N-heterocyclic carbene compound and application thereof

Abstract

The invention discloses an N-heterocyclic carbene compound and an application thereof. The invention provides a compound as shown in a formula I. The N-heterocyclic carbene compound disclosed by the invention is novel in structure and has a good application prospect in a monovalent copper catalyzed silylation reaction. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a class of nitrogen heterocyclic carbene compounds and applications thereof. Background Art

[0002] Transition metal asymmetric catalysis is one of the most efficient and rapid methods for constructing chiral compounds, and chiral ligands play a vital role in this process. Chiral nitrogen heterocyclic carbene ligands have been widely studied and developed due to their strong σ electron donation ability, stable structure, and ease of modular synthesis. (Dalton Trans., 2021, 50, 17467–17477.)

[0003] The synthesis of chiral nitrogen heterocyclic carbene often requires the use of chiral amines as chiral precursors. At present, the most extensive research is on nitrogen heterocyclic carbene ligands based on chiral 1,2-diphenylethylenediamine as the skeleton. A series of five-membered nitrogen heterocyclic carbene ligands can be synthesized by replacing the groups attached to the nitrogen atom. (J.Am.Chem.Soc.2017,139,9317–9324.) Professor Sawamura introduced phenolic hydroxyl groups as auxiliary coordination groups on the nitrogen substituents. (J.Am.Chem.Soc.2014,136,13932–13939.) In 2010, Professor McQuade also used chiral 1,2-diphenylethylenediamine as a chiral source to synthesize six-membered nitrogen heterocyclic carbene ligands. (Org. Lett., 2010, 12, 5008-5011.) Secondly, a series of nitrogen heterocyclic carbene ligands with chirality in the side chains can be synthesized by using α-chiral primary amines as chirality sources, which can be used in ruthenium-catalyzed asymmetric hydrogenation of olefins. (J.Am.Chem.Soc.2020,142,7100–7107.) In 2011, Professor Gawley used C2-symmetric aniline with a chiral center at the benzyl position as a chiral source to synthesize a C2-symmetric chiral nitrogen heterocyclic carbene ligand, which was used in the copper-catalyzed hydrosilation reaction of alkyl ketones (J.Am.Chem.Soc.2011,133,49,19680–19683.), and Professor Shi Shiliang modified the skeleton based on it and added a rigid aromatic ring (Angew.Chem.,Int.Ed.,2018,57,1376–1380.). α-Amino alcohols derived from α-amino acids can also be used as chiral sources for the synthesis of nitrogen heterocyclic carbenes and have been successfully used in palladium-catalyzed asymmetric CH bond activation reactions (Angew. Chem. Int. Ed. 2021, 60, 7245–7250.).

[0004]

[0005] However, most of the widely used nitrogen heterocyclic carbenes have chiral sources that are difficult to change (such as 1,2-diphenylethylenediamine), which are not easy to synthesize in series, resulting in the inability to finely control the steric hindrance and electronic properties of the ligand. Therefore, it is of great significance to design a chiral nitrogen heterocyclic carbene ligand with easy-to-change chiral groups, convenient modular synthesis, and multiple control sites.

[0006] The catalytic system of chiral nitrogen heterocyclic carbene and monovalent copper can realize the asymmetric silylation reaction of silicon. In 2013, Professor Oestreich (Angew.Chem.Int.Ed.2013,52,4650–4653.) and Professor Hayashi (J.Org.Chem.2013,78,5007-5017.) used different nitrogen heterocyclic carbene as ligands and reported the monovalent copper-catalyzed asymmetric silylation reaction. However, both reactions use allyl phosphate as substrate, and there are problems such as low atom economy. When using cheaper and more available allyl chloride as substrate, its enantioselective control is poor. Therefore, it is of great significance to develop a highly active nitrogen heterocyclic carbene ligand to realize the silylation reaction of allyl chloride as substrate. Summary of the invention

[0007] The technical problem to be solved by the present invention is to overcome the defect of less ligand types in the copper-catalyzed silylation reaction in the prior art. The present invention provides a class of nitrogen heterocyclic carbene compounds and applications thereof. The compounds of the present invention have good application prospects in the monovalent copper-catalyzed silylation reaction.

[0008] The present invention provides a compound as shown in formula I,

[0009]

[0010] in,

[0011] X is BF4 - or Cl - ;

[0012] R 1 is a C1-C6 alkyl, a C1-C6 alkoxy or a C6-C 14 The aromatic group;

[0013] R 2 1, 2 or 3 R 2-1 Substituted C6-C 10 Aryl or -CHR 2-2 R 2-3 ;

[0014] R 2-1is independently optionally replaced by 1, 2 or 3 R 2-1-1 Substituted C1-C6 alkyl, optionally substituted by 1, 2 or 3 R 2-1-2 Substituted C1-C6 alkoxy, C6-C 10 an aryl or hydroxyl group;

[0015] R 2-1-1 and R 2-1-2 are independently halogen;

[0016] R 2-2 C6-C 10 The aromatic group;

[0017] R 2-3 1, 2 or 3 R 2-3-1 Substituted C1-C6 alkyl;

[0018] R 2-3-1 are independently hydroxyl groups;

[0019] R 3 1, 2 or 3 R 3-1 Substituted C6-C 10 The aromatic group;

[0020] R 3-1 is a C1-C6 alkyl, a C1-C6 alkoxy or a C6-C 10 The aromatic group.

[0021] In a certain embodiment of the present invention, the C1-C6 alkyl group and the C1-C6 alkyl group in each substituted C1-C6 alkyl group are independently methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl or sec-butyl; preferably methyl, ethyl, tert-butyl or isopropyl.

[0022] In a certain embodiment of the present invention, the C1-C6 alkoxy group in each of the C1-C6 alkoxy groups and each of the substituted C1-C6 alkoxy groups is independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy; preferably methoxy.

[0023] In one embodiment of the present invention, R 1 In the C6-C 14 The aryl groups are independently phenyl or

[0024] In a certain embodiment of the present invention, each of the C6-C 10 The aryl group and each of the substituted C6-C 10 The C6-C 10 The aryl groups of are independently phenyl or naphthyl, for example phenyl.

[0025] In a certain embodiment of the present invention, the halogen is independently fluorine, chlorine, bromine or iodine; preferably fluorine.

[0026] In one embodiment of the present invention, X is BF4 - .

[0027] In one embodiment of the present invention, R 1 is a C1-C6 alkyl group or a C6-C 14 preferably a C1-C6 alkyl group.

[0028] In one embodiment of the present invention, R 2 For 1, 2 or 3 R 2-1 Substituted C6-C 10 The aromatic groups, for example

[0029] In one embodiment of the present invention, R 2-1 is independently optionally replaced by 1, 2 or 3 R 2-1-1 Substituted C1-C6 alkyl, C1-C6 alkoxy, C6-C 10 aryl or hydroxyl; preferably C1-C6 alkyl.

[0030] In one embodiment of the present invention, R 3-1 It is a C1-C6 alkyl group or a C1-C6 alkoxy group.

[0031] In one embodiment of the present invention, R 1 Methyl, phenyl or

[0032] In one embodiment of the present invention, R 2 for

[0033] In one embodiment of the present invention, R 3 for

[0034] In one embodiment of the present invention, the compound represented by formula I is a compound represented by formula I-1 or formula I-2.

[0035]

[0036] Among them, R 1 , R 2-1 and R 3 The definition of is as described in any embodiment of the present invention;

[0037] In a certain embodiment of the present invention, the compound as shown in formula I is any of the following structures,

[0038]

[0039] The present invention also provides a compound as shown in formula II,

[0040]

[0041] Among them, R 1 , R 2 and R 3 The definition of is as described in any embodiment of the present invention.

[0042] In a certain embodiment of the present invention, the compound shown in formula II is any of the following structures,

[0043]

[0044] The present invention also provides the use of the compound shown in formula I as described above and / or the compound shown in formula II as described above as a catalyst in a silylation reaction.

[0045] In one embodiment of the present invention, the silylation reaction comprises the following steps: in a solvent, in the presence of a catalyst and a base, compound A and compound B undergo a silylation reaction to prepare compound C;

[0046]

[0047] The catalyst is "cuprous chloride and the compound shown in formula I as described above" and / or "the compound shown in formula II as described in any scheme of the present invention".

[0048] The solvent is a conventional solvent for this type of reaction in the art; preferably an ether solvent; more preferably tetrahydrofuran.

[0049] The base is a conventional base for this type of reaction in the art; preferably an alkali metal salt of an alcohol; more preferably sodium methoxide.

[0050] The molar ratio of the compound B to the compound A is a conventional molar ratio for this type of reaction in the art; preferably (1.2-1.8):1; more preferably 1.5:1.

[0051] The molar ratio of the cuprous chloride to the compound represented by formula I is a conventional molar ratio for this type of reaction in the art; preferably (0.8-1.2):1; more preferably 1:1.

[0052] The molar ratio of the catalyst to the compound A is a conventional molar ratio for this type of reaction in the art; preferably (8-12):100; further preferably 10:100, wherein the amount of the catalyst is calculated as the sum of the compound shown in formula I and the compound shown in formula II.

[0053] The molar ratio of the base to the compound A is a conventional molar ratio for this type of reaction in the art; preferably (1.2-1.8):1; more preferably 1.5:1.

[0054] The mass volume ratio of the compound A to the solvent is a conventional mass volume ratio for this type of reaction in the art; preferably (0.012-0.018) g / mL; more preferably 0.015 g / mL.

[0055] The reaction time of the silyl allylation reaction is the conventional reaction time for this type of reaction in the art; preferably 8-16 hours; more preferably 12 hours.

[0056] The reaction temperature of the silylation reaction is the conventional reaction temperature of this type of reaction in the art; preferably -5-5°C; more preferably 0°C.

[0057] In one embodiment of the present invention, the silylation reaction further comprises the following post-treatment steps: quenching (eg, acetic acid quenching) and spin drying.

[0058] In a certain embodiment of the present invention, the reaction raw materials of the silylation reaction are the solvent, the cuprous chloride, the compound as shown in formula I, the base, the compound A and the compound B.

[0059] The present invention also provides a single crystal of a compound as shown in formula II-1,

[0060]

[0061] The single crystal belongs to the orthorhombic system, space group P212121, unit cell parameters: α=γ=β=90°, unit cell volume The number of asymmetric units in the unit cell is Z = 8, and the crystal density is 1.152 g / cm 3 .

[0062] definition

[0063] 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 the invention belongs. In addition, the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the present invention.

[0064] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0065] The term "alkyl" refers to a straight or branched chain alkyl group having a specified number of carbon atoms (e.g., C1-C6). Alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, etc.

[0066] The term "alkoxy" refers to a group R Z -O-, where R Z is an alkyl group as defined above.

[0067] The term "aryl" refers to a group having a specified number of ring carbon atoms (e.g., C6-C 10 or C6-C 14 ), an aromatic ring whose ring atoms consist only of carbon atoms, which is a cyclic or monocyclic ring. For example, a benzene ring, a naphthalene ring or

[0068] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0069] The reagents and raw materials used in the present invention are commercially available.

[0070] The positive progress of the present invention is that: the present invention provides a class of nitrogen heterocyclic carbene compounds and applications thereof. The nitrogen heterocyclic carbene compounds of the present invention have novel structures and have good application prospects in monovalent copper-catalyzed silylation reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] Figure 1 This is the single crystal diffraction pattern of Cu-NHC. DETAILED DESCRIPTION

[0072] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0073] Example 1 Synthesis of Compounds YC-1 to YC-11, Compounds YC-13 to YC-17, and Compounds YC-19 to YC-21:

[0074] (1) Synthesis of intermediate 1 and similar intermediates

[0075]

[0076] Experimental steps: Take a dry 100mL double-necked bottle equipped with a suitable magnetic rod, add 6-methyl-2-chloroquinoline (10mmol, 1.0equiv), phenylboronic acid (12mmol, 1.2equiv) and sodium carbonate (50mmol, 5.0equiv) in sequence. Move the reaction bottle into the glove box and add tetrakistriphenylphosphine palladium (0.2mmol, 0.02equiv). After the addition, move out of the glove box, add ultra-dry 1,4-dioxane (40mL, 0.2M) and degassed water (10mL, 0.2M), heat to 105℃ and react for 8h. After TLC confirms that the reaction is complete, cool naturally to room temperature, filter on diatomaceous earth, collect the organic phase, wash with saturated sodium chloride solution, dry with anhydrous sodium sulfate, spin dry the solvent, and purify by silica gel column chromatography to obtain 2.01g of the target product 1 with a yield of 92%.

[0077] When synthesizing other similar structures in the present invention, the synthesis of the intermediates in this step in YC-2, YC-3, YC-4, YC-20 and YC-21 is the same as the preparation method of the above-mentioned compound 1. For the synthesis of the intermediates in this step in compounds YC-5 to YC-19 (except YC-12 and YC-18), phenylboronic acid is replaced with other compounds and the same preparation method as the above-mentioned intermediate 1 is used to prepare the corresponding intermediates. See Table 1 below for details:

[0078] Table 1

[0079]

[0080] (2) Synthesis of intermediate 2 and similar intermediates

[0081]

[0082] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 1 (3mmol, 1.0equiv), Hans ester (7.5mmol, 2.5equiv) and chiral phosphoric acid CPA (0.06mmol, 0.02equiv) in sequence. Replace nitrogen three times, add ultra-dry toluene (Tol, 8mL, 0.38M), and react overnight at room temperature. After the reaction is completed, filter with diatomaceous earth, collect the organic phase, spin dry the solvent, and purify it with silica gel column chromatography to obtain 650mg of the target product 2 with a yield of 97%. The ee value of compound 2 was determined by high performance liquid chromatography>99%. (Characterization data are the same as J.Org.Chem.2023,88,3335–3339)

[0083] When synthesizing other similar structures in the present invention, the synthesis of the intermediates in this step in YC-2, YC-3, YC-4, YC-20 and YC-21 is the same as the preparation method of the above-mentioned compound 1. For the synthesis of the intermediates in this step in compounds YC-5 to YC-19 (except YC-12 and YC-18), compound 1 is replaced with the corresponding intermediates in Table 1 above, and the same preparation method as intermediate 2 is adopted to prepare the corresponding intermediates, as shown in Table 2 below.

[0084] Table 2

[0085]

[0086]

[0087] (3) Synthesis of intermediate 3 and similar intermediates

[0088]

[0089] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 2 (3mmol, 1.0equiv), replace nitrogen three times, add DCM (15mL, 0.2M), cool to 0℃, add NBS (N-bromosuccinimide, 3.15mmol, 1.05equiv) three times, and react at this temperature overnight. After the reaction is completed, the solvent is dried and separated by column chromatography to obtain 524mg of the target product 3, with a yield of 58%.

[0090] When synthesizing other similar structures in the present invention, the synthesis of the intermediates in this step in YC-2, YC-3, YC-4, YC-20 and YC-21 is the same as the preparation method of the intermediate 3 above. For the synthesis of the intermediates in this step in compounds YC-5 to YC-19 (except YC-12 and YC-18), replace intermediate 2 with the corresponding intermediates above, and use the same preparation method as intermediate 3 to prepare the corresponding intermediates. See Table 3 below for details:

[0091] Table 3

[0092]

[0093]

[0094] (4) Synthesis of intermediate 4 and similar intermediates

[0095]

[0096] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnet, add Pd2(dba)3 (tris dibenzylideneacetone palladium, 0.05mmol, 0.03equiv), X-Phos (2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 0.10mmol, 0.06equiv) and sodium tert-butoxide (3.13mmol, 1.8equiv) in sequence. Remove from the glove box, add ultra-dry toluene (8mL, 0.22M), complex at room temperature for 5min, then add mesitylene (2.1mmol, 1.2equiv) and compound 3 (1.75mmol, 1.0equiv) in sequence, and react at 90℃ for 3h after addition. After the raw materials are completely converted, filter with diatomaceous earth and spin dry the solvent. Silica gel column chromatography was used for separation and purification to obtain 564 mg of the target product 4 with a yield of 91%.

[0097] When synthesizing other similar structures in the present invention, for the synthesis of the intermediates in this step in compounds YC-2 to YC-21 (except YC-12 and YC-18), use intermediate 3 or the corresponding intermediates above, and replace mesitylene trimethylaniline with the corresponding structure, and adopt the same preparation method as intermediate 4 to prepare the corresponding intermediates. See Table 4 below for details:

[0098] Table 4:

[0099]

[0100]

[0101]

[0102] (5) Synthesis of Compounds YC-1 to YC-11, Compounds YC-13 to YC-17, and Compounds YC-19 to YC-21

[0103]

[0104] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 4 (1.58mmol, 1.0equiv), THF (4mL, 0.4M) and 1M methanolic hydrochloric acid solution (2.0mmol, 1.3equiv). After the addition, stir at room temperature for 10min and spin dry the solvent, add ammonium tetrafluoroborate (4.74mmol, 3.0equiv) and trimethyl orthoformate (5mL, 0.3M), heat to 100℃ and react for 3h. After the reaction is completed, spin dry the solvent and purify by silica gel column chromatography to obtain 530mg of the target product YC-1 with a yield of 74%.

[0105] When synthesizing other similar structures in the present invention (YC-2 to compound YC-21, excluding YC-12 and YC-18), intermediate 4 was replaced with the corresponding intermediate in Table 4 above, and the same preparation method as YC-1 was adopted to prepare the corresponding compounds YC-2 to compound YC-21 (excluding YC-12 and YC-18), as shown in Table 5 below.

[0106] Table 5

[0107]

[0108]

[0109]

[0110] Example 2 Synthesis of Compound YC-12 and Compound YC-18 (1) Synthesis of Intermediate 5 and Similar Intermediates

[0111]

[0112] Experimental steps: Take a dry 100mL double-necked bottle equipped with a suitable magnetic rod, add 6-bromoquinoline (17.3mmol, 1.0equiv), phenylboronic acid (22.5mmol, 1.3equiv) and potassium carbonate (52mmol, 3.0equiv) in sequence. Move the reaction bottle into the glove box and add tetrakistriphenylphosphine palladium (0.87mmol, 0.05equiv). After the addition, move out of the glove box, add ultra-dry ethylene glycol dimethyl ether (20mL, 0.58M) and degassed water (10mL, 0.58M), heat to 105℃ and react for 8h. After TLC confirms that the reaction is complete, cool naturally to room temperature, filter with diatomaceous earth, collect the organic phase, wash with saturated sodium chloride solution, dry with anhydrous sodium sulfate, spin dry the solvent, and purify with silica gel column chromatography to obtain 3.52g of the target product 5 with a yield of 100%.

[0113] For compound YC-18, the phenylboronic acid in the reaction needs to be replaced with 9-anthrylboronic acid, and the same preparation method as compound 5 is used to prepare the corresponding compound

[0114] (2) Synthesis of intermediate 6 and similar intermediates

[0115]

[0116] Experimental steps: Take a dry 100mL double-necked bottle equipped with a suitable magnetic, add 5 (17mmol, 1.0equiv), replace nitrogen three times, add toluene (17mL, 0.58M) to dissolve. Slowly add 3,5-dimethylbenzylmagnesium bromide (2M, 24mmol, 1.4equiv) dropwise at room temperature. After the addition, heat to 125℃ and react for 12h. After the reaction is completed, add saturated ammonium chloride to quench, separate the liquids, extract the aqueous phase with ethyl acetate, combine the organic phases, wash with saturated sodium chloride solution, dry with anhydrous sodium sulfate, spin dry, and purify by silica gel column chromatography to obtain 2.21g of the target product 6 with a yield of 42%.

[0117] When synthesizing other similar structures (compound YC-18) in the present invention, intermediate 5 is replaced by the above corresponding structure The same preparation method as intermediate 6 was used to prepare the corresponding intermediate

[0118] (3) Synthesis of intermediate 7 and similar intermediates

[0119]

[0120] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 6 (4mmol, 1.0equiv), Hans ester (10.0mmol, 2.5equiv) and chiral phosphoric acid CPA (0.08mmol, 0.02equiv) in sequence. Replace nitrogen three times, add ultra-dry toluene (8mL, 0.5M), and react overnight at room temperature. After the reaction is completed, filter with diatomaceous earth, collect the organic phase, spin dry the solvent, and purify it with silica gel column chromatography to obtain 1.35g of the target product 7, with a yield of >99%. The ee value of compound 7 determined by high-performance liquid chromatography is >99%.

[0121] When synthesizing other similar structures (compound YC-18) in the present invention, intermediate 6 is replaced by the above corresponding structure The same preparation method as intermediate 7 was used to prepare the corresponding compound

[0122]

[0123] (4) Synthesis of intermediate 8 and similar intermediates

[0124]

[0125] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 7 (4mmol, 1.0equiv), replace nitrogen three times, add DCM (10mL, 0.25M), cool to 0℃, add NBS (4.2mmol, 1.05equiv) three times, and react at this temperature overnight. After the reaction is completed, spin dry the solvent, separate by column chromatography to obtain 1.16g of the target product 8, with a yield of 74%.

[0126] When synthesizing other similar structures (compound YC-18) in the present invention, intermediate 7 is replaced by the above corresponding structure The same preparation method as intermediate 8 was used to prepare the corresponding intermediate

[0127]

[0128] (5) Synthesis of intermediate 9 and similar intermediates

[0129]

[0130] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnet, add Pd2(dba)3 (0.15mmol, 0.05equiv), X-Phos (0.30mmol, 0.10equiv) and sodium tert-butoxide (5.40mmol, 1.80equiv) in sequence. Remove from the glove box, add ultra-dry toluene (10mL, 0.33M), complex at room temperature for 5min, then add mesitylene (3.3mmol, 1.1equiv) and compound 8 (3.0mmol, 1.0equiv) in sequence, and react at 90℃ for 3h after addition. After the raw materials are completely converted, filter with diatomaceous earth, spin dry the solvent, and separate and purify by silica gel column chromatography to obtain 1.21g of the target product 9 with a yield of 91%.

[0131] When synthesizing other similar structures (compound YC-18) in the present invention, intermediate 8 is replaced by the above corresponding structure Replace with The same preparation method as compound 9 was used to prepare the corresponding intermediate

[0132] (6) Synthesis of Compounds YC-12 and YC-18

[0133]

[0134] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 9 (2.7mmol, 1.0equiv), THF (4mL, 0.68M) and 1M methanolic hydrochloric acid solution (3.5mmol, 1.3equiv). After the addition, stir at room temperature for 10min and spin dry the solvent, add ammonium tetrafluoroborate (8.1mmol, 3.0equiv) and trimethyl orthoformate (8mL, 0.34M), heat to 100℃ and react for 3h. After the reaction is completed, spin dry the solvent and purify by silica gel column chromatography to obtain 716mg of the target product YC-12 with a yield of 49%.

[0135] When synthesizing other similar structures (compound YC-18) in the present invention, compound 9 is replaced by the above corresponding structure The same preparation method as compound YC-18 was used to prepare the corresponding compound YC-18.

[0136] Example 3 Synthesis of YC-22-25

[0137] (1) Synthesis of intermediate 10 and similar intermediates

[0138]

[0139] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 2-aminophenol (10mmol, 1.0equiv), imidazole (15mmol, 1.5equiv) and DMF (15mL, 0.67M) in sequence. Add TBSCl (tert-butyldimethylsilyl chloride, 12mmol, 1.2equiv) at 0℃, warm to room temperature and react overnight. After the reaction is completed, extract with ether, wash with saturated NaCl, dry with anhydrous sodium sulfate, spin dry the solvent, and purify with silica gel column chromatography to obtain 2.03g of the target product 10 with a yield of 91%.

[0140] In other synthesis examples of the present invention, the 2-aminophenol in this step needs to be replaced with 6-amino-2-methylphenol, 2-amino-5-methylphenol, or o-amino-p-cresol; the same preparation method as intermediate 10 is used to prepare the corresponding

[0141] (2) Synthesis of intermediate 11 and similar intermediates

[0142]

[0143] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add Pd2(dba)3 (0.06mmol, 0.03equiv), X-Phos (0.12mmol, 0.06equiv) and sodium tert-butoxide (3.6mmol, 1.8equiv) in sequence. Remove from the glove box, add ultra-dry toluene (6mL, 0.33M), complex at room temperature for 5min, then add compound 10 (2.2mmol, 1.1equiv) and compound 3 (2.0mmol, 1.0equiv) in sequence, and react at 90℃ for 3h after addition. After the raw materials are completely converted, filter with diatomaceous earth, spin dry the solvent, and separate and purify by silica gel column chromatography to obtain 820mg of the target product 11 with a yield of 92%.

[0144] When synthesizing other similar structures in the present invention, the intermediate 10 is replaced by The same preparation method as intermediate 11 was used to prepare intermediate

[0145] (3) Synthesis of Compounds YC-22 to YC-25

[0146]

[0147] Experimental steps: Take a dry 50mL egg-shaped bottle equipped with a suitable magnetic rod, add 11 (1.9mmol, 1.0equiv), THF (4mL, 0.48M) and 1M methanol solution of hydrochloric acid (7.6mmol, 4.0equiv). After the addition, react at room temperature overnight. After the reaction is completed, spin dry the solvent, heat and drain under an oil pump, add ammonium tetrafluoroborate (5.7mmol, 3.0equiv) and trimethyl orthoformate (5mL, 0.38M), heat to 100℃ and react for 3h. After the reaction is completed, spin dry the solvent, and purify by silica gel column chromatography to obtain 463mg of the target product YC-22 with a yield of 57%.

[0148] When synthesizing other similar structures in the present invention, compound 11 is replaced by The same preparation method as YC-22 was used to prepare the corresponding

[0149] Example 4 Synthesis of Compound YC-26

[0150] (1) Synthesis of intermediate 12

[0151]

[0152] Experimental steps: Take a dry 100mL egg-shaped bottle equipped with a suitable magnetic rod, add D-phenylglycinol (10mmol, 1.0equiv), DMAP (dimethylaminopyridine, 1mmol, 0.1euqiv), triethylamine (20mmol, 2.0equiv) and DCM (15mL, 0.67M) in sequence. Add TBSCl (10mmol, 1.0equiv) at one time, and react at room temperature overnight. After the reaction is completed, spin dry the solvent and purify it by silica gel column chromatography to obtain 1.86g of the target product 12, with a yield of 74%.

[0153] (2) Synthesis of intermediate 14

[0154]

[0155] Note: The synthesis steps of intermediate 13 are the same as those of intermediate 3, and its ee value is >99%.

[0156] Experimental steps: Take a dry 50mL double-necked bottle equipped with a suitable magnetic rod, add Pd2(dba)3 (0.06mmol, 0.06equiv), rac-BINAP (2,2'-bis(diphenylphosphine)-1,1'-binaphthyl, 0.12mmol, 0.12equiv) and sodium tert-butoxide (2.0mmol, 2.0equiv) in sequence. Remove from the glove box, add ultra-dry toluene (5mL, 0.2M), complex at room temperature for 5min, then add compound 12 (1.2mmol, 1.2equiv) and compound 13 (1.0mmol, 1.0equiv) in sequence, and react at 125℃ for 3h after addition. After the raw materials are completely converted, filter with diatomaceous earth, spin dry the solvent, and separate and purify the target product 14 by silica gel column chromatography.

[0157] (3) Synthesis of Compound YC-26

[0158]

[0159] Experimental step K: Take a dry 50 mL egg-shaped bottle equipped with a suitable magnetic rod, add 14 (1.0 mmol, 1.0 equiv), THF (2 mL, 0.5 M) and 1 M methanolic hydrochloric acid solution (3 mmol, 3.0 equiv). After the addition, react at room temperature for 2 h. After the reaction is completed, spin dry the solvent, heat and drain under an oil pump, add ammonium tetrafluoroborate (5.7 mmol, 3.0 equiv) and trimethyl orthoformate (5 mL, 0.2 M), heat to 100 ° C and react for 3 h. After the reaction is completed, spin dry the solvent, and purify by silica gel column chromatography to obtain 325 mg of the target product YC-26 with a yield of 67%.

[0160] Example 5. Copper-catalyzed silylation reaction

[0161]

[0162] Experimental steps: Take a dry 25mL Schenk tube equipped with a suitable magnet, add cuprous chloride (0.01mmol, 0.1equiv), ligand (0.01mmol, 0.1equiv) and sodium methoxide (0.15mmol, 1.5equiv) in sequence. Remove from the glove box, add THF (1mL, 0.1M), complex at room temperature for 20min, then cool to 0℃, add silicon boron reagent (0.15mmol, 1.5equiv) and cinnamyl chloride (0.1mmol, 1.0equiv) in sequence, and react at this temperature for 12h. After the reaction is completed, add 20μL acetic acid to quench the reaction, spin dry the solvent, add nitromethane as an internal standard, use NMR to determine the reaction yield, and use HPLC to determine the enantioselectivity of the reaction. Product data: 1 H NMR(500MHz, CDCl3)δ7.40–7.26(m,5H),7.21–7.13(m,2H),7.11–7.04(m,1H),6.98–6.84(m,2H), 6.10(dt,J=18.7,10.0Hz,1H),5.01–4.81(m,2H),3.14(d,J=9.6Hz,1H),0.26(s,3H),0.24(s,3H). 13 C NMR (126MHz, CDCl3) δ141.62,137.74,136.70,134.32,129.11,128.13,127.45,124.71,113.03,44.27,-4.31,-4.89.

[0163] Optical rotation:[α] D 25 =-8.68 (c = 1.080, CHCl3).

[0164] The corresponding yields and ee values ​​of different ligands are as follows:

[0165]

[0166] Example 6. Synthesis of copper-carbene complex

[0167]

[0168] Take a dry 50mL Schenk bottle equipped with a suitable magnet, add YC-1 (1.0mmol, 1.0equiv) and cuprous chloride (1.1mmol 1.1equiv) into it. Take another 25mL egg-shaped bottle, add potassium tert-butoxide (1.1mmol, 1.1equiv) into it. After the addition, move it out of the glove box, add THF as solvent to the Schenk bottle (3mL, 0.33M) and the egg-shaped bottle (1.1mL, 1.0M), respectively, cool to 0℃, add sodium tert-butoxide solution dropwise to the Schenk bottle, warm to room temperature and react for 10min. After the reaction is completed, use an oil pump to drain the solvent in the system, add DCM (4mL, 0.25M) as solvent, and react at room temperature for 16h. After the reaction is completed, filter with diatomaceous earth under nitrogen protection, wash with a small amount of DCM, and use an oil pump to drain the solvent to obtain 399mg of the target product Cu-NHC, with a yield of 86%. The single crystal test conditions of Cu-NHC are shown in Table 6 below, the single crystal data are shown in Table 7 below, and the single crystal diffraction pattern is shown in Figure 1 .

[0169] Table 6

[0170]

[0171] Table 7

[0172]

[0173]

[0174] Example 7. Silylation of Copper-Carbene Complex

[0175]

[0176] The cuprous chloride and ligand in Example 5 were replaced by Cu-NHC, and the remaining reaction conditions were the same as in Example 5.

[0177] Ligand data

[0178]

[0179] 11H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 7.40–7.30 (m, 4H), 7.17–7.11 (m, 2H), 7.05 (s, 1H), 7.02 (s, 1H), 6.90 (s, 1H), 6.36–6.26 (dd, 1H), 3.17 (ddd, J = 17.2, 6.5, 4.5 Hz, 1H), 3.00 (ddd, J = 16.9, 8.6, 4.4 Hz, 1H), 2.70 (m, J = 13.3, 8.8, 4.5 Hz, 1H), 2.55–2.47 (m, 4H), 2.35 (s, 3H), 2.07 (s, 3H), 1.88 (s, 3H).

[0180] 13 13C NMR (101 MHz, CDCl3) δ 141.47, 139.67, 139.65, 139.21, 137.70, 136.21, 134.48, 134.46, 130.34, 130.21, 129.58, 129.37, 129.08, 128.32, 127.78, 126.67, 126.19, 125.78, 109.76, 59.07, 30.31, 22.11, 21.04, 21.00, 17.23, 17.14.

[0181] HRMS (ESI) m / z [M - BF4] + : calcd. 367.2169, found 367.2165.

[0182] IR (film): ν max (cm -1 ) 3128, 3034, 2925, 1609, 1537, 1503, 1455, 1300, 1276, 1204, 1058, 915, 841, 748, 703. Optical rotation (旋光度): [α] D 25 = 39.15 (c = 1.655, CHCl3).

[0183]

[0184] 1H NMR(400MHz,CDCl3)δ8.69(s,1H),7.59(t,J=7.8Hz,1H),7.42–7.32(m,6H),7.21–7.15(m,2H),6.91(s,1H),6.39(dd,J=6.6,4.4Hz,1H),3.24(ddd,J=17.0,7.1,4.5Hz,1H),3.04(ddd,J=16.9,8.2,4.4Hz,1H),2.76(ddt,J=13.0,8.6,4.3Hz,1H),2.59–2.47(m,5H),2.00(p,J=6.8Hz,1H),1.22(d,J=6.7Hz,3H),1.11(d,J=6.9 Hz,3H),1.08(d,J=6.8 Hz,3H),1.00(d,J=6.9 Hz,3H).

[0185] 13 C NMR(101 MHz,CDCl3)δ147.37,145.68,139.81,139.53,137.77,132.07,131.86,129.35,129.16,127.78,127.62,126.86,126.28,125.99,125.31,124.45,109.65,59.21,30.41,28.86,28.51,24.48,24.43,23.96,23.54,22.20,21.24.

[0186] HRMS(ESI)m / z[M-BF4] + :calcd.409.2638,found 409.2634.

[0187] IR(film):ν max (cm -1 )3113,2966,2930,2871,1537,1458,1275,1204,1059,915,808,750,701.

[0188] Optical rotation:[α] D 25 =47.10(c=1.800,CHCl3).

[0189]

[0190] 1H NMR(400 MHz,CDCl3)δ8.91(s,1H),7.62(t,J=1.7 Hz,1H),7.52(d,J=1.7Hz,2H),7.41–7.36(m,3H),7.32(s,1H),7.28–7.25(m,3H),6.25(dd,J=6.2,4.2 Hz,1H),3.16(dt,J=17.1,5.6 Hz,1H),3.10–2.99(m,1H),2.65(ddt,J=13.1,8.7,4.6 Hz,1H),2.57–2.48(m,4H),1.38(s,18H).

[0191] 13 C NMR(101 MHz,CDCl3)δ154.03,139.18,138.16,137.25,133.01,130.34,129.35,129.16,128.07,126.73,126.52,125.62,124.55,118.96,110.43,59.18,35.26,31.18,30.14,22.30,21.33.

[0192] HRMS(ESI)m / z[M-BF4] + :calcd.437.2951,found 437.2948.

[0193] IR(film):ν max (cm -1 )3142,2963,2869,1594,1543,1478,1207,1059,914,837,764,750,709.

[0194] Optical rotation:[α] D 25 =106.15(c=1.825,CHCl3).

[0195]

[0196] 1H NMR(400 MHz,CDCl3)δ8.70(s,1H),7.53(t,J=7.7 Hz,1H),7.36(m,5H),7.28(d,J=7.5 Hz,1H),7.21–7.14(m,2H),6.91(s,1H),6.36(dd,J=6.3,4.4 Hz,1H),3.22(ddd,J=17.2,6.7,4.5 Hz,1H),3.03(ddd,J=16.9,8.3,4.4 Hz,1H),2.74(ddt,J=13.1,8.6,4.1 Hz,1H),2.59–2.41(m,5H),2.32(dt,J=15.5,7.6 Hz,1H),2.20(dt,J=15.1,7.5Hz,1H),2.08(dq,J=14.9,7.5 Hz,1H),1.11(t,J=7.5 Hz,3H),0.99(t,J=7.6 Hz,3H).

[0197] 13 C NMR(101 MHz,CDCl3)δ142.29,140.82,139.79,139.26,137.64,131.68,131.11,129.59,129.35,129.14,127.63,127.49,127.20,126.81,126.22,125.86,109.77,59.16,30.29,24.13,23.51,22.14,21.07,14.92,14.31.

[0198] HRMS(ESI)m / z[M-BF4] + :calcd.381.2325,found 381.2323.

[0199] IR(film):ν max (cm -1 )3126,2970,2936,2878,1537,1504,1456,1300,1058,915,730,702.

[0200] Optical rotation:[α] D 25 =39.85(c=2.025,CHCl3).

[0201]

[0202] 1H NMR(400 MHz,CDCl3)δ8.64(s,1H),7.32(s,1H),7.18(d,J=7.9 Hz,2H),7.08–7.03(m,3H),7.03(s,1H),6.90(s,1H),6.28(dd,J=6.4,4.4 Hz,1H),3.19(ddd,J=17.1,7.0,4.6 Hz,1H),3.03(ddd,J=17.1,8.3,4.5 Hz,1H),2.69(ddt,J=12.9,8.6,4.3 Hz,1H),2.54–2.46(m,4H),2.37(s,3H),2.33(s,3H),2.09(s,3H),1.89(s,3H).

[0203] 13 C NMR(101 MHz,CDCl3)δ141.43,139.58,139.09,136.23,134.61,134.47,130.34,130.19,130.01,129.56,128.34,127.80,126.60,126.22,125.83,109.71,59.01,30.36,22.10,21.22,21.04,20.99,17.23,17.14.HRMS(ESI)m / z[M-BF4] + :calcd.381.2325,found 381.2322.

[0204] IR(film):ν max (cm -1 )3127,2926,2862,1538,1504,1449,1300,1203,1192,1061,915,730.

[0205] Optical rotation:[α] D 25 =32.86(c=1.810,CHCl3).

[0206]

[0207] 1H NMR(400 MHz,CDCl3)δ8.67(s,1H),7.31(s,1H),7.08(s,1H),7.03(s,1H),6.98(s,1H),6.91(s,1H),6.72(s,2H),6.26(dd,J=6.2,4.4 Hz,1H),3.18(dt,J=17.0,5.6Hz,1H),2.99(ddd,J=17.0,8.7,4.4 Hz,1H),2.70(ddt,J=13.2,8.7,4.5 Hz,1H),2.56–2.48(m,4H),2.37(s,3H),2.26(s,6H),2.11(s,3H),1.90(s,3H).

[0208] 13 C NMR(101 MHz,CDCl3)δ141.45,139.57,139.23,139.08,137.59,136.31,134.37,130.67,130.31,130.24,129.57,128.38,127.82,126.59,125.89,123.90,109.69,59.09,30.29,22.12,21.21,21.15,21.04,17.23,17.00.

[0209] HRMS(ESI)m / z[M-BF4] + :calcd.395.2482,found 395.2478.

[0210] IR(film):ν max (cm -1 )3124,2923,1608,1538,1454,1198,1059,914,842,730.

[0211] Optical rotation:[α] D 25 =53.76(c=2.090,CHCl3).

[0212]

[0213] 1H NMR(400 MHz,CDCl3)δ8.69(s,1H),7.59(d,J=8.0 Hz,2H),7.54(d,J=7.2Hz,2H),7.42(t,J=7.5Hz,2H),7.36–7.32(m,2H),7.25(d,J=7.9 Hz,2H),7.05(d,J=12.8 Hz,2H),6.92(s,1H),6.37(dd,J=6.3,4.4 Hz,1H),3.21(dt,J=17.2,5.4 Hz,1H),3.06(ddd,J=16.9,8.4,4.4 Hz,1H),2.73(ddt,J=13.2,8.8,4.4 Hz,1H),2.52(s,4H),2.36(s,3H),2.09(s,3H),1.91(s,3H).

[0214] 13 C NMR(101 MHz,CDCl3)δ142.04,141.47,139.88,139.68,139.18,136.55,136.21,134.47,130.37,130.21,129.58,128.79,128.32,128.01,127.78,127.66,126.98,126.76,126.69,125.78,109.77,58.89,30.32,22.11,21.14,21.03,17.23,17.17.

[0215] HRMS(ESI)m / z[M-BF4] + :calcd.443.2482,found 443.2480.

[0216] IR(film):ν max (cm -1 )3123,3031,2924,1537,1487,1449,1300,1059,914,841,769,731,699.

[0217] Optical rotation:[α] D 25 =47.03(c=2.080,CHCl3).

[0218]

[0219] 1H NMR(400 MHz,CDCl3)δ8.66(s,1H),7.31(s,1H),7.09(s,1H),7.02(s,2H),6.91(s,1H),6.79(s,2H),6.28(dd,J=6.4,4.4 Hz,1H),3.19(ddd,J=17.1,7.0,4.6 Hz,1H),3.01(ddd,J=16.8,8.4,4.4 Hz,1H),2.72(ddt,J=13.2,8.7,4.5 Hz,1H),2.62–2.48(m,8H),2.37(s,3H),2.12(s,3H),1.89(s,3H),1.16(t,J=7.6Hz,6H).

[0220] 13 C NMR(101 MHz,CDCl3)δ145.53,141.44,139.53,139.22,137.74,136.40,134.31,130.29,130.26,129.51,128.38,128.32,127.86,126.55,125.90,123.06,109.68,59.27,30.43,28.64,22.13,21.28,21.05,17.25,17.02,15.35.

[0221] HRMS(ESI)m / z[M-BF4] + :calcd.423.2795,found 423.2790.

[0222] IR(film):ν max (cm -1 )3124,2965,2931,2873,1604,1538,1461,1198,1059,914,853,730.

[0223] Optical rotation:[α] D 25 =47.29(c=1.835,CHCl3).

[0224]

[0225] 1H NMR(400 MHz,CDCl3)δ8.69(s,1H),7.87(d,J=8.5 Hz,1H),7.85–7.79(m,1H),7.78–7.71(m,1H),7.62(s,1H),7.53–7.47(m,2H),7.33(s,1H),7.26(s,1H),7.07(s,1H),7.01(s,1H),6.94(s,1H),6.54(t,J=5.4 Hz,1H),3.27–3.17(m,1H),3.03(ddt,J=15.9,8.0,4.7 Hz,1H),2.79(tt,J=8.6,4.2 Hz,1H),2.69–2.60(m,1H),2.54(s,3H),2.36(s,3H),2.11(s,3H),1.92(s,3H).

[0226] 13 C NMR(101 MHz,CDCl3)δ141.54,139.73,139.34,136.37,134.83,134.45,133.32,133.20,130.47,130.32,129.61,128.39,128.15,127.91,127.70,126.98,126.95,126.75,126.41,125.89,122.98,109.86,59.32,30.24,22.21,21.31,21.11,17.31,17.20.

[0227] HRMS(ESI)m / z[M-BF4] + :calcd.417.2325,found 417.2324.

[0228] IR(film):ν max (cm -1 )3126,2925,1607,1538,1505,1444,1196,1060,914,854,730.

[0229] Optical rotation:[α] D 25 =42.60(c=1.972,CHCl3).

[0230]

[0231] 1H NMR(400 MHz,CDCl3)δ8.63(s,1H),7.31(s,1H),7.08(s,1H),7.04(s,1H),6.90(s,1H),6.81(s,2H),6.17(dd,J=6.9,4.2 Hz,1H),3.71(s,3H),3.20(ddd,J=17.4,7.3,4.6 Hz,1H),3.03(dq,J=17.0,4.5 Hz,1H),2.68(ddd,J=13.6,7.9,3.8 Hz,1H),2.55–2.47(s,4H),2.37(s,3H),2.22(s,6H),2.10(s,3H),1.90(s,3H).

[0232] 13 C NMR(101 MHz,CDCl3)δ157.48,141.45,139.53,139.23,136.37,134.37,132.67,132.07,130.36,130.26,129.56,128.40,127.82,126.76,126.55,125.89,109.70,59.59,58.89,30.41,22.13,21.46,21.06,17.26,17.05,16.08.

[0233] HRMS(ESI)m / z[M-BF4] + :calcd.425.2587,found 425.2584.

[0234] IR(film):ν max (cm -1 )3122,2926,1538,1486,1300,1197,1147,1059,915,855,731.

[0235] Optical rotation:[α] D 25 =47.11(c=2.280,CHCl3).

[0236]

[0237] 1H NMR(400 MHz,CDCl3)δ8.61(s,1H),7.31(s,1H),7.07(s,1H),7.03(s,1H),6.90(s,1H),6.78(s,2H),6.18(dd,J=6.6,4.3 Hz,1H),3.19(ddd,J=16.9,7.3,4.6 Hz,1H),3.02(ddd,J=16.9,7.7,4.2 Hz,1H),2.68(ddt,J=12.9,8.5,4.5 Hz,1H),2.56–2.48(m,4H),2.37(s,3H),2.22(s,6H),2.14(s,3H),2.10(s,3H),1.90(s,3H).

[0238] 13 C NMR(101 MHz,CDCl3)δ141.44,139.47,139.28,137.61,136.45,136.22,134.39,134.30,130.37,130.28,129.54,128.44,127.90,126.50,125.98,125.33,109.68,59.04,30.36,22.15,21.43,21.08,20.53,17.29,17.05,15.15.

[0239] HRMS(ESI)m / z[M-BF4] + :calcd.409.2638,found 409.2635.

[0240] IR(film):ν max (cm -1 )3126,2926,1537,1486,1444,1300,1195,1059,914,853,730.

[0241] Optical rotation:[α] D 25 =47.70(c=2.140,CHCl3).

[0242]

[0243] 1H NMR(400 MHz,CDCl3)δ8.72(s,1H),7.58–7.52(m,2H),7.48–7.43(m,2H),7.42–7.37(m,1H),7.24(s,1H),7.09(s,1H),7.05(s,1H),7.01(s,1H),6.79(s,2H),6.29(dd,J=6.6,4.3 Hz,1H),3.30(ddd,J=17.0,6.9,4.3 Hz,1H),3.12(ddd,J=17.0,8.1,4.3 Hz,1H),2.76(ddd,J=17.0,8.4,4.2 Hz,1H),2.59(ddt,J=13.8,6.7,3.3 Hz,1H),2.38(s,3H),2.28(s,6H),2.15(s,3H),1.95(s,3H).

[0244] 13 C NMR(101 MHz,CDCl3)δ142.97,141.62,140.26,139.73,139.19,137.48,136.47,134.31,130.80,130.63,130.41,129.65,129.04,128.96,128.34,128.30,127.71,126.66,124.92,124.03,108.46,59.31,30.38,21.60,21.20,21.08,17.36,17.12.

[0245] HRMS(ESI)m / z[M-BF4] + :calcd.457.2638,found 457.2635.

[0246] IR(film):ν max (cm -1 )3123,3034,2923,1643,1537,1486,1214,1179,1059,913,855,766,731,700.Optical rotation:[α] D 25 =28.28(c=2.085,CHCl3).

[0247]

[0248] 1H NMR(400 MHz,CDCl3)δ8.64(s,1H),7.31(s,1H),6.98(s,1H),6.92(s,1H),6.77(d,J=2.8 Hz,1H),6.75–6.70(m,3H),6.23(dd,J=6.3,4.3 Hz,1H),3.84(s,3H),3.18(ddd,J=17.0,7.0,4.7 Hz,1H),3.00(ddd,J=16.9,8.3,4.4 Hz,1H),2.70(ddt,J=13.1,8.7,4.3 Hz,1H),2.56–2.48(m,4H),2.26(s,6H),2.12(s,3H),1.91(s,3H).

[0249] 13 C NMR(101 MHz,CDCl3)δ161.01,139.64,139.52,139.11,138.34,137.65,136.17,130.69,130.58,127.84,126.55,125.91,123.93,123.60,114.37,114.33,109.72,59.07,55.54,30.31,22.17,21.23,21.19,17.72,17.40.

[0250] HRMS(ESI)m / z[M-BF4] + :calcd.411.2431,found 411.2428.

[0251] IR(film):ν max (cm -1 )3123,2923,1600,1538,1327,1198,1160,1060,914,842,730.

[0252] Optical rotation:[α] D 25 =54.51(c=1.890,CHCl3).

[0253]

[0254] 1H NMR(400 MHz,CDCl3)δ8.67(s,1H),7.41(t,J=7.7 Hz,1H),7.33(s,1H),7.28(d,J=7.2 Hz,1H),7.24(d,J=7.6 Hz,1H),6.99(s,1H),6.91(s,1H),6.74(s,2H),6.24(dd,J=6.4,4.4 Hz,1H),3.19(ddd,J=17.0,6.1,3.6 Hz,1H),3.01(ddd,J=16.9,8.2,4.5 Hz,1H),2.71(dq,J=13.6,4.3 Hz,1H),2.57–2.50(m,4H),2.26(s,6H),2.15(s,3H),1.95(s,3H).

[0255] 13 C NMR(101 MHz,CDCl3)δ139.65,139.21,139.13,137.58,136.88,134.77,131.21,130.99,130.72,130.17,129.69,128.92,127.87,126.65,125.99,123.96,109.68,59.17,30.32,22.16,21.28,21.19,17.38,17.12.

[0256] HRMS(ESI)m / z[M-BF4] + :calcd.381.2325,found 381.2322.

[0257] IR(film):ν max (cm -1 )3127,2924,1606,1537,1504,1475,1300,1198,1061,914,844,730.

[0258] Optical rotation:[α] D 25 =53.00(c=1.775,CHCl3).

[0259]

[0260] 1H NMR(400 MHz,CDCl3)δ8.57(s,1H),7.35–7.29(d,J=3.4 Hz,4H),7.01(s,1H),6.97(s,1H),6.86(s,2H),6.10(dd,J=7.4,4.2 Hz,1H),3.20(ddd,J=17.0,7.8,4.7 Hz,1H),3.06(ddd,J=17.0,7.3,4.6 Hz,1H),2.69–2.61(m,1H),2.58–2.49(s,4H),2.38(s,3H),2.29(s,6H),2.09(s,3H).

[0261] 13 C NMR(101 MHz,CDCl3)δ139.26,139.19,138.55,138.22,136.96,132.09,131.65,131.55,130.93,130.90,127.97,127.70,126.39,125.73,124.43,110.19,59.43,30.20,22.15,21.78,21.21,20.61,16.81.HRMS(ESI)m / z[M-BF4] + :calcd.381.2325,found381.2322.

[0262] IR(film):ν max (cm -1 )3140,2924,1609,1541,1505,1462,1301,1058,914,841,729.

[0263] Optical rotation:[α] D 25 =57.97(c=1.905,CHCl3).

[0264]

[0265] 1 H NMR(400 MHz,CDCl3)δ8.72(s,1H),7.32(s,3H),7.30(s,1H),7.19(s,1H),7.01(s,1H),6.88(s,2H), 6.05(dd,J=7.3,4.3Hz,1H), 3.16(ddd,J=17.1,7.7,4.8Hz,1H), 3.07(ddd,J=17.1,7.1,4.7Hz,1H),2.6 4–2.48(m,5H),2.42(s,6H),2.29(s,6H).

[0266] 13C NMR(101 MHz,CDCl3)δ140.77,139.17,139.12,137.85,136.77,133.26,132.14,130.99,130.20,128.07,126.46,125.61,124.60,122.12,110.44,59.44,30.14,22.22,21.81,21.22,21.14.

[0267] HRMS(ESI)m / z[M-BF4] + :calcd.381.2325,found 381.2324.

[0268] IR(film):ν max (cm -1 )2923,1610,1543,1505,1470,1215,1058,913,843,730.

[0269] Optical rotation:[α] D 25 =87.88(c=1.880,CHCl3).

[0270]

[0271] 1 H NMR(400 MHz,CDCl3)δ8.63(s,1H),7.31(s,1H),7.26(d,J=2.1 Hz,1H),7.21(d,J=2.2 Hz,1H),6.98(s,1H),6.95(s,1H),6.75(s,2H),6.24(dd,J=6.5,4.3 Hz,1H),3.19(ddd,J=17.1,7.2,5.0 Hz,1H),3.01(ddd,J=16.9,8.4,4.4 Hz,1H),2.70(ddt,J=12.8,8.5,4.2 Hz,1H),2.59–2.48(m,4H),2.26(s,6H),2.15(s,3H),1.94(s,3H),1.35(s,9H).

[0272] 13C NMR(101 MHz,CDCl3)δ154.46,139.47,139.33,139.10,137.63,136.12,134.02,130.68,130.34,128.40,127.87,126.76,126.54,125.98,125.92,123.99,109.81,59.11,34.73,31.09,30.34,22.16,21.33,21.19,17.66,17.41.

[0273] HRMS(ESI)m / z[M-BF4] + :calcd.437.2951,found 437.2949.

[0274] IR(film):ν max (cm -1 )3124,2964,2868,1604,1538,1461,1197,1060,914,842,730.

[0275] Optical rotation:[α] D 25 =49.80(c=1.725,CHCl3).

[0276]

[0277] 1 H NMR(400 MHz,CDCl3)δ8.70(s,1H),8.54(s,1H),8.06(dd,J=8.3,3.6 Hz,2H),7.57–7.36(m,7H),7.22(s,1H),7.17(d,J=2.1 Hz,1H),7.13(d,J=2.2 Hz,1H),7.07(s,1H),7.03(s,2H),6.33(dd,J=8.2,4.2Hz,1H),3.41(ddd,J=17.5,8.8,4.7 Hz,1H),3.27–3.18(m,1H),2.89–2.80(m,1H),2.76–2.64(m,1H),2.35(s,6H),2.25(s,3H),2.05(s,3H),1.24(s,9H).

[0278] 13C NMR(101 MHz,CDCl3)δ154.53,140.43,139.95,139.37,137.18,136.18,134.32,133.77,131.23,131.08,130.46,130.40,130.02,129.28,128.72,128.43,128.29,128.05,127.68,126.91,126.57,126.44,126.01,125.97,125.64,125.43,125.08,124.62,112.97,59.90,34.66,30.99,30.63,22.37,21.28,17.78,17.58.

[0279] HRMS(ESI)m / z[M-BF4] + :calcd.599.3421,found 599.3418.

[0280] IR(film):ν max (cm -1 )3128,2964,1604,1537,1482,1444,1276,1194,1059,912,848,764,742.

[0281] Optical rotation:[α] D 25 =21.97(c=2.175,CHCl3).

[0282]

[0283] 1H NMR(400 MHz,CDCl3)δ8.66(s,1H),7.53(t,J=7.7 Hz,1H),7.39–7.31(m,2H),7.30–7.25(m,1H),6.98(s,1H),6.90(s,1H),6.74(s,2H),6.27(dd,J=6.5,4.3 Hz,1H),3.21(ddd,J=17.0,7.1,4.5 Hz,1H),3.01(ddd,J=17.0,8.4,4.4 Hz,1H),2.72(ddt,J=12.9,8.4,4.4 Hz,1H),2.57–2.44(m,5H),2.39–2.30(m,1H),2.28–2.19(m,7H),2.10(dt,J=14.8,7.5 Hz,1H),1.12(t,J=7.5 Hz,3H),1.00(t,J=7.6 Hz,3H). 13 C NMR(101 MHz,CDCl3)δ142.50,140.75,139.66,139.38,139.08,137.62,131.67,131.12,130.71,129.68,127.71,127.57,127.19,126.69,126.02,123.95,109.72,59.21,30.40,24.19,23.53,22.18,21.30,21.19,14.93,14.33.

[0284] HRMS(ESI)m / z[M-BF4] + :calcd.409.2638,found 409.2635.

[0285] IR(film):ν max (cm -1 )3119,2970,2935,1607,1537,1504,1465,1197,1058,914,843,730.

[0286] Optical rotation:[α] D 25 =69.60(c=1.760,CHCl3).

[0287]

[0288] 1H NMR(400 MHz,CDCl3)δ8.73(s,1H),8.28(s,2H),8.06(s,1H),7.42–7.36(m,3H),7.36–7.29(m,3H),7.18(s,1H),5.98(dd,J=8.0,4.2 Hz,1H),3.18(ddd,J=17.2,8.3,4.9 Hz,1H),3.09(dt,J=17.1,5.5Hz,1H),2.67–2.49(m,5H).

[0289] 13 C NMR(101 MHz,CDCl3) 13 C NMR(101 MHz,cdcl3)δ140.10,138.52,136.00,135.03,134.13(q,J=34.8 Hz),130.25,129.54,129.51,128.07,127.22,127.05,126.11(d,J=4.0 Hz)126.04,124.43–124.14(m),122.22(q,J=273.5 Hz),121.29,109.44,60.35,30.17,22.28,22.17.

[0290] 19 F NMR(376 MHz,CDCl3)δ-62.96,-152.53.

[0291] HRMS(ESI)m / z[M-BF4] + :calcd.461.1447,found 461.1447.

[0292] IR(film):ν max (cm -1 )3069,2933,1617,1548,1499,1391,1356,1187,1142,1060,908,764,750,701.Optical rotation:[α] D 25 =72.36(c=1.715,CHCl3).

[0293]

[0294] 1H NMR(400 MHz,CDCl3)δ8.85(s,1H),7.98(t,J=1.7 Hz,1H),7.87(d,J=1.6Hz,2H),7.73–7.65(m,4H),7.49–7.42(m,4H),7.41–7.35(m,5H),7.33(s,1H),7.32–7.26(m,3H),6.14(dd,J=7.1,4.2 Hz,1H),3.14(ddd,J=17.2,7.4,4.7 Hz,1H),3.04(ddd,J=17.1,7.4,4.6 Hz,1H),2.61(ddt,J=16.0,8.4,3.7Hz,1H),2.56–2.45(m,4H).

[0295] 13 C NMR(101 MHz,CDCl3)δ144.32,139.43,138.73,138.19,136.83,134.41,130.34,129.43,129.33,129.11,128.49,128.07,127.78,127.27,126.91,126.68,125.66,121.88,110.30,59.56,30.12,22.25,21.63.HRMS(ESI)m / z[M-BF4] + :calcd.477.2325,found 477.2321.

[0296] IR(film):ν max (cm -1 )3136,3062,1596,1577,1499,1297,1205,1058,912,837,762,731,701.

[0297] Optical rotation:[α] D 25 =107.23(c=2.065,CHCl3).

[0298]

[0299] 1H NMR(400 MHz,CDCl3)δ8.31(s,1H),7.40–7.30(m,4H),7.25–7.18(m,5H),7.11(s,1H),6.86(ddd,J=8.3,7.0,1.8 Hz,1H),5.86(dd,J=8.0,3.9 Hz,1H),3.19–3.08(m,1H),3.00(dt,J=17.1,5.3 Hz,1H),2.63–2.51(m,1H),2.46–2.37(m,4H).

[0300] 13 C NMR(101 MHz,CDCl3)δ151.45,139.06,138.45,136.39,131.93,130.85,129.53,129.47,127.57,126.87,126.38,126.26,125.03,120.30,120.25,118.57,111.11,59.91,30.67,22.12.

[0301] HRMS(ESI)m / z[M-BF4] + :calcd.341.1648,found 341.1646.

[0302] IR(film):ν max (cm -1 )3378,3139,3066,2929,1603,1545,1464,1351,1293,1208,1064,913,731.Optical rotation:[α] D 25 =92.88(c=1.340,CHCl3).

[0303]

[0304] 1H NMR(400 MHz,CDCl3)δ8.27(s,1H),7.38–7.29(m,5H),7.23(t,J=4.2 Hz,2H),7.16(dd,J=7.9,1.6 Hz,1H),7.10(s,1H),6.87(t,J=7.7 Hz,1H),5.83(dd,J=8.8,3.9Hz,1H),3.18(ddd,J=16.9,9.3,4.6Hz,1H),3.04(dt,J=17.1,5.1 Hz,1H),2.58(dq,J=14.4,5.0 Hz,1H),2.55–2.42(m,4H),2.21(s,3H). 13 C NMR(101 MHz,CDCl3)δ150.54,138.94,138.45,136.16,133.04,130.97,129.52,127.79,127.22,126.19,125.08,123.93,121.03,119.81,110.82,60.05,30.51,22.52,22.14,16.35.

[0305] HRMS(ESI)m / z[M-BF4] + :calcd.355.1805,found 355.1803.

[0306] IR(film):ν max (cm -1 )3408,3139,3064,2926,1601,1544,1489,1456,1300,1270,1205,1063,840,784,734,702.

[0307] Optical rotation:[α] D 25 =50.33(c=0.725,CHCl3).

[0308]

[0309] 1H NMR(400 MHz,CDCl3)δ8.30(s,1H),7.39–7.31(m,3H),7.24(dd,J=7.7,1.9Hz,3H),7.19(s,1H),7.13(s,1H),7.08(s,2H),5.85(dd,J=8.4,3.9 Hz,1H),3.16(ddd,J=17.0,8.8,4.6 Hz,1H),3.02(dt,J=17.2,5.2 Hz,1H),2.58(ddd,J=13.9,6.0,4.1 Hz,1H),2.51–2.40(m,4H),2.24(s,3H).

[0310] 13 C NMR(101 MHz,CDCl3)δ148.64,139.05,138.17,136.24,132.65,130.80,130.45,129.52,129.48,127.54,126.90,126.50,126.27,124.99,119.79,118.27,111.11,59.94,30.63,22.20,22.12,20.13.

[0311] HRMS(ESI)m / z[M-BF4] + :calcd.355.1805,found 355.1803.

[0312] IR(film):ν max (cm -1 )3365,3137,2928,1543,1516,1455,1295,1209,1062,823,734,702.

[0313] Optical rotation:[α] D 25 =34.76(c=1.125,CHCl3).

[0314]

[0315] 1 H NMR(400 MHz,CDCl3)δ8.26(s,1H),7.74(s,1H),7.41–7.32(m,3H),7.29–7.19(m,5H),7.12(s, 1H),7.05(d,J=1.8Hz,1H),6.72(dd,J=8.1,1.8Hz,1H),5.86(dd,J= 8.4,3.9Hz,1H),3.17(ddd,J=17.0 ,

[0316] 8.9,4.5 Hz,1H),3.03(dt,J=17.2,5.2 Hz,1H),2.60(ddt,J=14.5,6.1,4.3Hz,1H),2.54–2.44(m,4H),2.27(s,3H).

[0317] 13 C NMR(101 MHz,CDCl3)δ150.72,142.94,139.05,138.28,136.29,130.94,129.56,129.52,127.57,126.92,126.25,126.00,124.98,121.46,118.90,117.61,111.07,59.94,30.68,22.22,22.14,21.27.

[0318] HRMS(ESI)m / z[M-BF4] + :calcd.355.1805,found 355.1802.

[0319] IR(film):ν max (cm -1 )3379,3138,2926,1605,1545,1456,1297,1205,1134,1066,736,703.

[0320] Optical rotation:[α] D 25 =54.64(c=1.665,CHCl3).

[0321]

[0322] 1 H NMR(400 MHz,CDCl3)δ9.16(s,1H),7.46–7.30(m,5H),7.17(s,1H),7.01(s,1H),6.94(s,1H),6.84(s,2H),5.97(dd,J=7.1,4.2 Hz,1H),5.85(dd,J=9.5,3.7 Hz,1H),4.48(dd,J=12.0,9.6 Hz,1H),4.16(dd,J=12.1,3.6 Hz,1H),3.23–3.15(m,1H),3.03–2.92(m,1H),2.63–2.52(m,1H),2.51–2.37(m,5H),2.31–2.26(m,6H).

[0323] 13 C NMR(101 MHz,CDCl3)δ139.08,138.79,138.31,137.03,133.47,130.76,130.10,129.56,129.53,128.03,127.20,126.04,125.20,124.51,110.88,64.29,63.28,59.27,30.37,22.16,21.68,21.19.

[0324] HRMS(ESI)m / z[M-BF4] + :calcd.397.2274,found 397.2272.

[0325] IR(film):ν max (cm -1 )3132,2946,1695,1607,1544,1505,1343,1305,1203,1063,844,702.

[0326] Optical rotation:[α] D 25 =92.01(c=0.105,CHCl3).

[0327]

[0328] 1 H NMR(500 MHz,CDCl3)δ7.39–7.31(m,3H),7.05(s,1H),7.04(s,2H),7.01–6.97(m,2H),6.70(s,1H),5.93–5.86(m,1H),2.97(dt,J=16.8,4.6 Hz,1H),2.83(ddd,J=16.4,9.3,5.7 Hz,1H),2.61–2.53(m,2H),2.45(s,3H),2.39(s,3H),2.02(s,3H),1.98(s,3H).

[0329] 13 C NMR(126 MHz,CDCl3)δ140.01,139.44,135.52,135.35,132.91,132.61,129.78,129.64,129.56,129.08,128.29,125.89,123.21,123.07,108.97,59.09,31.00,21.82,21.12,20.82,17.91,17.82。

Claims

1. A compound as shown in formula I, characterized in that in, X is BF4 - or Cl - ; R 1 is a C1-C6 alkyl, a C1-C6 alkoxy or a C6-C 14 The aromatic group; R 2 1, 2 or 3 R 2-1 Substituted C6-C 10 Aryl or -CHR 2-2 R 2-3 ; R 2-1 is independently optionally replaced by 1, 2 or 3 R 2-1-1 Substituted C1-C6 alkyl, optionally substituted by 1, 2 or 3 R 2-1-2 Substituted C1-C6 alkoxy, C6-C 10 an aryl or hydroxyl group; R 2-1-1 and R 2-1-2 are independently halogen; R 2-2 C6-C 10 The aromatic group; R 2-3 1, 2 or 3 R 2-3-1 Substituted C1-C6 alkyl; R 2-3-1 are independently hydroxyl groups; R 3 1, 2 or 3 R 3-1 Substituted C6-C 10 The aromatic group; R 3-1 is a C1-C6 alkyl, a C1-C6 alkoxy or a C6-C 10 The aromatic group.

2. The compound as shown in formula I according to claim 1, characterized in that It satisfies one or more of the following conditions: (1) The C1-C6 alkyl group and the C1-C6 alkyl group in the substituted C1-C6 alkyl group are independently methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl or sec-butyl; preferably methyl, ethyl, tert-butyl or isopropyl; (2) The C1-C6 alkoxy groups in each of the C1-C6 alkoxy groups and each of the substituted C1-C6 alkoxy groups are independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy; preferably methoxy; (3)R 1 In the C6-C 14 The aryl groups are independently phenyl or (4) Each of the C6-C 10 The aryl group and each of the substituted C6-C 10 The C6-C 10 The aryl groups of are independently phenyl or naphthyl, for example phenyl; and (5) The halogen is independently fluorine, chlorine, bromine or iodine; preferably fluorine.

3. The compound as shown in formula I according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) X is BF4 - ; (2)R 1 is a C1-C6 alkyl or a C6-C 14 Aryl; preferably C1-C6 alkyl; (3)R 2 For 1, 2 or 3 R 2-1 Substituted C6-C 10 The aromatic groups, for example (4)R 2-1 is independently optionally replaced by 1, 2 or 3 R 2-1-1 Substituted C1-C6 alkyl, C1-C6 alkoxy, C6-C 10 aryl or hydroxyl; preferably C1-C6 alkyl; and (5)R 3-1 It is a C1-C6 alkyl group or a C1-C6 alkoxy group.

4. The compound as shown in formula I according to claim 1, characterized in that It satisfies one or more of the following conditions: (1)R 1 Methyl, phenyl or (2)R 2 for and (3)R 3 for 5. The compound as shown in formula I according to claim 1, characterized in that, The compound shown in formula I is a compound shown in formula I-1 or formula I-2, Among them, R 1 , R 2-1 and R 3 The definition as described in any one of claims 1 to 4.

6. The compound as shown in formula I according to claim 1, characterized in that, The compound shown in formula I is any of the following structures, 7. A compound as shown in formula II, characterized in that ； Among them, R 1 , R 2 and R 3 The definition as in any one of claims 1 to 6; Preferably, the compound as shown in Formula II is any of the following structures, 8. Use of a compound of formula I as claimed in any one of claims 1 to 6 and / or a compound of formula II as claimed in claim 7 as a catalyst in a silylation reaction.

9. The use according to claim 8, characterized in that The silylation reaction comprises the following steps: in a solvent, in the presence of a catalyst and a base, compound A and compound B undergo a silylation reaction to prepare compound C; The catalyst is "cuprous chloride and a compound as shown in formula I as described in claims 1-6" and / or "a compound as shown in formula II as described in claim 7"; 10. The use according to claim 9, characterized in that It meets one or more of the following conditions; (1) The solvent is an ether solvent; preferably tetrahydrofuran; (2) The base is an alkali metal salt of an alcohol; preferably sodium methoxide; (3) The molar ratio of the compound B to the compound A is (1.2-1.8):1; preferably 1.5:1; (4) The molar ratio of the cuprous chloride to the compound of formula I is (0.8-1.2):1; preferably 1:1; (5) The molar ratio of the catalyst to the compound A is (8-12):100; preferably 10:100; (6) The molar ratio of the base to the compound A is (1.2-1.8):1; preferably 1.5:1; (7) The mass volume ratio of the compound A to the solvent is (0.012-0.018) g / mL; preferably 0.015 g / mL; (8) The reaction time of the silylation reaction is 8-16 hours, preferably 12 hours; (9) The reaction temperature of the silylation reaction is -5-5°C; preferably 0°C; (10) The silylation reaction further comprises the following post-treatment steps: quenching and spin drying; the quenching may be acetic acid quenching; and (11) The reaction raw materials of the silylation reaction are the solvent, the cuprous chloride, the compound represented by formula I, the base, the compound A and the compound B.

11. A single crystal of a compound represented by formula II-1, The single crystal belongs to the orthorhombic system, space group P212121, unit cell parameters: α=γ=β=90°, unit cell volume The number of asymmetric units in the unit cell is Z = 8, and the crystal density is 1.152 g / cm 3 .

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