formula 3. Formula 1, Equation 2, Formula 3; In Equation 1, R 1 Selected from alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl; In Equation 2, R 2 R 3 and R 4 The same or different, independently selected from hydrogen, alkyl, cycloalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted aryl, substituted and unsubstituted heterocyclic aryl, halogen, nitro, cyano, carboxyl, ester, acyl, acyloxy, alkoxy, sulfonyl, amino, substituted amino, amide; the aryl group is selected from benzene, naphthalene, anthracene, phenanthrene, fluorene, pyridine, quinoline, isoquinoline, indole, pyrrole, pyrazine, pyrimidine, furan, benzofuran, benzothiazole, benzothiophene, carbazole; X is selected from halogens bromine and iodine.

2. The method according to claim 1, characterized in that, The specific steps for mixing the cobalt catalyst, chiral ligand, aldehyde with the structure shown in Formula 1, alkenyl halide with the structure shown in Formula 2, photoredox catalyst, halogen atom transfer reagent, and solvent are as follows: The cobalt catalyst and chiral ligand were dissolved in a solvent and stirred until homogeneous. Then, an aldehyde with the structure shown in Formula 1, an alkenyl halide with the structure shown in Formula 2, a photoredox catalyst, and a halogen atom transfer reagent were added.

3. The method according to claim 1 or 2, characterized in that, The cobalt catalyst is selected from any one of the following three categories: inorganic cobalt salts, small molecule organic cobalt complexes, and macrocyclic conjugated cobalt complexes. The inorganic cobalt salts are selected from cobalt iodide, cobalt chloride, cobalt bromide, cobalt fluoride, cobalt perchlorate, cobalt phosphate, cobalt nitrate, cobalt sulfate, cobalt fluoroborate, cobalt oxalate (II), cobalt trifluoromethanesulfonate, cobalt trifluoride, cobalt iodate (II), cobalt sulfide (II), cobalt thiocyanate (II), pentaammonia complex cobalt chloride (III), and cobalt tetrafluoroborate (II) hexahydrate; The small molecule organocobalt complexes are selected from cobalt(II) acetylacetonate, cobalt acetate, cobalt carbonate, cobalt octacarbonyl, N,N'-disalicylic acid ethylenediamine cobalt(II), cobalt(III) acetylacetonate, cobalt cyclopentane, cobalt naphthenate, cobalt isooctanoate, cobalt bis(triphenylphosphine) chloride, cobalt neodecanoate (II), cobalt(II) dihydrate of bis(2,4-pentanedione) cobalt(II), chloro(pyridine)bis(dimethylglyoxime) cobalt(III), cyclohexanediamine bis(di-tert-butylsalicylene) cobalt, cobalt(II) bis(hexafluoroacetylacetonate) cobalt(II) hydrate, cobalt(trifluoro-2,4-pentanedione) cobalt(II), cobalt(II) gluconate, cobalt(II) bis(N,N'-diisopropylacetamidine) cobalt(II), and tris(2,2,6,6-tetramethyl-3,5-heptadecanedione) cobalt(III). The macrocyclic conjugated cobalt complex is selected from meso-tetraphenylporphyrin cobalt, cobalt phthalocyanine, octahydroxycobalt phthalocyanine, tetratert-butylcobalt phthalocyanine, and 2,3-naphthocyanocobalt.

4. The method according to claim 1 or 2, characterized in that, The chiral ligand is selected from either substituted or unsubstituted chiral phosphine ligands or chiral P,N,N type tridentate ligands. The substituted or unsubstituted chiral phosphine ligands are monophosphine or bisphosphine compounds having R or S configurations, selected from (2R,4R)-(+)-2,4-bis(diphenylphosphine)pentane, (((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene))bis(diphenylphosphine), (1R,2R)-(-)-1,2-bis(diphenylphosphinemethyl)cyclohexane, (S,S)-(-)-1,2-bis(tert-butylmethylphosphino)benzene, (-)-1,2-bis((2R,5R)-2,5-dimethylphosphine), 1,1'-(3R)-3,3'(2H,2'H)-spirobis[benzofuran]-4,4'-diylbis[1,1-diphenylphosphine], (1R, 2R)-N,N'-bis(2-diphenylphosphinobenzoyl)-1,2-cyclohexanediamine, (R)-2,2'-bis(diphenylphosphine)-1,1'-binaphthyl, (R)-N,N'-bis(diphenylphosphine)binaphthylamine, (R)-4,12-bis(diphenylphosphine)[2.2]p-cycloarane, 1,1'-(1R)-[1,1'-binaphthyl]-2,2'-diylbis[di(4-methylphenyl)phosphine], 1,1'-[(5aR,8aR,14aR)-5a,6,7,8,8a,9-hexahydro-5H-benzopyran[3,2-d]oxanthracene-1,13-diyl]bis[1,1-diphenylphosphine], 1,1'-[(5aR,8aR,14aR)-5a,6,7,8,8, 8a,9-Hexahydro-5H-benzopyran[3,2-d]oxanthracene-1,13-diyl]bis[1,1-di(4-methylphenyl)phosphine], (4R)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydro-4-isopropyloxazole, (4S)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydro-4-phenyloxazole, (4S)-4-tert-butyl-2-[2-(diphenylphosphine)phenyl]-4,5-dihydrooxazole, (4S)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydro-4-(phenylmethyl)oxazole, (2S,4S)-1-Boc-4-diphenylphosphine-2-(diphenylphosphinemethyl)pyrrolidine, (3R,4R)-3,4-bis(diphenylphosphine)-1 -(phenylmethyl)pyrrolidine, [(R)-2'-methoxy[1,1'-binaphthyl]-2-yl]diphenylphosphine, (S)-2'-(diphenylphosphine)-[1,1'-binaphthyl]-2-phenol, 1,1'-[(1R)-2,2',3,3'-tetrahydro-1,1'-spirobis[1H-indene]-7,7'-diyl]bis[1,1-bis(4-methylphenyl)phosphine], 1,1'-[(4R)-[4,4'-di-1,3-benzodioxane]-5,5'-diyl]bis[1,1-diphenylphosphine], 1,1'-[(4R)-2,2,2',2'-tetrafluoro[4,4'-di-1,3-methylenedioxyphenyl]-5,5'-diyl]bis[1,1-diphenylphosphine], 1,1'-(4R)-[4,4'-di-1,3-benzodioxane]-5,5'-diylbis[1,1-bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine], (2R,2'R,3R,3'R)-3,3'-di-tert-butyl-2,2',3,3'-tetrahydro-2,2'-bis-1,3-benzoxoxophosphazenediene, 1,1'-(1S)-[1,1'-binaphthyl]-2,2'-bis[1,1-dicyclohexyl] [S(R)]-N-[(S)-2-(diphenylphosphine)phenylmethyl]-2-tert-butylsulfinamide, [S(R)]-N-[(S)-(3,5-bis-tert-butyl-4-methoxyphenyl)[2-(diphenylphosphine)phenyl]methyl]-2-tert-butylsulfinamide, [S(R)]-N-[(1S)-1-[2-(diphenylphosphine)phenyl]-2,2-dimethylpropyl]-2-tert-butylsulfinamide, [S(R)]-N- [(S)-[6-(diphenylphosphine)benzo[d][1,3]-dioxolane-5-yl]benzylmethyl]-2-tert-butylsulfinamide, [S(R)]-N-[(1S)-1-[(diphenylphosphine)methyl]-2-methylpropyl]-2-tert-butylsulfinamide, [S(R)]-N-[(R)-5-(diphenylphosphine)-9,9-dimethyl-9H-oxanthracenemethyl]-2-tert-butylsulfinamide, [S(R)]-N-[(1R] (3S)-1-[2-(di-tert-butylphosphine)phenyl]benzyl]-2-tert-butylsulfinamide, (3S)-4,4'-diphenylphosphine-2,2',6,6'-tetramethoxy-3,3'-dipyridine, (S)-4-(tert-butyl)-2-[2'-(diphenylphosphine)-2-(1,1'-biphenyl)]-4,5-dihydrooxazole, (4R,5S)-2-[2-(diphenylphosphine)phenyl]-4,5-dihydro-4,5-diphenyl-oxazole; The chiral P,N,N type tridentate ligand is a substituted tridentate phosphine-nitrogen compound with an R or S configuration, selected from (4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-(tert-butyl)-4,5-dihydrooxazole), (4S,4'S)-2,2'-((phenylphosphinediyl)bis(2,1-phenylene))bis(4-isopropyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-phenylphosphinebis(4-cyclohexyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-phenylphosphinebis(4-methyl-2-phenyl-4,5-dihydrooxazole), and (4S,4'S)-2,2'-phenylphosphine Bis(4-benzyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-phenylphosphine bis(4-phenyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S,5S,5'S)-2,2'-phenylphosphine bis(4,5-diphenyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(p-methoxyphenyl)phosphine bis(4-isopropyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(4-dimethylamino)phenylphosphine bis(4-isopropyl-2-phenyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxyphenyl)phosphine bis(4-isopropyl) (4S,4'S)-2,2'-(4-fluorobenzyl)phosphine bis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxybenzyl)phosphine bis(4-phenyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxybenzyl)phosphine bis(4-benzyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxybenzyl)phosphine bis(4-benzyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-methylphosphine bis(4-methyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(3,5-di-tert-butyl-4-methoxybenzyl)phosphine bis(4-phenyl ... 4-Methyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(phenylacetylene)phosphinebis(4-cyclohexyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(phenylacetylene)phosphinebis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(tert-butylacetylene)phosphinebis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(triisopropylsilylacetylene)phosphinebis(4-isopropyl-2-benzyl-4,5-dihydrooxazole), (4S,4'S)-2,2'-(phenylacetylene)phosphinebis(4-phenyl-2-benzyl-4,5-dihydrooxazole).

5. The method according to claim 1 or 2, characterized in that, The photo-oxidation-reduction catalyst is selected from any one of the following three categories: organic photocatalysts, iridium-based photocomplexes, and ruthenium-based photocomplexes. The organic photocatalyst is selected from 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, 2,4,5,6-tetrakis(diphenylamino)-isophthalonitrile, 5,6-bis(5-methoxythiophene-2-yl)pyrazine-2,3-dicarboxynitrile, 9-trimethyl-10-phenylacridine tetrafluoroborate, 3,6-di-tert-butyl-9-m-methyl-10-phenylacridine tetrafluoroborate, eosin B, eosin Y, and thioxanthone; The iridium-based photocomplex is selected from bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate), 4,4'-di-tert-butyl-2,2'-bipyridine di[5-methyl-2-(4-methyl-2-pyridyl)phenyl]iridium hexafluorophosphate, [2,2'-bi(4-tert-butylpyridine)]bis[2-(2,4-difluorophenyl)pyridine]iridium(III) hexafluorophosphate, and bis[2,4-difluorophenyl)-5-methylpyridine [2,2'-Bi(tetra-tert-butylpyridine)]iridium di(hexafluorophosphate), [5,5'-bis(trifluoromethyl)-2,2'-bipyridine]bis[3,5-difluoro-2-(5-trifluoromethyl-2-pyridyl)phenyl]iridium hexafluorophosphate, bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2,2'-bipyridine]iridium di(hexafluorophosphate), (2,2'-bipyridine)bis[2-(2,4-difluorophenyl)pyridine]iridium(III) hexafluorophosphate, (4,4'-di-tert-butylpyridine]iridium di(hexafluorophosphate) 4,4'-bis(1,1-dimethylethyl)-2,2'-bis[3,5-difluoro-2-(5-fluoro-2-pyridyl)phenyl]iridium(III) hexafluorophosphate, tris(2-phenylpyridine)iridium, bis[2-(3-tert-butylphenyl)-4-tert-butylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium(III) hexafluorophosphate, 4,4'-bis(1,1-dimethylethyl)-2,2'-bis[3,5-difluoro-2-(5-fluoro-2-pyridyl)phenyl]iridium hexafluorophosphate, [2,2'-bi(4-tert-butylpyridine)]bis[ 2-(4-fluorophenyl)pyridine]iridium(III) hexafluorophosphate, (2,2'-bipyridine)bis[2-(4-fluorophenyl)pyridine]iridium(III) hexafluorophosphate, tris[2-(2,4-difluorophenyl)pyridine]iridium(III), [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine]bis[3-fluoro-5-(trifluoromethyl)-2-(5-trifluoromethyl-2-pyridyl)phenyl]iridium, tris[2-(4-tert-butyl-2-pyridyl)-3,5-difluorophenyl]iridium; The ruthenium-based photocomplexes are selected from tris(2,2'-bipyridine)ruthenium di(hexafluorophosphate), cis-bis(2,2'-dipyridyl)ruthenium(II) dihydrate, carbonyl chloride tris(triphenylphosphine)ruthenium(II), Grubbs second-generation catalyst, tris(1,10-phenanthroline)ruthenium(II) bis(hexafluorophosphate), bis(1,10-phenanthroline)(2,2'-bipyridine)ruthenium(II) dichloride, (2,2'-bipyridine)bis(1,10-phenanthroline)ruthenium(2+) bis(hexafluorophosphate), and tris(acetonitrile)cyclopentadiene ruthenium hexafluorophosphate.

6. The method according to claim 1 or 2, characterized in that, The halogen atom transfer reagent is an amine compound selected from N-methyldicyclohexylamine, triethylamine, tripropylamine, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane, quinine ring, 1,8-diazabicyclo[5.4.0]undec-7-ene, tetramethylguanidine, tetramethylethylenediamine, N-methylmorpholine, N,N-dimethylpropylamine, tri-n-pentylamine, triisopentylamine, N,N,N',N'',N''-pentamethyldiethylenetriamine, N,N-diethylaniline, N,N-diethylethylenediamine, diisopropylamine, N,N,N',N'-tetramethyl-1,8-naphthyldiamine, tetra(dimethylamino)ethylene, N,N-diethyltrimethylsilylamine, triethylenediamine, triethanolamine, dicyclohexylamine, etc. The following is a list of amines, dibenzylamine, N,N-dimethylethanolamine, N,N,N',N'-tetramethyl-1,3-propanediamine, N,N-dimethylaniline, N,N,N'-trimethylethylenediamine, N,N'-dimethyltrifluoroacetamide, N,N-diethylbenzamide, triethylamineborane, N,N-diethylhydroxylamine, N,N'-dicyclohexylcarbodiimide, 4-(4-methylpiperazine)aniline, ethylenediaminetetraacetic acid, methyldibenzylamine, tetramethylmethanediamine, methimazole, 4-dimethylaminopyridine, 7-diethylamino-4-methylcoumarin, tropine, N-methylpiperazine, 1,3-dimethyl-2-imidazolinone, 6-amino-3-methylpurine, hypozoxytriacetic acid, and 1-methyl-4-piperidinol.

7. The method according to claim 1 or 2, characterized in that, The solvent is selected from one or more of the following solvents: alkane solvents, aromatic solvents, ether solvents, nitrile solvents, alcohol solvents, amide solvents, sulfoxide solvents, water, and pyridine. The alkane solvent is selected from any one of nitromethane, butyl acetate, carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloroethane, ethyl acetate, n-hexane, cyclohexane, heptane, n-pentane, and petroleum ether. The aromatic solvent is selected from any one of benzene, toluene, xylene, trimethylbenzene, trifluorotoluene, and chlorobenzene; The ether solvent is selected from any one of tetrahydrofuran, diethyl ether, isopropyl ether, ethylene glycol dimethyl ether, 1,4-dioxane or methyl tert-butyl ether; The nitrile solvent is acetonitrile; The alcohol solvent is selected from any one of methanol, ethanol, trifluoroethanol, hexafluoroisopropanol, isopropanol, n-propanol, n-butanol, isobutanol, and tert-butanol. The amide solvent is selected from any one of N,N-dimethylformamide and N,N-dimethylacetamide; The sulfoxide solvent is dimethyl sulfoxide.

8. The method according to claim 1 or 2, characterized in that: The molar ratio of the aldehyde to the alkenyl halide compound is (0.1~5.0):1; The molar ratio of the halogen atom transfer reagent to the alkenyl halide compound is (0.5~8.0):1; The molar ratio of the photo-oxidation-reduction catalyst to the alkenyl halide compound is (0.001~0.5):1; The molar ratio of the cobalt catalyst to the alkenyl halide compound is (0.001~0.5):1; The molar ratio of the chiral ligand to the alkenyl halide compound is (0.001~0.5):

1.

9. The method according to claim 1 or 2, characterized in that: The wavelength of the visible or near-visible light is 350~600nm; the light source of the visible or near-visible light is an LED lamp, an incandescent lamp, or an energy-saving lamp.

10. The method according to claim 1 or 2, characterized in that: The temperature for the asymmetric free radical addition reaction is -70℃ to 80℃.

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