; 1, 3-oxo-1, 1apos; synthesis method and application of spirobiindane chiral monophenol and chiral phosphite monophosphine ligand of spirobiindane chiral monophenol

Abstract

The invention discloses a synthesis method and application of a 3-oxo-1, 1 '-spirobiindane chiral monophenol and a chiral phosphite monophosphine ligand. In a nitrogen or inert gas atmosphere, 3-oxo-1, 1 '-spirobiindane chiral monophenol reacts with disubstituted phosphorus chloride for 1-10 hours in an organic solvent at the temperature of 0-50 DEG C by taking alkali as an acid-binding agent, and the chiral phosphite ligand is obtained through desolvation under reduced pressure and column chromatography in an argon atmosphere. And under the protection of nitrogen or inert gas, stirring and dissolving beta-dehydroamino-acid ester, the chiral phosphite monophosphine ligand, a rhodium metal precursor and an organic solvent, introducing hydrogen, and stirring and reacting for 24-60 hours in the atmosphere of 10-60 atmH2 at the temperature of-20-40 DEG C to obtain the optically active amino-acid ester. The asymmetric hydrogenation reaction achieves excellent enantioselectivity.

Description

Technical Field

[0001] The present invention relates to the field of chemical synthesis, and particularly to a method for synthesizing and applying 3-oxo-1,1′-spirobiindane chiral monophenol and its chiral phosphite monophosphine ligand. Background Art

[0002] Asymmetric catalysis is an efficient method for obtaining chiral pure substances and is widely used in the production of pesticides and pharmaceutical products. For example, the hydrogenation of rhodium-catalyzed dehydroamino acids can efficiently prepare the chiral drug L-DOPA (Knowles, W.S.; Sabacky, M.J.; Vineyard, B.D.; Weinkauff, D.J. J. Am. Chem. Soc. 1975, 97, 2567–2568). In asymmetric catalysis, chiral catalysts are the key to achieving efficient asymmetric catalytic reactions (Yoon, T.P.; Jacobsen, E.N. Privileged Chiral Catalysts. Science 2003, 299, 1691–1693). Therefore, the design and synthesis of new chiral ligands and catalysts are of great significance.

[0003] Among the existing chiral catalysts, catalysts containing a chiral spiroindane skeleton are one of the most efficient homogeneous catalysts to date. For example, an iridium catalyst of chiral spirocyclic pyridineamine phosphine can achieve a high turnover number of 4.55 million in the asymmetric catalytic hydrogenation of simple ketones (J-H, Xie.; X-Y, Liu.; J-B, X.; L-X, Wang.; and Q-L, Zhou. Angew. Chem. Int. Ed, 2011, 50, 7329–7332.). The chiral spirocyclic skeleton is an important type of "privileged ligand skeleton" ((a) Ding, K.; Han, Z.; Wang, Z. Chem.─Asian J. 2009, 4, 32-41. (b) Zhu, S.-F.; Zhou, Q.-L. Chiral spiro ligands. In Privileged chiral ligands and catalysts; Zhou, Q.-L., Ed.; Wiley-VCH: Weinheim, 2011; p 137-170.). Therefore, the development of new chiral spirocyclic skeleton ligands is of great significance for achieving asymmetric catalytic reactions with high efficiency and high selectivity.

[0004] Among them, chiral monodentate phosphite ligands are an important type of ligands (Guo Hongchao; Ding Kuiling; Dai Lixin. New Advances in Asymmetric Catalytic Hydrogenation - The Revival of Monodentate Phosphorus Ligands. Chinese Science Bulletin 2004, 49(16), 1575–1588.). However, due to the lack of suitable ligand skeletons, chiral phosphite monophosphine ligands are very rare and the asymmetric reactions they catalyze can only achieve moderate to good selectivity and yields (Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 2002, 124, 734–735.; Zhang, T.-Z.; Dai, L.-X.; Hou, X.-L. Tetrahedron Asymmetry 2007, 18, 251–259.). Therefore, the development of novel 3-oxo-1,1′-spirobiindane skeleton phosphite monophosphine ligands has important value and significance. Summary of the Invention

[0005] To solve the problems existing in the prior art, an object of the present invention is to provide a method for preparing 3-oxo-1,1′-spirobisindane chiral monophenol.

[0006] Another object of the present invention is to provide a method for preparing 3-oxo-1,1′-spirobisindane skeleton chiral phosphite monophosphine ligand from the 3-oxo-1,1′-spirobisindane chiral monophenol as a raw material.

[0007] Still another object of the present invention is to provide an application of 3-oxo-1,1′-spirobisindane skeleton chiral phosphite monophosphine ligand in asymmetric catalytic reactions.

[0008] For this purpose, the present invention adopts the following technical solutions:

[0009] A 3-oxo-1,1′-spirobisindane chiral monophenol is a compound having the following general formula 1:

[0010]

[0011] An asymmetric synthesis method of the above-mentioned 3-oxo-1,1′-spirobisindane chiral monophenol is prepared from the indanone compound of formula 3 as a starting material through the following reaction process:

[0012]

[0013] The specific steps of the above asymmetric synthesis method are as follows:

[0014] S1. At -30 to 10 °C, slowly drop the organic solution of the indanone compound shown in Formula 3 into the mixed solution of (R)-2-Me-CBS or (S)-2-Me-CBS and borane tetrahydrofuran. After the reaction is completed, quench, concentrate under vacuum, and purify by silica gel chromatography to obtain indanol (R)-4 or (S)-4; preferably:

[0015] In the organic solution of the indanone compound, the concentration of the indanone compound is 0.1 - 1.5 M;

[0016] The molar ratio of (R)-2-Me-CBS or (S)-2-Me-CBS to the indanone compound is (5 - 30):100;

[0017] The equivalent ratio of the borane tetrahydrofuran to the indanone compound is (1.1 - 3):1;

[0018] In the mixed solution, the volume of the solvent is 1.5 - 2 times the volume of the borane tetrahydrofuran;

[0019] The dropping is completed within 2 - 3 h; preferably, it is dropped at a rate of 1 drop / 5 s.

[0020] S2. Put indanol (R)-4 or (S)-4, triethyl orthoacetate, and an acid as a catalyst into a reaction vessel, and react at 80 - 160 °C for 2 - 6 hours. After the reaction is completed, remove the excess triethyl orthoacetate, and purify the residue by silica gel chromatography to obtain compound (R)-5 or (S)-5; preferably:

[0021] The equivalent ratio of the triethyl orthoacetate to indanol (R)-4 or (S)-4 is (5 - 30):1;

[0022] The molar ratio of the acid to indanol (R)-4 or (S)-4 is (2 - 30):100;

[0023] S3. Add palladium carbon to the organic solution of compound (R)-5 or (S)-5, and react at 10 - 60 °C for 8 - 24 hours under a hydrogen pressure of 1 - 60 atm. The obtained mixture is filtered, washed, and concentrated under vacuum to obtain compound (R)-6 or (S)-6; preferably, the molar ratio of the palladium carbon to compound (R)-5 or (S)-5 is (5 - 30):100;

[0024] S4. Add an organic solvent, water, and a base to compound (R)-6 or (S)-6, and react at room temperature to 110 °C for 7 - 24 hours. After cooling, extract, wash, dry, and remove the solvent under reduced pressure to obtain compound (R)-7 or (S)-7; preferably:

[0025] The concentration of (R)-6 or (S)-6 in the organic solvent is 0.5 - 2 M;

[0026] The volume ratio of the organic solvent to water is (1 - 3):1;

[0027] The equivalent ratio of the base to compound (R)-6 or (S)-6 is (2.0 - 6.0):1;

[0028] S5. Under a nitrogen or inert gas atmosphere, trifluoromethanesulfonic acid is added to an organic solution of compound (R)-7 or (S)-7, and the reaction is carried out at -78 to 60 °C for 2 - 24 hours. After the reaction is completed, compound (R)-8 or (S)-8 is obtained through quenching, extraction, solvent stripping under reduced pressure, and silica gel column chromatography; preferably: the equivalent ratio of the trifluoromethanesulfonic acid to compound (R)-7 or (S)-7 is (3 - 30):1;

[0029] S6. Under a nitrogen or inert gas atmosphere, at -78 to 0 °C, boron tribromide is slowly added dropwise to an organic solution of compound (R)-8 or (S)-8, and then the temperature is raised to room temperature. The reaction is carried out for 8 - 24 hours, and after quenching, extraction, and purification by silica gel column chromatography, 3-oxo-1,1′-spirobiindane chiral monophenol (R)-1 or (S)-1 is obtained; preferably: in the organic solution of compound (R)-8 or (S)-8, the concentration of the organic solution of compound (R)-8 or (S)-8 is 0.1 - 1 mmol / ml.

[0030] In the above asymmetric synthesis method:

[0031] Preferably, in S1, the organic solution and the solvent in the mixed solution are the same, and are selected from one or more of tetrahydrofuran, dichloromethane, diethyl ether, and 1,4-dioxane;

[0032] Preferably, in S2, the acid is one or more of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, and pivalic acid;

[0033] Preferably, in S3, the solvent of the organic solution is selected from one or more of tetrahydrofuran, dichloromethane, ethyl acetate, 1,4-dioxane, methanol, ethanol, and n-propanol;

[0034] Preferably, in S4, the organic solvent is one or more of tetrahydrofuran, dichloromethane, methanol, and ethanol; the base is one or more of lithium hydroxide, sodium hydroxide, and potassium hydroxide;

[0035] Preferably, in the organic solution of S5, the solvent is selected from one or more of tetrahydrofuran, dichloromethane, and toluene;

[0036] Preferably, in the organic solution of S6, the solvent is selected from one or more of tetrahydrofuran, dichloromethane, and toluene.

[0037] A method for preparing a 3-oxo-1,1'-spirobiindane chiral phosphite monophosphine ligand from the above-mentioned 3-oxo-1,1'-spirobiindane chiral monophenol as a raw material, the reaction formula and reaction process are as follows:

[0038]

[0039] Under a nitrogen or inert gas atmosphere, 3-oxo-1,1'-spirobiindane chiral monophenol reacts with a disubstituted phosphorus chloride in an organic solvent at 0-50 °C for 1-10 hours using a base as an acid-binding agent. Under an argon atmosphere, after solvent removal under reduced pressure and column chromatography, a chiral phosphite ligand is obtained, where:

[0040] The equivalent ratio of the base, disubstituted phosphorus chloride to 3-oxo-1,1'-spirobiindane chiral monophenol is (1.5-3):(1.0-3.0):1.

[0041] In the above reaction formula, R 1 is an alkyl group or an aryl group. The alkyl group is preferably methyl, ethyl, propyl or butyl; the aryl group is phenyl or phenyl substituted by an alkyl group or an alkoxy group.

[0042] In the above method, the organic solvent is one or more of dichloromethane, toluene, and tetrahydrofuran; the base is triethylamine, diisopropylethylamine or 4-dimethylaminopyridine; the disubstituted phosphorus chloride is diaryl phosphorus chloride or dialkyl phosphorus chloride.

[0043] Application of a 3-oxo-1,1'-spirobiindane skeleton chiral phosphite monophosphine ligand prepared by the above method in an asymmetric catalytic reaction, where the asymmetric catalytic reaction is hydrogenation, hydroformylation, hydrosilylation, hydroboration, hydroxyhydroxylation, hydroamination, hydrocyanation, isomerization formylation, hydroaminomethylation, transfer hydrogenation, allylation, olefin metathesis, ring isomerization, Diels-Alder reaction, asymmetric coupling reaction, Aldol reaction, Michael addition reaction, asymmetric epoxidation reaction, kinetic resolution or [m+n] cyclization reaction.

[0044] In the above application, the reaction process is as follows:

[0045]

[0046] Under nitrogen or inert gas protection, in a hydrogenation autoclave, add β-dehydroamino acid ester, 3-oxo-1,1'-spirobiindane skeleton chiral phosphite monophosphine ligand, a rhodium metal precursor and an organic solvent and stir to dissolve. Then, fill with hydrogen and stir and react at -20 °C to 40 °C and in a H2 atmosphere of 10-60 atm for 24-60 hours to obtain an optically active amino acid ester, where:

[0047] The molar ratio of the 3-oxo-1,1′-spirobiindane framework chiral phosphite monophosphine ligand to the rhodium metal precursor is 2:1;

[0048] The molar ratio of the rhodium metal precursor to the β-dehydro amino acid ester is 1:(0.5 - 10).

[0049] In the above application:

[0050] The rhodium metal precursor is [Rh(cod)Cl]2 (cod = cyclooctadiene), [Rh(cod)2]BF4, [Rh(cod)2]PF6, [Rh(cod)2]SbF6 or [Rh(cod)2]OTf);

[0051] The organic solvent is one or more of dichloromethane, toluene, tetrahydrofuran, methanol, ethanol, isopropanol, and tert-butanol; preferably, the concentration of the substrate in the solvent is 0.1 - 0.5 mmol / ml; the preferred organic solvent is a mixed solvent of dichloromethane and tert-butanol, wherein the volume ratio of the two is (1 - 3):1;

[0052] R 2 and R 3 are alkyl, aryl or hydrogen atom; preferably:

[0053] The alkyl is methyl, ethyl, propyl or butyl;

[0054] The aryl is phenyl which is substituted or unsubstituted by alkyl, alkoxy, halogen atom; wherein the alkoxy is methoxy, ethoxy, propoxy or butoxy;

[0055] R 4 is an amine protecting group, and R 4 is selected from acetyl, alkoxycarbonyl, p-toluenesulfonyl and benzyl.

[0056] The chiral phosphite monophosphine ligand prepared by the present invention can be used as a chiral ligand in asymmetric catalytic reactions, such as in the asymmetric hydrogenation reaction of rhodium-catalyzed dehydro amino acid esters, and has high application value in the field of asymmetric catalysis.

[0057] Compared with the prior art, the present invention has the following beneficial effects:

[0058] 1. The chiral 3-oxo-1,1′-spirobisindane chiral monophenol has central chirality and can be used for the design and synthesis of chiral spirocyclic ligands, such as the design and synthesis of 3-oxo-1,1′-spirobiindane phosphite monophosphine ligands.

[0059] 2. 3-oxo-1,1′-spirobiindane phosphite monophosphine ligand can be applied to asymmetric hydrogenation reactions. This ligand has high activity and enantioselectivity for the hydrogenation of β-dehydroamino acid esters in organic solvents. For example, excellent enantioselectivity can be achieved in the rhodium-catalyzed asymmetric catalytic hydrogenation reaction of dehydroamino acid esters, with a yield of 99% and an enantiomeric excess (ee) of 80% ee to >99% ee.

[0060] 3. The synthetic methods of the 3-oxo-1,1′-spirobiindane chiral monophenol and chiral monophosphine ligand in the present invention are simple and economical. The obtained chiral monophosphine ligand has important application value and great potential in the synthesis of chiral drugs, flavors, and fragrances. Specific Embodiments

[0061] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the following embodiments are only part of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

[0062] In the following embodiments, the experimental methods without specific conditions are usually carried out according to conventional conditions and the conditions described in the manuals, or according to the conditions recommended by the manufacturers; the general equipment, materials, reagents, etc. used, unless otherwise specified, can be obtained from commercial sources.

[0063] The following compounds are used in the following embodiments:

[0064] (R)-2-Me-CBS: (R)-2-methyl-CBS-oxazaborolidine;

[0065] (S)-2-Me-CBS: (S)-2-methyl-CBS-oxazaborolidine;

[0066] MeC(OEt)3: Triethyl orthoacetate;

[0067] pivalic acid: Trimethylacetic acid;

[0068] Pd / C: Palladium on carbon (10%), moistened with 55% water.

[0069] TfOH: Trifluoromethanesulfonic acid;

[0070] BH3·THF: Borane tetrahydrofuran.

[0071] Example 1

[0072] An asymmetric synthesis method of 3-oxo-1,1′-spirobiindane chiral monophenol (R)-1 or (S)-1, comprising the following steps:

[0073] S1. Synthesis of (R)-4-methoxy-3-phenyl-1H-inden-1-ol ((R)-4). The reaction formula and process are as follows:

[0074]

[0075] Under an argon atmosphere, at -20 °C, (S)-2-Me-CBS (1 mL, 1.0 mmol, 1 M, toluene solution) and BH3·THF (22 mL, 22.0 mmol, 1 M, THF) were added to a flask containing 40 mL of THF, and then stirred for 10 minutes. Subsequently, at -20 °C, a THF solution (1 M) of indanone 3 (4.7 g, 20.0 mmol) was slowly added dropwise to the above reaction system via a syringe over 2 hours. After the reaction was completed, the reaction was quenched with methanol (5 mL). Then it was concentrated under vacuum and purified by silica gel chromatography using ethyl acetate / petroleum ether (v / v = 1:6) as the eluent to obtain the target product indanol (R)-4. White solid, 4.40 g, 92% yield, 95% ee. Melting point: 124–126 °C, 95% ee, (c 0.5,CHCl3). 1 H NMR (400 MHz, CDCl3): δ 7.53–7.47 (m, 2H), 7.39–7.30 (m, 3H), 7.26–7.19 (m, 2H), 6.85 (d, J = 7.7 Hz, 1H), 6.20 (d, J = 2.2 Hz, 1H), 5.21 (dd, J = 9.6, 1.8 Hz, 1H), 3.64 (s, 3H), 1.73 (d, J = 9.6 Hz, 1H). 13 C NMR (101 MHz, CDCl3): δ 154.4, 149.3, 146.3, 136.8, 134.4, 129.0, 128.6, 128.3, 127.6, 127.4, 116.9, 112.6, 76.6, 55.6. HRMS (ESI-TOF) m / z: [M + H] + calcd for C 16 H 15 O2 + 239.1067; Found 239.1062. HPLC conditions: Chiralcel AD-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 95:5; temp, 26 °C; flow rate = 1.0 mL / min; 210 nm UV detector; pressure, 43 bar; t R = 14.89 min (major), t R= 17.76 min (minor).

[0076] S2. Synthesis of ethyl (S)-2-(7-methoxy-1-phenyl-1H-inden-1-yl)acetate ((S)-5), the reaction formula and process are as follows:

[0077]

[0078] Add the indanol (R)-4 (4.8 g, 20.0 mmol) obtained from S1, triethyl orthoacetate (55 mL, 300.0 mmol), and pivalic acid (230 μL, 2.0 mmol) into a 250 ml round-bottom flask. The resulting mixture was stirred in an oil bath at 150 °C for 3 h. After the reaction was completed, the excess triethyl orthoacetate was removed under vacuum. The resulting residue was purified by silica gel chromatography using ethyl acetate / petroleum ether (v / v = 1:6) as the eluent to obtain 4.51 g of a pale yellow oily liquid (S)-5 with a yield of 73% and 98% ee, (c0.5, CHCl3). 1 1H NMR (400 MHz, CDCl3): δ 7.28–7.13 (m, 6H), 6.94 (d, J = 7.4 Hz, 1H), 6.78 (d, J = 5.4 Hz, 1H), 6.73 (d, J = 5.5 Hz, 1H), 6.68 (d, J = 8.2 Hz, 1H), 3.98–3.85 (m, 2H), 3.70 (s, 3H), 3.66 (d, J = 14.2 Hz, 1H), 3.12 (d, J = 14.1 Hz, 1H), 0.99 (t, J = 7.1 Hz, 3H). 13 13C NMR (101 MHz, CDCl3): δ 171.3, 155.7, 145.3, 145.1, 139.6, 136.5, 130.0, 129.4, 128.2, 126.6, 126.5, 114.6, 109.2, 60.2, 59.0, 55.5, 38.6, 14.1. HRMS (ESI-TOF) m / z: [M + H] + calcd for C 20 H 21 O3 + 309.1485; Found 309.1485. HPLC conditions: Chiralcel IC-3 column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 99:1; temp, 26 °C; flow rate = 1.0 mL / min; 210 nm UV detector; pressure, 99 bar; t R= 9.66 min (major), t R = 11.66 min (minor)

[0079] S3. Synthesis of ethyl (R)-2-(7-methoxy-1-phenyl-2,3-dihydro-1H-inden-1-yl)acetate ((R)-6). The reaction formula and process are as follows:

[0080]

[0081] In a 250 mL schlenk flask, add the compound (S)-5 (6.2 g, 20.0 mmol) obtained from S2, ethanol (80 mL) (dissolve only), and palladium on carbon (wet, 1.93 g, 1.0 mmol). Then replace it with a hydrogen atmosphere, and the resulting mixture is stirred at room temperature for 10 hours in an atmospheric hydrogen atmosphere. The reaction mixture is filtered through silica gel, the filter residue is washed with ethyl acetate, and the combined filtrate is concentrated in vacuo to obtain (R)-6, which can be directly used in the next step without further purification. (R)-6 is a colorless oily liquid, 6.02 g, yield 97%, melting point: 144–146 °C, (c 0.5, CHCl3). 1 1H NMR (400 MHz, CDCl3): δ 10.67 (s, 1H), 7.26–7.11 (m, 6H), 6.84 (d, J = 7.4 Hz, 1H), 6.70 (d, J = 8.1 Hz, 1H), 3.68 (s, 3H), 3.39 (d, J = 15.2 Hz, 1H), 3.30 (d, J = 15.2 Hz, 1H), 2.92–2.76 (m, 2H), 2.70–2.60 (m, 1H), 2.51–2.43 (m, 1H). 13 13C NMR (101 MHz, CDCl3): δ 177.4, 156.9, 146.7, 146.1, 133.9, 129.1, 128.2, 126.3, 126.2, 117.5, 109.1, 55.3, 54.5, 43.4, 40.7, 31.1. HRMS (ESI-TOF) m / z: [M + H] + calcd for C 18 H 19 O3 + 283.1329; Found 283.1323.

[0082] S4. Synthesis of ethyl (R)-2-(7-methoxy-1-phenyl-2,3-dihydro-1H-inden-1-yl)acetate ((R)-7). The reaction formula and process are as follows:

[0083]

[0084] (R)-6 (6.02 g, 19.4 mmol) obtained from S3, lithium hydroxide monohydrate (2.44 g, 58.2 mmol), tetrahydrofuran (30 mL), ethanol (30 mL) and water (30 mL) were added to a 250 mL flask. The mixture was heated to 70 °C in an oil bath and reacted for 7 h. After cooling to room temperature, it was acidified to pH = 1 with 1 N hydrochloric acid and extracted with ethyl acetate (50 mL × 3 times). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain carboxylic acid (R)-7, which could be directly used in the next step without further purification. Melting point: 144–146 °C, (c 0.5, CHCl3). 1 H NMR (400 MHz, CDCl3): δ 10.67 (s, 1H), 7.26–7.11 (m, 6H), 6.84 (d, J = 7.4 Hz, 1H), 6.70 (d, J = 8.1 Hz, 1H), 3.68 (s, 3H), 3.39 (d, J = 15.2 Hz, 1H), 3.30 (d, J = 15.2 Hz, 1H), 2.92–2.76 (m, 2H), 2.70–2.60 (m, 1H), 2.51–2.43 (m, 1H). 13 C NMR (101 MHz, CDCl3): δ 177.4, 156.9, 146.7, 146.1, 133.9, 129.1, 128.2, 126.3, 126.2, 117.5, 109.1, 55.3, 54.5, 43.4, 40.7, 31.1. HRMS (ESI-TOF) m / z: [M + H] + calcd for C 18 H 19 O3 + 283.1329; Found 283.1323.

[0085] Synthesis of S5, ethyl (R)-7′-methoxy-2′,3′-dihydro-1,1′-spirobi[indene]-3(2H)-one ((R)-8). The reaction scheme and reaction process are as follows:

[0086]

[0087] Under an argon atmosphere, trifluoromethanesulfonic acid (33 mL, 372.0 mmol) was added to a solution of carboxylic acid (R)-7 (5.26 g, 18.6 mmol) obtained from S4 in dichloromethane (60 mL) (dissolved just fine) at 0 °C, and then the temperature was raised to room temperature and stirred for 3 h. After the reaction was completed, ice water (20 mL) was slowly added to the mixture at 0 °C to quench the reaction, and then extracted with dichloromethane (60 mL × 3 times). Subsequently, the organic phases were combined and concentrated under reduced pressure, and the resulting mixture was purified by silica gel column chromatography using ethyl acetate / petroleum ether (v / v = 1:20) as the eluent to obtain the spiro compound (R)-8, which was then recrystallized from dichloromethane and petroleum ether to further increase the ee value of (R)-8 from 98% to greater than 99.9%. White solid, 3.96 g, yield 75%. Melting point: 81 - 83 °C, >99.9% ee (recrystallized), (c 0.5,CHCl3). 1 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 7.6 Hz, 1H), 7.49 (td, J = 7.7, 1.2 Hz, 1H), 7.38–7.30 (m, 1H), 7.20 (t, J = 7.8 Hz, 2H), 6.92 (dd, J = 7.6, 0.9 Hz, 1H), 6.61 (d, J = 8.1 Hz, 1H), 3.47 (s, 3H), 3.30–3.18 (m, 2H), 3.16–3.06 (m, 1H), 2.79 (d, J = 18.5 Hz, 1H), 2.55–2.46 (m, 1H), 2.45–2.36 (m, 1H). 13 13C NMR (101 MHz, CDCl3): δ 206.4, 161.9, 156.1, 145.4, 135.8, 134.9, 134.8, 129.3, 127.4, 124.5, 122.8, 117.2, 109.1, 55.0, 53.8, 51.0, 42.4, 32.0. HRMS (ESI-TOF) m / z: [M + H] + calcd for C 18 H 17 O2 + 265.1223; Found 265.1223. HPLC conditions: Chiralcel OJ-3 column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 97:3; temp, 26 °C; flow rate = 1.0 mL / min; 210 nm UV detector; pressure, 80 bar; t R = 17.44 min.

[0088] Synthesis of (R)-7′-hydroxy-2′,3′-dihydro-1,1′-spirobi[indene]-3(2H)-one ((R)-1). The reaction formula and process are as follows:

[0089]

[0090] Under an argon atmosphere, at -78 °C, boron tribromide (25.0 mmol, 2 M, dichloromethane solution) was added dropwise to a solution of spiro compound (R)-8 (2.54 g, 10.0 mmol) in dichloromethane (50 mL) (0.2 mmol / ml). Subsequently, the reaction system was slowly warmed to room temperature and stirred for 8 h. After the reaction was completed, ice water (20 mL) was added at 0 °C to quench the reaction, and then it was extracted with dichloromethane (50 mL × 3). Subsequently, the organic phases were combined, and the resulting mixture was purified by silica gel column chromatography (dichloromethane / ethyl acetate / petroleum ether v / v / v = 1:1:5) to obtain (R)-3-oxo-1,1′-spirodihydroindenol monophenol (R)-1. White solid, 2.41 g, yield 96%, melting point: 185–188 °C, (c 0.5,CHCl3). 1 H NMR(400MHz,DMSO-d6):δ9.08(s,1H),7.70–7.48(m,2H),7.39(t,J = 7.1Hz,1H),7.26(d,J = 7.5Hz,1H),7.02(t,J = 7.4Hz,1H),6.77(d,J = 7.1Hz,1H),6.48(d,J = 7.6Hz,1H),3.26–2.94(m,3H),2.82(d,J = 18.5Hz,1H),2.37(t,J = 7.0Hz,2H). 13 C NMR(101MHz,DMSO-d6):δ205.2,161.5,153.4,145.1,135.4,135.0,133.0,128.7,127.3,124.7,122.0,115.5,113.5,53.0,50.1,41.7,31.4.HRMS(ESI-TOF)m / z:[M+H] + calcd for C 17 H 15 O2 + 251.1067; Found 251.1068.

[0091] Examples 2-16 are different examples of each step. The reaction conditions, products, and results are shown in the following table:

[0092]

[0093]

[0094] Example 17

[0095] Synthesis of (R)-7-diphenylphosphinyloxy-3-oxo-1,1′-spirobiindane (R)-2a. The reaction formula and process are as follows:

[0096]

[0097] Under a nitrogen atmosphere, (R)-3-oxo-1,1′-spirobiindanol monophenol ((R)-1) (100 mg, 0.4 mmol), 4-dimethylaminopyridine (DMAP) (98 mg, 0.8 mmol), and diphenylphosphinous chloride (88 mg, 0.4 mmol) were added to a 25 mL dry Schlenk tube, and dry tetrahydrofuran was added. The reaction was carried out at 0 °C for 3 h; under an argon atmosphere, the solvent was removed under reduced pressure, and column chromatography (petroleum ether / ethyl acetate = 20:1) was used to separate the ligand (R)-2a, 167 mg, with a yield of 96%. Optical rotation: (c = 1, CHCl3). 1 1H NMR (400 MHz, CDCl3): δ 7.37–7.20 (m, 8H), 7.19–7.13 (m, 2H), 7.12–7.08 (m, 1H), 7.07–6.94 (m, 5H), 6.84 (dd, J = 7.7, 1.5 Hz, 1H), 3.29 (d, J = 15.7 Hz, 1H), 2.99 (t, J = 7.3 Hz, 2H), 2.69 (d, J = 15.7 Hz, 1H), 2.36–2.26 (m, 1H), 2.20–2.09 (m, 1H). 13 13C NMR (101 MHz, CDCl3): δ 205.4, 162.0, 153.4, 153.3, 146.5, 139.9, 139.8, 139.7, 139.6, 135.8, 135.8, 135.7, 135.7, 134.9, 130.8, 130.6, 130.2, 130.0, 130.0, 129.4, 129.3, 128.5, 128.4, 128.2, 128.2, 127.3, 124.7, 123.0, 118.5, 115.0, 114.8, 50.6, 44.0, 31.6, 29.7. 31 31P NMR (162 MHz, CDCl3): δ 106.70. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 29 H 24 O2P +435.1508; Found: 435.1510.

[0098] Example 18

[0099] (R)-7-Bis-(3,5-dimethyl)phenylphosphinyloxy-3-oxo-1,1'-spirobiindane (R)-2b was synthesized. The reaction formula and process are as follows:

[0100]

[0101] Under a nitrogen atmosphere, (R)-3-oxo-1,1'-spirobiindane monophenol (R)-1 (100 mg, 0.4 mmol), DMAP (98 mg, 0.8 mmol), and bis-(3,5-dimethyl)phenylphosphine chloride (111 mg, 0.4 mmol) were added to a 25 mL dry Schlenk tube. Redistilled tetrahydrofuran was added, and the reaction was carried out at room temperature for 3 h; under an argon atmosphere, the solvent was removed under reduced pressure, and rapid column chromatography (petroleum ether / ethyl acetate = 20:1) was used to separate the ligand (R)-2b, 169 mg, with a yield of 86%. Optical rotation: (c = 1, CHCl3), melting point: 40–41 °C. 1 H NMR (600 MHz, CDCl3): δ 7.49–7.41 (m, 2H), 7.23–7.13 (m, 3H), 7.00–6.92 (m, 3H), 6.88 (s, 1H), 6.80 (d, J = 8.6 Hz, 2H), 6.63 (d, J = 8.5 Hz, 2H), 3.13–3.02 (m, 3H), 2.77 (d, J = 18.4 Hz, 1H), 2.39–2.32 (m, 1H), 2.31–2.18 (m, 13H). 13 C NMR (151 MHz, CDCl3): δ 205.3, 162.0, 153.9, 153.8, 146.3, 139.9, 139.8, 139.5, 139.4, 138.0, 137.9, 137.6, 137.5, 135.8, 135.8, 135.5, 134.7, 131.8, 131.4, 129.3, 128.2, 128.0, 128.0, 127.8, 127.0, 124.4, 122.8, 118.3, 115.4, 115.3, 53.7, 50.6, 44.0, 31.6, 21.3, 21.3. 31 P NMR (162 MHz, CDCl3): δ 109.49. HRMS (ESI-TOF) m / z: [M + H] + calcd for C 33 H 32 O2P+ 491.2134; Found 491.2130.

[0102] Example 19

[0103] Synthesis of (R)-7-bis-(3,5-di-tert-butyl)-phenylphosphinyloxy-3-oxo-1,1'-spirobiindane (R)-2c. The reaction formula and process are as follows:

[0104]

[0105] Under a nitrogen atmosphere, (R)-3-oxo-1,1'-spirobiindanol monophenol (R)-1 (100 mg, 0.4 mmol), triethylamine (98 mg, 0.8 mmol), and bis-(3,5-di-tert-butyl)-phenylphosphine chloride (178 mg, 0.4 mmol) were added to a 25 mL dry Schlenk tube. Distilled tetrahydrofuran was added, and the reaction was carried out at room temperature for 3 h; under an argon atmosphere, the solvent was removed under reduced pressure, and column chromatography (petroleum ether / ethyl acetate = 20:1) was used to separate the ligand (R)-2c, 129 mg, with a yield of 49%, optical rotation: (c = 1, CHCl3), melting point: 45–46 °C. 1 H NMR (400 MHz, CDCl3): δ 7.42–7.30 (m, 3H), 7.22–7.06 (m, 5H), 7.06–6.92 (m, 4H), 6.88 (d, J = 8.2 Hz, 1H), 3.20–3.01 (m, 3H), 2.74 (d, J = 18.4 Hz, 1H), 2.37–2.18 (m, 2H), 1.32–1.19 (m, 36H). 13 C NMR (101 MHz, CDCl3): δ 204.6, 161.4, 154.2, 154.1, 150.5, 150.4, 150.2, 150.1, 146.1, 138.9, 138.7, 137.9, 137.8, 136.1, 136.1, 135.3, 134.4, 129.2, 127.0, 125.5, 125.2, 125.0, 124.8, 124.1, 124.1, 124.0, 122.6, 118.4, 116.1, 115.9, 53.6, 50.6, 43.9, 34.9, 31.5, 31.4, 31.4. 31 P NMR (162 MHz, CDCl3): δ 113.43. HRMS (ESI-TOF) m / z: [M+H] + calcd for C 45 H 56 O2P +659.4012; Found 659.4014.

[0106] Example 20

[0107] (Z)-Ethyl 3-acetamido-3-phenylacrylate asymmetric catalytic hydrogenation method, the reaction formula and reaction process are as follows:

[0108]

[0109] Under a nitrogen atmosphere, in a glove box, weigh (Z)-ethyl 3-acetamido-3-phenylacrylate (58 mg, 0.25 mmol), ligand (R)-7-bis-(3,5-dimethyl)phenylphosphinyloxy-3-oxo-1,1'-spirobiindane (R)-2b (2.6 mg, 0.005 mmol) and Rh(COD)2BF4 (1 mg, 0.0025 mmol) into a dry and clean hydrogenation inner tube and seal it and take it out. Place the hydrogenation inner tube in a high-pressure autoclave, replace the atmosphere in the autoclave with nitrogen, add anhydrous dichloromethane (1 mL) and anhydrous tert-butanol (1 mL) and stir to dissolve. Replace the atmosphere in the autoclave with hydrogen three times, and charge 40 atm of hydrogen, seal it, and stir the reaction at 30 °C. After reacting for 24 h, slowly release the hydrogen in the reaction kettle, and determine the conversion rate by NMR after desolvation. The crude product is obtained as the hydrogenated product after column chromatography. The enantioselectivity of the product is determined by chiral HPLC. HPLC conditions: Chiralcel AD-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 95:5; temp, 26 °C; flow rate = 1.0 mL / min; 210 nm UV detector; pressure, 53 bar; t R = 27.02 min (minor), t R = 30.36 min (major). Yield 97%, 94% ee. 1 1H NMR (400 MHz, CDCl3): δ 7.36–7.22 (m, 5H), 6.72 (d, J = 6.8 Hz, 1H), 5.49–5.34 (m, 1H), 4.06 (q, J = 7.1 Hz, 2H), 2.91 (dd, J = 15.6, 6.0 Hz, 1H), 2.80 (dd, J = 15.6, 6.1 Hz, 1H), 2.00 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H)

[0110] Example 21

[0111] (Z)-Methyl 3-acetamido-3-phenylacrylate asymmetric catalytic hydrogenation method, the reaction formula and reaction process are as follows:

[0112]

[0113] Under a nitrogen atmosphere, in a glove box, take methyl (Z)-3-acetamido-3-phenylacrylate (55 mg, 0.25 mmol), ligand (R)-7-bis-(3,5-dimethyl)phenylphosphinooxy-3-oxo-1,1′-spirobiindane (R)-2b (2.6 mg, 0.005 mmol) and Rh(COD)2BF4 (1 mg, 0.0025 mmol) and place them in a dry and clean hydrogenation inner tube, then seal and take out. Place the hydrogenation inner tube in an autoclave, displace the atmosphere in the autoclave with nitrogen, add anhydrous dichloromethane (1 mL) and anhydrous tert-butanol (1 mL), and stir to dissolve. Displace the atmosphere in the autoclave with hydrogen three times, then charge 60 atm of hydrogen, seal, and stir the reaction at -20 °C. After reacting for 24 h, slowly release the hydrogen in the reaction kettle, remove the solvent, and determine the conversion rate by NMR. The crude product is obtained as a hydrogenated product after column chromatography. The enantioselectivity of the product is determined by chiral HPLC. HPLC conditions: Chiralcel AD-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temp, 26 °C; flow rate = 1.0 mL / min; 210 nm UV detector; pressure, 53 bar; t R = 16.38 min (minor), t R = 17.50 min (major). The yield is 99%, 93% ee. 1 H NMR (400 MHz, CDCl3): δ 7.38–7.22 (m, 5H), 6.63 (s, 1H), 5.48–5.38 (m, 1H), 3.61 (s, 3H), 2.94 (dd, J = 15.8, 5.9 Hz, 1H), 2.83 (dd, J = 15.8, 6.0 Hz, 1H), 2.02 (s, 3H).

[0114] Example 22

[0115] (Z)-3-acetamido-3-(4-methoxyphenyl)ethyl acrylate asymmetric catalytic hydrogenation method, the reaction formula and reaction process are as follows:

[0116]

[0117] Under a nitrogen atmosphere, in a glove box, take ethyl (Z)-3-acetamido-3-(4-methoxyphenyl)acrylate (66 mg, 0.25 mmol), ligand (R)-7-di-(3,5-dimethyl)-phenylphosphinyloxy-3-oxo-1,1′-spirobiindane (R)-2b (2.6 mg, 0.005 mmol) and Rh(COD)2BF4 (1 mg, 0.0025 mmol) and place them in a dry and clean inner hydrogenation tube, then seal and take out. Place the inner hydrogenation tube in an autoclave, displace the atmosphere in the autoclave with nitrogen, add anhydrous dichloromethane (1 mL) and anhydrous tert-butanol (1 mL), and stir to dissolve. Displace the atmosphere in the autoclave with hydrogen three times, then charge 40 atm of hydrogen, seal, and stir the reaction at 0 °C. After reacting for 24 h, slowly release the hydrogen in the reaction kettle, remove the solvent, and determine the conversion rate by NMR. The crude product is obtained as the hydrogenated product after column chromatography. The enantioselectivity of the product is determined by chiral HPLC. HPLC conditions: Chiralcel AD-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temp, 26 °C; flow rate = 1.0 mL / min; 210 nm UV detector; pressure, 53 bar; t R = 26.60 min (minor), t R = 30.67 min (major). The yield is 98%, 95% ee. 1 1H NMR (600 MHz, CDCl3): δ 7.22 (d, J = 8.2 Hz, 2H), 6.85 (d, J = 8.2 Hz, 2H), 6.58 (d, J = 8.4 Hz, 1H), 5.41–5.33 (m, 1H), 4.07 (q, J = 7.2 Hz, 2H), 3.78 (s, 3H), 2.90 (dd, J = 15.7, 6.0 Hz, 1H), 2.78 (dd, J = 15.5, 6.2 Hz, 1H), 1.99 (s, 3H), 1.17 (t, J = 7.1 Hz, 3H).

[0118] Example 23

[0119] (Z)-3-acetamido-3-(2-thienyl)acrylate asymmetric catalytic hydrogenation method, the reaction formula and reaction process are as follows:

[0120]

[0121] Under a nitrogen atmosphere, in a glove box, take ethyl (Z)-3-acetamido-3-(2-thienyl)acrylate (60 mg, 0.25 mmol), ligand (R)-7-bis-(3,5-dimethyl)phenylphosphinooxy-3-oxo-1,1′-spirodihydroindene (R)-2b (2.6 mg, 0.005 mmol) and Rh(COD)2BF4 (1 mg, 0.0025 mmol) and place them in a dry and clean hydrogenation inner tube, then seal and take out. Place the hydrogenation inner tube in an autoclave, replace the atmosphere in the autoclave with nitrogen, add anhydrous dichloromethane (1 mL) and anhydrous tert-butanol (1 mL), stir to dissolve. Replace the atmosphere in the autoclave with hydrogen three times, and then charge 40 atm of hydrogen, seal, and place it under stirring at 0 °C for reaction. After reacting for 24 h, slowly release the hydrogen in the autoclave, remove the solvent, and determine the conversion rate by NMR. The crude product is obtained as the hydrogenated product after column chromatography. The enantioselectivity of the product is determined by chiral HPLC. HPLC conditions: Chiralcel OD-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temp, 26 °C; flow rate = 1.0 mL / min; 210 nm UV detector; pressure, 60 bar; t R = 20.68 min (minor), t R = 22.03 min (major). The yield is 98%, 94% ee. 1 1H NMR (400 MHz, CDCl3): δ 7.22–7.15 (m, 1H), 6.99–6.90 (m, 2H), 6.79 (d, J = 8.8 Hz, 1H), 5.75–5.64 (m, 1H), 4.12 (q, J = 7.1 Hz, 2H), 2.96 (dd, J = 15.9, 5.5 Hz, 1H), 2.87 (dd, J = 15.9, 5.8 Hz, 1H), 2.01 (s, 3H), 1.21 (t, J = 7.2 Hz, 3H). 13 13C NMR (151 MHz, CDCl3): δ 171.1, 169.1, 144.4, 126.9, 124.6, 124.4, 60.9, 45.5, 40.1, 23.4, 14.1. HRMS (ESI-TOF) m / z: [M+H] + calcd for C 11 H 16 NO3S + 242.0845; Found 242.0843.

[0122] The above description is a detailed description of the preferred and feasible embodiments of the present invention. However, the above embodiments are not intended to limit the protection scope of the present invention. Any equivalent changes or modifications made under the technical spirit of the present invention fall within the protection scope covered by the present invention.

Claims

1. A 3-oxo-1,1'-spirobiindane chiral monophenol, characterized in that it is A compound having the following general formula 1:

2. An asymmetric synthesis method of the 3-oxo-1,1'-spirobiindane chiral monophenol described in claim 1, characterized in that: Prepared from the indanone compound of formula 3 through the following reaction process:

3. The asymmetric synthesis method according to claim 2, characterized in that, The specific steps are as follows: S1, at -30 to 10 °C, slowly drop the organic solution of the indanone compound shown in formula 3 into the mixed solution of (R)-2-Me-CBS or (S)-2-Me-CBS and borane tetrahydrofuran. After the reaction is completed, quench, concentrate under vacuum, and purify by silica gel chromatography to obtain indanol (R)-4 or (S)-4; preferably: In the organic solution of the indanone compound, the concentration of the indanone compound is 0.1 - 1.5 M; The molar ratio of (R)-2-Me-CBS or (S)-2-Me-CBS to the indanone compound is (5 - 30):100; The equivalent ratio of the borane tetrahydrofuran to the indanone compound is (1.1 - 3):1; In the mixed solution, the volume of the solvent is 1.5 - 2 times the volume of the borane tetrahydrofuran; The dropping is completed within 2 - 3 h; preferably, it is dropped at a rate of 1 drop / 5 s. S2, put indanol (R)-4 or (S)-4, triethyl orthoacetate, and an acid as a catalyst into a reaction vessel, react at 80 - 160 °C for 2 - 6 hours. After the reaction is completed, remove the excess triethyl orthoacetate, and purify the residue by silica gel chromatography to obtain compound (R)-5 or (S)-5; preferably: The equivalent ratio of the triethyl orthoacetate to indanol (R)-4 or (S)-4 is (5 - 30):1; The molar ratio of the acid to indanol (R)-4 or (S)-4 is (2 - 30):100; S3, add palladium carbon to the organic solution of compound (R)-5 or (S)-5, react at 10 - 60 °C for 8 - 24 hours under a hydrogen pressure of 1 - 60 atm. The obtained mixture is filtered, washed, and concentrated under vacuum to obtain compound (R)-6 or (S)-6; preferably, the molar ratio of the palladium carbon to compound (R)-5 or (S)-5 is (5 - 30):100; S4, add an organic solvent, water, and a base to compound (R)-6 or (S)-6, react at room temperature to 110 °C for 7 - 24 hours. After cooling, extract, wash, dry, and remove the solvent under reduced pressure to obtain compound (R)-7 or (S)-7; preferably: The concentration of (R)-6 or (S)-6 in the organic solvent is 0.5 - 2 M; The volume ratio of the organic solvent to water is (1 - 3):1; The equivalent ratio of the base to compound (R)-6 or (S)-6 is (2.0 - 6.0):1; S5, under a nitrogen or inert gas atmosphere, add trifluoromethanesulfonic acid to the organic solution of compound (R)-7 or (S)-7, react at -78 to 60 °C for 2 - 24 hours. After the reaction is completed, quench, extract, remove the solvent under reduced pressure, and perform silica gel column chromatography to obtain compound (R)-8 or (S)-8; preferably: the equivalent ratio of the trifluoromethanesulfonic acid to compound (R)-7 or (S)-7 is (3 - 30):1; S6. Under a nitrogen or inert gas atmosphere, at -78 to 0 °C, boron tribromide is slowly added dropwise to an organic solution of compound (R)-8 or (S)-8, then the temperature is raised to room temperature, and the reaction is carried out for 8 - 24 hours. After quenching, extraction, and purification by silica gel column chromatography, chiral monophenol (R)-1 or (S)-1 of 3-oxo-1,1'-spirobisdihydroindene is obtained. Preferably, in the organic solution of compound (R)-8 or (S)-8, the concentration of the organic solution of compound (R)-8 or (S)-8 is 0.1 - 1 mmol / ml.

4. The asymmetric synthesis method according to claim 3, wherein: Preferably, the solvents in the organic solution and the mixed solution in S1 are the same, and are selected from one or more of tetrahydrofuran, dichloromethane, diethyl ether, and 1,4-dioxane; Preferably, the acid in S2 is one or more of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, and pivalic acid; Preferably, the solvent of the organic solution in S3 is selected from one or more of tetrahydrofuran, dichloromethane, ethyl acetate, 1,4-dioxane, methanol, ethanol, and n-propanol; Preferably, the organic solvent in S4 is one or more of tetrahydrofuran, dichloromethane, methanol, and ethanol; the base is one or more of lithium hydroxide, sodium hydroxide, and potassium hydroxide; Preferably, in the organic solution of S5, the solvent is selected from one or more of tetrahydrofuran, dichloromethane, and toluene; Preferably, in the organic solution of S6, the solvent is selected from one or more of tetrahydrofuran, dichloromethane, and toluene.

5. A method for preparing a 3-oxo-1,1'-spirobiindane chiral phosphite monophosphine ligand from the 3-oxo-1,1'-spirobiindanylene chiral monophenol described in claim 1, characterized in that, The reaction formula and reaction process are as follows: Under a nitrogen or inert gas atmosphere, in an organic solvent, 3-oxo-1,1'-spirobisdihydroindene chiral monophenol reacts with disubstituted phosphorus chloride at 0 - 50 °C for 1 - 10 hours using a base as an acid-binding agent. Under an argon atmosphere, after concentration under reduced pressure and column chromatography, a chiral phosphite ligand is obtained, wherein: The equivalent ratio of the base, disubstituted phosphorus chloride to 3-oxo-1,1'-spirobisdihydroindene chiral monophenol is (1.5 - 3):(1.0 - 3.0):

1.

6. The method according to claim 5, wherein: R 1 is an alkyl or aryl group, where the alkyl group is methyl, ethyl, propyl or butyl; and the aryl group is phenyl or phenyl substituted by an alkyl or alkoxy group.

7. The method according to claim 5, wherein: The organic solvent is one or more of dichloromethane, toluene, and tetrahydrofuran; The base is triethylamine, diisopropylethylamine, or 4-dimethylaminopyridine; The disubstituted phosphorus chloride is diarylphosphorus chloride or dialkylphosphorus chloride.

8. The application of the 3-oxo-1,1'-spirodihydroindene skeleton chiral phosphite monophosphine ligand prepared by the method of any one of claims 5 - 7 in an asymmetric catalytic reaction, wherein: The asymmetric catalytic reaction is hydrogenation reaction, hydroformylation reaction, hydrosilylation reaction, hydroboration reaction, hydroxyhydroxylation reaction, hydroamination reaction, hydrocyanation reaction, isomerization formylation reaction, hydroaminomethylation reaction, transfer hydrogenation reaction, allylation reaction, olefin metathesis reaction, ring isomerization reaction, Diels - Alder reaction, asymmetric coupling reaction, Aldol reaction, Michael addition reaction, asymmetric epoxidation reaction, kinetic resolution, or [m + n] cyclization reaction.

9. The application according to claim 8, wherein The reaction process is as follows: Under the protection of nitrogen or inert gas, add β-dehydro amino acid ester, 3-oxo-1,1'-spirodihydroindene skeleton chiral phosphite monophosphine ligand, rhodium metal precursor and organic solvent into the hydrogenation kettle and stir to dissolve. Then, charge hydrogen and stir and react for 24 - 60 hours in an H2 atmosphere at -20°C to 40°C and 10 - 60 atm to obtain optically active amino acid ester, where: The molar ratio of the 3-oxo-1,1'-spirodihydroindene skeleton chiral phosphite monophosphine ligand to the rhodium metal precursor is 2:1; The molar ratio of the rhodium metal precursor to the β-dehydro amino acid ester is 1:(0.5 - 10).

10. The application according to claim 9, wherein: The rhodium metal precursor is [Rh(cod)Cl]2 (cod = cyclooctadiene), [Rh(cod)2]BF4, [Rh(cod)2]PF6, [Rh(cod)2]SbF6 or [Rh(cod)2]OTf); The organic solvent is one or more of dichloromethane, toluene, tetrahydrofuran, methanol, ethanol, isopropanol, tert-butanol; preferably, the concentration of the substrate in the solvent is 0.1 - 0.5 mmol / ml; the preferred organic solvent is a mixed solvent of dichloromethane and tert-butanol, where the volume ratio of the two is (1 - 3):1; R 2 、R 3 is an alkyl group, an aryl group or a hydrogen atom; preferably: The alkyl group is methyl, ethyl, propyl or butyl; The aryl group is a phenyl group substituted or unsubstituted by an alkyl group, an alkoxy group, a halogen atom; where the alkoxy group is methoxy, ethoxy, propoxy or butoxy; R 4 is an amino protecting group, R 4 is selected from acetyl, alkoxycarbonyl, p-toluenesulfonyl and benzyl.

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