Tribenzo[b,f]azepine phosphoramidite ligand and its preparation method and application

Abstract

The present invention discloses a tribenzo[b,f]azepine phosphoramidite ligand, a preparation method thereof, and an application thereof. The structural formula thereof is shown in formula (I): In the tribenzo[b,f]azepine phosphoramidite ligand of the present invention, the N-terminal structure is an asymmetric benzoiminostilbene. The benzoiminostilbene makes the fused ring system at the N-terminal of the ligand larger, and the conjugated system and the π electron cloud are expanded. This not only increases the coordination ability of the metal and the ligand, but also has a certain steric hindrance effect, which not only helps to promote the occurrence of asymmetric reactions, but also can expand the scope of application of the ligand, making the ligand suitable for catalyzing a variety of different asymmetric reactions.

Description

Technical Field

[0001] The present invention belongs to the technical field of asymmetric catalysis, and in particular relates to a tribenzo[b,f]azepine phosphoramidite ligand, a preparation method and an application thereof. Background Art

[0002] Phosphoramidites They are currently recognized as a highly versatile and readily available class of chiral ligands suitable for asymmetric catalysis. Their modular structure enables the creation of ligand libraries and facilitates fine-tuning for specific catalytic reactions. Their molecular structure is characterized by the presence of a coordinating PN bond, which can coordinate with a variety of metals to form chiral species, thereby catalyzing asymmetric reactions. They have a wide range of applications and can induce the generation of a variety of chiral environments. Moreover, as the field continues to develop, their monodentate properties are also essential in combinatorial catalysis using mixed ligands.

[0003] Since 1996, Feringa et al. Angew. Chem., Int. Ed. 1996, 35 , 2374.) developed the first chiral phosphoramidite ligand (an axially chiral monodentate phosphorus ligand with C2 symmetry derived from BINOL), a large number of phosphoramidite ligands derived from the BINOL skeleton have been developed and applied.

[0004] Recently, due to the pioneering contributions of Zhou Qilin et al. and Birman et al. ( Tetrahedron: Asymmetry. 1999, 10 , 125−131; Tetrahedron: Asymmetry. 2002, 13 , 1363−1366; Acc. Chem. Res. 2008, 41 ,581−593; Acc. Chem. Res. 2012, 45 , 1365−1377.), SPINOL has become another superior chiral scaffold, whose rigid conformation and chemical robustness are the outstanding features that endow this structure and its variants with crucial properties for asymmetric catalysis, and the application of its scaffold in phosphoramidites has also been effectively developed.

[0005] While both BINOL and SPINOL are versatile, their properties and catalytic behaviors, including those of their phosphoramidite derivatives, are sometimes complementary. For example, BINOL-based catalysts sometimes exhibit superior catalytic activity, while SPINOL-based catalysts often exhibit superior asymmetric induction. Consequently, a dilemma arises when synergy between these two characteristics cannot be achieved.

[0006] Recently, Sun Jianwei et al. developed a new structure SPHENOL ( J. Am. Chem. Soc. 2021, 143 ,12445−12449.), which is a new skeleton that is expected to combine the advantages of BINOL and SPINOL skeletons. Its application has not been fully developed, so the SPHENOL skeleton can be introduced into phosphoramidite.

[0007] So far, the molecular skeleton of phosphoramidite ligand has undergone changes from BINOL, SPINOL, TADDOL to today's SPHENOL:

[0008]

[0009] Compared with the first three well-developed phosphoramidite skeletons, phosphoramidite ligands with the fourth skeleton (i.e., the SPHENOL bisphenol skeleton) have greater room for development. However, existing SPHENOL spirophosphoramidite ligands have the following shortcomings: (1) Most modifications to SPHENOL spirophosphoramidite ligands remain at the chiral control end of the bisphenol, while modifications to the aromatic ring at the N-terminus have not yet involved modifications to add condensed aromatic hydrocarbons; (2) The N-terminus of SPHENOL spirophosphoramidite ligands is generally symmetrical, and asymmetric structures are relatively rare. Summary of the Invention

[0010] The present invention aims to provide a tribenzo[b,f]azepine phosphoramidite ligand, a preparation method and an application thereof. The tribenzo[b,f]azepine phosphoramidite ligand has a novel structure and excellent asymmetric catalytic performance and chiral induction performance.

[0011] In order to achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0012] The tribenzo[b,f]azepine phosphoramidite ligand has a structural formula as shown in formula (I):

[0013] (Ⅰ).

[0014] In the tribenzo[b,f]azepine phosphoramidite ligand of the present invention, the N-terminal structure is an asymmetric benzoiminostilbene. The benzoiminostilbene makes the fused ring system at the N-terminus of the ligand larger, and the conjugated system and the π electron cloud are expanded. This not only increases the coordination ability between the metal and the ligand, but also has a certain steric hindrance effect, which not only helps to promote the occurrence of asymmetric reactions, but also can expand the scope of application of the ligand, making the ligand suitable for catalyzing a variety of different asymmetric reactions.

[0015] The present invention also provides a method for preparing the above-mentioned tribenzo[b,f]azepine phosphoramidite ligand, which comprises the following steps:

[0016] (1) Benzoimidostilbene was synthesized from 1-iodonaphthalene and o-bromoaniline via a palladium-catalyzed cross-coupling reaction under an inert atmosphere.

[0017] Wherein, the reaction system of step (1) further contains a base, a solvent catalyst and an additive, wherein the catalyst is selected from palladium acetate, the base is selected from cesium carbonate, and the additive is selected from triphenylphosphine;

[0018] In the reaction system, the equivalent ratio of 1-iodonaphthalene, o-bromoaniline, norbornene and cesium carbonate is 1:1:2:2, the content of triphenylphosphine is 8-10 mol%, and the content of palladium acetate is 4 mol%;

[0019] The solvent is selected from dichloromethane or tetrahydrofuran;

[0020] React at 120-150℃ for 45-55 hours;

[0021] (2) Under an inert atmosphere, the tribenzo[b,f]azepine phosphoramidite ligand is synthesized by a nucleophilic substitution reaction using benzoimidostilbene, a phosphorus donor and a SPHENOL bisphenol skeleton as raw materials;

[0022] Specifically, step (2) includes:

[0023] (a) A base, a solvent, and a phosphorus donor are mixed and uniformly mixed in an ice bath to obtain a solution A;

[0024] The base is used to remove the hydrogen from the benzoiminostilbene, so any base including triethylamine can be used in the present invention as long as it does not react with the substrate; the phosphorus donor includes phosphorus trichloride, which is used to accept the attack of the iminostilbene N anion to form an intermediate with an NP bond;

[0025] The solvent includes ultra-dry dichloromethane, tetrahydrofuran or other solvents that do not affect the reaction;

[0026] The equivalent ratio of triethylamine to SPHENOL bisphenol skeleton is (6-10):1, more preferably 8:1; the equivalent ratio of phosphorus trichloride to SPHENOL bisphenol skeleton is (1-2.5):1, more preferably 1.5:1;

[0027] (b) under an inert atmosphere, adding benzoimidostilbene to solution A, mixing in an ice bath, and stirring at 25-55° C. (more preferably 40-50° C.) overnight to obtain solution B;

[0028] Wherein, the equivalent ratio of benzoimidostilbene to SPHENOL bisphenol skeleton is (1-3):1, more preferably 1.5:1;

[0029] (c) Under an inert atmosphere, add the SPHENOL bisphenol skeleton to solution B, first react in an ice bath for 3-15 minutes (more preferably 3-5 minutes), and then react at room temperature for 4-5 hours to obtain the tribenzo[b,f]azepine phosphoramidite ligand.

[0030] The present invention also provides the use of the above-mentioned tribenzo[b,f]azepine phosphoramidite ligand in catalyzing the [4+2] cyclization reaction of indole alkynamine and o-benzylcyanophenyl borate; and, preferably, the content of the tribenzo[b,f]azepine phosphoramidite ligand in the reaction system is 10 mol%.

[0031] Under the catalysis of tribenzo[b,f]azepine phosphoramidite ligand and rhodium, the target product methyl1-(3-amino-2-phenylnaphthalen-1-yl)-1 H The yield of -indole-2-carboxylate reached 58% and the ee value reached 60%, indicating that the tribenzo[b,f]azepine phosphoramidite ligand can effectively catalyze the reaction and induce the generation of axial chirality.

[0032] The present invention also provides the use of the above-mentioned tribenzo[b,f]azepine phosphoramidite ligand in catalyzing the [2+2+2] cycloaddition reaction of alkynamines; and, preferably, the content of the tribenzo[b,f]azepine phosphoramidite ligand in the reaction system is 5 mol%.

[0033] Under the catalysis of tribenzo[b,f]azepine phosphoramidite ligand and iridium, the yield of the target product naphthalen-1-yl1-(4,7-dimethyl-6-phenyl-2-tosylisoindolin-5-yl)-1H-indole-2-carboxylate reached 71% and the ee value reached 72%, indicating that the tribenzo[b,f]azepine phosphoramidite ligand can effectively catalyze the reaction and has good chiral induction effect.

[0034] The present invention also provides the use of the above-mentioned tribenzo[b,f]azepine phosphoramidite ligand in catalyzing an asymmetric azide-internal alkyne [3 + 2] cycloaddition reaction; and, preferably, the content of the tribenzo[b,f]azepine phosphoramidite ligand in the reaction system is 5 mol%.

[0035] Under the catalysis of tribenzo[b,f]azepine phosphoramidite ligand and rhodium, the yield of the target product 1-(1-(naphthalen-1-ylmethyl)-4-phenyl-1H-1,2,3-triazol-5-yl)naphthalen-2-ol reached 73% and the ee value reached 53%, indicating that the tribenzo[b,f]azepine phosphoramidite ligand can effectively catalyze the reaction and has certain chiral control capabilities.

[0036] Compared with the prior art, the beneficial effects of the present invention are embodied in:

[0037] In the tribenzo[b,f]azepine phosphoramidite ligand of the present invention, the N-terminal structure is an asymmetric benzoiminostilbene, which makes the fused ring system at the N-terminus of the ligand larger, and the conjugated system and the π electron cloud are expanded. This not only increases the coordination ability of the metal and the ligand, but also has a certain steric hindrance, which not only helps to promote the occurrence of asymmetric reactions, but also can expand the scope of application of the ligand, making the ligand suitable for catalyzing a variety of different asymmetric reactions, including but not limited to the [4+2] cyclization reaction of indole alkynamine and o-benzylcyanophenyl borate, the [2+2+2] cycloaddition reaction of alkynamine, and the asymmetric azide-internal alkyne [3+2] cycloaddition reaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The synthetic route of the tribenzo[b,f]azepine phosphoramidite ligand of the present invention is as follows;

[0039] Wherein, equiv represents equivalent, PCl3 represents phosphorus trichloride, NRt3 represents triethylamine, DCM(dry) represents dichloromethane (ultra-dry), rt represents room temperature, and yield represents yield; the same below;

[0040] Figure 2 The following is a synthetic route for benzoimidostilbene;

[0041] Figure 3 This is the NMR analysis spectrum of benzoiminostilbene;

[0042] Figure 4 This is the nuclear magnetic analysis spectrum of the tribenzo[b,f]azepine phosphoramidite ligand of the present invention;

[0043] Figure 5 The reaction scheme for the rhodium-catalyzed [4+2] cyclization of indole alkynamines and o-benzylcyanophenylboronic acid esters is shown.

[0044] Among them, Catalyst means catalyst, Ligand means ligand, and solvent means solvent;

[0045] Figure 6The reaction scheme for the iridium-catalyzed [2+2+2] cycloaddition of alkynylamines;

[0046] Wherein, [Ir(COD)Cl]2 represents COD iridium chloride dimer, Zn(OTf)2 represents zinc trifluoromethanesulfonate, and toluene represents toluene;

[0047] Figure 7 The reaction scheme for the rhodium-catalyzed asymmetric azide-alkyne [3 + 2] cycloaddition reaction;

[0048] Wherein, [Rh(COD)Cl]2 represents COD rhodium chloride dimer, Represents 0.4 nanometer molecular sieve. DETAILED DESCRIPTION

[0049] The technical solution of the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0050] Example 1 Synthesis of Tribenzo[b,f]azepine Phosphoramidite Ligand

[0051] The tribenzo[b,f]azepine phosphoramidite ligand of this embodiment has a structural formula as shown in formula (I):

[0052] (Ⅰ).

[0053] The preparation method of the tribenzo[b,f]azepine phosphoramidite ligand (reaction scheme see Figure 1 ) includes the following steps:

[0054] (1) Benzoimidostilbene was synthesized by palladium-catalyzed cross-coupling reaction with 1-iodonaphthalene and o-bromoaniline under inert atmosphere (synthesis route see Figure 2 );

[0055] Specifically, take a sealed tube, fill and discharge nitrogen three times, and in a nitrogen atmosphere, press the preset amount (see Figure 2 ) triphenylphosphine, palladium acetate and cesium carbonate, 1-iodonaphthalene, o-bromoaniline, and norbornene were added in sequence, and then ultra-dry DMF was added. The reaction was incubated at 130°C for 48 h. The reaction was monitored by spot plate. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate and filtered, extracted three times with water, dried over anhydrous MgSO4, and the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography using petroleum ether:ethyl acetate = 30-20:1 to obtain benzoimidostilbene.

[0056] The obtained benzoimidostilbene was subjected to NMR analysis, and the results were as follows: Figure 3 As shown, the results of NMR analysis are:

[0057] 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.6 Hz, 1H), 7.69 (d, J = 8.2 Hz,1H), 7.63 (d, J = 8.8 Hz, 1H), 7.48 - 7.42 (m, 1H), 7.37 - 7.31 (m, 1H), 7.21(d, J = 11.8 Hz, 1H), 7.13 - 7.07 (m, 1H), 6.99 (d, J = 7.4 Hz, 1H), 6.96 - 6.90(m, 1H), 6.84 (d, J = 8.6 Hz, 1H), 6.79 (d, J = 11.4 Hz, 1H), 6.64 (d, J = 7.8 Hz,1H);

[0058] HRMS (ESI, m / z )calcd. for C 18 H 13 NNa [M + Na]+: 266.0940, found: 266.0942.

[0059] (2) Under an inert atmosphere, the tribenzo[b,f]azepine phosphoramidite ligand of this embodiment is synthesized by a nucleophilic substitution reaction using benzoimidostilbene, a phosphorus donor and a SPHENOL bisphenol skeleton as raw materials;

[0060] Specifically, it includes:

[0061] (a) Under an inert atmosphere, triethylamine, extra-dry dichloromethane, and phosphorus trichloride are mixed and thoroughly stirred in an ice bath to obtain a solution A;

[0062] Specifically, first take a sealed tube and several syringes, put them in an oven, inflate a balloon, take ice for later use, and set the stirring heater temperature to 45°C; take out the sealed tube when it is very hot, screw on the lid immediately, and do not need to be completely sealed, then use a vacuum pump to evacuate, wait for cooling, adjust the double-row nitrogen, and after the sealed tube cools down, fill and discharge nitrogen three or four times, and then let the sealed tube be in a nitrogen atmosphere; then take the baked syringe and needle, first exhaust the air and evacuate the nitrogen three times, and extract triethylamine (8 equivalents); under a nitrogen atmosphere, carefully open the sealed tube lid and inject triethylamine, and similarly take dichloromethane (ultra-dry) (5mmol / 20ml) and add it to the sealed tube, and then place the sealed tube in an ice-water bath, and in the same way take phosphorus trichloride (1.5 equivalents) and add it to the sealed tube, then cover the lid, turn off the nitrogen, and place it in an ice bath and stir for 15 minutes to obtain solution A;

[0063] (b) Under an inert atmosphere, benzoimidostilbene was added to solution A, mixed in an ice bath, and stirred at 45°C overnight to obtain solution B;

[0064] Specifically, 1.5 equivalents of benzoimidostilbene were weighed and added to a sealed tube under a nitrogen atmosphere, placed in an ice bath for 3 minutes, and then stirred at 45°C overnight to obtain solution B;

[0065] (c) Under an inert atmosphere, the SPHENOL bisphenol skeleton was added to solution B, and the reaction was first carried out in an ice bath for 5 minutes and then at room temperature for 4-5 hours to obtain the tribenzo[b,f]azepine phosphoramidite ligand of this example;

[0066] Specifically, under a nitrogen atmosphere, a SPHENOL bisphenol skeleton (1 equivalent) was weighed and added to a sealed tube. The tube was reacted in an ice bath for 5 minutes, then removed and allowed to react at room temperature for 4 to 5 hours until the reaction was essentially complete. After the reaction was complete, silica gel powder was added, the tube was spin-dried, and the column was passed using a developing solvent of petroleum ether: ethyl acetate = 50 to 20:1 to obtain the tribenzo[b,f]azepine phosphoramidite ligand.

[0067] The obtained tribenzo[b,f]azepine phosphoramidite ligand was analyzed by nuclear magnetic resonance and high resolution mass spectrometry. Figure 4 As shown, the analysis results are:

[0068] 1 H NMR (400 MHz, CDCl3) δ 8.09 (d, J= 9.2 Hz, 1H), 7.84 – 7.58 (m, 5H), 7.57 – 7.42 (m, 4H), 7.42 – 7.32 (m, 3H), 7.30 – 7.27 (m, 1H), 7.25 – 7.13 (m, 5H), 7.12 – 7.04 (m, 1H), 7.04 – 6.97 (m, 1H), 6.86 – 5.81 (m, 1H), 3.51 – 3.21 (m, 2H), 3.13 – 2.93 (m, 2H), 2.46 – 2.08 (m, 2H), 2.05 – 1.88 (m, 2H).

[0069] mz calcd. for C 40 H 30 NNaO2P [M + Na] + : 623.2014, found: 623.2011.

[0070] Example 2 Application of Tribenzo[b,f]azepine Phosphoramidite Ligand in Catalyzing the [4+2] Cyclization of Indole Alkynamine and o-Benzyl Cyanophenyl Boronate

[0071] The reaction scheme for the rhodium-catalyzed [4+2] cyclization of indole alkynamines and o-benzylcyanophenylboronic acid esters is shown in Figure 5 As can be seen, in this example, the amounts of the raw materials used are: indole alkynamine (1a) 0.05 mmol, o-benzyl cyanophenyl borate (2a) 0.1 mmol (2 equivalents), catalyst (catalyst) 4 mol%, ligand 10 mol%, potassium carbonate solvent 0.1 mmol (2 equivalents), solvent (tetrahydrofuran) 1 mL; before adding 1a and 2a to the reaction system, the catalyst and ligand were mixed and stirred for 40 minutes. In this example, different ligands were added to the reaction system. Under different ligands and corresponding reaction conditions, the yield (determined by 1H NMR with 1,3,5-trimethoxybenzene as the internal standard) and ee value (determined by chiral high-performance liquid chromatography) of the target product (3a) are shown in Table 1.

[0072] Table 1

[0073] reaction catalyst ligand Reaction conditions Yield (%) ee value (%) 1 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 20 h trace 5 2 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 20 h 30 racemic 3 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 20 h 32 5 4 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 20 h 25 54 5 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 11 h trace 50 6 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 11 h 35 60 7 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 11 h 40 racemic 8 <![CDATA[[Rh(COD)OH]2]]> #timg# Tetrahydrofuran, 25°C, 15 h 58 60

[0074] As can be seen from Table 1, when the tribenzo[b,f]azepine phosphoramidite ligand (i.e., L8) is used in the rhodium-catalyzed [4+2] cyclization reaction of indole alkynamine and o-benzylcyanophenyl borate, it can effectively induce the formation of this axial chirality, with the yield of the target product reaching 58% and the ee value reaching 60%.

[0075] Example 3 Application of Tribenzo[b,f]azepine Phosphoramidite Ligand in Catalyzing Alkynamine [2+2+2] Cycloaddition Reaction

[0076] The reaction route of the iridium-catalyzed [2+2+2] cycloaddition reaction of alkynylamines is as follows: Figure 6 As shown, this reaction is a reaction known to those skilled in the art. The reaction conditions of this embodiment remain unchanged, and only tribenzo[b,f]azepine phosphoramidite ligand is used as the ligand.

[0077] Depend on Figure 6 It can be seen that with the participation of the tribenzo[b,f]azepine phosphoramidite ligand, the yield of the target product naphthalen-1-yl1-(4,7-dimethyl-6-phenyl-2-tosylisoindolin-5-yl)-1H-indole-2-carboxylate reached 71% and the ee value reached 72%, indicating that the tribenzo[b,f]azepine phosphoramidite ligand can also play a good chiral induction role in the iridium-catalyzed alkynamine [2+2+2] cycloaddition reaction.

[0078] Example 4 Application of Tribenzo[b,f]azepine Phosphoramidite Ligand in Catalyzing Asymmetric Azide-Internal Alkyne [3 + 2] Cycloaddition Reaction

[0079] The reaction route of the rhodium-catalyzed asymmetric azide-alkyne [3 + 2] cycloaddition reaction is as follows: Figure 7 As shown, this reaction is a reaction known to those skilled in the art. The reaction conditions of this embodiment remain unchanged, and only tribenzo[b,f]azepine phosphoramidite ligand is used as the ligand.

[0080] Depend on Figure 7 It can be seen that with the participation of the tribenzo[b,f]azepine phosphoramidite ligand, the yield of the target product 1-(1-(naphthalen-1-ylmethyl)-4-phenyl-1H-1,2,3-triazol-5-yl)naphthalen-2-ol reached 73%, and the ee value reached 53%, indicating that the tribenzo[b,f]azepine phosphoramidite ligand also has a certain chiral control ability in the rhodium-catalyzed asymmetric azide-internal alkyne [3+ 2] cycloaddition reaction.

Claims

1. A tribenzo[b,f]azepine phosphoramidite ligand, characterized in that: The structural formula is shown in formula (I): （Ⅰ）。 2. The method for preparing the tribenzo[b,f]azepine phosphoramidite ligand according to claim 1, wherein: The following steps are involved: (1) Benzoimidostilbene was synthesized by cross-coupling reaction using 1-iodonaphthalene, norbornene and o-bromoaniline as raw materials under inert atmosphere; The reaction system further contains a base, a solvent, a catalyst and an additive, wherein the catalyst is selected from palladium acetate, the base is selected from cesium carbonate, the additive is selected from triphenylphosphine, and the solvent is selected from dichloromethane or tetrahydrofuran; React at 120-150℃ for 45-55 hours; (2) Under an inert atmosphere, the tribenzo[b,f]azepine phosphoramidite ligand is synthesized by a nucleophilic substitution reaction using benzoimidostilbene, a phosphorus donor and a SPHENOL bisphenol skeleton as raw materials.

3. The method for preparing the tribenzo[b,f]azepine phosphoramidite ligand according to claim 2, wherein: In the reaction system of step (1), the equivalent ratio of 1-iodonaphthalene, o-bromoaniline, norbornene and cesium carbonate is 1:1:2:

2.

4. The method for preparing the tribenzo[b,f]azepine phosphoramidite ligand according to claim 2, wherein: Step (2) includes: (a) A base, a solvent, and a phosphorus donor are mixed and uniformly mixed in an ice bath to obtain a solution A; (b) Under an inert atmosphere, benzoimidostilbene was added to solution A, mixed in an ice bath, and stirred at 25-55° C. overnight to obtain solution B; (c) Under an inert atmosphere, the SPHENOL bisphenol skeleton is added to solution B, and the reaction is first carried out in an ice bath for 3-15 minutes and then at room temperature for 4-5 hours to obtain the tribenzo[b,f]azepine phosphoramidite ligand.

5. The preparation method according to claim 4, wherein In step (a), the base is selected from triethylamine, the phosphorus donor is selected from phosphorus trichloride, and the solvent is selected from extra-dry dichloromethane or tetrahydrofuran; The equivalent ratio of triethylamine to SPHENOL bisphenol skeleton is (6-10):1; the equivalent ratio of phosphorus trichloride to SPHENOL bisphenol skeleton is (1-2.5):1; In step (b), the equivalent ratio of the benzoimidostilbene to the SPHENOL bisphenol skeleton is (1-3):

1.

6. Use of the tribenzo[b,f]azepine phosphoramidite ligand according to claim 1 in catalyzing the [4+2] cyclization reaction of indole alkynamine and o-benzylcyanophenyl borate.

7. Use of the tribenzo[b,f]azepine phosphoramidite ligand according to claim 1 in catalyzing the [2+2+2] cycloaddition reaction of alkynamines.

8. Use of the tribenzo[b,f]azepine phosphoramidite ligand according to claim 1 in catalyzing an asymmetric azide-internal alkyne [3+2] cycloaddition reaction.

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