A process for the preparation of chiral sulfonamides

Abstract

The application discloses a preparation method of chiral sulfonimidate. Specifically, the method of the application comprises the following steps: under an inert atmosphere, reacting a sulfonimidate shown in formula I-b with aryl iodide shown in formula I-a in the presence of a base, an additive, a cobalt source and a chiral ligand to obtain a sulfonimidate compound shown in formula I-c; wherein each group is defined in the description. The product sulfonimidate of the application can be further resolved to obtain chiral sulfonimidate, which is an important skeleton for preparing drugs and chiral catalysts, and has wide application prospects.

Description

Technical Field

[0001] This invention belongs to the field of organic chemistry, and specifically relates to a method for preparing chiral sulfinamides. Background Technology

[0002] Sulfur-containing functional groups are ubiquitous in pharmaceuticals and natural products, serving as a dominant skeletal structure in medicinal chemistry. Their diverse oxidation states enable flexible molecular geometries, enhance metabolic stability, and possess tunable pharmacological properties. Between 2017 and 2021, the US FDA approved nearly 30 sulfur-containing drugs, fully demonstrating the crucial role of sulfur in modern drug development. Among these, high-enantiomerically pure S-chiral sulfinamides have become a research focus. These compounds can serve as key reagents in stereoselective transformations, used to prepare structurally complex sulfur-containing molecules (such as sulfinylimide fluorides, thioimides, and thiooxyimides). Furthermore, they can act as asymmetric catalysts and bifunctionalization reagents, promoting reactions such as the aminoarylation of olefins. Based on these multifunctional applications, the synthesis of chiral sulfinamides has received widespread attention in recent decades.

[0003] Traditional methods for preparing chiral sulfinamides typically rely on multi-step reaction processes and the use of chiral auxiliaries. While these stoichiometric methods are effective, their inherent drawbacks cannot be ignored, including poor atom economy and cumbersome purification steps. In contrast, catalytic enantioselectivity strategies offer a more efficient and sustainable alternative. Based on the pioneering work of research teams such as Miller, Ellman, and Shibata in asymmetric sulfinylation reactions, significant breakthroughs have been achieved in the field of catalytic asymmetric synthesis. For example, the research groups of Tan, Yan, Guo, and Robin have developed efficient sulfinylation schemes, enabling the synthesis of diverse chiral sulfinates / sulfinamides from sulfinates or sulfonyl cyanides. Recently, Yu et al. have also innovatively used thioamides as sulfur reagents to prepare sulfinamides. In recent years, sulfinylimides (R-NSO) have emerged as a novel electrophilic sulfur source, providing a unique alternative to traditional methods that rely on chiral auxiliaries, thiols, disulfides, or moisture-sensitive sulfonyl chlorides. These reagents offer advantages such as simple synthesis, good air / moisture stability, and avoidance of the use of malodorous thiols, making them attractive in various applications. Of particular note is the conversion of sulfinylimides into chiral sulfinamides via nucleophilic addition or heteroene reactions. For example, Shi's group and our group independently developed enantioselective synthetic methods for constructing S-chiral aryl sulfinamides using arylborane reagents and sulfinylimides, respectively [14g, 14h]. Despite these advances, the use of aryl halides (rather than stoichiometric organometallic reagents) as a catalytic strategy remains crucial for improving atom and step economy. Willis's team's groundbreaking work on the palladium-catalyzed reaction of aryl halides with sulfinylimides to synthesize sulfinamides has yet to achieve an enantioselective version of this conversion, hindering the progress in obtaining high-enantiomeric-purity sulfinamides via this route.

[0004] Therefore, there is an urgent need in the field to develop a method for preparing chiral sulfinamides with high enantioselectivity to meet the needs of drug development. Summary of the Invention

[0005] One object of the present invention is to provide a novel method for preparing chiral sulfinamide compounds.

[0006] Another object of the present invention is to provide a chiral sulfinamide compound of formula Ic.

[0007] In a first aspect of the present invention, a method for preparing a sulfinamide compound of formula Ic is provided, comprising the following steps:

[0008]

[0009] Under an inert atmosphere, in the presence of a base, additives, a cobalt source and a chiral ligand, the sulfinimide represented by formula Ib reacts with the aryl iodide represented by formula Ia to give the sulfinamide compound represented by formula Ic.

[0010] In the formula, Selected from the group consisting of phenyl, naphthyl, or 5-6 heteroaryl groups containing 1-3 heteroatoms each independently selected from N, O, and S;

[0011] R1 is independently selected from the group consisting of: H, halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted 5-6 membered heteroaryl; or, R1 on two adjacent carbon atoms together with the carbon atom to which they are connected forms a substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-6 membered heterocyclic group, or substituted or unsubstituted 5-6 membered heteroaryl; wherein substitution means that one or more hydrogen atoms on the group are substituted by a group selected from the group consisting of: halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy;

[0012] n is 0, 1, 2, 3, 4 or 5; m is 1 or 2;

[0013] The heterocyclic group and heteroaryl group each independently contain 1-3 heteroatoms independently selected from N, O and S.

[0014] In another preferred example, m is 1.

[0015] In another preferred embodiment, n is 0, 1, 2, or 3.

[0016] In another preferred embodiment, R1 is not adjacent to I.

[0017] In another preferred embodiment, R1 is in the opposite or intermediate position of I.

[0018] In another preferred embodiment, the halogen in R1 and the halogen atom in the halogenation are fluorine, chlorine or bromine; preferably fluorine or chlorine.

[0019] In another preferred embodiment, Selected from the following group: phenyl, naphthyl, pyridyl, thiophene, furanyl, pyrimidine, pyridazine, imidazolyl, pyrazolyl.

[0020] In another preferred embodiment, R1 is selected from the group consisting of: H, halogen, nitro, hydroxyl, amino, cyano, C1-C4 alkyl, halo-C1-C4 alkyl, hydroxy-C1-C4 alkyl, C1-C4 alkoxy, halo-C1-C4 alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted 5-6-membered heteroaryl; or, R1 on two adjacent carbon atoms together with the carbon atom to which they are connected forms a substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-6-membered heterocyclic group, or substituted or unsubstituted 5-6-membered heteroaryl; wherein the substitution refers to one or more hydrogen atoms on the group being substituted by a group selected from the group consisting of: halogen, nitro, hydroxyl, amino, cyano, C1-C4 alkyl, halo-C1-C4 alkyl, hydroxy-C1-C4 alkyl, C1-C4 alkoxy, halo-C1-C4 alkoxy.

[0021] In another preferred embodiment, the sulfinamide compound represented by formula Ic is in the S configuration, the R configuration, or a mixture thereof.

[0022] In another preferred embodiment, the sulfinamide compound represented by formula Ic has the following configuration:

[0023]

[0024] In another preferred embodiment, when the aryl iodide represented by formula Ia contains one iodine, and when m is 1, the sulfinamide compound represented by formula Ic has the following structure:

[0025]

[0026] Preferably, the sulfinamide compound represented by formula Ic has the following structure:

[0027] In another preferred embodiment, the sulfinamide compound represented by Formula Ic has an ee value ≥ 85%; more preferably, an ee value ≥ 90%; more preferably, an ee value ≥ 92%; more preferably, an ee value ≥ 95%; and even more preferably, an ee value ≥ 97% (≥ 99%).

[0028] In another preferred embodiment, the sulfinamide compound represented by formula Ic has the following configuration:

[0029]

[0030] In the formula, n, R1 and m are as described in the first aspect of the present invention.

[0031] In another preferred embodiment, the reaction temperature is 0-100°C; more preferably 30-80°C; and even more preferably 55-70°C.

[0032] In another preferred embodiment, the reaction time is 6-48 hours.

[0033] In another preferred embodiment, the chiral ligand is a chiral phosphine ligand; more preferably, the chiral ligand is one or more chiral phosphine ligands selected from the group consisting of:

[0034]

[0035] In another preferred embodiment, the chiral ligand is one or more chiral phosphine ligands selected from the group consisting of:

[0036]

[0037] In another preferred embodiment, the chiral ligand is one or more chiral phosphine ligands selected from the group consisting of:

[0038]

[0039] In another preferred embodiment, the cobalt source is cobalt, divalent cobalt, trivalent cobalt, or a combination thereof; the cobalt source is one or more selected from the group consisting of: CoCl2, CoF2, CoI2, CoBr2, CoCl2·6H2O, CoSO4·7H2O, Co(OAc)2·4H2O, Co(acac)2, and Co(acac)3.

[0040] In another preferred embodiment, the cobalt source is divalent cobalt; more preferably, it is CoF2, CoI2, or CoBr2.

[0041] In another preferred embodiment, the cobalt source and the chiral ligand form a chiral cobalt ligand that participates in the reaction.

[0042] In another preferred embodiment, the cobalt source and chiral ligand are synthesized in situ to allow the chiral cobalt ligand to participate in the reaction.

[0043] In another preferred embodiment, the reaction is carried out in an inert solvent, preferably selected from the group consisting of ether solvents, aromatic solvents, amide solvents, alcohol solvents, alkane solvents, ketone solvents, sulfone solvents, nitrile solvents, ester solvents, or combinations thereof; more preferably tetrahydrofuran, trifluorotoluene, 1,4-dioxane, methyl tert-butyl ether, diethyl ether, methyl cyclopentyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, isopropanol, dichloromethane, 1,2-dichloroethane, chloroform, toluene, m-xylene, o-xylene, p-xylene, fluorobenzene, acetone, dimethyl sulfoxide, acetonitrile, ethyl acetate, or combinations thereof.

[0044] In another preferred embodiment, the base is selected from the group consisting of organic bases, inorganic bases, or combinations thereof; more preferably, the base is selected from the group consisting of triethylamine, tetramethylethylenediamine, diisopropylethylamine, pyridine, 2,6-dimethylpyridine, potassium bicarbonate, potassium hydroxide, cesium carbonate, cesium acetate, sodium carbonate, sodium bicarbonate, sodium tert-butoxide, or combinations thereof.

[0045] In another preferred embodiment, the additive is selected from the group consisting of: Molecular sieves Molecular sieves Molecular sieves, sodium iodide, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, silver trifluoromethanesulfonate, silver perchlorate, silver hexafluorophosphate, silver tetrafluoroborate, silver fluoride, silver sulfate, silver carbonate, or combinations thereof.

[0046] In another preferred embodiment, the additive is selected from the group consisting of: Molecular sieves Molecular sieves Molecular sieves, or combinations thereof.

[0047] In another preferred embodiment, the molar ratio of the sulfinimide represented by formula Ib to the aryl iodide represented by formula Ia is 1:(1-4); more preferably 1:(1-3).

[0048] In another preferred embodiment, the molar ratio of the sulfinimide compound represented by formula Ib to the cobalt source is 1:(0.01 to 0.5); more preferably 1:(0.05 to 0.3); and even more preferably 1:(0.05 to 0.1).

[0049] In another preferred embodiment, the molar ratio of the sulfinimide compound of formula Ib to the chiral ligand is 1:(0.01 to 0.5); more preferably 1:(0.05 to 0.3); and even more preferably 1:(0.05 to 0.15).

[0050] In another preferred embodiment, the molar ratio of the sulfinimide compound represented by formula Ib to the base is 1:(0.01-6); more preferably 1:(0.5-4); and even more preferably 1:(1-2).

[0051] In another preferred embodiment, the molar ratio of the sulfinimide compound represented by formula Ib to the additive is 1:(0.01-6); more preferably 1:(0.02-4); and even more preferably 1:(0.05-2).

[0052] In another preferred embodiment, the method includes the steps of:

[0053] Additives, bases, sulfinimide (Formula Ib), and aryl iodide (Formula Ia) are added to a solution of cobalt source and chiral phosphine ligand in an inert solvent, and the mixture is reacted at 0-100 °C for 6-48 h to obtain sulfinamide compound (Formula Ic).

[0054] In another preferred embodiment, the reaction further includes chiral separation.

[0055] In another preferred embodiment, the reaction includes post-processing.

[0056] In another preferred embodiment, the post-processing includes: filtration, vacuum concentration, and separation of the residue by column chromatography to obtain the corresponding chiral sulfinamide compound.

[0057] In a second aspect of the invention, a compound of formula I-c1 is provided:

[0058]

[0059] In the formula,

[0060] Selected from the group consisting of phenyl, naphthyl, or 5-6 heteroaryl groups containing 1-3 heteroatoms each independently selected from N, O, and S;

[0061] R1 is independently selected from the group consisting of: H, halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted 5-6 membered heteroaryl; or, R1 on two adjacent carbon atoms together with the carbon atom to which they are connected forms a substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-6 membered heterocyclic group, or substituted or unsubstituted 5-6 membered heteroaryl; wherein substitution means that one or more hydrogen atoms on the group are substituted by a group selected from the group consisting of: halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy;

[0062] n is 0, 1, 2, 3, 4 or 5; m is 1 or 2;

[0063] The heterocyclic group and heteroaryl group each independently contain 1-3 heteroatoms independently selected from N, O and S.

[0064] In another preferred embodiment, the compound represented by formula I-c1 is selected from the group consisting of:

[0065]

[0066] In another preferred embodiment, the compound represented by formula I-c1 is prepared by the method described in the first aspect of the present invention.

[0067] A third aspect of the present invention provides the use of a compound of formula I-c1 for preparing compounds as shown below:

[0068]

[0069] in, R1 and n are as defined in the first aspect of this invention.

[0070] In a fourth aspect, the present invention provides the use of a compound of formula I-c1 for preparing compounds as shown below:

[0071]

[0072] in, R1 and n are as defined in the first aspect of this invention.

[0073] In a fifth aspect, the present invention provides the use of a compound of formula I-c1 for preparing compounds as shown below:

[0074]

[0075] in, R1 and n are as defined in the first aspect of this invention.

[0076] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Detailed Implementation

[0077] Through extensive and in-depth research, the inventors have, for the first time, provided a novel method for preparing chiral sulfinamides. This method utilizes cobalt and chiral phosphine ligands as catalysts, reacting aryl iodides with sulfinamides as raw materials to obtain chiral sulfinamides. The sulfinamides obtained by this method have an ee value as high as 95% and a high product yield. Chiral sulfinamides are important frameworks for the preparation of drugs and chiral catalysts, thus possessing broad application prospects. Based on this, the inventors completed this invention.

[0078] the term

[0079] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0080] As used herein, the terms “containing” or “including (comprise)” can be open-ended, semi-closed, or closed. In other words, the terms also include “consistently made of” or “composed of”.

[0081] In this invention, the term 1-6 refers to 1, 2, 3, 4, 5, or 6. Other similar terms have similar meanings.

[0082] As used in this article, the term "halogenated" or "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0083] As used in this article, the term "hydroxyl group" refers to the -OH group.

[0084] As used in this article, the term "amino" refers to the -NH2 group.

[0085] As used in this article, the term "cyano" refers to the -CN group.

[0086] As used in this article, the term "nitro" refers to the -NO2 group.

[0087] As used herein, the term "alkyl" refers to a saturated aliphatic hydrocarbon group comprising a straight or branched chain with a specified number of carbon atoms, preferably containing 1-6 carbon atoms (or 1-4, 1-3). Examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, neopentyl, pteropentyl, or similar groups.

[0088] As used herein, the term "alkoxy" refers to -O-alkyl, wherein the alkyl group is defined as described above. It includes, without limitation, methoxy, ethoxy, propoxy, isopropoxy, and butoxy compounds. C1-C4 alkoxy compounds are preferred.

[0089] As used herein, the term "cycloalkyl" refers to a cyclic alkyl group having 3 to 10 (preferably 3 to 6) carbon atoms and possessing a monocyclic or polycyclic structure (e.g., fused ring, spirocyclic, bridged ring, etc.). In fused ring systems, one or more rings may be cycloalkyl, heterocyclic, aryl, or heteroaryl, as long as the linking site is a ring through a cycloalkyl group. Suitable examples of cycloalkyl groups include, for example, adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclooctyl.

[0090] As used herein, the term "aryl" refers to a monovalent aromatic carbocyclic group comprising 6 to 10 (preferably 6) carbon atoms, having a monocyclic (e.g., phenyl) or fused ring structure. If the bonding point is on an aromatic carbon atom, the fused ring may be non-aromatic (e.g., 2-benzoxazolone, 2H-1,4-benzoxazine-3(4H)-one-7-yl, etc.). Preferred aryl groups include phenyl and naphthyl groups.

[0091] As used herein, the term "heterocyclic group" refers to a saturated, partially saturated, or unsaturated group (but not aromatic) having a monocyclic or fused ring (including bridged and spirocyclic systems, having 1 to 10 carbon atoms and 1 to 4 heteroatoms selected from nitrogen, sulfur, or oxygen; in fused ring systems, one or more rings may be cycloalkyl, aryl, or heteroaryl, provided the junction passes through a non-aromatic ring). In one embodiment, the nitrogen and / or sulfur atoms of the heterocyclic group are optionally oxidized to provide an N-oxide, a sulfinyl group, and a sulfonyl moiety.

[0092] As used herein, the term "heteroaryl" refers to an aromatic group having 1 to 10 carbon atoms and 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur within a ring. Such a heteroaryl can be monocyclic (e.g., pyridyl or furanyl) or fused-ring (e.g., indolizinyl or benzothiophene), wherein the fused ring can be non-aromatic and / or contain one heteroatom, provided the bonding point is through an atom of an aromatic heteroaryl. In one embodiment, the ring atom nitrogen and / or sulfur of the heteroaryl is optionally oxidized to N-oxide (NO), sulfinyl, or sulfonyl. Preferably, heteroaryls include pyridyl, pyrroleyl, indolyl, thiophene, and furanyl. In one embodiment, a heteroaryl refers to a 5- to 10-membered heteroaryl, preferably a 5- to 6-membered heteroaryl.

[0093] In this invention, the term "substitution" refers to the substitution of one or more hydrogen atoms on a specific group by a specific substituent. The specific substituent is the substituent described accordingly above, or the substituent appearing in the various embodiments. Unless otherwise specified, a substituted group may have a substituent selected from a specific group at any substituted site of that group, and the substituents may be the same or different at each position. Those skilled in the art will understand that the combinations of substituents contemplated in this invention are stable or chemically feasible combinations. Such substituents include, but are not limited to: halogens, hydroxyl groups, carboxyl groups (-COOH), C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C3-C8 cycloalkyl groups, 3- to 12-membered heterocyclic groups, aryl groups, heteroaryl groups, C1-C8 aldehyde groups, C2-C10 acyl groups, C2-C10 ester groups, amino groups, C1-C6 alkoxy groups, C1-C10 sulfonyl groups, etc.

[0094] As used in this article, "TIPS" refers to triisopropylsilane.

[0095] sulfinimide

[0096] The sulfinylimide used in this invention has The structure shown.

[0097] The aforementioned sub

[0098] The method includes the following steps:

[0099] Triisopropylchlorosilane reacts with ammonia in diethyl ether at low temperature to give triisopropylsilane; then, in the presence of triethylamine, triisopropylsilane reacts with thionyl chloride in diethyl ether at low temperature to give the sulfinylimide of formula Ib of this invention.

[0100] Preparation method

[0101] This invention provides a novel method for preparing chiral sulfinamide compounds, the method comprising the steps of:

[0102]

[0103] Under an inert atmosphere, in the presence of a base, additives, a cobalt source and a chiral ligand, the sulfinimide represented by formula Ib reacts with the aryl iodide represented by formula Ia to give the sulfinamide compound represented by formula Ic.

[0104] In the formula, Selected from the group consisting of phenyl, naphthyl, or 5-6 heteroaryl groups containing 1-3 heteroatoms each independently selected from N, O, and S;

[0105] R1 is independently selected from the group consisting of: H, halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted 5-6 membered heteroaryl; or, R1 on two adjacent carbon atoms together with the carbon atom to which they are connected forms a substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-6 membered heterocyclic group, or substituted or unsubstituted 5-6 membered heteroaryl; wherein substitution means that one or more hydrogen atoms on the group are substituted by a group selected from the group consisting of: halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy;

[0106] n is 0, 1, 2, 3, 4 or 5; m is 1 or 2;

[0107] The heterocyclic group and heteroaryl group each independently contain 1-3 heteroatoms independently selected from N, O and S.

[0108] The raw material used in this invention is an aryl iodide having the structure shown in formula Ia; wherein, It is an aromatic group, such as phenyl, naphthyl, 5-6 membered heteroaryl, etc. It contains at least one iodine (I) group and at most two iodine (I) groups, as well as one or more R1 substituents; the two R1 groups can form heterocycles (including heteroaromatic rings and heterocyclic groups) or carbocycles (including aryl and heteroaryl groups) together with the atoms they are attached to, which are in harmony with... The connection method can be bridging, fusion, or screwing; the resulting heterocyclic or carbon ring can also be optionally substituted.

[0109] The reaction time and temperature of the method disclosed in this invention are not particularly limited and can be adjusted according to the specific reaction progress. Specifically, the reaction time of the method of this invention is 1-60 h; preferably 6-48 h; more preferably 12-24 h. The reaction temperature of the method of this invention is 0-100℃; preferably 20-80℃; preferably 30-70℃; preferably 35-60℃; preferably room temperature.

[0110] In one specific embodiment, the inert gas used in this invention is not particularly limited and can be a chemically stable gas commonly used in the art, and can be an inert gas selected from the group consisting of nitrogen, argon, etc.

[0111] In one specific embodiment, the base used in this invention is not particularly limited and can be an organic base or an inorganic base, or a combination thereof. It can be a base selected from the group consisting of: triethylamine, tetramethylethylenediamine, diisopropylethylamine, pyridine, 2,6-dimethylpyridine, potassium bicarbonate, potassium hydroxide, cesium carbonate, cesium acetate, sodium carbonate, sodium bicarbonate, sodium tert-butoxide, or a combination thereof.

[0112] In one specific embodiment, the chiral ligand used in this invention is a chiral phosphine ligand, specifically, the chiral phosphine ligand in this invention has the structure defined in the specification.

[0113] In one specific embodiment, there are no particular limitations on the cobalt source used in this invention. The cobalt or cobalt salts of different valence states used in this invention are mainly used to form chiral cobalt ligands for catalytic reactions with chiral phosphine ligands. Therefore, the cobalt source in the method of this invention can be cobalt in the zero valence state, or it can be in the form of divalent or trivalent cobalt, or a divalent or trivalent cobalt salt. Preferably, the cobalt source used in this invention is selected from the group consisting of: CoCl2, CoF2, CoI2, CoBr2, CoCl2·6H2O, CoSO4·7H2O, Co(OAc)2·4H2O, Co(acac)2, and Co(acac)3.

[0114] In one specific embodiment, the reaction of the present invention is carried out in an inert solvent. There are no particular limitations on the inert solvent used in the method of the present invention; it can be a commonly used organic solvent in the art. Preferably, the inert solvent is selected from the group consisting of ether solvents, aromatic solvents, amide solvents, alcohol solvents, alkane solvents, ketone solvents, sulfone solvents, nitrile solvents, ester solvents, or combinations thereof. More preferably, it is tetrahydrofuran, trifluorotoluene, 1,4-dioxane, methyl tert-butyl ether, diethyl ether, methyl cyclopentyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, isopropanol, dichloromethane, 1,2-dichloroethane, chloroform, toluene, m-xylene, o-xylene, p-xylene, fluorobenzene, acetone, dimethyl sulfoxide, acetonitrile, ethyl acetate, or combinations thereof.

[0115] In one specific embodiment, the additives used in this invention are primarily used to increase the reaction yield; the additives are mainly selected from the following group: Molecular sieves Molecular sieves Molecular sieves, sodium iodide, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, silver trifluoromethanesulfonate, silver perchlorate, silver hexafluorophosphate, silver tetrafluoroborate, silver fluoride, silver sulfate, silver carbonate, or combinations thereof.

[0116] In one specific embodiment, the molar ratio of the sulfinimide represented by Formula Ib to the aryl iodide represented by Formula Ia is not particularly limited, generally 1:(1-6); preferably 1:(1-4); more preferably 1:(1-3). The molar ratio of the sulfinimide represented by Formula Ib to the cobalt source is not particularly limited, generally 1:(0.01-0.5); preferably 1:(0.05-0.3); more preferably 1:(0.05-0.1). The molar ratio of the sulfinimide represented by Formula Ib to the chiral ligand is not particularly limited, generally 1:(0.01-0.5); preferably 1:(0.05-0.3); more preferably 1:(0.05-0.15). The molar ratio of the sulfinimide shown in Formula Ib to the base is not particularly limited, but generally it is 1:(0.01-6); preferably 1:(0.5-4); and more preferably 1:(1-2). The molar ratio or mass ratio of the sulfinimide shown in Formula Ib to the additive is not particularly limited and can be selected according to the reaction conventions, for example, 1:(0.01-6); preferably 1:(0.02-4); and more preferably 1:(0.05-2).

[0117] Specifically, in this invention, the chiral ligand and the cobalt source can be mixed and reacted before the reaction to form a chiral cobalt ligand, which is then added to the reaction system. Alternatively, the chiral cobalt ligand can be synthesized in situ in the reaction solution to catalyze the reaction. Specifically, the molar ratio of the cobalt source to the chiral ligand is 1:(1±0.5); preferably 1:(1-1.5); and more preferably 1:(1-1.2).

[0118] The method of the present invention also includes post-processing steps, including filtration, separation, concentration, and purification. Since the products of the present invention have chiral configurations, column chromatography is used to separate chiral sulfinamide products with different configurations.

[0119] The proportions of the reactants and raw materials described above, as well as the reaction conditions, are not intended to limit the scope of this invention, but are merely illustrative examples. Those skilled in the art can make conventional selections and reasonable adjustments based on specific reaction conditions, all of which are within the scope of this invention.

[0120] A specific preparation method of the present invention includes the following steps:

[0121] In a glove box at room temperature, 0.01-0.2 mmol of cobalt catalyst, 0.01-0.2 mmol of chiral ligand, and 1-10 mL of dry inert solvent were added to a dry sealed tube and stirred for 1-3 h. Then, 0.1-0.4 mmol of sulfinamide, 0.1-0.4 mmol of base, 0.1-2.0 mmol of additive, and 0.4-1.6 mmol of aryl iodide were added. The reaction was carried out in an oil bath at 15-60 °C. After the reaction was completed as monitored by TLC, the reaction solution was filtered, the solvent was removed under reduced pressure, and the residue was separated by column chromatography to obtain the corresponding chiral sulfinamide compound. The yield was 46-83%, with an ee of 85-95%.

[0122] Chiral sulfinamides and their applications

[0123] The compounds of formula Ic or I-c1 obtained by the method of the present invention can be used to further prepare sulfonyl fluoride compounds, sulfonamide compounds, and sulfonyl ester compounds for the synthesis of valuable chiral derivatives.

[0124] Typically, the method for preparing sulfonyl fluoride compounds using the compounds represented by formulas I-c1 of the present invention is as follows:

[0125]

[0126] Typically, the method for preparing sulfonamide compounds using the compounds represented by formula I-c1 of the present invention is as follows:

[0127]

[0128] Typically, the method for preparing sulfonyl ester compounds using the compounds represented by formulas I-c1 of the present invention is as follows:

[0129]

[0130] Compared with the prior art, the main advantages of the present invention include:

[0131] 1. The method of the present invention has excellent chemoselectivity and enantioselectivity, a wide range of applicable substrates, and can efficiently construct aryl chiral sulfinamides in one step.

[0132] 2. The method of the present invention has mild reaction conditions, is easy to operate, and is suitable for large-scale industrial production.

[0133] 3. The chiral compounds produced by the method of this invention are important frameworks for the preparation of drugs and chiral catalysts, and can also be used to construct chiral natural products, showing broad application prospects.

[0134] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods not specifically described in the following embodiments, or those following the manufacturer's recommended conditions, are performed. Unless otherwise stated, percentages and parts are by weight.

[0135] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this invention. The preferred embodiments and materials described herein are for illustrative purposes only.

[0136] Preparation method

[0137] Triisopropylchlorosilane (32.85 g, 170.38 mmol, 1.0 equivalent) was dissolved in anhydrous diethyl ether (340 mL) in a 1 L round-bottom flask that had been dried in an oven. After cooling the reaction mixture to -78 °C, anhydrous ammonia gas was bubbled into the solution for 2 hours, immediately forming a white precipitate. The reaction system was then heated to 0 °C and stirred openly for 3 hours to remove excess ammonia gas. When bubbling ceased, the reaction slurry was filtered through a 3-4 cm thick anhydrous sodium sulfate pad, washed with diethyl ether (20 mL), and concentrated under vacuum to obtain a colorless oily substance, triisopropylsilane (29.14 g, 168.23 mmol, 99% yield).

[0138] Triisopropylsilylamine (5.23 g, 30.20 mmol, 1.00 equivalent) was added to a 1 L round-bottom flask that had been dried in an oven. After sealing the container, three nitrogen evacuation cycles were performed, followed by the addition of anhydrous diethyl ether (600 mL). The solution was cooled to 0 °C, and anhydrous triethylamine (8.67 mL, 62.21 mmol, 2.06 equivalent) was added, followed by the slow dropwise addition of freshly distilled thionyl chloride (2.27 mL, 31.11 mmol, 1.03 equivalent). The reaction slurry was stirred vigorously at 0 °C for 2 hours, and then filtered through a 3–4 cm thick anhydrous sodium sulfate mat. The solvent was removed under vacuum to give a pale yellow oil, TIPS-NSO 1 (6.59 g, 30.03 mmol, 99% yield).

[0139] Example 1

[0140] In a glove box at room temperature, 0.02 mmol of cobalt iodide, 0.024 mmol of different chiral ligands, and 0.5 mL of dry ethyl acetate were added to a dry sealed tube and stirred for 1 h. Then, 0.2 mmol of sulfinimide 2, 0.4 mmol of diisopropylethylamine, and 50 mg of [unspecified ingredient] were added. MS and 0.6 mmol of aryl iodide 1a were transferred to an oil bath at 60 °C for reaction. After the reaction was completed by TLC monitoring, the reaction solution was filtered, the solvent was removed under reduced pressure, and the residue was separated by column chromatography to obtain the corresponding chiral sulfinamide compound 3a. The yield and ee value were determined by NMR and HPLC, respectively.

[0141] The reaction formula and the results prepared using different chiral ligands in this embodiment are as follows:

[0142]

[0143] Example 2

[0144] In a glove box at room temperature, 0.02 mmol of different cobalt catalysts, 0.03 mmol of chiral ligand, and 0.5 mL of dry ethyl acetate were added to a dry sealed tube and stirred for 1 h. Then, 0.2 mmol of sulfinimide 2, 0.4 mmol of diisopropylethylamine, and 100 mg of [unspecified ingredient] were added. MS, 0.05 mmol sodium iodide and 0.6 mmol aryl iodide 1a. The reaction was carried out in an oil bath at 60 °C. After the reaction was completed by TLC monitoring, the reaction solution was filtered, the solvent was removed under reduced pressure, and the residue was separated by column chromatography to obtain the corresponding chiral sulfinamide compound 3a. The yield and ee value were determined by NMR and HPLC, respectively.

[0145] The reaction formula and the results of preparation using different cobalt sources in this embodiment are as follows:

[0146]

[0147]

[0148] Example 3

[0149] In a glove box at room temperature, 0.02 mmol of cobalt iodide, 0.024 mmol of chiral ligand, and 0.5 mL of dry solvent were added to a dry sealed tube and stirred for 1 h. Then, 0.2 mmol of sulfinimide 2, 0.4 mmol of diisopropylethylamine, and 50 mg of [unspecified ingredient] were added. MS and 0.6 mmol of aryl iodide 1a were transferred to an oil bath at 60 °C for reaction. After the reaction was completed by TLC monitoring, the reaction solution was filtered, the solvent was removed under reduced pressure, and the residue was separated by column chromatography to obtain the corresponding chiral sulfinamide compound 3a. The yield and ee value were determined by NMR and HPLC, respectively.

[0150] The reaction formula and the results of preparation using different solvents in this embodiment are as follows:

[0151]

[0152]

[0153] Example 4

[0154] In a glove box at room temperature, 0.02 mmol of cobalt iodide, 0.03 mmol of chiral ligand, and 0.5 mL of dry ethyl acetate were added to a dry sealed tube and stirred for 1 h. Then, 0.2 mmol of sulfinimide 2, 0.4 mmol of diisopropylethylamine, and 100 mg of [unspecified ingredient] were added. MS and 0.6 mmol of aryl iodide 1a were transferred to an oil bath at 60 °C for reaction. After the reaction was completed by TLC monitoring, the reaction solution was filtered, the solvent was removed under reduced pressure, and the residue was separated by column chromatography to obtain the corresponding chiral sulfinamide compound. The yield and ee value were determined by NMR and HPLC, respectively.

[0155]

[0156]

[0157] Example 5: Preparation of chiral thioimine 3

[0158] In a glove box at room temperature, 0.02 mmol of cobalt iodide, 0.03 mmol of chiral ligand, and 0.5 mL of dry ethyl acetate were added to a dry sealed tube and stirred for 1 h. Then, 0.2 mmol of sulfinyl imide, 0.4 mmol of diisopropylethylamine, and 100 mg of [unspecified ingredient] were added. MS, 0.05 mmol sodium iodide and 0.6 mmol aryl iodide. The reaction was carried out in an oil bath at 60 °C. After the reaction was completed by TLC, the reaction solution was filtered, the solvent was removed under reduced pressure, and the residue was separated by column chromatography to obtain the corresponding chiral sulfinamide compound. The yield and ee value were determined by NMR and HPLC, respectively.

[0159] The following are the 1H NMR spectra of different chiral thioimine compounds. 13 The C NMR spectral data show that all compounds can be prepared using any of the methods in Examples 1-5, with some differences in yield and enantioselectivity.

[0160]

[0161]

[0162]

[0163] Structural characterization of compound 3a: 1 H NMR (400MHz, CDCl3) δ7.78–7.68(m,2H),7.23–7.13(m,2H),3.67(s,1H),1.29–1.24(m,3H),1.19–1.11(m,18H). 13 C NMR (101MHz, CDCl3) δ164.2 (d, J = 252.5Hz), 145.8 (d, J = 3.0Hz), 127.3 (d, J = 9.1Hz), 116.0 (d, J = 23.2Hz), 17.9, 17.8, 11.8. 19 F NMR(376MHz, CDCl3)δ-109.84.[α] D 20 =82.8(c=0.2,CHCl3).HRMS(ESI)m / zcalcd.for C 15 H 26 FNNaOSSi[M+Na] + =338.1381, found=338.1378. HPLC conditions: Daicel Chiralpak IBN-5column.hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 4.95min (minor), 6.65min (major).

[0164] Structural characterization of compound 3b: 1H NMR (400MHz, CDCl3) δ7.86(d,J=8.2Hz,2H),7.75(d,J=8.2Hz,2H),3.75(s,1H),1.32–1.22(m,3H),1.20–1.07(m,18H). 13 CNMR(101MHz, CDCl3)δ153.9,132.7(q,J=32.3Hz),125.9(q,J=6.1Hz),125.6,123.6(q,J=273.7Hz),17.9,17.8,11.8. 19 F NMR(376MHz, CDCl3)δ-62.79.[α] D 20 =38.6(c=0.2,CHCl3).HRMS(ESI)m / zcalcd.for C 16 H 26 F3NNaOSSi[M+Na] + =388.1349, found=388.1344. HPLC conditions: Daicel Chiralpak IBN-5column.hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 4.05min (minor), 10.24min (major).

[0165] Structural characterization of compound 3c: 1 H NMR (400MHz, CDCl3)δ 1 H NMR (400MHz, CDCl3) δ7.78(d,J=8.9Hz,2H),7.34(d,J=8.4Hz,2H),3.70(s,1H),1.26(q,J=2.6Hz,3H),1.15(t,J=6.5Hz,18H). 13 C NMR (101MHz, CDCl3) δ150.9, 148.5, 134.9 (q, J = 12.1Hz), 127.0, 121.2, 17.9, 17.8, 11.8. 19 F NMR(376MHz, CDCl3)δ-57.54.[α] D 20 =19.4(c=0.2,CHCl3).HRMS(ESI)m / z calcd.for C 16 H 26 F3NNaO2SSi[M+Na] +=404.1298, found=404.1290. HPLCconditions: Daicel Chiralpak IBN-5column.hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 4.02min (minor), 6.61min (major).

[0166] Structural characterization of compound 3d: 1 H NMR (400MHz, CDCl3) δ7.62(d,J=8.3Hz,2H),7.29(d,J=8.0Hz,2H),3.66(s,1H),2.41(s,3H),1.32–1.22(m,3H),1.18–1.07(m,18H). 13 C NMR (101MHz, CDCl3) δ147.2,140.9,129.6,124.9,21.3,17.9,17.8,11.8.[α] D 20 =57.9(c=0.2,CHCl3).HRMS(ESI)m / z calcd.for C 16 H 29 NNaOSSi[M+Na] + =334.1631, found=334.1630. HPLC conditions: Daicel Chiralpak IBN-5column.hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 7.05min (major), 8.07min (minor).

[0167] Structural characterization of compound 3e: 1 H NMR (400MHz, CDCl3) δ7.65(d,J=8.3Hz,2H),7.35(d,J=8.3Hz,2H),3.69(s,1H),3.02–2.95(m,1H),1.30–1.22(m,9H),1.15(t,J=6.8Hz,18H). 13 CNMR(101MHz, CDCl3)δ158.1,151.8,127.1,125.1,34.0,23.8,17.9,17.8,11.8.[α] D 20 =31.9(c=0.2,CHCl3).HRMS(ESI)m / z calcd.forC 18 H33 NNaOSSi[M+Na] + =362.1944, found=362.1950. HPLC conditions: DaicelChiralpak IBN-5column.hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 6.51min (minor), 9.08min (major).

[0168] Structural characterization of compound 3f: ¹H NMR (400MHz, CDCl₃) δ 7.71–7.61 (m, 2H), 7.55–7.48 (m, 2H), 3.70 (s, 1H), 1.34 (s, 9H), 1.29–1.26 (m, 3H), 1.15 (t, J = 6.9Hz, 18H). ¹³C NMR (101MHz, CDCl₃) δ 154.1, 146.9, 126.0, 124.9, 31.2, 18.0, 17.8, 11.8. [α]D₂O = 94.1 (c = 0.1, CHCl₃). HRMS (ESI) m / z calcd. for C₁₁₉H₃₅NNaOSSi[M+Na]⁺ = 376.2101, found = 376.2100. HPLC conditions: Daicel Chiralpak IBN-5column.hexane / 2-propanol=95 / 5,1.0mL / min.Retention times:5.44min(minor),7.98min(major).

[0169] Structural characterization of compound 3g: 1 H NMR (400MHz, CDCl3) δ7.61–7.34(m,3H),7.20–7.08(m,1H),3.74(s,1H),1.30–1.23(m,3H),1.18–1.03(m,18H). 13 C NMR (101MHz, CDCl3) δ162.8 (d, J = 251.5Hz), 152.6 (d, J = 5.1Hz), 130.6 (d, J = 7.1Hz ),120.7(d,J=3.0Hz),117.7(d,J=22.2Hz),112.3(d,J=24.2Hz),17.9,17.8,11.8. 19 FNMR(376MHz,CDCl3)δ-110.33.[α] D 20=48.2(c=0.2,CHCl3).HRMS(ESI)m / zcalcd.for C 15 H 26 FNNaOSSi[M+Na] + =338.1381, found=338.1379. HPLC conditions: Daicel Chiralpak ODH column. hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 5.35min (minor), 6.20min (major).

[0170] Structural characterization of compound 3h: 1 H NMR (400MHz, CDCl3) δ7.58 (s, 1H), 7.50 (d, J = 7.8Hz, 1H), 7.37 (t, J = 7.6Hz, 1H), 7.2 7(d,J=8.2Hz,1H),3.68(s,1H),2.42(s,3H),1.29–1.25(m,3H),1.20–1.08(m,18H). 13 C NMR (101MHz, CDCl3) δ157.6,139.1,131.4,128.8,125.2,122.0,21.5,17.9,17.8,11.8.[α] D 20 =84.4(c=0.1,CHCl3).HRMS(ESI)m / z calcd.forC 16 H 29 NNaOSSi[M+Na] + =334.1631, found=334.1626.HPLCconditions: Daicel ChiralpakOZH column.hexane / 2-propanol=95 / 5, 1.0mL / min.Retention times: 5.59min (minor), 6.27min (major).

[0171] Structural characterization of compound 3i: 1 H NMR (400MHz, CDCl3) δ8.28(d,J=5.3Hz,1H),7.20-7.14(m,1H),7.11(s,1H),3.97(s,3H),3.75(s,1H),1.35-1.20(m,3H),1.14(t,J=6.1Hz,18H). 13C NMR (101MHz, CDCl3) δ164.8,161.6,151.3,147.8,112.2,107.0,54.0,17.9,17.8,11.8.[α] D 20 =73.4(c=0.4,CHCl3).HRMS(ESI)m / z calcd.for C 15 H 28 N₂NaO₂SSi[M+Na] + =351.1533, found=351.1535. HPLC conditions: Daicel Chiralpak IBN-5 column; hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 7.43min (minor), 11.27min (major).

[0172] Structural characterization of compound 3j: 1 H NMR (400MHz, CDCl3) δ7.78–7.68(m,1H),7.46–7.38(m,1H),7.29–7.21(m,1H),3.91(s,1H),1.30–1.24(m,3H),1.16–1.06(m,18H). 13 C NMR (101MHz, CDCl3) δ150.6,127.7,126.0,124.6,17.9,17.8,11.7.[α] D 20 =11.2(c=0.3,CHCl3).HRMS(ESI)m / z calcd.for C 13 H 25 NNaOS2Si[M+Na]+=326.1039, found=326.1039. HPLC conditions: Daicel Chiralpak ADH column; hexane / 2-propanol=95 / 5, 1.0mL / min. Retention times: 6.93min (major), 7.39min (minor).

[0173] Structural characterization of compound 3k: 1H NMR (400 MHz, CDCl3) δ 7.25–7.20 (m, 1H), 7.17 (d, J=1.8 Hz, 1H), 6.89 (d, J=8.1 Hz, 1H), 6.03 (s, 2H), 3.66 (s, 1H), 1.29–1.23 (m, 3H), 1.13 (t, J=6.6 Hz, 18H). 13 C NMR (101 MHz, CDCl3) δ 143.8, 119.5, 108.4, 105.3, 101.8, 17.9, 17.8, 11.8. HRMS (ESI) m / z calcd. for C 16 H 27 NNaO3SSi [M+Na] + =364.1373, found=364.1374. HPLC conditions: Daicel Chiralpak IBN-5 column, hexane / 2-propanol=95 / 5, 1.0 mL / min. Retention times: 10.89 min (minor), 11.92 min (major).

[0174] Structural characterization of compound 3l: 1 H NMR (400 MHz, CDCl3) δ 6.88 (d, J=2.3 Hz, 2H), 6.51 (t, J=2.3 Hz, 1H), 3.82 (s, 6H), 3.75 (s, 1H), 1.30–1.24 (m, 3H), 1.18–1.10 (m, 18H). 13 C NMR (101 MHz, CDCl3) δ 161.1, 152.5, 103.3, 102.4, 55.6, 17.9, 17.8, 11.8. [α] D 20 =47.9 (c=0.5, CHCl3). HRMS (ESI) m / z calcd. for C 17 H 31 NNaO3SSi [M+Na] + =380.1686, found=380.1687. HPLC conditions: Daicel Chiralpak IBN-5 column, hexane / 2-propanol=95 / 5, 1.0 mL / min. Retention times: 5.56 min (minor), 6.88 min (major).

[0175] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for preparing a sulfinamide compound of formula Ic, characterized in that, Includes the following steps: Under an inert atmosphere, in the presence of a base, additives, a cobalt source and a chiral ligand, the sulfinimide represented by formula Ib reacts with the aryl iodide represented by formula Ia to give the sulfinamide compound represented by formula Ic. In the formula, Selected from the group consisting of phenyl, naphthyl, or 5-6 heteroaryl groups containing 1-3 heteroatoms each independently selected from N, O, and S; R1 is independently selected from the group consisting of: H, halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted 5-6 membered heteroaryl; or, R1 on two adjacent carbon atoms together with the carbon atom to which they are connected forms a substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-6 membered heterocyclic group, or substituted or unsubstituted 5-6 membered heteroaryl; wherein substitution means that one or more hydrogen atoms on the group are substituted by a group selected from the group consisting of: halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy; n is 0, 1, 2, 3, 4 or 5; m is 1 or 2; The heterocyclic group and heteroaryl group each independently contain 1-3 heteroatoms independently selected from N, O and S.

2. The preparation method according to claim 1, characterized in that, The sulfinamide compound represented by formula Ic has the following configuration: In the formula, n, R1, and m are as described in claim 1.

3. The preparation method according to claim 1, characterized in that, The chiral ligand is a chiral phosphine ligand, preferably, the chiral ligand is one or more chiral phosphine ligands selected from the group consisting of:

4. The preparation method according to claim 1, characterized in that, The cobalt source is cobalt, divalent cobalt, trivalent cobalt, or a combination thereof; the cobalt source is one or more selected from the group consisting of: CoCl2, CoF2, CoI2, CoBr2, CoCl2·6H2O, CoSO4·7H2O, Co(OAc)2·4H2O, Co(acac)2, and Co(acac)3.

5. The preparation method according to claim 1, characterized in that, The reaction is carried out in an inert solvent, preferably selected from the group consisting of ether solvents, aromatic solvents, amide solvents, alcohol solvents, alkane solvents, ketone solvents, sulfone solvents, nitrile solvents, ester solvents, or combinations thereof; more preferably tetrahydrofuran, trifluorotoluene, 1,4-dioxane, methyl tert-butyl ether, diethyl ether, methyl cyclopentyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, isopropanol, dichloromethane, 1,2-dichloroethane, chloroform, toluene, m-xylene, o-xylene, p-xylene, fluorobenzene, acetone, dimethyl sulfoxide, acetonitrile, ethyl acetate, or combinations thereof.

6. The preparation method according to claim 1, characterized in that, The alkali is selected from the group consisting of organic alkalis, inorganic alkalis, or combinations thereof; preferably, the alkali is selected from the group consisting of triethylamine, tetramethylethylenediamine, diisopropylethylamine, pyridine, 2,6-dimethylpyridine, potassium bicarbonate, potassium hydroxide, cesium carbonate, cesium acetate, sodium carbonate, sodium bicarbonate, sodium tert-butoxide, or combinations thereof.

7. The preparation method according to claim 1, characterized in that, The additives mentioned are selected from the following group: Molecular sieves Molecular sieves Molecular sieves, sodium iodide, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, silver trifluoromethanesulfonate, silver perchlorate, silver hexafluorophosphate, silver tetrafluoroborate, silver fluoride, silver sulfate, silver carbonate, or combinations thereof.

8. The preparation method according to claim 1, characterized in that, The reaction has one or more of the following characteristics: The molar ratio of the sulfinimide represented by formula Ib to the aryl iodide represented by formula Ia is 1:(1-4); preferably 1:(1-3); The molar ratio of the sulfinimide compound represented by formula Ib to the cobalt source is 1:(0.01-0.5); preferably 1:(0.05-0.3); more preferably 1:(0.05-0.1). The molar ratio of the sulfinimide compound of formula Ib to the chiral ligand is 1:(0.01-0.5); preferably 1:(0.05-0.3); more preferably 1:(0.05-0.15). The molar ratio of the sulfinimide compound of formula Ib to the base is 1:(0.01-6); preferably 1:(0.5-4); more preferably 1:(1-2); and / or The molar ratio of the sulfinimide compound represented by Formula Ib to the additive is 1:(0.01-6); preferably 1:(0.02-4); more preferably 1:(0.05-2).

9. The preparation method according to claim 1, characterized in that, The method includes the following steps: Additives, bases, sulfinimide (Formula Ib), and aryl iodide (Formula Ia) are added to a solution of cobalt source and chiral phosphine ligand in an inert solvent, and the mixture is reacted at 0-100 °C for 6-48 h to obtain sulfinamide compound (Formula Ic).

10. A compound represented by formula I-c1: In the formula, Selected from the group consisting of phenyl, naphthyl, or 5-6 heteroaryl groups containing 1-3 heteroatoms each independently selected from N, O, and S; R1 is independently selected from the group consisting of: H, halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted 5-6 membered heteroaryl; or, R1 on two adjacent carbon atoms together with the carbon atom to which they are connected forms a substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-6 membered heterocyclic group, or substituted or unsubstituted 5-6 membered heteroaryl; wherein substitution means that one or more hydrogen atoms on the group are substituted by a group selected from the group consisting of: halogen, nitro, hydroxyl, amino, cyano, C1-C6 alkyl, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy; n is 0, 1, 2, 3, 4 or 5; m is 1 or 2; The heterocyclic group and heteroaryl group each independently contain 1-3 heteroatoms independently selected from N, O and S.

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