Spiral bisindole skeleton compound and catalytic construction method thereof

Abstract

The invention relates to the technical field of chemical synthesis, and particularly discloses a spiral bisindole skeleton compound and a catalytic construction method thereof, the spiral bisindole skeleton compound has excellent configuration stability, a part of compounds present a wide absorption band between 300-500 nm, especially have obvious peak values at 360, 420, 450 and 480 nm, and under a light source of 365 nm, the spiral bisindole skeleton compound has a wide absorption band at 300-500 nm. Obvious green luminescence can be displayed, and the quantum yield is 60% due to the unique rigidity of the spiral frame. An emission spectrum of the compound shows a plurality of emission bands, has a maximum emission peak (lambda max) at 530 nm, shows perfect mirror image CPL light at the maximum emission peak at 510 nm under excitation of 365 nm, can be divided into a levorotation type and a dextrorotation type, and can be used for developing novel materials such as fluorescent polymers and coatings. The method is applied to security identification, decoration, anti-counterfeiting technologies and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and specifically discloses a spiral bisindole skeleton compound and a catalytic construction method thereof. Background Art

[0002] Axial chiral elements are widely used in bioactive molecules, functional materials, and asymmetric catalysis. The rational design and enantioselective construction of axial chiral skeletons have attracted widespread attention in the synthesis community in recent decades. Among these skeletons, the helical skeleton has become a hot topic in various research fields including asymmetric catalysis and functional materials due to its excellent configurational stability. For example, as fluorescent polymers and coatings in functional materials, they can be applied to security identification, decoration and anti-counterfeiting technology, the development of new optical coatings and filters to improve the performance of optical devices, etc., or as ligands in asymmetric hydrogenation catalysts to prepare specific chiral compounds.

[0003] The expansion of the structural diversity of the helical framework can further develop the application of axial chirality elements in various fields. Summary of the invention

[0004] In order to solve the problems existing in the prior art, the first aspect of the present invention provides a spirobisindole skeleton compound, as represented by formula (I):

[0005]

[0006] The Carbon represents a carbon atom;

[0007] Said represents a single bond;

[0008] The L1 part is

[0009] The L2 part is Alternatively, the L2 portion is

[0010] The carbon atom Carbon is in (R) configuration, or (S) configuration, or is an achiral carbon atom;

[0011] The carbon atom Carbon is in (R) configuration, or (S) configuration, or is an achiral carbon atom;

[0012] The ' in L1 and L2 indicates a bond connection with the carbon atom Carbon;

[0013] The R1, R 10 Each is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl;

[0014] The R2 and R9 are each independently selected from H, alkyl, aryl, monocyclic heterocyclic group, alkoxy, and fused heterocyclic group;

[0015] The R3 and R8 are each independently selected from H, an alkyl group, an aryl group, and a borate group;

[0016] The R4 and R7 are each independently selected from H, alkyl, halogen, amino, carbonyl heterocyclic group, carbonyl alkyl, monocyclic heterocyclic group, condensed heterocyclic group;

[0017] Said R5 and R6 are each independently selected from H, halogen, alkyl, alkylthio, alkoxy, aldehyde, carbonylalkyl;

[0018] The R 11 Selected from H, C1-C8 alkyl;

[0019] The hydrogen in the formula (I) is optionally replaced by D until it is completely deuterated.

[0020] In some specific embodiments of the first aspect of the present invention, R1, R 10 , R3, and R8 are selected from monocyclic aromatic groups and naphthyl groups, R2 and R9 are selected from monocyclic aromatic groups and condensed heterocyclic groups, R4 and R7 are selected from amino groups, methyl groups, pyridine, and furan groups, and R5 and R6 are selected from hydroxyethyl groups, bromine groups, and -S-Ph groups.

[0021] In some specific embodiments of the first aspect of the present invention, the alkyl group is selected from C1-C8 alkyl groups, the alkenyl group is selected from C2-C8 alkenyl groups, the alkynyl group is selected from C2-C8 alkynyl groups, and the cycloalkyl group is selected from C3-C10 cycloalkyl groups.

[0022] In some specific embodiments of the first aspect of the present invention,

[0023] The R1, R 10 Each independently selected from aryl, said R1, R 10 The optional H is R a Substitute, the R a Selected from alkyl;

[0024] The R2 and R9 are independently selected from aryl, monocyclic heterocyclic group, condensed heterocyclic group, and the H on R2 and R9 is optionally replaced by R b Substitute, the R b Selected from alkyl, alkoxy, halogen;

[0025] The R3 and R8 are independently selected from aryl groups, and the H on the R3 and R8 is optionally replaced by R c Substitute, the R c is selected from alkyl, wherein H on the alkyl is optionally substituted by halogen;

[0026] The H on R4 and R7 is optionally replaced by R d Substitute, the R d is selected from aminothioformyl, wherein the H on the aminothioformyl is optionally substituted by isothiocyanate;

[0027] The R5 and R6 are each independently selected from an alkyl group, and the H on the R5 and R6 is optionally substituted by a hydroxyl group.

[0028] In some specific embodiments of the first aspect of the present invention, the R5, R6 and the atoms to which they are connected together form a ring Ar, such as formula (II):

[0029]

[0030] The ring Ar is selected from a carbocyclic group, an aryl group, and a heterocyclic group.

[0031] In some specific embodiments of the first aspect of the present invention, the optional methylene group on the ring Ar is replaced by -O- or Substitute, the R e is selected from aryl, alkyl, cycloalkyl, monocyclic heterocyclic group, condensed heterocyclic group, and / or the ring Ar has at least one double bond.

[0032] The second aspect of the present invention proposes the specific structure of the spirobisindole skeleton compound described in the first aspect:

[0033]

[0034]

[0035] The carbon atom marked with "*" mentioned above may be in the (R) configuration or the (S) configuration, or may be an achiral carbon atom.

[0036] The third aspect of the present invention provides a method for synthesizing the spirobisindole skeleton compound described in the first aspect, comprising:

[0037]

[0038] The R 11 Selected from H, the compound of formula (III) is mixed with a catalyst Cat in an organic solvent to obtain a compound of formula (IV);

[0039]

[0040] or,

[0041] The R 11 The compound of formula (III) is mixed with a catalyst Cat in an organic solvent to obtain a compound of formula (V);

[0042] The (S)-C9 is selected from The R1, R 10 Each is independently selected from H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C10 cycloalkyl, and aryl;

[0043] The R2 and R9 are each independently selected from H, C1-C8 alkyl, aryl, monocyclic heterocyclic group, condensed heterocyclic group;

[0044] The R3 and R8 are each independently selected from H, C1-C8 alkyl, and borate group;

[0045] The R4 and R7 are each independently selected from H, C1-C8 alkyl, amino, carbonyl heterocyclic group, carbonyl alkyl, monocyclic heterocyclic group, condensed heterocyclic group; the R5 and R6 are each independently selected from H, halogen, C1-C8 alkyl, alkylthio, alkoxy, aldehyde group, carbonyl alkyl:

[0046] The catalyst Cat is selected from

[0047]

[0048] The carbon atom marked with "*" is in (S) configuration;

[0049] Or, the catalyst Cat is selected from

[0050]

[0051] The carbon atom marked with "*" is in the (R) configuration.

[0052] In a fourth aspect, the present invention provides a compound of formula (III) having a structure as follows

[0053]

[0054] The R1, R 10 Each is independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C10 cycloalkyl, and aryl;

[0055] The R2 and R9 are each independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, aryl, monocyclic heterocyclic group, condensed heterocyclic group;

[0056] The R3 and R8 are each independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, and borate group;

[0057] The R4 and R7 are each independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, amino, carbonyl heterocyclic group, carbonyl alkyl, monocyclic heterocyclic group, condensed heterocyclic group;

[0058] The R5 and R6 are each independently selected from H, halogen, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, alkylthio, alkoxy, aldehyde, carbonyl alkyl:

[0059] The fifth aspect of the present invention provides an application of the spirobisindole skeleton compound described in the first aspect or the second aspect in organic photoluminescent materials.

[0060] The term "aryl" refers to a single-ring aromatic group or a condensed-ring aromatic group, exemplified by benzene and naphthalene.

[0061] The term "alkyl" refers to a saturated straight-chain alkyl or branched-chain alkyl, exemplified by methyl, ethyl, and isopropyl.

[0062] The term "carbocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon group, which may contain 3 to 20 carbon atoms, preferably 3 to 12 (e.g. 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) carbon atoms, and more preferably 3 to 6 carbon atoms. The partially unsaturated monocyclic or polycyclic hydrocarbon group is a saturated cycloalkyl group or may optionally contain one, two or more double bonds and / or triple bonds on the ring, thereby forming a so-called cycloalkenyl group or cycloalkynyl group.

[0063] The term "heterocyclic group" refers to a substituted or unsubstituted non-aromatic fully saturated or partially unsaturated cyclic group (e.g., a 3- to 7-membered monocyclic ring) having at least one heteroatom in a ring containing at least one carbon atom. Preferably, the heterocyclic group is a 5-membered or 6-membered heterocyclic group. Each ring of the heterocyclic group containing a heteroatom may have 1, 2, 3 or 4 heteroatoms selected from nitrogen atoms, oxygen atoms and / or sulfur atoms, wherein the nitrogen and sulfur heteroatoms may be optionally oxidized and the nitrogen heteroatom may be optionally quaternized. Non-limiting exemplary heterocyclic groups include thienyl, furanyl, pyrrolyl, pyrazole, imidazole, oxazole, isoxazole, thiazole, isothiazole, pyridazinyl, pyrimidinyl, pyrazinyl, piperidinyl, piperazinyl.

[0064] The term "boronic acid ester group" refers to an ester group formed by a boronic acid group and an alcohol, and for example, a boronic acid group and pinacol form a boronic acid pinacol ester group, such as

[0065]

[0066] The term "carbonylheterocyclyl" refers to a heterocyclyl or fused heterocyclyl group attached to the parent molecular moiety through a carbonyl group, as defined herein.

[0067] The term "alkylthio" refers to a thiol group substituted with an alkyl group and can be represented by the general formula -SR x Indicates that here R xIt is represented by a carbocyclic ring (group), an aryl group, a straight-chain alkyl group or a branched-chain alkyl group.

[0068] The term "alkylhydroxy" refers to -R y -OH, where R y It can be represented by any of carbocyclic ring, aryl group, straight chain alkyl group or branched chain alkyl group.

[0069] The term "carbonylalkyl" refers to -(C=O)-R z , where R z It is represented by a carbocyclic ring (group), an aryl group, a straight-chain alkyl group or a branched-chain alkyl group.

[0070] The term "carbamothioyl" refers to

[0071] The term "isothiocyanate" refers to

[0072] The term "NTf" refers to trifluoromethanesulfonyl.

[0073] "Room temperature" refers to the indoor ambient temperature, which can be 12℃~37℃ or 20℃~30℃.

[0074] In the present invention, the compounds 1a to 1ac are specifically as follows:

[0075]

[0076] In the present invention, the compounds (S)-2a to (S)-2ab and 2ac are specifically as follows:

[0077]

[0078]

[0079] The drugs used in the present invention are all purchased from the open legal market and have not been further purified.

[0080] Advantages of the present invention:

[0081] The present invention discloses a spiral bi-indole skeleton compound and a catalytic construction method thereof, and realizes enantioselective construction through an intramolecular dehydration cyclization reaction catalyzed by chiral phosphoric acid. Compared with the classic SPINOL skeleton, the phenolic group is replaced by an indole group, making the ketone substrate more nucleophilic, thereby avoiding the cumbersome pre-activation process. At the same time, the spiral bi-indole skeleton compound prepared by the present invention has specific absorption and emission under different wavelength spectra. For example, the ultraviolet-visible absorption spectra of (R)-16 and (S)-16 are basically overlapped, showing a wide absorption band between 300-500nm, and having obvious peaks at 360, 420, 450 and 480nm respectively. Under a 365nm light source, (R)-16 shows obvious green luminescence in the air. The emission spectra of (R)-16 and (S)-16 show multiple emission bands with a maximum emission peak (λmax) at 530nm. The enantiomers show perfect mirror-image CPL spectra at the maximum emission peak of 510nm under 365nm excitation. The photophysical properties of the compounds of the present invention demonstrate the prospects for the application of the spirobisindole compounds in optical materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0082] Figure 1 Shows the NMR hydrogen spectrum data of compound (S)-2a;

[0083] Figure 2 Shows the NMR carbon spectrum data of compound (S)-2a;

[0084] Figure 3 : shows the NMR hydrogen spectrum data of compound 2ac;

[0085] Figure 4 : shows the NMR carbon spectrum data of compound 2ac;

[0086] Figure 5 Shows the NMR hydrogen spectrum data of compound (S)-16;

[0087] Figure 6 Shows the NMR carbon spectrum data of compound (S)-16;

[0088] Figure 7 Shown are the CPL spectra of (R)-16 and (S)-16;

[0089] Figure 8 The g of (R)-16 and (S)-16 lum curve;

[0090] Fig. 9 The UV-visible spectra and fluorescence spectra of (R)-16 and (S)-16 are shown;

[0091] Fig.10 Show the fluorescence properties of (R)-16; DETAILED DESCRIPTION

[0092] Through the following further detailed description of the embodiments of the present invention in combination with the accompanying drawings and specific implementation methods, those skilled in the art will more clearly and thoroughly understand the further features, advantages and effects of the present invention.

[0093] 1a Synthesis:

[0094]

[0095] At -40°C, a solution of a-1 (40 mmol, 5.80 g) in tetrahydrofuran (THF) (40 mL) was added dropwise to a mixture of anhydrous tetrahydrofuran (THF) (200 mL) containing potassium tert-butoxide (120 mmol). The reaction mixture was stirred at -40°C for 10 minutes, and then acetone (1.5 mL) in tetrahydrofuran was added.

[0096] (THF) (20mL) solution. The solution was stirred at -40°C for 3 hours. The reaction was slowly quenched with 1M hydrochloric acid (100mL) at 0°C, and then extracted with ethyl acetate (150mL×3). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure, and then quickly purified by silica gel (THF / PE) column chromatography to obtain pure product b-1.

[0097] 500 mg of Raney nickel was washed three times with THF and added to a solution of THF (50 mL) and MeOH (50 mL) containing intermediate b-1 (20 mmol). The resulting mixture was stirred at room temperature under a hydrogen atmosphere. When thin layer chromatography (TLC) showed that the reaction was complete, the solution was carefully poured into another bottle, and the Raney nickel was adsorbed on the magnetic stirring bar and left. The resulting crude product was then purified by silica gel column chromatography to obtain pure product 1a.

[0098] 1 H NMR(400MHz,Chloroform-d)δ8.19(s,2H),7.25(d,J=8.0Hz,2H),7.19-7.17(m,2H),7.12(t,J =8.0Hz,2H),6.91(d,J=4.0Hz,2H),6.54(s,2H),3.20(t,J=7.6Hz,4H),2.84(t,J=7.6Hz,4H).

[0099] 13 C NMR (100MHz, Chloroform-d) δ210.4,135.7,133.1,126.9,123.8,122.1,118.9,109.2,100.7,77.3,77.00,76.7,43.6,27.5.

[0100] HRMS(ESI)Calcd for C 21 H 21 N2O + [M+H] + 317.1648; Found:317.1643.

[0101] 1b~1g synthesis:

[0102]

[0103] In a Schlenk flask with a magnetic stir bar, 6-bromo-1H-indole-4-carboxaldehyde (1.0 equivalent), RB (OR 1 )2(where RB(OR 1 )2 is for different ligands 1b-1g using the corresponding aryl boronic acid or vinyl boronic acid pinacol ester, such as methyl boronic acid pinacol ester, potassium ethylene trifluoroborate, 4-fluorophenyl boronic acid, 4-methoxyphenyl boronic acid, 4-tert-butylphenyl boronic acid, 3,5-dimethylphenyl boronic acid)

[0104] Then add palladium / ligand and inorganic base. Then seal the Schlenk bottle with a rubber septum, evacuate and then pass argon (this process is repeated three times). Add the solvent from the septum to the Schlenk bottle through a syringe and seal it. After stirring the reaction under argon atmosphere for 12 hours, cool it to room temperature. After adding water, extract the reaction mixture with ethyl acetate. After combining the organic layers, wash with saturated brine, dry over anhydrous sodium sulfate, and finally remove the solvent under reduced pressure. Then purify by silica gel column chromatography to obtain pure product a-2.

[0105] At -40°C, a tetrahydrofuran solution (40 mL) of a-2 (40 mmol, 5.80 g) was added dropwise to a mixture of anhydrous tetrahydrofuran (200 mL) containing potassium tert-butoxide (120 mmol). After the reaction mixture was stirred at -40°C for 10 minutes, a solution of acetone (20 mmol, 1.5 mL) in tetrahydrofuran (20 mL) was added. The solution was stirred at -40°C for 3 hours, and the reaction was slowly quenched with 1M hydrochloric acid (100 mL) at 0°C, and then extracted with ethyl acetate (150 mL×3). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure, and then quickly purified by silica gel (THF / PE) column chromatography to obtain pure product b-2.

[0106] 500 mg of Raney nickel was washed three times with THF and then added to a solution of THF (50 mL) and MeOH (50 mL) containing intermediate b-2 (20 mmol). The resulting mixture was stirred at room temperature under a hydrogen atmosphere. When thin layer chromatography (TLC) showed that the reaction was complete, the solution was carefully poured into another bottle, and the Raney nickel was adsorbed on the magnetic stirring bar and left. The crude product was then purified by silica gel column chromatography to obtain pure product 1b~1g (RB (OR 1 )2 is methylboronic acid pinacol ester, potassium trifluoroborate of ethylene, 4-fluorophenylboric acid, 4-methoxyphenylboric acid, 4-tert-butylphenylboric acid, 3,5-dimethylphenylboric acid, and 1b~1g) are obtained respectively.

[0107] Synthesis of 1h-1m:

[0108]

[0109] 40 mmol of a-1 and 40 mmol of (CH3COCH)PPh3 were dissolved in 100 mL of toluene. After the solution was stirred at 120°C for 2 hours, it was allowed to cool to room temperature, and the solvent was removed under reduced pressure, and then purified by silica gel column chromatography to obtain compound a-5a (7.0 g, 95% yield).

[0110] Compound a-5a (36 mmol) was dissolved in 100 mL of anhydrous tetrahydrofuran (THF), and a solution of DMAP (40 mmol, 4.8 g) was added at 0°C. After the reaction mixture was stirred at 0°C for 10 minutes, a solution of THF (20 mL) containing Boc2O (40 mmol, 8.7 g) was added. The solution was stirred at 0°C for 3 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride (NH4Cl) (100 mL) at 0°C and extracted with ethyl acetate (50 mL×3). After the organic layers were combined, they were dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure, and finally purified by silica gel column chromatography to obtain a-5b (9.9 g, 97% yield).

[0111] a-5b (30 mmol) was dissolved in 100 mL of anhydrous tetrahydrofuran (THF), and a solution of LDA (33 mmol, 1.1 equivalent) was slowly added dropwise under an argon atmosphere at -78 °C. After stirring for 1 hour, a solution of TMSCl (33 mmol, 1.1 equivalent) was added dropwise to the reaction mixture. The resulting mixture was slowly warmed to room temperature and stirred for 3 hours. The solvent was then removed under reduced pressure, and the obtained crude product was added to n-hexane (100 mL), filtered, and the solvent was evaporated under reduced pressure. The resulting intermediate was directly used in the next step reaction.

[0112] The intermediate obtained at last was dissolved in 50 mL of anhydrous tetrahydrofuran (THF), and a solution of NBS (30 mmol, 1.0 equivalent) was added at -40 °C. The reaction mixture was stirred at -40 °C until thin layer chromatography (TLC) showed that the reaction was complete. The reaction mixture was extracted with ethyl acetate (50 mL × 3). After the organic layers were combined, they were washed with saturated brine and dried over anhydrous sodium sulfate, and finally the solvent was removed under reduced pressure. Then it was purified by silica gel column chromatography to obtain a-5c (6.58 g, 63% yield).

[0113] a-5c (10 mmol) and triphenylphosphine (PPh3) (10 mmol) were dissolved in 20 mL of toluene under an argon atmosphere. The solution was stirred at 80 °C for 3 hours, then allowed to cool to room temperature, and the solvent was removed under reduced pressure. The reaction mixture was dissolved in 10 mL of dichloromethane (CH2Cl2), and then 10 mL of 1.0 M potassium hydroxide aqueous solution was added and stirred at room temperature for 5 hours. The solution was extracted with dichloromethane (10 mL×3), and the solvent was removed under reduced pressure. The resulting crude phosphorus a-5d was directly used for the next step reaction.

[0114] Crude a-5d (0.75 mmol), indole-4-carboxaldehyde (0.5 mmol) and toluene (5 mL) stirred at 120°C for 12 hours were mixed. Silica gel (10 g, 100-200 mesh) and toluene (30 mL) were added. Stirred at 120°C for 5 hours, then allowed to cool to room temperature, filtered, and the solvent evaporated under reduced pressure. The resulting intermediate b-2 was directly used in the next step.

[0115] 30 mg of Raney nickel was washed three times with THF and added to a mixed solution of THF (5 mL) and MeOH (5 mL) containing intermediate b-2. The mixture was stirred at room temperature under a hydrogen atmosphere. When thin layer chromatography (TLC) showed that the reaction was complete, the solution was carefully poured into another bottle, and the Raney nickel was adsorbed on the magnetic stirring bar and left. The crude product was then purified by silica gel column chromatography to obtain pure products 1h~1m.

[0116] Synthesis of 1n-1p:

[0117]

[0118] A mixture of indole-4-carboxylate (40 mmol) in anhydrous dichloromethane (CH2Cl2) (300 mL) was placed at 0°C and triethylsilane was added dropwise.

[0119] The reaction mixture was stirred at 0°C for 10 minutes, and then a solution of trifluoroacetic acid (CF3COOH) (0.8 mol, 64 mL) was added. The solution was stirred at room temperature overnight. The mixture was quenched with a saturated aqueous solution of ammonium chloride (NH4Cl) and extracted with dichloromethane (CH2Cl2) (150 mL×3). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure, and then purified by silica gel column chromatography to obtain the pure product aa-1 (80%).

[0120] aa-1 (15 mmol) was dissolved in a mixture of toluene and 1,4-dioxane (60 mL), placed at 0°C, and a solution of tetrabutylammonium tribromide [(nBu)4N+(Br3)-] (15 mmol, 4.8 g) was added dropwise. After stirring the solution for 30 minutes, water was added, and the reaction mixture was extracted with ethyl acetate (30 mL×3). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and finally the solvent was removed under reduced pressure. Then, the product was purified by silica gel column chromatography, and after separation, the pure products a-3a and a-4a were obtained with yields of 35% and 37%, respectively.

[0121] A-3a or a-4a (10 mmol), ferric chloride (FeCl3) (1 mmol, 10 mol%, 160 mg), 1,10-phenanthroline (1 mmol, 10 mol%, 180 mg) and TEMPO (12 mmol, 1.9 g) were added to a Schlenk bottle containing a magnetic stirring bar. The Schlenk bottle was then sealed with a rubber septum, and argon was introduced after vacuuming (this process was repeated three times). DMSO (30 mL) was added to the Schlenk bottle through the septum via a syringe and sealed. The reaction was stirred at 120 ° C for 12 hours under an argon atmosphere and then cooled to room temperature. After adding water, the reaction mixture was extracted with ethyl acetate (50 mL×3). After the organic layers were combined, they were washed with saturated brine and dried over anhydrous sodium sulfate, and finally the solvent was removed under reduced pressure. Then, the pure product a-3b or a-4b was obtained by purification by silica gel column chromatography with yields of 86% and 83%, respectively.

[0122] A THF solution (10 mL) of a-3b or a-4b was added dropwise to a mixture of lithium aluminum hydride (LiAlH4) (16 mmol) in anhydrous tetrahydrofuran (THF) (50 mL) at 0°C. The resulting mixture was allowed to warm to room temperature and stirred for 6 hours. Subsequently, the mixture was quenched with a saturated aqueous sodium bicarbonate (NaHCO3) solution and extracted with ethyl acetate (50 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting intermediate was dried and used directly in the next reaction.

[0123] IBX (40 mmol) was dissolved in DMSO and placed at 0°C, and then a solution of the final intermediate in DMSO (10 mL) was added dropwise. The resulting mixture was allowed to warm to room temperature and stirred for 12 hours. The mixture was quenched with a saturated aqueous sodium bicarbonate (NaHCO3) solution and extracted with ethyl acetate (50 mL×3). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and finally the solvent was removed under reduced pressure. Purification by silica gel column chromatography, using a-3b or a-4b as a substrate, respectively, gave pure products a-3c and a-4c (yields were 35% and 42%, respectively).

[0124] a-3c or a-4c (5mmol), Pd(PPh3)4 (0.25mmol, 288mg), potassium carbonate (K2CO3) (10mmol, 1.3g) and 4-methylphenylboronic acid (7.5mmol) were added to a Schlenk bottle containing a magnetic stirring bar. Then the Schlenk bottle was sealed with a rubber septum, and argon was introduced after vacuum (this process was repeated three times). Tetrahydrofuran (10mL) and water (2mL) were added to the Schlenk bottle through the septum through a syringe and sealed. The reaction was stirred at 80°C for 12 hours under argon atmosphere and then cooled to room temperature. The reaction mixture was extracted with ethyl acetate (50mL×3). After the organic layers were combined, they were washed with saturated brine and dried over anhydrous sodium sulfate, and finally the solvent was removed under reduced pressure. Then it was purified by silica gel column chromatography, and a-3c or a-4c was added as a substrate to obtain pure product a-3 or a-4 respectively.

[0125] Dissolve 20 mmol of potassium tert-butoxide in 20 mL of anhydrous tetrahydrofuran, and add a solution of 4 mmol of a-3 or a-4 in THF (5 mL) dropwise at 0°C. After the reaction mixture was stirred at 0°C for 10 minutes, a solution of 2 mmol (0.15 mL) of acetone in THF (2 mL) was added. The solution was stirred at room temperature for 3 hours. The reaction was slowly quenched with 1 M hydrochloric acid (10 mL) at 0°C. Extract with ethyl acetate (15 mL × 3). After combining the organic layers, dry them over anhydrous magnesium sulfate, filter them, and evaporate the solvent under reduced pressure. Then purify them by silica gel column chromatography (THF / PE), and react with a-3 or a-4 as a substrate to obtain intermediate 2 and intermediate 2', respectively.

[0126] 50 mg of Raney nickel was washed three times with THF and added to a solution containing intermediate 2 (1.0 mmol) or intermediate 2' (1.0 mmol) in THF (5 mL) and MeOH (5 mL). The mixture was stirred at room temperature under a hydrogen atmosphere. When thin layer chromatography (TLC) showed that the reaction was complete, the solution was carefully poured into another bottle, and the Raney nickel was adsorbed on the magnetic stirring bar and left. The crude product was then purified by silica gel column chromatography to obtain pure products 1h~1p.

[0127] Synthesis of 1ab:

[0128]

[0129] 1a (0.5 mmol) was dissolved in a mixture of acetone (5 mL), and potassium hydroxide (5 mmol, 10.0 equivalents) was added. After stirring for 10 minutes, iodomethane (2.5 mmol, 5.0 equivalents) was added dropwise. The resulting mixture was heated to 40 ° C and stirred for 12 hours. The reaction was then quenched with aqueous ammonium chloride and extracted with ether. The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / dichloromethane) to obtain the product 1ab.

[0130] Synthesis of 1ac

[0131]

[0132] A Schlenk flask containing a magnetic stirring bar was added with a-1 (10 mmol), Ru(p-cymene)Cl2 (0.5 mmol, 5 mol%) and KOH (30 mmol, 3.0 equiv). The Schlenk flask was sealed with a rubber septum, then evacuated and backfilled with argon (this process was repeated three times). Methanol (30 mL) was added to the septum via a syringe, and the Schlenk flask was sealed. The reaction was stirred at 120 °C under an argon atmosphere for 24 hours and then cooled to room temperature. After adding water, the reaction mixture was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography to obtain the pure product a-7 (934 mg, yield 58%).

[0133] A mixture of IBX (30 mmol) dissolved in DMSO was slowly added dropwise to a DMSO solution of a-7 (10 mL) at 0°C. The resulting mixture was warmed to room temperature and stirred for 12 hours. The reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (50 mL × 3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography to obtain the pure product a-8 (860 mg, yield 93%).

[0134] Crude a-5d (0.75 mmol), 3-methylindole-4-carboxaldehyde (0.5 mmol) and toluene (5 mL) stirred at 120°C for 12 hours were mixed. Silica gel (10 g, 100-200 mesh) and toluene (30 mL) were added. Stirred at 120°C for 5 hours, then allowed to cool to room temperature, filtered, and the solvent evaporated under reduced pressure. The resulting intermediate b-2 was directly used in the next step reaction.

[0135] 50 mg of Raney nickel was washed three times with THF and added to a solution containing intermediate intermediate b-2 in THF (5 mL) and MeOH (5 mL). The mixture was stirred at room temperature under a hydrogen atmosphere. When thin layer chromatography (TLC) showed that the reaction was complete, the solution was carefully poured into another bottle, and the Raney nickel was adsorbed on the magnetic stirring bar and left. The resulting crude product was then purified by silica gel column chromatography to obtain pure product 1ac.

[0136] Embodiment 1:

[0137] Mix 1a (0.05 mmol), trichloroethane (5 ml), MgSO4 (50 mg) and catalyst (R)-C4 or (S)-C4 (0.005 mmol), seal the reaction container, heat to 90°C, stir, react for 96 hours, add (R)-C4 or (S)-C4 to obtain the corresponding (S)-2a (94ee%, 95yield%) or (R)-2a (90ee%, 91yield%).

[0138]

[0139] The NMR data are:

[0140] 1 H

[0141] NMR (400MHz, Acetone-d6) δ9.73 (s, 2H), 7.14 (d, J = 8.0Hz, 2H), 7.02 (m, 2H), 6.77 (m, 2H), 6.69 (d, J = 2.1Hz, 2H), 3.10-2.93 (m, 4H), 2.26-2.19 (m, 2H), 2.06-2.03 (m, 2H). 13 CNMR(100MHz,Acetone-d6)δ206.4,135.4,131.8,127.6,122.9,122.4,118. 7,116.2,109.2,37.9,36.1,30.6,30.4,30.2,30.0,29.8,29.6,29.4,25.6.

[0142] HRMS(ESI)CalcdforC 21 H 18 N2 + [M+H]+299.1543; Found:299.1538.

[0143] Embodiment 2:

[0144] 1b to 1m (0.2 mmol) were respectively put into a reaction vessel and mixed with catalyst (R)-C4 (0.02 mmol), trichloroethane (20 ml) and MgSO4 (200 mg). The reaction vessel was sealed, heated to 90°C, stirred, and reacted for 96 hours to obtain products (S)-2b to (S)-2m (1b to 1m, (S)-2b to (S)-2m structures are as described above), and the ee% and yield% were measured.

[0145]

[0146] Entry Reactants product Yield(%) ee(%) 9 1b (S)-2b 90 92 10 1c (S)-2c 92 92 11 1d (S)-2d 75 95 12 1e (S)-2e 68 99 13 1f (S)-2f 78 94 14 1g (S)-2g 83 97 15 1h (S)-2h 92 93 16 1i (S)-2i 87 97 17 1j (S)-2j 84 98 18 1k (S)-2k 78 97 19 1l (S)-2l 76 98 20 1m (S)-2m 79 97

[0147] NMR data of (S)-2b:

[0148] 1 H NMR(400MHz,Chloroform-d)δ7.66(s,2H),6.99(s,2H),6.80(s,2H),6.54(d,J=2 .0Hz,2H),3.37-2.95(m,4H),2.54(s,6H),2.34-2.28(m,2H),2.14-2.08(m,2H). 1313C NMR (100 MHz, Chloroform-d) δ 134.2, 132.4, 131.2, 124.3, 121.9, 117.7, 116.8, 108.0, 77.3, 77.0, 76.7, 36.7, 35.1, 24.6, 22.2.

[0149] HRMS (ESI) Calcd for C 23 H 22 N2 + [M + H] + 327.1856; Found: 327.1851.

[0150] (S)-2 c 13C NMR data:

[0151] 1 1H NMR (400 MHz, Chloroform-d) δ 7.71 (s, 2H), 7.02 (s, 2H), 6.81 (s, 2H), 6.62 - 6.61 (m, 2H), 3.17 - 2.93 (m, 4H), 2.80 (q, J = 7.6 Hz, 4H), 2.35 - 2.28 (m, 2H), 2.15 - 2.08 (m, 2H), 1.34 (t, J = 7.6 Hz, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 139.3, 134.2, 131.2, 124.6, 122.0, 117.0, 116.7, 106.8, 77.3, 77.00, 76.7, 36.7, 35.1, 29.7, 24.7, 16.7.

[0152] HRMS (ESI) Calcd for C 25 H 27 N2 + [M + H] + 355.2169; Found: 355.2163.

[0153] (S)-2d's NMR data:

[0154] 1 1H NMR (400 MHz, Acetone-d6) δ 9.94 (s, 2H), 7.71 - 7.62 (m, 4H), 7.40 (s, 2H), 7.20 - 7.13 (m, 4H), 7.10 (s, 2H), 6.80 (d, J = 2.0 Hz, 2H), 3.28 - 3.04 (m, 4H), 2.34 - 2.28 (m, 2H), 2.14 - 2.08 (m, 2H). 13C NMR(100MHz,Acetone-d6)δ206.4,164.1,161.7,141.0(d,J CF =3.0Hz),135.9,135.7,132.4,130.0,129.9,127.3,122.4,119.8,116.4,116.2(d,J CF =6.0Hz),108.1,38.0,36.3,30.6,30.4,30.2,30.0,29.8,29.6,29.4,25.7. 19 F NMR(376MHz,Acetone-d6)δ-119.20.

[0155] HRMS(ESI)Calcd for C 33 H 25 F2N2 + [M+H] + 487.1980; Found:487.1972.

[0156] NMR data of (S)-2e:

[0157] . 1 H NMR (400MHz, DMSO-d6) δ10.60(s,2H),7.56(d,J=8.8Hz,4H),7.28(s,2H),7.02(s,2H),6.98(d,J=8.8 Hz,4H),6.68(d,J=1.6Hz,2H),3.77(s,6H),3.25-3.02(m,4H),2.23-2.17(m,2H),2.03-1.98(m,2H). 13 C NMR(100MHz,DMSO-d6)δ158.5,135.7,134.8,134.8,131.2,128.4,125.9,121.0,118.9 ,115.0,114.7,106.8,55.6,40.6,40.4,40.2,40.0,39.8,39.6,39.4,37.3,35.2,25.0.

[0158] HRMS(ESI)Calcd for C 35 H 31 N2O2 + [M+H] + 511.2380; Found:511.2377.

[0159] NMR data of (S)-2f:

[0160] 1 1H NMR (400 MHz, Chloroform-d) δ 7.85 (s, 2H), 7.61 (d, J = 8.6 Hz, 4H), 7.48 (d, J = 8.6 Hz, 4H), 7.40 (s, 2H), 7.21 (s, 2H), 6.70 - 6.72 (d, J = 2.0 Hz, 2H), 3.20 - 3.11 (m, 4H), 2.41 - 2.36 (m, 2H), 2.22 - 2.16 (m, 2H), 1.39 (s, 18H). 13 13C NMR (101 MHz, Chloroform-d) δ 149.3, 140.3, 136.6, 134.4, 131.5, 127.3, 125.7, 125.5, 122.1, 118.1, 116.3, 106.9, 77.3, 77.0, 76.7, 36.7, 35.2, 34.5, 31.4, 24.8.

[0161] HRMS (ESI) Calcd for C 41 H 43 N2 + [M + H] + 563.3421; Found: 563.3413.

[0162] (S)-2g NMR data:

[0163] 1 1H NMR (400 MHz, Chloroform-d) δ 7.84 (s, 2H), 7.39 (s, 2H), 7.29 (s, 4H), 7.20 (s, 2H), 6.99 (s, 2H), 6.71 (d, J = 1.6 Hz, 2H), 3.24 - 3.07 (m, 4H), 2.41 (s, 12H), 2.40 - 2.37 (m, 2H), 2.22 - 2.16 (m, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 143.2, 138.0, 136.9, 134.3, 131.5, 128.1, 125.8, 128.6, 122.0, 118.1, 116.3, 107.0, 77.3, 77.0, 76.7, 36.7, 35.1, 24.8, 21.5.

[0164] HRMS (ESI) Calcd for C 37 H 35 N2 + [M + H] + 507.2795; Found: 507.2789.

[0165] (S)-2h NMR data:

[0166] 1 H NMR (400 MHz, Chloroform-d) δ 7.66 (s, 1H), 7.57 (s, 1H), 7.21 - 7.16 (m, 2H), 7.02 (s, 1H), 6.97 (d, J = 6.4 Hz, 1H), 6.87 (s, 1H), 6.62 (d, J = 1.6 Hz, 1H), 6.54 (d, J = 1.6 Hz, 1H), 3.17 - 3.01 (m, 4H), 2.83 (q, J = 8.0 Hz, 2H), 2.38 - 2.29 (m, 2H), 2.17 - 2.11 (m, 2H), 1.37 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, Chloroform-d) δ 139.4, 134.2, 133.8, 131.6, 131.2, 126.4, 124.6, 122.5, 122.1, 121.9, 117.5, 117.0, 116.7, 115.9, 108.0, 106.9, 77.3, 77.0, 76.7, 36.7, 36.5, 35.1, 29.7, 24.7, 24.7, 16.7.

[0167] HRMS (ESI) Calcd for C 23 H 23 N2 + [M + H] + 327.1856; Found: 327.1852.

[0168] (S)-2i NMR data:

[0169] 1 H NMR (400 MHz, Chloroform-d) δ 7.77 - 7.70 (m, 2H), 7.28 (s, 1H), 7.22 - 7.18 (m, 2H), 7.17 - 7.10 (m, 3H), 7.01 - 6.96 (m, 1H), 6.91 (d, J = 8.0 Hz, 1H), 6.68 - 6.60 (m, 2H), 6.02 (s, 2H), 3.21 - 3.04 (m, 4H), 2.38 - 2.33 (m, 2H), 2.20 – 2.13 (m, 2H). 13C NMR(100MHz,Chloroform-d)δ147.9,146.4,137.7,136.4,134.3,133.9,131.6,131.5,126.3,125.6,122.5,122.0,122. 0,120.9,118.1,117.5,116.1,116.0,108.4,108.2,108.1,106.8,101.0,77.3,77.0,76.7,36.7,36.5,35.1,24.8,24.7.

[0170] HRMS(ESI)Calcd for C 28 H 23 N2O2 + [M+H] + 419.1754; Found:419.1748.

[0171] NMR data of (S)-2j:

[0172] 1 H NMR(400MHz,Chloroform-d)δ7.67(s,2H),7.63(d,J=8.4Hz,2H),7.51(d,J=8.4Hz,2H),7.36(s,1H),7.25-7.17(m, 3H), 6.99 (d, J = 7.6Hz, 1H), 6.60-6.63 (m, 2H), 3.23-3.06 (m, 4H), 2.40-2.33 (m, 2H), 2.21-2.13 (m, 2H), 1.43 (s, 9H). 13 C NMR(101MHz,Chloroform-d)δ149.3,140.3,136.5,134.3,133.9,131.5,127.2,126.3,125.66,125.6,122.5,122 .0,121.9,118.07,117.6,116.2,115.9,108.1,106.9,77.3,77.0,76.7,36.7,36.6,35.1,34.5,31.4,24.8,24.7.

[0173] HRMS(ESI)Calcd for C 31 H 31 N2 + [M+H] + 431.2482; Found:431.2471

[0174] NMR data of (S)-2k:

[0175] 1 1H NMR (400 MHz, Acetone-d6) δ 9.84 (s, 1H), 9.71 (s, 1H), 7.58 (d, J = 7.6 Hz, 2H), 7.38 - 7.32 (m, 3H), 7.10 (d, J = 8.0 Hz, 1H), 7.04 (s, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.74 (d, J = 7.2 Hz, 1H), 6.71 (d, J = 2.0 Hz, 1H), 6.66 (d, J = 2.4 Hz, 1H), 3.06 - 2.92 (m, 4H), 2.23 - 2.16 (m, 2H), 2.03 - 1.98 (m, 2H). 13 13C NMR (100 MHz, Acetone-d6) δ 205.0, 141.8, 134.6, 134.0, 133.7, 131.1, 131.0, 130.3, 128.3, 128.1, 126.8, 126.1, 126.0, 121.5, 121.0, 120.7, 118.5, 117.3, 114.8, 114.5, 107.8, 106.6, 36.5, 36.4, 34.7, 29.1, 28.9, 28.7, 28.5, 28.3, 28.1, 28.0, 24.2, 24.1.

[0176] HRMS (ESI) Calcd for C 27 H 21 ClN2 + [M + H] + 409.1466; Found: 409.1457.

[0177] NMR data of (S)-2l:

[0178] 1 1H NMR (400 MHz, Chloroform-d) δ 8.11 (s, 1H), 7.93 - 7.82 (m, 4H), 7.76 (d, J = 8.4 Hz, 2H), 7.54 - 7.46 (m, 3H), 7.36 (s, 1H), 7.22 - 7.18 (m, 2H), 6.98 (t, J = 4.4 Hz, 1H), 6.68 (d, J = 2.0 Hz, 2H), 3.24 - 3.06 (m, 4H), 2.43 - 2.35 (m, 2H), 2.22 - 2.14 (m, 2H). 1313C NMR (100 MHz, Chloroform-d) δ 140.5, 136.4, 134.4, 133.9, 133.8, 132.2, 131.8, 131.5, 128.1, 128.1, 127.6, 126.5, 126.3, 126.1, 125.9, 125.8, 125.5, 122.5, 122.1, 121.9, 118.4, 117.6, 116.4, 116.0, 108.1, 107.4, 77.3, 77.0, 76.7, 36.7, 36.6, 35.1, 24.8, 24.7.

[0179] HRMS (ESI) Calcd for C 31 H 25 N2 + [M + H] + 425.2012; Found: 425.2002.

[0180] (S)-2m NMR data:

[0181] 1 1H NMR (400 MHz, Methylene Chloride-d2) δ 8.00 - 7.90 (m, 2H), 7.85 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.60 - 7.54 (m, 2H), 7.45 - 7.27 (m, 4H), 7.22 - 7.15 (m, 2H), 6.95 (d, J = 4.0 Hz, 1H), 6.72 (d, J = 2.4 Hz, 1H), 6.68 (d, J = 2.0 Hz, 1H), 3.21 - 3.04 (m, 4H), 2.36 - 2.29 (m, 2H), 2.18 - 2.12 (m, 2H). 13 13C NMR (100 MHz, Methylene Chloride-d2) δ 147.4, 141.9, 139.9, 134.9, 134.7, 132.8, 132.2, 129.7, 127.7, 127.1, 125.2, 124.6, 123.9, 123.3, 123.1, 122.8, 122.5, 119.8, 118.9, 118.3, 116.7, 115.9, 108.8, 107.3, 54.7, 54.5, 54.2, 53.9, 53.7, 37.5, 35.8, 25.4.

[0182] HRMS (ESI) Calcd for C 29 H 23 N2S + [M + H]+ 431.1576; Found:431.1572.

[0183] Embodiment 3:

[0184] 0.2 mmol each of 1n, 1aa, 1ab and 1p were mixed with catalyst (R)-C4 (0.02 mmol), trichloroethane (20 ml) and MgSO4 (200 mg) respectively. The reaction vessel was sealed and heated to 90°C with stirring for 96 hours. The yield% and ee% of (S)-2n, (S)-2aa, (S)-2ab and (S)-2p were measured.

[0185]

[0186]

[0187]

[0188] NMR data of (S)-2n:

[0189] 1 H NMR (400MHz, Chloroform-d) δ7.88 (s, 2H), 7.44 (d, J = 8.4Hz, 4H), 7.31-7.27 (m, 8H), 6.80 (d, J = 2. 0Hz,2H),3.28-3.20(m,2H),3.13-3.07(m,2H),2.45(s,6H),2.36-2.30(m,2H),2.18-2.12(m,2H). 13 C NMR(100MHz,Chloroform-d)δ138.5,135.7,133.3,129.9,129.5,128.7,128.4 ,126.5,124.6,122.8,118.1,108.3,77.3,77.0,76.7,36.7,34.4,24.0,21.1.

[0190] HRMS(ESI)Calcd for C 35 H 31 N2O2 + [M+H] + 511.2380; Found:511.2377.

[0191] Embodiment 4:

[0192]

[0193] 1ac (0.05 mmol) was mixed with catalyst (S)-C9 (0.005 mmol) and trichloroethane (5 ml), the reaction vessel was sealed, and heated to 50 °C for 96 hours to obtain 2ac (48 yield%, 61 ee%, where * indicates the carbon chiral center)

[0194] 1 HNMR(400MHz,Chloroform-d)δ7.79(s,2H),7.22-7.18(m,2H),7.09(d,J=8.2Hz,1H),6.98-6.95(m,2H),6.82(d,J=8.3Hz,1H), 6.67-6.63(m,1H),3.57-3.38(m,2H),3.15-3.07(m,2H),2.53(s,3H),2.50-2.39(m,2H),2.25-2.18(m,1H),2.10-2.05(m,1H). 13 CNMR(100MHz,Chloroform-d)δ141.6,136.1,134.5,133.9,131.8,127.0,124.7,122.6,122.4,121 .9,118.1,117.3,115.9,111.8,1094,108.0,77.3,77.0,76.7,47.2,41.2,37.0,28.9,25.9,11.6.

[0195] Embodiment 5:

[0196]

[0197] (S)-2a (2 mmol, 99% enantiomeric excess) and [RuCl2(p-cymene)] (0.1 mmol, 5 mol%) were added to a Schlenk flask with a magnetic stirring bar. The Schlenk flask was sealed with a rubber septum, then evacuated and backfilled with argon. Toluene (20 mL) and diethylsilane (Et2SiH2, 20 mmol, 10.0 equivalents) were added to the septum via a syringe, and the Schlenk flask was sealed. The reaction was stirred at 120 °C under argon atmosphere for 36 hours and then cooled to room temperature. The mixture was concentrated under reduced pressure. THF (10 mL),

[0198] [Ir(COD)Cl]2 (0.1 mmol, 5 mol%), dtppy (0.2 mmol, 10 mol%), (Bpin)2 (8 mmol, 4.0 equivalents) and HBpin (0.4 mmol, 0.4 equivalents). The mixture was heated to 80°C and stirred for 5 hours.

[0199] The mixture was then cooled to room temperature, and an aqueous sodium acetate solution (10 mL, 3.0 M) was added and stirred for 12 hours. The reaction mixture was extracted with ethyl acetate (20 mL × 3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain the pure product (S)-2o.

[0200]

[0201] (S)-2o (0.2 mmol, 99% enantiomeric excess), Pd(PPh3)4 (0.01 mmol, 5 mol%), ArBr (3.0 equiv.) and potassium carbonate (1.0 mmol, 5.0 equiv.) were added to a Schlenk flask with a magnetic stirring bar. The Schlenk flask was sealed with a rubber septum, then evacuated and backfilled with argon (repeated three times). THF (1 mL) and water (0.2 mL) were added to the septum via a syringe under argon atmosphere. The solution was heated to 80 °C and stirred for 12 h. The reaction mixture was extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain the products (S)-2p, (S)-2q, and (S)-2r (wherein (S)-2p, (S)-2q, and (S)-2r respectively use the corresponding ArBr type bromides).

[0202] NMR data of (S)-2o:

[0203] 1 H NMR(400MHz,Chloroform-d)δ8.74(s,2H),7.65(d,J=7.2Hz,2H),6.97(d,J=7.2Hz,2H),6. 76(d,J=2.0Hz,2H),3.18-3.02(m,4H),2.36-2.29(m,2H),2.18-2.12(m,2H),1.39(s,24H). 13 C NMR (100MHz, Chloroform-d) δ139.1,135.8,129.9,125.3,121.7,117.4,115.9,83.5,77.3,77.0,76.7,36.8,35.1,25.1,24.9.

[0204] HRMS(ESI)Calcd for C 33 H 41 B2N2O4 + [M+H] +551.3247; Found: 551.3241.

[0205] (S)-2p NMR data:

[0206] 1 H NMR (400 MHz, Chloroform-d) δ 8.14 (s, 2H), 7.31 (s, 4H), 7.26 - 7.24 (m, 2H), 7.06 - 7.02 (m, 4H), 6.73 (d, J = 2.1 Hz, 2H), 3.25 - 3.18 (m, 2H), 3.14 - 3.07 (m, 2H), 2.43 (s, 12H), 2.41 - 2.35 (m, 2H), 2.23 - 2.17 (m, 2H). 13 C NMR (100 MHz, Chloroform-d) δ 139.4, 138.6, 131.8, 130.8, 128.7, 126.6, 125.7, 123.1, 122.5, 122.2, 117.8, 116.7, 77.3, 77.0, 76.7, 36.7, 35.0, 24.7, 21.5.

[0207] HRMS (ESI) Calcd for C 37 H 35 N2 + [M + H] + 507.2795; Found: 507.2788.

[0208] (S)-2q NMR data:

[0209] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 - 8.06 (m, 6H), 7.91 (s, 2H), 7.29 (d, J = 7.3 Hz, 2H), 7.12 (d, J = 7.6 Hz, 2H), 6.82 (d, J = 2.0 Hz, 2H), 3.29 - 3.11 (m, 4H), 2.45 - 2.39 (m, 2H), 2.26 - 2.21 (m, 2H). 13 C NMR (100 MHz, Chloroform-d) δ 141.8, 132.9, 132.8, 132.6, 132.3, 131.9, 131.4, 127.4, 127.2, 124.7, 123.0, 122.8, 122.0, 120.7, 120.7, 120.6, 119.9, 119.3, 118.5, 117.3, 77.3, 77.0, 76.7, 36.5, 35.0, 24.7. 19F NMR(376MHz,Chloroform-d)δ-62.76.

[0210] HRMS(ESI)Calcd for C 37 H 22 F 12 N2 + [M+H] + 723.1664; Found:723.1647.

[0211] NMR data of (S)-2r:

[0212] 1 H NMR(400MHz,Chloroform-d)δ7.95-7.81(m,6H),7.67-7.46(m,8H),7.42-7.31(m,2H),7.24(d,J=7.2Hz,2H ),7.08(d,J=7.2Hz,2H),6.72(s,1H),6.60(s,1H),3.32-3.10(m,4H),2.49-2.39(m,2H),2.31–2.21(m,2H). 13 C NMR(100MHz,Chloroform-d)δ137.0,133.9,133.0,131.6,131.1,128.4,127.7,127.5,1 26.2,126.2,126.1,125.9,125.8,124.1,122.2,121.3,117.8,116.3,36.7,35.1,24.8.

[0213] HRMS(ESI)Calcd for C 41 H 31 N2 + [M+H] + 551.2482; Found:551.2470.

[0214] Embodiment 6:

[0215]

[0216] Compound 2a (0.5 mmol, 99% enantiomeric excess) was dissolved in a mixture of NMP (2 mL), and a portion of tBuOK solution (1.05 mmol, 3.0 equivalents) dissolved in NMP (2 mL) was slowly added dropwise. After stirring for 5 minutes, O-(diphenylphosphinyl)hydroxylamine (1.5 mmol, 3.0 equivalents) was added. The resulting mixture was stirred at room temperature for 1 hour. The reaction was then quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain compound 3.

[0217] NMR data of compound 3:

[0218] 1 H NMR(400MHz,Chloroform-d)δ7.25-7.16(m,4H),6.95-6.88(m,2H),6.62(s,2H),4.66(s,4H),3.17-3.01(m,4H),2.33-2.26(m,2H),2.13-2.07(m,2H). 13 C NMR (100MHz, Chloroform-d) δ134.8,131.4,124.6,123.1,122.6,118.9,115.8,105.6,77.3,77.0,76.7,36.6,34.4,24.6.

[0219] HRMS(ESI)Calcd for C 21 H 21 N4 + [M+H] + 329.1761; Found:329.1753.

[0220] Compound 3 (0.2 mmol) was dissolved in a mixture of acetonitrile (2 mL), and a solution of 3,5-bis(trifluoromethyl)phenylisothiocyanate (0.4 mmol, 2.0 equivalents) was slowly added dropwise, and stirred at room temperature for 12 hours until TLC showed that the reaction was complete. The solvent was then removed under reduced pressure, and purified by silica gel column chromatography to obtain compound 4.

[0221] NMR data of compound 4:

[0222] 1H NMR (400MHz, Acetone-d6) δ10.16(s,2H),9.79(s,2H),8.22(s,4H),7.78(s,2H),7 .19(d,J=3.6Hz,4H),6.95(t,J=4.0Hz,4H),3.16-2.98(m,4H),2.29-2.05(m,4H). 13 C NMR (100MHz, Acetone-d6) δ205.0,182.1,140.6,135.2,130.9,130.6,130.3,130.0,127.0,125.0,124.3,123.5,122. 1,121.6,121.3,118.9,118.1,117.4,114.9,107.9,106.3,35.5,34.2,29.2,29.0,28.8,28.6,28.4,28.2,28.0,23.6. 19 F NMR(376MHz,Acetone-d6)δ-63.48.

[0223] HRMS(ESI)Calcd for C 39 H 27 F 12 N6S2 + [M+H] + 871.1542; Found:871.1502.

[0224] Embodiment 7:

[0225]

[0226] 2a (0.2 mmol, 99% enantiomeric excess) was dissolved in a mixture of dichloromethane (5 mL), and NBS (0.4 mmol, 2.0 equivalents) was added at -40 °C. The solution was stirred at -40 °C for 10 minutes until TLC showed that the reaction was complete. The reaction mixture was extracted with dichloromethane (10 mL × 3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure, and then purified by silica gel column chromatography to obtain 7.

[0227] NMR data of compound 7:

[0228] 1H NMR (400MHz, Acetone-d6) δ10.32(s,2H),7.13(d,J=8.0Hz,2H),7.05(t,J=7.6Hz,2H),6.83 (d,J=7.2,2H),3.13-3.05(m,2H),2.97-2.87(m,2H),2.35-2.28(m,2H),2.21-2.14(m,2H). 13 C NMR (100MHz, Acetone-d6) δ205.0,134.5,129.8,127.1,122.0,115.9,115.7,107.3,102.8,35.3,34.7,24.0.

[0229] HRMS(ESI)Calcd for C 21 H 17 Br2N2 + [M+H] + 454.9753; Found:454.9740.

[0230] Embodiment 8:

[0231]

[0232] 2a (0.5 mmol, 99% enantiomeric excess) was dissolved in a mixture of anhydrous DMSO (5 mL) and KOH (1.5 mmol, 3.0 equivalents) was added. After stirring for 10 minutes, iodomethane (1.2 mmol, 2.4 equivalents) was slowly added dropwise. The resulting mixture was warmed to room temperature and stirred for 5 hours. The reaction was then quenched with aqueous ammonium chloride and extracted with ether. The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain 2ab.

[0233] NMR data of compound 2ab:

[0234] 1 H NMR(400MHz,Chloroform-d)δ7.21(t,J=8.0Hz,2H),7.14(d,J=8.4Hz,2H),6.93(d,J=7.2H z,2H),6.55(s,2H),3.72(s,6H),3.14-3.04(m,4H),2.38-2.31(m,2H),2.15-2.09(m,2H). 13C NMR (101MHz, Chloroform-d) δ134.9,131.7,126.6,122.2,122.1,121.1,115.3,106.3,77.3,77.0,76.7,36.8,35.0,32.7,24.8.

[0235] HRMS(ESI)Calcd for C 23 H 23 N2 + [M+H] + 327.1856; Found:327.1848.

[0236] 2ab (0.2 mmol) was dissolved in a mixture of toluene (2 mL), and diphenyl disulfide (0.6 mmol, 3.0 equivalents) and copper iodide (0.04 mmol, 0.2 equivalents) were added. The reaction solution was stirred at 120 ° C for 12 hours and then cooled to room temperature. The mixture was extracted with ethyl acetate, and the combined organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain compound 8.

[0237] NMR data of compound 8:

[0238] 1 H NMR(400MHz,Chloroform-d)δ7.26(t,J=7.2Hz,2H),7.13-7.06(m,6H),7.03-6.97(m,2H),6.91(d,J=7 .0Hz,2H),6.59(d,J=7.2Hz,4H),3.43(s,6H),3.13-3.05(m,2H),2.94-2.80(m,4H),2.10-2.04(m,2H). 13 C NMR(100MHz,Chloroform-d)δ138.5,136.3,132.7,128.6,126.8,126.6,125.0 ,124.6,123.5,120.2,115.7,106.6,77.3,77.0,76.7,37.1,36.4,29.4,24.6.

[0239] HRMS(ESI)Calcd for C 35 H 31 N2S2 + [M+H] + 543.1923; Found:543.1910.

[0240] Embodiment 9:

[0241]

[0242] 2a (0.2 mmol, 99% enantiomeric excess) and DMAP (0.1 mmol, 0.5 equivalents) were dissolved in dry dichloromethane (1 mL), and triethylamine (1.0 mmol, 5.0 equivalents) and 2-pyridinecarbonyl chloride (0.5 mmol, 2.5 equivalents) were slowly added dropwise at 0 ° C under argon protection. The mixture was stirred at 60 ° C for 6 hours, and then the reaction was quenched with saturated ammonium chloride solution. The mixture was extracted with ethyl acetate, and the combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, and then purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain compound 5.

[0243] NMR data of compound 5:

[0244] 1 H NMR(400MHz,Chloroform-d)δ8.58(d,J=1.2Hz,2H),8.25-8.05(m,2H),8.00(d,J=7.8Hz,2H),7.86(t,J=6.4Hz,2H),7.55(s, 2H),7.46-7.40(m,2H),7.33(t,J=7.2Hz,2H),7.15(d,J=7.2Hz,2H),3.15-2.99(m,4H),2.32-2.25(m,2H),2.20-2.13(m,2H).

[0245] 13 C NMR(100MHz,Chloroform-d)δ165.8,152.3,148.5,137.2,135.0,131.1,128.8,12 6.5,126.0,125.5,125.4,121.6,121.6,114.5,77.3,77.0,76.7,35.2,34.7,24.1.

[0246] HRMS(ESI)Calcd for C 33 H 25 N4O2 + [M+H] + 509.1972; Found:509.1958.

[0247] Embodiment 10:

[0248]

[0249] 2a (2.0 mmol, 99% enantiomeric excess), CuI (0.2 mmol, 10 mol%), KOH (10.0 mmol, 5.0 equivalents) and toluene (10 mL) were added to a Schlenk flask with a magnetic stirring bar, followed by 2-bromopyridine (5.0 mmol, 2.5 equivalents). The Schlenk flask was sealed with a rubber septum, then evacuated and backfilled with argon (repeated three times). The solution was stirred at 110 ° C for 24 hours. After the reaction was completed, the mixture was cooled to room temperature, the organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated and purified by silica gel column chromatography (CH2Cl2 / MeOH) to obtain compound 6.

[0250] NMR data of compound 6:

[0251] 1 H NMR(400MHz,Chloroform-d)δ8.49–8.45(m,2H),8.04(d,J=8.4Hz,2H),7.74-7.69(m,2H),7.40(d,J=9.6Hz,2H) ,7.34(s,2H),7.30(t,J=7.6Hz,2H),7.08-7.03(m,4H),3.21-3.09(m,4H),2.48-2.41(m,2H),2.24-2.13(m,2H). 13 C NMR(100MHz,Chloroform-d)δ152.9,148.7,138.1,133.5,131.7,128.7,124.4 ,123.9,119.2,119.1,118.3,113.3,111.1,77.3,77.0,76.7,36.0,34.9,24.6.

[0252] HRMS(ESI)Calcd for C 33 H 29 N4O2 + [M+H] + 453.2074; Found 453.2062.

[0253] Embodiment 11:

[0254]

[0255] Compound 6 (1.0 mmol, 99% enantiomeric excess), Mn(CO)5Br (0.05 mmol, 5 mol%), paraformaldehyde (6.0 mmol, 6.0 equivalents) and sodium acetate (0.05 mmol, 5 mol%) were added to a Schlenk flask with a magnetic stirring bar. The Schlenk flask was sealed with a rubber septum, then evacuated and backfilled with argon (repeated three times). 1,4-Dioxane (5 mL) was added to the septum via a syringe, and the Schlenk flask was sealed. The reaction was stirred at 90 ° C for 48 hours under an argon atmosphere and then cooled to room temperature. The reaction mixture was extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain compound 10.

[0256] NMR data of compound 10:

[0257] 1 H NMR (400MHz, Chloroform-d) δ8.53-8.48(m,2H),7.94-7.88(m,2H),7.78(d,J=8. 0Hz,2H),7.39(d,J=8.2Hz,2H),7.26-7.22(m,2H),7.01(d,J=7.1Hz,2H),6.15(t, J=6.4Hz,2H),4.51(dd,J=13.2,6.0Hz,2H),4.38(dd,J=13.2,6.0Hz,2H),3.20-3 .12(m,2H),3.03-2.97(m,2H),2.43-2.37(m,2H),2.26-2.18(m,2H),1.57(s,2H). 13 C NMR(100MHz,Chloroform-d)δ151.9,148.4,138.9,134.6,133.9,132.0,127.4,12 3.8,121.1,121.0,119.3,118.0,108.1,77.3,77.0,76.7,54.1,36.4,35.9,24.6.

[0258] HRMS(ESI)Calcd for C 33 H 29 N4O2 + [M+H] + 513.2285; Found:513.2271.

[0259] Embodiment 12:

[0260]

[0261] Compound 6 (0.2 mmol, 99% enantiomeric excess), Rh(Cp*)Cl2 (0.02 mmol, 10 mol%) and silver hexafluoroantimonate (0.04 mmol, 0.2 equivalents) were added to a Schlenk flask with a magnetic stirring bar. The Schlenk flask was sealed with a rubber septum, then evacuated and backfilled with argon (repeated three times). Toluene (1 mL) and methanol (1 mL) were added to the septum via a syringe, and the Schlenk flask was sealed. The reaction was stirred at 80 ° C for 24 hours under an argon atmosphere and then cooled to room temperature. The reaction mixture was extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain compound 9.

[0262] NMR data of compound 9:

[0263] 1 H NMR(400MHz,Chloroform-d)δ8.60(d,J=4.8Hz,2H),7.81-7.73(m,2H),7.67(d,J=8.0Hz,2H),7.51(d,J=8.0Hz,2H ),7.21-7.15(m,4H),7.03(d,J=7.2Hz,2H),3.21(s,6H),3.13-3.10(m,4H),2.73-2.66(m,2H),2.15-2.08(m,2H). 13 C NMR(100MHz,Chloroform-d)δ151.2,148.7,145.6,138.0,131.2,130.0,125.6,12 2.7,120.4,118.4,118.2,109.1,105.1,77.3,77.0,76.7,62.3,35.9,34.7,24.7.

[0264] HRMS(ESI)Calcd for C 33 H 29 N4O2 + [M+H] + 513.2285; Found:513.2275.

[0265] Embodiment 13:

[0266]

[0267] Compound 10 (0.2 mmol, 99% enantiomeric excess) was dissolved in DMSO (5 mL), and IBX (2.0 mmol, 10.0 equivalents) was added. Stir at room temperature for 12 hours. The reaction was quenched with aqueous sodium bicarbonate solution, and then extracted with ethyl acetate (10 mL × 3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain compound 11.

[0268] NMR data of compound 11:

[0269] 1 H NMR(400MHz,Chloroform-d)δ9.78(s,2H),8.62-8.58(m,2H),7.87-7.82(m,2H),7.42-7. 31(m,8H),7.06(d,J=6.8Hz,2H),3.30-3.22(m,2H),3.14-3.08(m,2H),2.62-2.49(m,4H). 13 C NMR(100MHz,Chloroform-d)δ180.1,151.3,148.9,138.2,138.0,136.8,133.6,12 9.1,128.9,125.6,122.3,121.5,118.7,109.3,77.3,77.0,76.7,37.6,36.8,24.5.

[0270] HRMS(ESI)Calcd for C 33 H 25 N4O2 + [M+H] + 509.1972; Found:509.1961

[0271] Embodiment 14:

[0272]

[0273] Compound 10 (0.2 mmol, 99% enantiomeric excess) was dissolved in dichloromethane (2 mL), SOCl2 (0.2 mmol, 1.0 equivalent) was added in batches, and the reaction was stirred. The reaction was stirred for 1 hour. The reaction was quenched with aqueous sodium bicarbonate solution and extracted with dichloromethane. The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain compound 12.

[0274] NMR data of compound 12:

[0275] 1H NMR(400MHz,Chloroform-d)δ8.71-8.68(m,2H),7.92-7.87(m,2H),7.66(d,J=8.0Hz,2H),7.55(d,J=8.0Hz,2H),7.34-7.24(m,4H),7.06(d ,J=7.2Hz,2H),4.94(d,J=13.6Hz,2H),4.77(d,J=13.6Hz,2H),3.45-3.36(m,2H),3.07-2.95(m,2H),2.62-2.50(m,2H),2.13-2.05(m,2H). 13 C NMR(100MHz,Chloroform-d)δ151.5,149.4,138.4,135.4,131.5,126.5,125.8,12 4.9,124.3,121.3,120.2,118.1,109.3,77.3,77.0,76.7,56.5,36.0,35.9,24.8.

[0276] HRMS(ESI)Calcd for C 33 H 27 N4O + [M+H] + 495.2179; Found:495.2164.

[0277] Embodiment 15:

[0278]

[0279] Compound 10 (0.5 mmol, 99% enantiomeric excess) and sodium iodide (3.0 mmol, 6.0 equivalents) were dissolved in acetonitrile (5 mL), phenylphosphine chloride (1.0 mmol, 2.0 equivalents) was added at 0°C, and the solution was stirred at 80°C for 6 hours. The reaction was quenched with aqueous sodium bicarbonate solution and then extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography (CH2Cl2 / methanol) to obtain pure product 13.

[0280] NMR data of compound 13:

[0281] 1H NMR(400MHz,Chloroform-d)δ8.52-8.50(m,1H),8.37-8.35(m,1H),7.98(d,J=8.0Hz,1H),7.91-7.87(m,1H),7.41-7.37(m,1H),7.34-7.27(m,2H),7.25-7.20(m,1H),7.20-7.12(m,2H),7.12-7.04(m,5H),7.04-6.97(m,3H),6.63(d,J=8.0Hz,1H),4.38-4.30(m,1H),4.10-3.85(m,3H),3.35-3.24(m,2H),3.08-2.98(m,2H),2.49-2.35(m,2H),2.24-2.15(m,2H).

[0282] 13 C NMR(100MHz,Chloroform-d)δ151.5,150.5,149.0,148.8,138.8,137.9,136.1,134.7,132.6,131.7,131.4,131.3,131.0,130.6,130.2,130.2,128.5,128.4,127.2,127.2,127.0,126.9,123.9,123.8,123.2,122.5,122.4,122.2,122.1,121.9,121.9,121.2,121.1,120.5,119.4,118.2,117.8,108.0,107.4,77.3,77.0,76.7,36.2,36.1,35.3,34.8,27.1,26.4,24.6,24.6,23.7,23.0. 31 P NMR(162MHz,Chloroform-d)δ31.15.

[0283] HRMS(ESI)Calcd for C 39 H 32 N4OP + [M+H] + 603.2308;Found:603.2293.

[0284] Compound 13 (0.2 mmol) was dissolved in anhydrous dichloromethane, and MeOTf (0.48 mmol, 2.4 equivalents) was slowly added dropwise at 0°C under an argon atmosphere. The solution was stirred at room temperature for 24 hours. Then the solvent was removed under reduced pressure. Sodium hydroxide (1.0 mL, 2.0 M) aqueous solution and methanol (1 mL) were added and stirred at 60°C for 12 hours. The reaction was quenched with aqueous ammonium chloride solution, and then extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Then it was purified by silica gel column chromatography (CH2Cl2 / methanol) to obtain compound 14.

[0285] NMR data of compound 14:

[0286] 1 H NMR(400MHz,DMSO-d6)δ10.87(s,1H),10.29(s,1H),7.55(t,J=5.6Hz,1H),7 .44-7.40(m,2H),7.34-7.29(m,2H),7.10(d,J=8.1Hz,1H),6.97(m,3H),6.7 4(d,J=6.8Hz,2H),3.80-3.74(m,1H),3.49-3.40(m,1H),3.18-3.10(m,3H), 3.06-2.98(m,1H),2.83-2.76(m,2H),2.18-2.09(m,2H),1.93–1.75(m,2H).

[0287] 13 C NMR (100MHz, DMSO-d6) δ134.3,133.7,133.6,132.8,132.3,131.4,131.3,130. 0,128.9,128.8,127.9(d,J=2.9Hz),127.7,122.8,122.8,122.5,122.4,117.7, 117.6,117.2,117.2,116.0,115.7,108.4,40.6,40.4,40.2,40.0,39.8,39.6, 39.4,36.2,35.6,35.5(d,J=3.2Hz),29.5,28.8,28.4,27.7,24.9(d,J=5.1Hz).

[0288] 31 P NMR (162 MHz, DMSO-d6) δ 30.01.

[0289] HRMS(ESI)Calcd for C 29 H26 N2OP + [M+H] + 449.1777; Found:449.1766.

[0290] Embodiment 16:

[0291]

[0292] (S)-7 (0.5 mmol, 99% enantiomeric excess) was dissolved in THF (5 mL) and NaH (1.5 mmol, 3.0 equivalents) was added. After stirring for 10 minutes, iodomethane (1.2 mmol, 2.4 equivalents) was slowly added dropwise. The resulting mixture was warmed to room temperature and stirred for 5 hours. The reaction was quenched with aqueous ammonium chloride and extracted with ether. The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain (S)-15.

[0293] NMR data of (S)-15:

[0294] 1 H NMR(400MHz,Chloroform-d)δ7.19(t,J=7.6Hz,2H),7.13(d,J=8.0Hz,2H),6.92(d,J=6.8Hz, 2H),3.73(s,6H),3.15-3.07(m,2H),2.98-2.92(m,2H),2.41-2.33(m,2H),2.23-2.18(m,2H). 13 C NMR (101MHz, Chloroform-d) δ135.2,130.7,126.6,122.2,116.2,116.0,108.2,106.3,77.3,77.0,76.7,35.8,34.6,31.2,24.5.

[0295] HRMS(ESI)Calcd for C 23 H 21 Br2N2 + [M+H] + 483.0066; Found:483.0054.

[0296] Compound (S)-15 (0.2 mmol, 99% enantiomeric excess), Pd(PPh3)4 (0.001 mmol, 5 mol%), potassium trifluoro(vinyl)borate (0.4 mmol, 2.0 equivalents) and cesium carbonate (0.8 mmol, 4.0 equivalents) were added to a Schlenk flask with a magnetic stirring bar. The Schlenk flask was sealed with a rubber septum, and then evacuated and backfilled with argon (repeated three times). THF (1 mL) and water (0.2 mL) were added to the septum via a syringe, and the Schlenk flask was sealed. The reaction was stirred at 90 °C under an argon atmosphere for 24 hours and then cooled to room temperature. The reaction mixture was extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain (S)-16.

[0297] Embodiment 17:

[0298]

[0299] (R)-2a (0.2 mmol, 99% enantiomeric excess) was dissolved in a mixture of dichloromethane (5 mL) and added at -40 °C.

[0300] NBS (0.4 mmol, 2.0 equivalents). The solution was stirred at -40 °C for 10 minutes until TLC showed the reaction was complete. The reaction mixture was extracted with dichloromethane (10 mL × 3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure, and then purified by silica gel column chromatography to obtain (R)-7.

[0301]

[0302] (R)-7 (0.5 mmol, 99% enantiomeric excess) was dissolved in THF (5 mL) and NaH (1.5 mmol, 3.0 equivalents) was added. After stirring for 10 minutes, iodomethane (1.2 mmol, 2.4 equivalents) was slowly added dropwise. The resulting mixture was warmed to room temperature and stirred for 5 hours. The reaction was quenched with aqueous ammonium chloride and extracted with ether. The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain (R)-15.

[0303] Compound (R)-15 (0.2 mmol, 99% enantiomeric excess), Pd(PPh3)4 (0.001 mmol, 5 mol%), potassium trifluoro(vinyl)borate (0.4 mmol, 2.0 equivalents) and cesium carbonate (0.8 mmol, 4.0 equivalents) were added to a Schlenk flask with a magnetic stirring bar. The Schlenk flask was sealed with a rubber septum, and then evacuated and backfilled with argon (repeated three times). THF (1 mL) and water (0.2 mL) were added to the septum via a syringe, and the Schlenk flask was sealed. The reaction was stirred at 90 °C under an argon atmosphere for 24 hours and then cooled to room temperature. The reaction mixture was extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. It was then purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain (R)-16.

[0304] Example 18: Fluorescence analysis

[0305] The UV-visible absorption spectra of (R)-16 and (S)-16 are basically overlapping, showing a broad absorption band between 300-500nm, with obvious peaks at 360, 420, 450 and 480nm, respectively. Under a 365nm light source. The emission spectra of (R)-16 and (S)-16 show multiple emission bands, with a maximum emission peak (λmax) at 530nm. In addition, in a CH2Cl2 solution in air, its lifetime is 9ns, confirming that it is a fluorescent molecule. More importantly, the enantiomers exhibit perfect mirror-image CPL spectra at the maximum emission peak of 510nm under 365nm excitation. The favorable photophysical properties of compounds (R)-16 and (S)-16 highlight the potential of helical bisindoles in optical material research.

[0306] The embodiments described above are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments can still be modified, or some of the technical features can be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application, and should be included in the protection scope of the present application.

Claims

1. A spirobisindole skeleton compound represented by formula (I): The Carbon represents a carbon atom; Said represents a single bond; The L1 part is The L2 part is Alternatively, the L2 portion is The carbon atom Carbon is in (R) configuration, or (S) configuration, or is an achiral carbon atom; The ' in L1 and L2 indicates a bond connected to the carbon atom Carbon; The R1, R 10 Each is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl; The R2 and R9 are each independently selected from H, alkyl, aryl, monocyclic heterocyclic group, alkoxy, and fused heterocyclic group; The R3 and R8 are each independently selected from H, an alkyl group, an aryl group, and a borate group; The R4 and R7 are each independently selected from H, alkyl, halogen, amino, carbonyl heterocyclic group, carbonyl alkyl, monocyclic heterocyclic group, condensed heterocyclic group; Said R5 and R6 are each independently selected from H, halogen, alkyl, alkylthio, alkoxy, aldehyde, carbonylalkyl; The R 11 Selected from H, C1-C8 alkyl; The hydrogen in the formula (I) is optionally replaced by D.

2. The compound of formula (I) according to claim 1, characterized in that , said R1, R 10 , R3, R8 are selected from monocyclic aromatic groups, naphthyl groups, and / or, R2, R9 are selected from monocyclic aromatic groups, condensed heterocyclic groups, and / or, R4, R7 are selected from amino groups, methyl groups, pyridine, furan groups, and / or, R5, R6 are selected from hydroxyethyl groups, bromine groups, -S-Ph groups.

3. The compound of formula (I) according to claim 1, characterized in that , the alkyl group is selected from C1 to C8 alkyl groups, the alkenyl group is selected from C2 to C8 alkenyl groups, the alkynyl group is selected from C2 to C8 alkynyl groups, and the cycloalkyl group is selected from C3 to C10 cycloalkyl groups.

4. The compound of formula (I) according to claim 1, characterized in that , The R1, R 10 Each independently selected from aryl, said R1, R 10 The optional H is R a Substitute, the R a Selected from alkyl; The R2 and R9 are independently selected from aryl, monocyclic heterocyclic group, condensed heterocyclic group, and the H on R2 and R9 is optionally replaced by R b Substitute, the R b Selected from alkyl, alkoxy, halogen; The R3 and R8 are each independently selected from aryl groups, and the H on the R3 and R8 is optionally replaced by R c Substitute, the R c is selected from alkyl groups, wherein R c The H on is optionally substituted by halogen; The R4 and R7 are each independently selected from amino groups, and the H on the R4 and R7 is optionally replaced by R d Substitute, the R d is selected from aminothioformyl, wherein the H on the aminothioformyl is optionally substituted by isothiocyanate; The R5 and R6 are each independently selected from an alkyl group, and the H on the R5 and R6 is optionally substituted by a hydroxyl group.

5. A compound of formula (I) according to any one of claims 1 to 4, characterized in that , said R5, R6 and the atoms to which they are connected together form a ring Ar, such as formula (II): The ring Ar is selected from a carbocyclic group, an aryl group, and a heterocyclic group.

6. The compound of formula (II) according to claim 5, characterized in that , the optional methylene group on the ring Ar is -O- or Substitute, the R e is selected from aryl, alkyl, cycloalkyl, monocyclic heterocyclic group, condensed heterocyclic group, and / or the ring Ar has at least one double bond.

7. A spiral bisindole skeleton compound, specifically: The carbon atom marked with "*" mentioned above may be in the (R) configuration, or in the (S) configuration, or may be an achiral carbon atom.

8. A method for synthesizing a spirobisindole skeleton compound represented by formula (I), comprising: The R 11 Selected from H, the compound of formula (III) is mixed with a catalyst Cat in an organic solvent to obtain a compound of formula (IV); or, The R 11 The compound of formula (III) is mixed with catalyst (S)-C9 in an organic solvent to obtain a compound of formula (V); The R1, R 10 Each is independently selected from H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C10 cycloalkyl, and aryl; The R2 and R9 are each independently selected from H, C1-C8 alkyl, aryl, monocyclic heterocyclic group, condensed heterocyclic group; The R3 and R8 are each independently selected from H, C1-C8 alkyl, borate group, and aryl group; The R4 and R7 are each independently selected from H, C1-C8 alkyl, amino, carbonyl heterocyclic group, carbonyl alkyl, monocyclic heterocyclic group, condensed heterocyclic group; the R5 and R6 are each independently selected from H, halogen, C1-C8 alkyl, alkylthio, alkoxy, aldehyde group, carbonyl alkyl: The catalyst Cat is selected from The carbon atom marked with "*" is in (S) configuration; Or, the catalyst Cat is selected from The carbon atom marked with "*" is of (R) configuration.

9. A compound of formula (III) having a structure such as The R1, R 10 Each is independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C10 cycloalkyl, and aryl; The R2 and R9 are each independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, aryl, monocyclic heterocyclic group, condensed heterocyclic group; The R3 and R8 are each independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, borate group, and aryl group; The R4 and R7 are each independently selected from H, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, amino, carbonyl heterocyclic group, carbonyl alkyl, monocyclic heterocyclic group, condensed heterocyclic group; The R5 and R6 are independently selected from H, halogen, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, alkylthio, alkoxy, aldehyde, and carbonyl alkyl.

10. Use of the spirobisindole skeleton compound according to any one of claims 1 to 7 in organic photoluminescent materials.

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