A methyl sulfide C(sp 3 )-H bond boride, synthesis method and application

Abstract

The present invention provides a dimethyl sulfide C(sp 3 )-H bond boride, synthesis method and application, belonging to the field of organic synthesis. The present invention relates to a methyl sulfide C (sp 3 The invention discloses a selective synthesis method of )-H bond boron compounds, wherein a methyl sulfide compound and a pinacol boron ester are reacted under the synergistic catalysis of a novel bipyridine ligand and a transition metal iridium catalyst. The synthesis method achieves high selectivity of methyl C (sp) from a methyl sulfide compound without a directing group without using a protecting group. 3 )-H bond borylation reaction, the product selectivity is high, the yield is generally 65-85%, the reaction conditions are mild, and the operation is simple.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and relates to a dimethyl sulfide boron compound, a synthesis method and an application thereof, and in particular to a dimethyl sulfide C(sp 3 )-H bond boride, preparation method and application. Background Art

[0002] The development of C-H bond functionalization reactions has provided a powerful tool for the advancement of organic synthetic chemistry and is currently attracting widespread attention in fields such as organic chemistry, materials chemistry, medicinal chemistry, and pesticides. Compared to traditional synthetic methods, functionalized C-H bonds eliminate the need to introduce potentially reactive functional groups into the molecule during organic synthesis, significantly improving synthesis efficiency.

[0003] However, relative to C(sp 2 )-H bond functionalization reaction has developed rapidly, C(sp 3 )-H bond functionalization has been slow to develop. This is because C(sp 3 )-H bond has a high bond energy (90~100 kcal / mol), low acidity (45~60 kcal / mol), and high spatial freedom, which makes its functionalization reaction very difficult. In addition, C(sp 2 )-H bond π-electron pre-complexation also makes C(sp 2 )-H bond reactivity is much higher than that of C(sp 3 )-H bond. Therefore, when the molecule contains both C(sp 2 )-H and C(sp 3 )-H bonds, the transition metal-catalyzed CH functionalization reaction occurs preferentially at C(sp 2 )-H key.

[0004] Currently, although the transition metal iridium catalyzed C(sp 3 )-H bond borylation reaction methodology has been successfully established, but most of these methods still rely on traditional directing group strategies to achieve the target C(sp 3 )-H bond activation. However, it is difficult to achieve C(sp 3 )-H bond functionalization. Summary of the Invention

[0005] In view of the problems existing in the prior art, the present invention provides a dimethyl sulfide C (sp 3 )-H bond boride, synthesis method and application, the methyl sulfide C(sp 3)-H bond boride has high selectivity, mild reaction conditions and simple operation.

[0006] One of the objects of the present invention is to provide a dimethyl sulfide C(sp 3 )-H bond boride synthesis method, characterized in that the synthesis method comprises reacting a methyl sulfide compound shown in formula 2 and a pinacol boron ester under the synergistic catalysis of a novel bipyridine ligand shown in formula 3 and a metal iridium catalyst.

[0007]

[0008] Where n≥2;

[0009] X is CH2 or O;

[0010] R1 includes one or more of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, ester, cyano, amido, aldehyde, keto, optionally substituted amino, sulfonyl or silicon;

[0011] R2 includes any one of an optionally substituted alkyl group, an optionally substituted alkoxy group, an optionally substituted phenyl group, a halogen group, a nitro group, a trifluoromethyl group, or an aliphatic hydrocarbon-substituted pinacol boronate group.

[0012] Preferably, R1 includes hydrogen, halogen, optionally substituted C1~C 10 Alkyl, optionally substituted C1~C 12 One or more of the group consisting of an alkoxy group, a C1~C6 ester group, a cyano group, a C1~C6 acylamino group, an aldehyde group, a ketone group, an optionally substituted amino group, a sulfonyl group or a silicon group.

[0013] Preferably, R2 includes any one of an optionally substituted C1-C6 alkyl group, an optionally substituted C1-C6 alkoxy group, an optionally substituted phenyl group, a halogen group, a nitro group, a trifluoromethyl group, or an aliphatic hydrocarbon-substituted diol boronate group.

[0014] Preferably, the metallic iridium catalyst comprises [Ir(COD)Cl]2.

[0015] Preferably, the molar ratio of the metal iridium catalyst to the novel bipyridine ligand is 1:2.

[0016] Preferably, the pinacol borate comprises diboric acid pinacol borate and / or isopropyl pinacol borate.

[0017] Preferably, the molar ratio of the methyl sulfide compound to the pinacol borate is 1:0.5~0.75.

[0018] Preferably, the molar ratio of the dimethyl sulfide compound to the novel bipyridine ligand is 1:0.03-0.06.

[0019] Preferably, the molar ratio of the dimethyl sulfide compound to the metal iridium catalyst is 1:0.015~0.03.

[0020] Preferably, the reaction is carried out in an organic solvent, which includes a non-polar organic solvent and / or a weakly polar organic solvent.

[0021] Preferably, the organic solvent includes one or more of toluene, p-xylene, mesitylene, n-hexane or cyclohexane.

[0022] Preferably, the reaction temperature is 60-85°C.

[0023] Preferably, the reaction time is 12 to 24 hours.

[0024] Preferably, the synthesis method further comprises the step of isolating the product.

[0025] Preferably, after the reaction is completed, the solvent is removed under reduced pressure, and then the product is separated by thin layer chromatography or column chromatography.

[0026] The second object of the present invention is to provide a dimethyl sulfide C (sp 3 )-H bond boride, the boride having a structure as shown in Formula 1:

[0027]

[0028] Where n≥2;

[0029] X is CH2 or O;

[0030] R1 includes one or more of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, ester, cyano, amido, aldehyde, keto, optionally substituted amino, sulfonyl or silicon.

[0031] Preferably, R1 includes hydrogen, halogen, optionally substituted C1~C 10 Alkyl, optionally substituted C1~C 12 One or more of the group consisting of an alkoxy group, a C1~C6 ester group, a cyano group, a C1~C6 acylamino group, an aldehyde group, a ketone group, an optionally substituted amino group, a sulfonyl group or a silicon group.

[0032] The third object of the present invention is to provide a dimethyl sulfide C (sp 3 Application of )-H bond boronates in organic synthesis, organic functional materials and pharmaceutical intermediates.

[0033] The beneficial effects of the present invention include:

[0034] The present invention provides a dimethyl sulfide C(sp 3 A selective synthesis method for )-H bond boronates, wherein a methyl sulfide compound and a pinacol boron ester are reacted under the synergistic catalysis of a novel bipyridine ligand and a transition metal iridium. The method achieves high selectivity for the methyl C(sp)-H bond boronates of methyl sulfide compounds without directing groups without using a protecting group. 3 )-H bond borylation reaction, the product selectivity is high, the yield is above 50%, generally 65~85%, the reaction conditions are mild and the operation is simple. DETAILED DESCRIPTION

[0035] In the following description, certain specific details are included to provide a thorough understanding of the various disclosed embodiments. However, one skilled in the relevant art will recognize that the embodiments can be implemented without one or more of these specific details and with other methods, components, materials, etc.

[0036] Unless otherwise required in this application, the words "include" and "comprising" should be construed in an open, inclusive sense, ie, "including, but not limited to."

[0037] Reference throughout this specification to "one embodiment" or "an embodiment" or "a preferred embodiment" or "certain embodiments" means that the specific referenced elements, structures, or features described in connection with that embodiment are included in at least one embodiment. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" or "in a preferred embodiment" or "in certain embodiments" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the specific elements, structures, or features may be combined in any suitable manner in one or more embodiments.

[0038] According to a first aspect of the present invention, there is provided a dimethyl sulfide C(sp 3 )-H bond boride synthesis method, characterized in that the synthesis method comprises reacting a methyl sulfide compound shown in formula 2 and a pinacol boron ester under the synergistic catalysis of a novel bipyridine ligand shown in formula 3 and a metal iridium catalyst.

[0039]

[0040] Where n≥2;

[0041] X is CH2 or O;

[0042] R1 includes one or more of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, ester, cyano, amido, aldehyde, keto, optionally substituted amino, sulfonyl or silicon;

[0043] R2 includes any one of an optionally substituted alkyl group, an optionally substituted alkoxy group, an optionally substituted phenyl group, a halogen group, a nitro group, a trifluoromethyl group, or an aliphatic hydrocarbon-substituted pinacol boronate group.

[0044] In the present invention, when the number of atoms between S and the benzene ring is greater than or equal to 3, that is, n≥2, the borylation reaction occurs entirely at the C (sp 3 )-H bond; when the number of atoms between S and the benzene ring is less than 3, that is, n≤1, the borylation reaction will occur on the C(sp 2 )-H key.

[0045] The number of substituents R1 on the benzene ring in the dimethyl sulfide compound can be 1, 2, 3, 4 or 5, and the position of the substituent R1 can be para, ortho or meta.

[0046] In the present invention, to achieve the methyl sulfide compound C (sp 3 )-H bond borylation needs to overcome the following two difficulties: 1) C(sp 2 ) competition with the H-bond reactivity; 2) the inability to form conventional cyclometallated intermediates with the aid of directing groups.

[0047] The present invention introduces an electron-withdrawing group R2 into the bipyridine ligand to form a novel bipyridine ligand as shown in Formula 3. The novel bipyridine ligand is a Lewis-Acid type bipyridine ligand. Under the action of the electron-withdrawing group, the two N atoms in the novel bipyridine ligand exhibit unequal complexing abilities. During the reaction, the sulfur atom replaces the nitrogen atom with weaker complexing ability to form a three-membered ring iridium intermediate with the catalytic center of the metal iridium catalyst, thereby achieving the thiomethyl C(sp 3 )-H bond selective borylation reaction.

[0048] In a preferred embodiment of the present invention, R1 includes hydrogen, halogen, optionally substituted C1~C 10 Alkyl, optionally substituted C1~C 12 One or more of the group consisting of an alkoxy group, a C1~C6 ester group, a cyano group, a C1~C6 acylamino group, an aldehyde group, a keto group, an optionally substituted amino group, a sulfonyl group or a silicon group.

[0049] Wherein, the R1 includes halogen, preferably any one or more of fluorine, chlorine, bromine or iodine;

[0050] R1 includes optionally substituted C1~C 10 Alkyl, preferably unsubstituted C1~C 10的 Alkyl, further preferably including C1~C 10 Straight chain alkyl, C1~C10 Branched alkyl or C1~C 10 The cycloalkyl group further preferably includes one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isopropyl, tert-butyl, isobutyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

[0051] R1 includes optionally substituted C1~C 12 Alkoxy, preferably including fluorine-substituted or unsubstituted C1~C 12 The alkoxy group further preferably includes one or more of methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, n-heptyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, n-undecyloxy, n-dodecyloxy or trifluoromethoxy.

[0052] R1 includes a C1-C6 ester group, preferably one or more of a formate group, an acetate group, a n-propionate group, an isopropionate group, a n-butyrate group, a n-valerate group or a n-hexanoate group.

[0053] R1 includes C1-C6 acylamino groups, preferably one or more of formamide, acetamide, propionamide, butyramide, valeramide or hexamamide.

[0054] R1 includes amino, preferably includes one or more of N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, N,N-dibutylamino, N,N-diisopropylamino or N,N-dicyclohexylamino.

[0055] R1 includes a silicon group, preferably one or more of a trimethylsilyl group, a triethylsilyl group, a trimethoxysilyl group or a triethoxysilyl group.

[0056] In a preferred embodiment of the present invention, R1 includes one or more of hydrogen, fluorine, chlorine, bromine, methyl, methylsulfonyl, methoxy, carbomethoxy, cyano, trifluoromethyl, dioxymethyl or tert-butyl.

[0057] In a preferred embodiment of the present invention, R2 includes any one of an optionally substituted C1-C6 alkyl group, an optionally substituted C1-C6 alkoxy group, an optionally substituted phenyl group, a halogen group, a nitro group, a trifluoromethyl group, or an aliphatic hydrocarbon-substituted diol boronate group.

[0058] Wherein, the R2 includes an optionally substituted C1~C6 alkyl group, preferably includes an unsubstituted C1~C6 alkyl group, and further preferably is any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl.

[0059] The R2 includes an optionally substituted C1~C6 alkoxy group, preferably an unsubstituted C1~C6 alkoxy group, and more preferably any one of methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy or n-hexoxy.

[0060] The R2 includes optionally substituted phenyl, preferably unsubstituted phenyl, and phenyl substituted by fluorine, nitro, optionally substituted methyl, optionally substituted boron ester, methoxy or N,N-dimethylamino, and further preferably includes any one of 4-fluorophenyl, 4-trifluoromethylphenyl, perfluorophenyl, 4-nitrophenyl, 4-methoxyphenyl, and 4-N,N-dimethylaminophenyl.

[0061] The R2 includes an aliphatic hydrocarbon-substituted diol boron ester group, preferably any one of 1,3-ethylene glycol boron ester group, 2,4-dibutanol boron ester group, 2,2-dimethyl-1,3-dipropanol boron ester group, 2-methyl-2,4-dipentanol boron ester group or 1,1,2,2-tetrakistrifluoromethyl-1,2-ethylene glycol boron ester group.

[0062] In a preferred embodiment of the present invention, the metal iridium catalyst includes one or more of [Ir(COD)Cl]2, [Ir(COD)OMe]2 and [Ir(COD)BF4]2, preferably [Ir(COD)Cl]2.

[0063] In the present invention, the metal iridium catalyst is, for example, [Ir(COD)Cl]2, [Ir(COD)OMe]2, [Ir(COD)BF4]2, [Ir(COD)Cl]2 and [Ir(COD)OMe]2, [Ir(COD)Cl]2 and [Ir(COD)BF4]2, [Ir(COD)OMe]2 and [Ir(COD)BF4]2, or a combination of [Ir(COD)Cl]2, [Ir(COD)OMe]2 and [Ir(COD)BF4]2.

[0064] Preferably, the molar ratio of the metal iridium catalyst to the novel bipyridine ligand is 1:2.

[0065] In a preferred embodiment of the present invention, the molar ratio of the dimethyl sulfide compound to the novel bipyridine ligand is 1:0.03-0.06, for example, 1:0.032, 1:0.035, 1:0.04, 1:0.045, 1:0.05, 1:0.055 or 1:0.058.

[0066] In the present invention, when the molar ratio of the methyl sulfide compound to the novel bipyridine ligand is less than 1: 0.03, the methylthio C (sp 3 )-H bond borylation product yield will be reduced; when the molar ratio of the methyl sulfide compound to the novel bipyridine ligand is greater than 1:0.06, the C (sp 2 )-H borylation product ratio will increase, resulting in C(sp 3 )-H selectivity decreased.

[0067] Preferably, the molar ratio of the dimethyl sulfide compound to the metal iridium catalyst is 1:0.015~0.03, for example, 1:0.016, 1:0.018, 1:0.02, 1:0.022, 1:0.024, 1:0.026, 1:0.028 or 1:0.029.

[0068] In the present invention, when the amount of the dimethyl sulfide compound added is 1 mmol and the amount of the metal iridium catalyst added is less than 0.015 mmol, C(sp 3 )-H bond borylation product yield is very low, only about 20%; when the molar ratio of the metal iridium catalyst is greater than 0.03mmol, C(sp 3 The yield of the borylation product of the )-H bond no longer increases.

[0069] In a preferred embodiment of the present invention, the reaction is carried out in an organic solvent. Since polar solvents may affect the complexing ability of the novel bipyridine ligand and the metal iridium catalyst, the organic solvent of the present invention includes a non-polar organic solvent and / or a weakly polar organic solvent.

[0070] Preferably, the organic solvent comprises one or more of toluene, p-xylene, mesitylene, n-hexane or cyclohexane, for example, toluene, p-xylene, mesitylene, n-hexane, cyclohexane, toluene and p-xylene, toluene and mesitylene, toluene and n-hexane, toluene and cyclohexane, toluene, p-xylene and mesitylene, toluene, p-xylene and n-hexane, p-xylene and mesitylene, p-xylene and n-hexane, toluene, n-hexane and cyclohexane, or a combination of p-xylene, mesitylene and n-hexane.

[0071] In a preferred embodiment of the present invention, the reaction temperature is 60-85°C.

[0072] In a preferred embodiment of the present invention, the reaction time is 12 to 24 hours.

[0073] In a preferred embodiment of the present invention, the synthesis method further comprises the step of isolating the product.

[0074] Preferably, after the reaction is completed, the solvent is removed under reduced pressure, and then the product is separated by thin layer chromatography or column chromatography.

[0075] In the present invention, the synthesis method specifically comprises:

[0076] In a dry reaction vessel, a methyl sulfide compound as shown in Formula 2, a pinacol boron ester, a metal iridium catalyst and a novel bipyridine ligand as shown in Formula 3 are added in sequence, and then a solvent is added. The reaction is carried out at 60-85° C. for 12-24 hours. After the reaction is completed, the solvent is removed under reduced pressure, and the mixture is separated by column chromatography and thin layer chromatography to obtain a methyl sulfide compound C (sp 3 )-H bond boride.

[0077] According to a second aspect of the present invention, there is provided a dimethyl sulfide C(sp 3 )-H bond boride, wherein the boride has a structure as shown in Formula 1:

[0078]

[0079] Where n≥2;

[0080] X is CH2 or O;

[0081] R1 includes one or more of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, ester, cyano, amido, aldehyde, keto, optionally substituted amino, sulfonyl or silicon.

[0082] In a preferred embodiment of the present invention, R1 includes hydrogen, halogen, optionally substituted C1~C 10 Alkyl, optionally substituted C1~C 12 One or more of the group consisting of an alkoxy group, a C1~C6 ester group, a cyano group, a C1~C6 acylamino group, an aldehyde group, a keto group, an optionally substituted amino group, a sulfonyl group or a silicon group.

[0083] Wherein, the R1 includes halogen, preferably any one or more of fluorine, chlorine, bromine or iodine;

[0084] R1 includes optionally substituted C1~C 10 Alkyl, preferably unsubstituted C1~C 10 The alkyl group preferably includes C1~C 10 Straight chain alkyl, C1~C 10 Branched alkyl or C1~C 10The cycloalkyl group further preferably includes one or more of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isopropyl, tert-butyl, isobutyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

[0085] R1 includes optionally substituted C1~C 12 Alkoxy, preferably including fluorine-substituted or unsubstituted C1~C 12 The alkoxy group further preferably includes one or more of methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, n-heptyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, n-undecyloxy, n-dodecyloxy or trifluoromethoxy.

[0086] R1 includes a C1-C6 ester group, preferably one or more of a formate group, an acetate group, a n-propionate group, an isopropionate group, a n-butyrate group, a n-valerate group or a n-hexanoate group.

[0087] R1 includes C1-C6 acylamino groups, preferably one or more of formamide, acetamide, propionamide, butyramide, valeramide or hexamamide.

[0088] R1 includes amino, preferably includes one or more of N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, N,N-dibutylamino, N,N-diisopropylamino or N,N-dicyclohexylamino.

[0089] R1 includes a silicon group, preferably one or more of a trimethylsilyl group, a triethylsilyl group, a trimethoxysilyl group or a triethoxysilyl group.

[0090] In a preferred embodiment of the present invention, R1 includes one or more of hydrogen, fluorine, chlorine, bromine, methyl, methylsulfonyl, methoxy, carbomethoxy, cyano, trifluoromethyl, dioxymethyl or tert-butyl.

[0091] In a preferred embodiment of the present invention, the methyl sulfide C(sp 3 )-H bond boride is at least one of the compounds shown below:

[0092]

[0093] According to a third aspect of the present invention, there is provided a dimethyl sulfide C(sp 3 Application of )-H bond boronates in organic synthesis, organic functional materials and pharmaceutical intermediates.

[0094] Specifically, C(sp3 The products generated by borylation of )-H bonds can be further transformed. For example, organoboron compounds can act as carbon nucleophiles in many transformations, forming carbon-carbon or carbon-heteroatom bonds. This property can be exploited to indirectly convert C-H bonds to C-C, CO, CN, CX, C-CN, and other bonds, finding applications in the synthesis of natural products, organic materials, and pharmaceutical ingredients.

[0095] Example

[0096] The present invention will be further described in detail below in conjunction with the embodiments. It will be appreciated that the specific embodiments described herein are intended only to explain the invention and are not intended to limit the invention. It should be noted that, unless there is a conflict, the embodiments and features of the embodiments in this application may be combined with each other.

[0097] To better illustrate the present invention and facilitate understanding of the technical solutions of the present invention, typical but non-limiting embodiments of the present invention are as follows:

[0098] Example 1

[0099] 1. First, synthesize the new bipyridine ligand Ligand as shown in Formula 5.

[0100]

[0101]

[0102] To a flask equipped with a reflux apparatus were added 5-bromo-2,2'-bipyridine (1.00 g, 4.27 mmol), 1,2-bis(4,4,5,5-tetramethyl-1,3,2-boronyl)benzene (1.41 g, 4.27 mmol), Pd(PPh3)4 (745 mg, 0.640 mmol) and sodium carbonate (2.30 g, 21.5 mmol) in sequence. 1,4-dioxane (40 mL), ethanol (28 mL) and water (28 mL) were then added to the reaction system. The reaction was refluxed at 80°C for 5 hours. After the reaction was completed, the reaction solution was cooled to room temperature and extracted twice with ethyl acetate (20 ml). The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by chromatography to obtain 5-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolato)phenyl)-2,2'-bipyridine.

[0103]

[0104]

[0105] 5-(2-(4,4,5,5-tetramethyl-1,3,2-boronyl)phenyl)-2,2'-bipyridine (1.00 g, 2.79 mmol), NH4OAc (1.08 g, 14.0 mmol), NaIO4 (2.98 g, 14.0 mmol), acetone, and water were added to a flask. A mixed volume of acetone and water (1 / 1) was added to the reaction system. The reaction was stirred at room temperature for 24 hours. The acetone was evaporated under reduced pressure, and the reaction solution was extracted twice with 20 ml of ethyl acetate. The organic layers were combined, concentrated under reduced pressure, and separated by column chromatography to obtain 2-(2,2'-bipyridin-5-yl)phenylboronic acid.

[0106]

[0107] (3) Synthesis of a new bipyridine ligand, the reaction is shown in Equation 24:

[0108]

[0109] 2-(2,2'-bipyridin-5-yl)phenylboronic acid (100 mg, 0.360 mmol), 1-trifluoromethyl-1,2-ethanediol (2.0 equiv), and chloroform (20 mL) were added to a flask and dissolved. The mixture was then reacted under reflux for 12 hours. After evaporation of the solvent, the crude yellow product was separated by chromatography to yield the novel bipyridine ligand.

[0110] The yield is 70%.

[0111]

[0112] Then, the prepared novel bipyridine ligand Ligand was used to synthesize dimethyl sulfide C(sp 3 )-H bond boride, the reaction is shown in formula 4:

[0113]

[0114] Example 2

[0115] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0116] To a dry reaction tube, 3-phenylpropylmethyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added in sequence, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 15 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-phenylpropyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Equation 6.

[0117]

[0118] The total yield of the boronate was 61%, a colorless oil.

[0119]

[0120] Example 3

[0121] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0122] To a dry reaction tube, 3-(4-methylphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added in sequence, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 20 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(4-methylphenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Equation 7.

[0123]

[0124] The total yield of the boride was 64%, a colorless oil.

[0125]

[0126] Example 4

[0127] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0128] To a dry reaction tube, 3-(4-methylsulfonylphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added in sequence, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 3 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(4-methylsulfonylphenyl)propyl)thio)methyl)-pinacolato borane ester, the chemical structure of which is shown in Formula 8.

[0129]

[0130] The total yield of boride was 60%, a colorless oil.

[0131]

[0132] Example 5

[0133] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0134] To a dry reaction tube, 3-(4-bromophenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was allowed to proceed at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 20 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(4-bromophenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Equation 9.

[0135]

[0136] The total yield of boride was 70%, and the product was a light yellow oil.

[0137]

[0138] Example 6

[0139] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0140] To a dry reaction tube, 3-(3-methoxyphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(3-methoxyphenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 10.

[0141]

[0142] The total yield of boride was 70%, and the product was a light yellow oil.

[0143]

[0144] Example 7

[0145] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0146] To a dry reaction tube, 3-(3-fluorophenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1–0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was allowed to proceed at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 20 / 1) to yield 4,4,5,5-tetramethyl-2-(((3-(3-fluorophenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 11.

[0147]

[0148] The total yield of boride was 65%, and the product was a light yellow oil.

[0149]

[0150] Example 8

[0151] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0152] To a dry reaction tube, 3-(3-carbomethoxyphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 8 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(3-carbomethoxyphenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 12.

[0153]

[0154] The total yield of boride was 65%, and the product was a light yellow oil.

[0155]

[0156] Example 9

[0157] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0158] To a dry reaction tube, 3-(3-cyanophenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1–0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was allowed to proceed at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(3-cyanophenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 13.

[0159]

[0160] The total yield of boride was 54%, and the product was a light yellow oil.

[0161]

[0162] Example 10

[0163] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0164] To a dry reaction tube, 3-(3-chlorophenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added in sequence, followed by 2 mL of p-xylene as solvent. The reaction was allowed to proceed at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 20 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(3-chlorophenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 14.

[0165]

[0166] The total yield of the borylation product was 69%, and the product was a light yellow oil.

[0167]

[0168] Example 11

[0169] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0170] To a dry reaction tube, 3-(3-trifluoromethylphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1–0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was allowed to proceed at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to yield 4,4,5,5-tetramethyl-2-(((3-(3-trifluoromethylphenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Equation 15.

[0171]

[0172] The total yield of the borylation product was 72%, and the product was a light yellow oil.

[0173]

[0174] Example 12

[0175] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0176] To a dry reaction tube, 3-(3-bromophenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was allowed to proceed at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 15 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(3-bromophenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 16.

[0177]

[0178] The total yield of the borylation product was 59%, and the product was a light yellow oil.

[0179]

[0180] Example 13

[0181] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0182] To a dry reaction tube, 3-(1,3-dioxymethylphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 25 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(1,3-dioxymethylphenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 17.

[0183]

[0184] The total yield of the borylation product was 52%, a light yellow oil.

[0185]

[0186] Example 14

[0187] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0188] To a dry reaction tube, 3-(3,5-di-tert-butylphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 15 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(3,5-di-tert-butylphenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Formula 18.

[0189]

[0190] The total yield of the borylation product was 52%, a light yellow oil.

[0191] Example 15

[0192] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0193] To a dry reaction tube, 3-(3,5-fluorophenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1–0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 15 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(3,5-difluorophenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Equation 19.

[0194]

[0195] The total yield of the borylation product was 50%, a light yellow oil.

[0196]

[0197] Example 16

[0198] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0199] To a dry reaction tube, 3-(2,3-dimethylphenyl)propyl methyl sulfide (0.2 mmol), B2Pin2 (0.1-0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added sequentially, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 15 / 1) to obtain 4,4,5,5-tetramethyl-2-(((3-(2,3-dimethylphenyl)propyl)thio)methyl)-pinacolatoborane ester, the chemical structure of which is shown in Equation 20.

[0200]

[0201] The total yield of the borylation product was 73%, and the product was a light yellow oil.

[0202]

[0203] Example 17

[0204] This embodiment provides a dimethyl sulfide C(sp 3 A method for synthesizing a )-H bond boride, the method comprising:

[0205] To a dry reaction tube, 2-(3-methoxyphenoxy)ethyl methyl sulfide (0.2 mmol), B2Pin2 (0.1–0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and Ligand (0.012 mmol) were added in sequence, followed by 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 15 / 1) to yield 2-(((2-(3-methoxyphenoxy)ethyl)mercapto)methyl)-4,4,5,5-tetramethyl-1,3,2-boron ester, the chemical structure of which is shown in Equation 21.

[0206]

[0207] The total yield of the borylation product was 62%, a light yellow oil.

[0208]

[0209] Comparative Example 1

[0210] The novel bipyridine ligand Ligand in Example 2 was replaced by 4,4'-di-tert-butyl bipyridine ligand dtbpy. The other conditions were the same as those in Example 2. The borylation reaction occurred entirely at the C (sp 2)-H key.

[0211] The reaction is shown in Equation 25:

[0212]

[0213] To a dry reaction tube, 3-phenylpropylmethyl sulfide (0.2 mmol), B2Pin2 (0.1–0.15 mmol), [Ir(COD)Cl]2 (0.006 mmol), and 4,4'-di-tert-butylbipyridyl ligand (0.012 mmol) were added sequentially, followed by the addition of 2 mL of p-xylene as solvent. The reaction was continued at 80°C for 12 hours. After completion, the solvent was removed under reduced pressure, and the products were separated by column chromatography (petroleum ether / ethyl acetate = 15 / 1) to yield 4,4,5,5-tetramethyl-2-(3-(3-methylthio)phenyl)-1,3,2-boronate (chemical structure shown in Equation 22) and 2,2'-(5-(3-(methylthio)propyl)-1,3-phenyl)-bis-(4,4,5,5-tetramethyl-1,3,2-boronate) (chemical structure shown in Equation 23).

[0214]

[0215] Comparative Example 2

[0216] The 3-phenylpropyl methyl sulfide in Example 2 was replaced by 3-phenylethyl methyl sulfide, and the other conditions were the same as those in Example 2. The borylation reaction occurred entirely at the ortho-C (sp 2 )-H key.

[0217] The reaction is shown in Equation 26:

[0218]

[0219] The total yield of the borylation product was 72%, and the product was a light yellow oil.

[0220]

[0221] The applicant declares that the present invention is intended to illustrate the detailed structural features of the present invention through the above-described embodiments, but the present invention is not limited to the above-described detailed structural features. This does not mean that the present invention must rely on the above-described detailed structural features in order to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent replacements for selected components, additions of auxiliary components, and selection of specific embodiments, etc., fall within the scope of protection and disclosure of the present invention.

[0222] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

[0223] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0224] In addition, the various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A methyl sulfide C(sp 3 )-H bond boride synthesis method, characterized in that, The synthesis method comprises reacting a methyl sulfide compound shown in Formula 2 and a pinacol diboronate under the synergistic catalysis of a bipyridine ligand shown in Formula 5 and [Ir(COD)Cl]2; Where n≥2; X is CH2 or O; R1 is selected from one or more of hydrogen, halogen, methyl, methoxy, cyano, trifluoromethyl, and tert-butyl.

2. The synthesis method according to claim 1, wherein The molar ratio of the [Ir(COD)Cl]2 to the bipyridine ligand is 1:

2.

3. The synthesis method according to claim 1, wherein the molar ratio of the dimethyl sulfide compound to the diboric acid pinacol ester is 1:0.5 to 0.

75.

4. The synthesis method according to claim 1, wherein The molar ratio of the dimethyl sulfide compound to the bipyridine ligand is 1:0.03-0.06; The molar ratio of the dimethyl sulfide compound to the [Ir(COD)Cl]2 is 1:0.015-0.

03.

5. The synthesis method according to claim 1, wherein The reaction is carried out in an organic solvent, which includes one or more of toluene, p-xylene, mesitylene, n-hexane or cyclohexane; The reaction temperature is 60-85°C; The reaction time is 12 to 24 hours.

6. The synthesis method according to claim 1, wherein The synthesis method further comprises the step of isolating the product: After the reaction is completed, the solvent is removed under reduced pressure, and then the product is separated by thin layer chromatography or column chromatography.

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