Chiral 2, 2-, 3, 3-or 2, 3-substituted spiro-bipyridine compound, oxynitride thereof and preparation of chiral 2, 2-, 3, 3-or 2, 3-substituted spiro-bipyridine compound

Abstract

The invention discloses a chiral 2, 2 '-, 3, 3'-or 2, 3 '-substituted spiro-bispyridine compound, a nitrogen oxide compound thereof and a preparation method of the chiral 2, 2'-, 3, 3 '-or 2, 3'-substituted spiro-bispyridine compound. According to the invention, 2, 2-bis (butyl-3-alkynyl) malononitrile and terminal alkyne are taken as starting materials, and the catalyst is prepared in an asymmetric [2 + 2 + 2] cycloaddition reaction system catalyzed by metal cobalt / bis-oxazoline-phosphine; the method has the advantages of easily available raw materials, economical steps, specific regioselectivity, high enantioselectivity and the like. The novel chiral spiro-bipyridine oxynitride can be used as an organic catalyst, and shows good activity and stereoselectivity in an asymmetric allyl addition reaction.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical engineering, and relates to a preparation method of chiral compounds, in particular to a chiral 2,2′-, 3,3′- or 2,3′-substituted spirobipyridine compound, its N-oxide compound and a preparation method thereof. Background Art

[0002] Asymmetric catalysis is an important means for synthesizing optically active compounds, and asymmetric transition metal or organocatalysis is the main branch in this field. Chiral ligands and chiral organocatalysts can not only improve the reaction activity, but also control the stereoselectivity. Designing and synthesizing novel chiral ligands and chiral organocatalysts is a long-term goal of organic chemists. Chiral spiro-containing compounds exhibit outstanding advantages and powerful applications. Among them, ligands or chiral organocatalysts with a chiral spiroindane skeleton substituted by 2,2′- or 3,3′- have attracted the attention of many scientists and have been widely used in the field of asymmetric catalysis [(a) Lin, X.;Wang, L.;Han, Z.;Chen, Z. Chin. J. Chem. 2021, 39, 802;(b) Woldegiorgis, A. G.;Han, Z.;Lin, X. J. Mole. Stru. 2024, 1297(1), 136919;(c) Yang, L.-L.;Evans, D.;B. Xu, B.;Li, W.-T.;Li, M.-L.;Zhu, S.-F.;Houk, K. N.;Zhou, Q.-L. J. Am. Chem. Soc. 2020, 142, 12394;(d) Xu, B.;Zhu, S.-F.;Zhang, Z.-C.;Yu, Z.-X.;Ma, Y.;Zhou, Q.-L. Chem. Sci. 2014, 5, 1442;(e) Zhang, X.-Y.;Zhu, D.;Huo, Y.-X.;Chen, L.-L.;Chen, Z.-M. Org. Lett. 2023, 25, 3445]. The 2,2′- or 3,3′-substituents play a key role in enhancing the stereocontrol ability of chiral ligands and chiral organocatalysts. Replacing the two benzene rings in the chiral spiroindane skeleton with two pyridines gives a chiral spirobipyridine skeleton, and the two pyridine rings in this skeleton can bring about changes in the coordination environment and catalytic activity. However, the development and application of chiral ligands and chiral catalysts based on the chiral spirobipyridine skeleton have not been reported before. The asymmetric synthesis of 2,2′- or 3,3′-substituted chiral spirobipyridine compounds similar to the 2,2′- or 3,3′-substituted chiral spiroindane skeleton and their applications in asymmetric synthesis have also not been reported. Synthesizing such compounds is very meaningful.

[0003] The synthesis of chiral spirobipyridines has been sporadically reported before. In 1999, the Saá research group reported the synthesis of racemic spirobipyridines through carbonyl cobalt-mediated [2+2+2] cycloaddition. However, this reaction requires the use of 30 mol% of CpCo(I) complex, and the reaction yield is very low (7 to 33%), and it cannot synthesize 2,2'- or 3,3'-substituted spirobipyridines [J.A. Varela, L. Castedo, C. Saá, Org. Lett. 1999, 1, 2141]. In 2007, the Tanaka research group reported the enantioselective intramolecular [2+2+2] cycloaddition reaction of divinyl dinitriles catalyzed by rhodium(I), and enantiomerically enriched fully substituted spirobipyridines were synthesized with up to 71% ee [A. Wada, K. Noguchi, M. Hirano, K. Tanaka, Org. Lett. 2007, 9, 1295]. The Liu Wenbo research group reported the preparation of nickel-catalyzed polysubstituted chiral spirobipyridine compounds in a 2020 patent and a 2025 article [(a) W.-B. Liu, J.-H. Cai, CN111646992A, 2020; (b) J. Am. Chem. Soc. 2025, doi.org / 10.1021 / jacs.5c01653]. Whether it is the Tanaka or the Liu Wenbo research group, they both reported the synthesis of polysubstituted spirobipyridines. Too many substituents increase the steric hindrance around the pyridine, which is not conducive to its coordination with metals as a chiral ligand or its catalysis of reactions as an organic catalyst, limiting its application in asymmetric catalysis. And although the structural formula of the polysubstituted spirobipyridine in the report of the Liu Wenbo research group lists that R1, R3, and R4 can be hydrogen; in fact, its synthesis route cannot prepare chiral spirobipyridine compounds with only 2,2'-substitution. The present invention discovers that chiral spirobipyridine compounds with 2,2'- or 3,3'-substitution can more effectively construct a C2-symmetric chiral environment, and the catalysts based on this are expected to be applied in asymmetric reactions, but the preparation methods of such structures have not been reported before.

[0004] In 2021, the inventors' research group reported a cobalt / chiral bisoxazoline-phosphine-catalyzed asymmetric one-pot [2 + 2 + 2] cycloaddition reaction for the selective synthesis of 5-alkyl-substituted or 6-aryl-substituted α-cyano-substituted all-carbon quaternary chiral pyridine compounds [K. Li, L. Wei, M. Sun, B. Li, M. Liu, C. Li, Angew. Chem. Int. Ed. 2021, 60, 20204]. However, under the same catalytic conditions, the diallyl-substituted malononitrile substrate cannot undergo a bis[2 + 2 + 2] cycloaddition reaction to form a chiral spirobipyridine product. The pyridine structure formed in the first [2 + 2 + 2] cycloaddition reaction has a certain coordination inhibitory effect on the catalyst, making it difficult to achieve the second [2 + 2 + 2] cycloaddition reaction. The diyne structure itself can also undergo polymerization or oligomerization reactions, further consuming the raw materials and reducing the yield, which limits the efficient preparation of chiral spirobipyridines. Summary of the Invention

[0005] In view of the limitations and challenges in the prior art, the object of the present invention is to provide a method for preparing chiral spirobipyridine compounds and chiral spirobipyridine N-oxides with high efficiency and high enantioselectivity. Based on optimizing factors such as reducing agents, additives, and metal cobalt precursors, the present invention enhances the reaction activity of the metal cobalt catalyst, overcomes the influence of the pyridine formed in the first step, and realizes two [2 + 2 + 2] cycloaddition reactions (including bis[2 + 2 + 2] cycloaddition reaction and the second [2 + 2 + 2] cycloaddition reaction), efficiently and highly enantioselectively preparing 2,2'- or 3,3'-substituted chiral spirobipyridine compounds, which can form complexes with metals as ligands.

[0006] The present invention further oxidizes to prepare 2,2'- or 3,3'-substituted chiral spirobipyridine N-oxides, which can catalyze asymmetric allylic addition reactions as organic catalysts to obtain high yields and good enantioselectivities. Among them,

[0007]

[0008] The object of the present invention is achieved by the following technical solutions:

[0009] [First aspect]

[0010] The present invention relates to a chiral spirobipyridine compound, which has a chiral spirobipyridine structure, and the substituents are at the 2,2'-position, 3,3'-position or 2,3'-position.

[0011] As an embodiment of the present invention, the structural formula of the chiral 2,2'-substituted spirobipyridine compound is shown in Formula 1 or 2; the structural formula of the chiral 3,3'-substituted spirobipyridine compound is shown in Formula 3 or 4; the structural formula of the chiral 2,3'-substituted spirobipyridine compound is shown in Formula 5:

[0012]

[0013] wherein, R 1 and R 2 are respectively selected from C6-C20 aryl, C4-C20 heteroaryl, C6-C20 substituted aryl containing nitrogen, oxygen or halogen, C2-C20 alkenyl; and R 1 and R 2 are different;

[0014] R 3 and R 4 are respectively selected from C1-C20 alkyl, trisubstituted silyl, C3-C20 cycloalkyl, or heteroatom-containing C1-C20 alkyl; the heteroatom is one or more of silicon, nitrogen, oxygen, halogen; the substituents of the trisubstituted silyl are C1-C6 alkyl or phenyl; and R 3 and R 4 are different;

[0015] * represents a chiral center.

[0016] As an embodiment of the present invention, the C6-C20 aryl is phenyl, substituted phenyl or naphthyl; the substituents in the substituted phenyl are C1-C10 alkyl, C6-C10 aryl, or substituents containing nitrogen, sulfur, oxygen or halogen atoms. Further, the substituents containing nitrogen, sulfur, oxygen or halogen atoms may be selected from dimethylamino, hydroxyl, methoxy, halogen, ester group.

[0017] As an embodiment of the present invention, the C4-C20 heteroaryl may be selected from C4-C20 heteroaryl containing nitrogen, sulfur or oxygen atoms.

[0018] As an embodiment of the present invention, the C4-C20 heteroaryl is benzofuranyl, thiophenyl, substituted or unsubstituted pyridyl, quinolinyl, isoquinolinyl or ferrocenyl; the substituted pyridyl is C1-C6 alkyl, phenyl or pyridyl substituted with nitrogen, oxygen, halogen.

[0019] As an embodiment of the present invention, the C2-C20 alkenyl includes C3-C20 cycloalkenyl.

[0020] As an embodiment of the present invention, the C1-C20 alkyl is n-octyl, C1-C14 alkyl containing phenyl.

[0021] As an embodiment of the present invention, the C3-C20 cycloalkyl group includes cyclopropyl.

[0022] As an embodiment of the present invention, the trisubstituted silyl group is trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl or triisopropylsilyl.

[0023] [Second aspect]

[0024] The present invention relates to a method for preparing a chiral spirobipyridine compound; wherein,

[0025] The method for preparing the chiral spirobipyridine compound shown in Formula 1 or Formula 3 includes the following steps:

[0026] S11. Using a cobalt catalyst and a ligand as catalysts, in the presence of an organic solvent, an additive and a reducing agent, the raw materials 7-1 or 7-3 and the raw material 6 undergo a bis[2+2+2] cycloaddition reaction;

[0027] S12. After the reaction is completed, separate and purify to obtain the chiral spirobipyridine compound shown in Formula 1 or Formula 3;

[0028] The reaction equation is as follows:

[0029] Wherein Co catalyst refers to a metal cobalt catalyst; Ligand refers to a ligand; Reductant refers to a reducing agent; Additive refers to an additive; Solvent refers to an organic solvent.

[0030] The method for preparing the chiral spirobipyridine compound shown in Formula 2, Formula 4 or Formula 5 includes the following steps:

[0031] S21. Using a cobalt catalyst and a ligand as catalysts, in the presence of an organic solvent and a reducing agent, the raw materials 7-1 or 7-3 and the raw material 6 undergo a first [2+2+2] cycloaddition reaction;

[0032] S22. After the reaction is completed, separate and purify to obtain the 2- or 3-substituted pyridine compound 8 or 9 containing a cyano quaternary carbon chiral center;

[0033] S23. Using a cobalt catalyst and a ligand as catalysts, in the presence of an organic solvent, an additive and a reducing agent, the intermediate 8 or 9 reacts with the raw materials 7-2 or 7-4 to undergo a second [2+2+2] cycloaddition reaction;

[0034] S24. After the reaction is completed, separate and purify to obtain the chiral spirobipyridine compound shown in Formula 2, Formula 4 or Formula 5; the reaction equation is as follows:

[0035] Among them, Co catalyst refers to a metal cobalt catalyst; Ligand refers to a ligand; Reductant refers to a reducing reagent; Additive refers to an additive; Solvent refers to an organic solvent.

[0036] In the above S21 - S24, using a metal cobalt catalyst precursor and a ligand as a catalyst, adding a reducing reagent, a bis[2 + 2 + 2] cycloaddition reaction occurs in an organic solvent; using a cobalt catalyst precursor and a ligand as a catalyst, adding a reducing reagent, a [2 + 2 + 2] cycloaddition reaction occurs once in an organic solvent to obtain intermediate products 8 and 9; using a cobalt catalyst precursor and a ligand as a catalyst, adding a reducing reagent, a second [2 + 2 + 2] cycloaddition reaction occurs in an organic solvent to obtain products 2, 4 or 5.

[0037] As an embodiment of the present invention; the cobalt catalyst is a monovalent cobalt or divalent cobalt catalyst. The monovalent cobalt catalyst includes tris(triphenylphosphine)cobalt chloride or chiral bisoxazoline - phosphine cobalt iodide, and the divalent cobalt catalyst includes cobalt iodide, cobalt (hexa - hydrate) tetrafluoroborate, cobalt (tetra - hydrate) acetate, cobalt trifluoromethanesulfonate or cobalt bromide.

[0038] As an embodiment of the present invention, the ligand is a chiral bisoxazoline - phosphine tridentate ligand, and its structural formula is as follows:

[0039] Among them, R 5 is selected from C6 - C20 aryl, C4 - C20 heteroaryl containing an oxygen atom, a nitrogen atom or a sulfur atom, C1 - C20 alkyl, C6 - C20 substituted aryl, and the substituent is selected from C1 - C8 alkyl or methoxy; R 6 is methyl, ethyl, isopropyl, isobutyl, cyclohexyl, benzyl or phenyl.

[0040] Furthermore, the ligand is the following structure or its enantiomer:

[0041]

[0042] As an embodiment of the present invention, the reducing reagent is one of silane, borane, zinc powder, indium powder, manganese powder.

[0043] As an embodiment of the present invention, the additive is one of sodium tetrakis(3,5 - bis(trifluoromethyl)phenyl)borate, zinc trifluoromethanesulfonate, scandium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, indium trifluoromethanesulfonate.

[0044] As an embodiment of the present invention, the organic solvent is one of dichloroethane, acetonitrile, dichloromethane, toluene, benzonitrile, trifluorotoluene, hexafluoroisopropanol, trifluoroethanol, N,N′ - dimethylformamide.

[0045] As an embodiment of the present invention, in S11, the molar ratio of the cobalt catalyst to the ligand is 1:(1-2). The molar ratio of the raw material 7-1 or 7-3 to the raw material 6 is (2.5-4):1. The molar ratio of the cobalt catalyst to the raw material 6 is 1:(10-1000). The molar ratio of the reducing agent to the raw material 6 is 1:(10-1000). The molar ratio of the additive to the cobalt catalyst is 1:(1-2). The reaction temperature is 0-100 °C.

[0046] As an embodiment of the present invention, in S21, the molar ratio of the cobalt catalyst to the ligand is 1:(1-2). The molar ratio of the raw material 7-1 or 7-3 to the raw material 6 is (1-2):1. The molar ratio of the cobalt catalyst to the raw material 6 is 1:(10-1000). The molar ratio of the reducing agent to the raw material 6 is 1:(2.5-1000). The reaction temperature is 0-100 °C.

[0047] As an embodiment of the present invention, in S23, the molar ratio of the cobalt catalyst to the ligand is 1:(1-2). The molar ratio of the additive to the cobalt catalyst is (1-2):1. The molar ratio of the intermediate 8 or 9 to the raw material 7-2 or 7-4 is 1:2. The molar ratio of the cobalt catalyst to the intermediate 8 or 9 is 1:(10-1000). The molar ratio of the reducing agent to the intermediate 8 or 9 is 1:(2.5-1000). The reaction temperature is 0-100 °C.

[0048] As an embodiment of the present invention, the reaction temperature is 0-80 °C. The reaction time is 12-36 hours.

[0049] [Third aspect]

[0050] The present invention relates to a 2,2'- or 3,3'-substituted chiral spirobipyridine N-oxide compound, and its structural formula is shown in Formulas 10 and 11:

[0051] Wherein, R 1 are respectively selected from C6-C20 aryl, C4-C20 heteroaryl, C6-C20 substituted aryl containing nitrogen, oxygen or halogen, C2-C20 alkenyl; R 3 are respectively selected from a hydrogen atom, C1-C20 alkyl, trisubstituted silyl, C3-C20 cycloalkyl, C1-C14 alkyl containing a phenyl group or C1-C20 alkyl containing a heteroatom; the heteroatom is one or more of silicon, nitrogen, oxygen, halogen; * represents a chiral center.

[0052] As an embodiment of the present invention, the C6-C20 aryl group is phenyl, substituted phenyl or naphthyl; the substituents in the substituted phenyl group are C1-C10 alkyl groups, C6-C10 aryl groups, or substituents containing nitrogen, sulfur, oxygen or halogen atoms. Further, the substituents containing nitrogen, sulfur, oxygen or halogen atoms may be selected from dimethylamino, hydroxy, methoxy, halogen, and ester groups.

[0053] As an embodiment of the present invention, the C4-C20 heteroaryl group may be selected from C4-C20 heteroaryl groups containing nitrogen, sulfur or oxygen atoms.

[0054] As an embodiment of the present invention, the C4-C20 heteroaryl group is benzofuranyl, thienyl, substituted or unsubstituted pyridyl, quinolinyl, isoquinolinyl or ferrocenyl; the substituted pyridyl group is a C1-C6 alkyl group, a phenyl group or a pyridyl group substituted with nitrogen, oxygen or halogen.

[0055] As an embodiment of the present invention, the C2-C20 alkenyl group includes a C3-C20 cycloalkenyl group. For example, it may be cyclopropyl.

[0056] As an embodiment of the present invention, the C1-C20 alkyl group is n-octyl, a C1-C14 alkyl group containing a phenyl group.

[0057] As an embodiment of the present invention, the trisubstituted silyl group is trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl or triisopropylsilyl.

[0058] [Fourth aspect]

[0059] The present invention relates to a method for preparing a 2,2'- or 3,3'-substituted chiral spirobipyridine N-oxide compound, and the method comprises the following steps:

[0060] S1. Add an equivalent amount of an oxidizing reagent, and react raw material 1 or 3 in an organic solvent;

[0061] S2. After the reaction is completed, separate and purify to obtain the 2,2'- or 3,3'-substituted chiral spirobipyridine N-oxide compound 10 or 11;

[0062] The reaction equation is as follows:

[0063] Among them,

[0064] oxidant refers to the oxidizing reagent, and solvent refers to the organic solvent.

[0065] As an embodiment of the present invention, the oxidizing reagent is one of m-chloroperbenzoic acid, hydrogen peroxide, perbenzoic acid, peracetic acid, trifluoroperacetic acid, tert-butyl hydroperoxide, peroxyacetone, etc.

[0066] As an embodiment of the present invention, the organic solvent is one of dichloromethane, dichloroethane, etc.

[0067] As an embodiment of the present invention, the molar ratio of raw material 1 or 3 to the oxidizing agent is 1:2 to 4.

[0068] As an embodiment of the present invention, the reaction temperature is 0°C to 100°C, and the reaction time is 2 to 12 hours.

[0069] [Fifth aspect]

[0070] The present invention relates to the application of a chiral 2,2'-substituted spirobipyridine compound represented by Formula 1 or 2 in coordinating with a transition metal as a ligand;

[0071] wherein, R 1 , R 2 are each independently selected from C6-C20 aryl, C4-C20 heteroaryl, C6-C20 substituted aryl containing nitrogen, oxygen or halogen, C2-C20 alkenyl; and R 1 , R 2 are different.

[0072] As an embodiment of the present invention, the structure of the complex obtained by coordination is as follows:

[0073]

[0074] [Sixth aspect]

[0075] The present invention relates to the application of a 2,2'- or 3,3'-substituted chiral spirobipyridine N-oxide compound as an organocatalyst in asymmetric synthesis.

[0076] As an embodiment of the present invention, the 2,2'- or 3,3'-substituted chiral spirobipyridine N-oxide compound is used as a Lewis base in an asymmetric allylic addition reaction to achieve the asymmetric synthesis of compound 13:

[0077]

[0078] Compared with the prior art, the present invention has the following beneficial effects:

[0079] 1) The present invention provides a novel structure of 2,2'-, 3,3'- and 2,3'-substituted chiral spirobipyridine compounds.

[0080] 2) The present invention provides a novel structure of 2,2'- and 3,3'-substituted chiral spirobipyridine N-oxide organocatalysts.

[0081] 3) The method provided by the present invention has the advantages of simple operation, readily available raw materials, atom economy of reaction, mild reaction conditions, high regioselectivity, high enantioselectivity and good substrate compatibility.

[0082] 4) The present invention uses abundant metal catalysts, which are low-priced and environmentally friendly.

[0083] 5) The 2,2′- and 3,3′-substituted chiral spirocyclic bipyridine and spirocyclic tetrapyridine compounds prepared by the present invention can effectively complex with metal salts to form metal complexes.

[0084] 6) The chiral spirocyclic bipyridine nitrogen oxide compound provided by the present invention can be used as a Lewis base organic catalyst in an asymmetric allylic addition reaction, showing high reaction activity and good enantioselectivity, with a yield of 99% and an ee of 88%, respectively. DETAILED DESCRIPTION

[0085] The present invention is described in detail below in conjunction with embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, some adjustments and improvements can also be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0086] In the present invention, the general formula of compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 is as follows:

[0087]

[0088] The terminal alkynes 7 used in the present invention are all commercially available.

[0089] The preparation method comprises the following steps:

[0090] S1-1:

[0091]

[0092] Wherein, equiv represents equivalent; Ar represents an aromatic substituent, or a heterocyclic aromatic group other than pyridine and substituted pyridine; mol% represents relative molar amount; DCE represents dichloroethane; RT represents room temperature; yield represents separation yield; and ee represents enantioselectivity.

[0093] In a nitrogen-filled glove box, CoI2 (3.1 mg, 0.01 mmol, 5 mol%) and ligand L3-NPNPh,Bn (7.0 mg, 0.012 mmol, 6 mol%) were successively added to a 10 mL Schlenk tube that had been dried at high temperature, followed by dichloroethane (0.5 mL). After stirring for 5 minutes, the reducing reagent indium powder (4.6 mg, 0.04 mmol, 20 mol%) was added. Stirring was continued for 5 minutes, and then starting material 6 (34.0 mg, 0.2 mmol, 1.0 equiv) and aryl terminal alkyne 7 (0.6 mmol, 3.0 equiv) were added to the system. Finally, NaBAr F 4 (17.7 mg, 0.02 mmol, 10 mol%) was added. The reaction tube was removed from the glove box and stirred at room temperature for 24 hours. After the reaction was completed, an appropriate amount of ethyl acetate was added for dilution, and the reaction progress was monitored by TLC. The crude product was obtained by concentration under reduced pressure, and the target product 1 was obtained by further flash column chromatography separation.

[0094] S1-2:

[0095]

[0096] In a nitrogen-filled glove box, complex CoI2-L9 (10.4 mg, 0.01 mmol, 10 mol%) and 0.5 mL of trifluorotoluene were successively added to a 10 mL Schlenk tube that had been dried at high temperature. Then, the reducing reagent indium powder (4.6 mg, 0.04 mmol, 40 mol%) was added, and the reaction was stirred for 5 minutes. Starting material 6 (17.0 mg, 0.1 mmol, 1.0 equiv) and 2-ethynylpyridine analogue 7 (0.25 mmol, 2.5 equiv) were added, and finally NaBAr F 4 (17.7 mg, 0.02 mmol, 20 mol%) was added. The reaction tube was removed from the glove box and stirred in an oil bath at 40 °C for 24 hours. After the reaction was completed, an appropriate amount of ethyl acetate was added for dilution, and the reaction progress was monitored by TLC. The crude product was obtained by concentration under reduced pressure, and the target product chiral spirotetrapyridine 1 was obtained by further flash column chromatography separation.

[0097] S1-3:

[0098]

[0099] In a nitrogen-filled glove box, into a 10 mL Schlenk tube that had been dried at high temperature, the complex CoI2-L10 (20.1 mg, 0.02 mmol, 10 mol%) and a mixed solvent of 0.5 mL CF3Ph and 0.1 mL HFIP were successively added. During stirring, the reducing reagent indium powder (9.2 mg, 0.08 mmol, 40 mol%) was continuously added, and stirring was continued for 5 minutes. The raw materials 6 (34.0 mg, 0.2 mmol, 1.0 equiv) and 7-3 (0.8 mmol, 4.0 equiv) were added, and finally NaBAr F 4 (35.4 mg, 0.04 mmol, 20 mol%) was added. The reaction tube was transferred outside the glove box and stirred at 40 °C in an oil bath for 36 hours. After the reaction was completed, an appropriate amount of ethyl acetate was added for dilution, and the reaction progress was monitored by TLC. The crude product was obtained by concentration under reduced pressure, and the target product 3 was obtained by further flash column chromatography separation.

[0100] S2-1:

[0101]

[0102] In a nitrogen-filled glove box, a 10 mL Schlenk tube that had been dried at high temperature was taken, and Co(BF4)2·6H2O (3.4 mg, 0.01 mmol, 5 mol%), ligand L3 (7.0 mg, 0.012 mmol, 6 mol%) and 0.5 mL of DCE were successively added, and the reaction was stirred for 30 minutes. Ph2SiH2 (3.7 mg, 0.02 mmol, 10 mol%) was added, and the reaction was continued to stir for 5 minutes, and then the raw material 6 (34 mg, 0.2 mmol) and aryl terminal alkyne 7 (0.4 mmol, 2.0 equiv) were added. The reaction tube was removed from the glove box and placed in a water bath at 30 °C for heating and reaction for 24 hours. After the reaction was completed, an appropriate amount of ethyl acetate was added for dilution, and the reaction progress was monitored by TLC. The reaction solution was dried by rotary evaporation under reduced pressure, and the crude product was separated by further flash column chromatography (PE / EA eluent) to obtain the target product 8.

[0103] S2-2:

[0104]

[0105] In a nitrogen-filled glove box, a 10 mL Schlenk tube that has been dried at high temperature is taken, and Co(BF4)2·6H2O (3.4 mg, 0.01 mmol, 5 mol%) is added successively, followed by ligand L10 (8.3 mg, 0.012 mmol, 6 mol%) and 0.5 mL of HFIP. The mixture is stirred for 30 minutes. Ph2SiH2 (3.7 mg, 0.02 mmol, 10 mol%) is added, and stirring is continued for 5 minutes. Then, starting material 6 (34 mg, 0.2 mmol) and alkyl terminal alkyne 7 (0.4 mmol, 2.0 equiv) are added. The reaction tube is removed from the glove box and heated in an oil bath at 60 °C for 24 hours. After the reaction is complete, an appropriate amount of ethyl acetate is added for dilution, and the reaction progress is monitored by TLC. The reaction solution is rotary evaporated under reduced pressure, and the crude product is separated by further flash column chromatography (using PE / EA as the eluent) to obtain the target product 9.

[0106] S2-3:

[0107]

[0108] In a nitrogen-filled glove box, CoI2 (3.1 mg, 0.01 mmol, 5 mol%) and ligand L3-NPN Ph,Bn (7.0 mg, 0.012 mmol, 6 mol%) are successively added to a 10 mL Schlenk tube that has been dried at high temperature, followed by dichloroethane (0.5 mL). After stirring for 5 minutes, the reducing agent indium powder (4.6 mg, 0.04 mmol, 20 mol%) is added. Stirring is continued for 5 minutes, and starting material 8 or 9 (0.2 mmol, 1.0 equiv) and aryl terminal alkyne 7 (0.4 mmol, 2.0 equiv) are added to the system. Finally, NaBAr F 4 (17.7 mg, 0.02 mmol, 10 mol%) is added. The reaction tube is removed from the glove box and stirred at room temperature for 24 hours. After the reaction is complete, an appropriate amount of ethyl acetate is added for dilution, and the reaction progress is monitored by TLC. The reaction solution is concentrated under reduced pressure to obtain the crude product, and further flash column chromatography gives the target product 2,2'-substituted chiral spirobipyridine compound 2 or 2,3'-substituted chiral spirobipyridine compound 5.

[0109] S2-4:

[0110]

[0111] In a nitrogen-filled glove box, the complex CoI2-L9 (10.4 mg, 0.01 mmol, 10 mol%) and 0.5 mL of trifluorotoluene were successively added to a 10 mL Schlenk tube that had been dried at high temperature. Then, the reducing agent indium powder (4.6 mg, 0.04 mmol, 40 mol%) was added, and the mixture was stirred for 5 minutes. The starting materials 8 or 9 (0.2 mmol, 1.0 equiv) and the 2-ethynylpyridine analogue 7 (0.4 mmol, 2.0 equiv) were added, and finally NaBAr F 4 (17.7 mg, 0.02 mmol, 20 mol%) was added. The reaction tube was removed from the glove box and stirred in an oil bath at 40 °C for 24 hours. After the reaction was completed, an appropriate amount of ethyl acetate was added for dilution, and the reaction progress was monitored by TLC. The crude product was obtained by concentration under reduced pressure, and the target product, the 2,2′-substituted chiral spirotripyridine compound 2 or the 2,3′-substituted chiral spirotripyridine compound 5, was further obtained by flash column chromatography.

[0112] S2-5:

[0113]

[0114] In a nitrogen-filled glove box, the complex CoI2-L10 (20.1 mg, 0.02 mmol, 10 mol%) and a mixed solvent of 0.5 mL of CF3Ph and 0.1 mL of HFIP were successively added to a 10 mL Schlenk tube that had been dried at high temperature. During stirring, the reducing agent indium powder (9.2 mg, 0.08 mmol, 40 mol%) was continuously added, and stirring was continued for 5 minutes. The starting materials 8 or 9 (0.2 mmol, 1.0 equiv) and the alkyl terminal alkyne 7 (0.4 mmol, 2.0 equiv) were added, and finally NaBAr F 4 (35.4 mg, 0.04 mmol, 20 mol%) was added. The reaction tube was transferred outside the glove box and stirred in an oil bath at 40 °C for 36 hours. After the reaction was completed, an appropriate amount of ethyl acetate was added for dilution, and the reaction progress was monitored by TLC. The crude product was obtained by concentration under reduced pressure, and the target product, the 2,3′-substituted chiral spirobipyridine compound 5 or the 3,3′-substituted chiral spirobipyridine compound 4, was further obtained by flash column chromatography.

[0115] Among them, the chiral spirobipyridine compounds prepared in step 3 are all asymmetric.

[0116] See the following specific examples for details:

[0117] Example 1

[0118] In this example, (R)-2,2'-diphenyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0119]

[0120] White solid (67.3 mg, 90% yield), m.p. 136.2 °C - 136.5 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.03 - 7.83 (m, 4H), 7.62 (d, J = 7.9 Hz, 2H), 7.50 (d, J = 7.9 Hz, 2H), 7.44 - 7.35 (m, 4H), 7.35 - 7.28 (m, 2H), 3.55 (dt, J = 15.9, 8.0 Hz, 2H), 3.02 (ddd, J = 15.8, 8.6, 3.9 Hz, 2H), 2.85 (ddd, J = 12.4, 8.4, 3.9 Hz, 2H), 2.34 (dt, J = 12.6, 8.3 Hz, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.5, 155.6, 140.0, 135.2, 132.8, 128.5, 128.3, 126.8, 118.4, 60.2, 37.9, 29.0. [α] 25 D = 478.779 (c = 0.655, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd. for C 27 H 22 N2Na + 397.1675; found 397.1668. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 6.733 min (major) and 10.691 min (minor), 96% ee.

[0121] Example 2

[0122] In this example, (R)-2,2'-di-p-tolyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0123]

[0124] White solid (52.8 mg, 66% yield), m.p. 154.0 °C - 154.4 °C. 1 H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.1 Hz, 4H), 7.60 (d, J = 7.9 Hz, 2H), 7.48 (d, J = 7.9 Hz, 2H), 7.20 (d, J = 8.0 Hz, 4H), 3.65 - 3.48 (m, 2H), 3.09 - 2.94 (m, 2H), 2.91 - 2.78 (m, 2H), 2.37 (s, 6H), 2.36 - 2.25 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 169.5, 155.6, 138.1, 137.3, 134.8, 132.7, 129.2, 126.7, 118.1, 60.2, 37.9, 29.0, 21.3. [α] 25 D = 438.182 (c = 0.165, CHCl3). HRMS (ESI) m / z: [M+H] + calcd. for C 29 H 27 N2 + 403.2169; found 403.2165. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 1:99, 0.5 mL / min), 40 °C, 254 nm, Rt = 17.259 min (minor) and 18.727 min (major), 99% ee.

[0125] Example 3

[0126] In this example, (R)-2,2'-bis(4-tert-butylphenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0127]

[0128] Yellow solid (71.9 mg, 74% yield), m.p. 121.1 °C - 121.5 °C. 11H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.5 Hz, 4H), 7.60 (d, J = 7.9 Hz, 2H), 7.49 (d, J = 7.9 Hz, 2H), 7.44 (d, J = 8.5 Hz, 4H), 3.66 - 3.49 (m, 2H), 3.11 - 2.96 (m, 2H), 2.93 - 2.80 (m, 2H), 2.42 - 2.27 (m, 2H), 1.36 (s, 18H). 13 13C NMR (101 MHz, CDCl3) δ 169.5, 155.6, 151.2, 137.3, 134.8, 132.7, 126.5, 125.5, 118.2, 60.2, 37.9, 34.6, 31.4, 29.0. [α] 25 25 D = 466.667 (c = 0.135, CHCl3). HRMS (ESI) m / z: [M+H] + + calcd. for C 35 35 H 29 29 N2 + + 487.3108; found 487.3108. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i i PrOH:Hexane = 1:99, 0.5 mL / min), 40 °C, 254 nm, Rt = 10.479 min (minor) and 15.109 min (major), 95% ee.

[0129] Example 4

[0130] In this example, (R)-2,2'-bis(4-biphenylyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0131]

[0132] Yellow solid (93.0 mg, 88% yield), m.p. 233.8 °C - 234.2 °C. 1 11H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.4 Hz, 4H), 7.71 - 7.59 (m, 10H), 7.56 (d, J = 7.9 Hz, 2H), 7.49 - 7.42 (m, 4H), 7.40 - 7.33 (m, 2H), 3.68 - 3.52 (m, 2H), 3.14 - 2.99 (m, 2H), 2.95 - 2.81 (m, 2H), 2.44 - 2.30 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.6, 155.2, 141.0, 140.9, 138.9, 135.3, 132.9, 128.8, 127.3, 127.3, 127.2, 127.1, 118.4, 60.3, 37.9, 29.1. [α] 25 D = 610.588 (c = 0.340, CHCl3). HRMS (ESI) m / z: [M+H] + calcd. for C 39 H 31 N2 + 527.2482; found 527.2478. 99% ee.

[0133] Example 5

[0134] In this example, (R)-2,2'-bis(4-methoxyphenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0135]

[0136] White solid (62.6 mg, 72% yield), m.p. 145.4 °C - 145.8 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.00 - 7.81 (m, 4H), 7.58 (d, J = 7.9 Hz, 2H), 7.43 (d, J = 7.9 Hz, 2H), 6.98 - 6.86 (m, 4H), 3.81 (s, 6H), 3.61 - 3.47 (m, 2H), 3.07 - 2.95 (m, 2H), 2.89 - 2.79 (m, 2H), 2.38 - 2.26 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.4, 159.9, 155.3, 134.4, 132.7, 127.9, 117.6, 113.9, 60.2, 55.3, 37.9, 29.0. [α] 25D = 716.364 (c = 0.110, CHCl3). HRMS (ESI) m / z: [M+H] + calcd. for C 29 H 27 N2O2 + 435.2067; found 435.2061. HPLC (Shimadzu LC-2030) (Daicel OD-H Column, i PrOH:Hexane = 2:98, 1 mL / min), 40 °C, 220 nm, Rt = 13.457 min (major) and 20.110 min (minor), 95% ee.

[0137] Example 6

[0138] In this example, (R)-2,2'-bis(4-chlorophenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0139]

[0140] White solid (61.1 mg, 69% yield), m.p. 221.7 °C - 222.1 °C. 1 H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.6 Hz, 4H), 7.61 (d, J = 7.9 Hz, 2H), 7.46 (d, J = 7.9 Hz, 2H), 7.33 (d, J = 8.6 Hz, 4H), 3.57 - 3.44 (m, 2H), 3.10 - 2.95 (m, 2H), 2.90 - 2.76 (m, 2H), 2.41 - 2.24 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 169.6, 154.4, 138.3, 135.6, 134.3, 133.0, 128.7, 128.0, 118.3, 60.2, 37.9, 29.0. [α] 25 D = 464.242 (c = 0.165, CHCl3). HRMS (ESI) m / z: [M+H] + calcd. for C 27 H 21 Cl2N2 + 443.1076; found 443.1067. HPLC (Shimadzu LC-2030) (Daicel AD-H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 9.064 min (minor) and 10.128 min (major), 97% ee.

[0141] Example 7

[0142] In this example, diethyl (R)-4,4'-(5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-2,2'-diyl)dibenzoate was prepared, and its structural formula is as follows:

[0143]

[0144] White solid 4-4l (69.0 mg, 67% yield), m.p. 174.6 °C - 175.0 °C. 1 H NMR (400 MHz, CDCl3) δ 8.13 - 8.00 (m, 4H), 8.01 - 7.88 (m, 4H), 7.63 (d, J = 7.9 Hz, 2H), 7.53 (d, J = 7.9 Hz, 2H), 4.37 (q, J = 7.1 Hz, 4H), 3.63 - 3.47 (m, 2H), 3.11 - 2.97 (m, 2H), 2.90 - 2.79 (m, 2H), 2.43 - 2.26 (m, 2H), 1.39 (t, J = 7.1 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 169.7, 166.6, 154.3, 143.9, 136.2, 133.0, 130.0, 129.8, 126.5, 119.0, 60.9, 60.2, 37.8, 29.0, 14.4. [α] 25 D = 547.273 (c = 0.110, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 33 H 30 N2NaO4 + 541.2098; found 541.2089. HPLC (Shimadzu LC - 2030) (Daicel AD-H Column, i PrOH:Hexane = 4:96, 1 mL / min), 40 °C, 220 nm, Rt = 19.129 min (minor) and 32.456 min (major), 96% ee.

[0145] Example 8

[0146] In this example, (R)-2,2'-bis(4-trifluoromethylphenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0147]

[0148] White solid (63.3 mg, 62% yield), m.p. 184.1 °C - 184.4 °C. 1 H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.2 Hz, 4H), 7.72 - 7.57 (m, 6H), 7.53 (d, J = 7.9 Hz, 2H), 3.61 - 3.46 (m, 2H), 3.13 - 2.98 (m, 2H), 2.92 - 2.78 (m, 2H), 2.44 - 2.29 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 169.7, 154.1, 143.1, 136.3, 133.1, 130.1 (d, J = 32.5 Hz, 1C), 126.9, 125.4 (d, J = 273.1 Hz, 1C), 125.4 (d, J = 3.7 Hz, 1C), 118.9, 60.2, 37.8, 29.0. 19 F NMR (377 MHz, CDCl3) δ -62.52. [α] 25 D = 273.750 (c = 0.160, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 29 H 21 F6N2 + 511.1603; found 511.1602. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 6.565 min (minor) and 7.952 min (major), 99% ee.

[0149] Example 9

[0150] In this example, (R)-2,2'-bis(3-fluorophenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0151]

[0152] White solid (57.8 mg, 70% yield), m.p. 165.1 °C to 165.5 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.81 - 7.55 (m, 6H), 7.54 - 7.43 (m, 2H), 7.38 - 7.28 (m, 2H), 7.06 - 6.91 (m, 2H), 3.65 - 3.46 (m, 2H), 3.12 - 2.95 (m, 2H), 2.90 - 2.72 (m, 2H), 2.45 - 2.16 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.6, 164.5, 162.1, 154.1 (d, J = 2.5 Hz, 1C), 142.2 (d, J = 7.6 Hz, 1C), 135.9, 133.0, 129.9 (d, J = 8.2 Hz, 1C), 122.1 (d, J = 2.8 Hz, 1C), 118.5, 114.3 (dd, J = 146.1, 21.4 Hz, 1C), 60.1, 37.8, 29.0. 19 19F NMR (377 MHz, CDCl3) δ -113.50. [α] 25 D = 317.727 (c = 0.220, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 27 H 21 F2N2 + 411.1667; found 411.1665. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 6.566 min (major) and 7.585 min (minor), 90% ee.

[0153] Example 10

[0154] In this example, (R)-2,2'-bis(2-bromophenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0155]

[0156] Colorless oily liquid (60.2 mg, 57% yield). 1 H NMR (400 MHz, CDCl3) δ 7.67 - 7.54 (m, 4H), 7.46 (dd, J = 7.7, 1.7 Hz, 2H), 7.37 - 7.27 (m, 4H), 7.16 (td, J = 7.7, 1.7 Hz, 2H), 3.38 - 3.25 (m, 2H), 3.10 - 2.98 (m, 2H), 2.82 - 2.67 (m, 2H), 2.45 - 2.32 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 168.7, 156.7, 141.8, 135.8, 133.3, 132.0, 131.8, 129.2, 127.3, 122.6, 122.2, 60.7, 37.8, 28.8. [α] 25 D = 208.148 (c = 0.540, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 27 H 21 Br2N2 + 531.0066; found 531.0063. HPLC (Shimadzu LC - 2030) (Daicel OJ - H Column, i PrOH:Hexane = 0.8:99.2, 0.5 mL / min), 40 °C, 220 nm, Rt = 32.016 min (major) and 43.854 min (minor), 98% ee.

[0157] Example 11

[0158] In this example, (R)-2,2'-bis(2-methoxyphenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0159]

[0160] Yellow solid (44.2 mg, 51% yield), m.p. 139.0 °C - 139.5 °C. 1 H NMR (400 MHz, CDCl3) δ 7.73 (dd, J = 7.6, 1.8 Hz, 2H), 7.62 (d, J = 7.9 Hz, 2H), 7.52 (d, J = 7.9 Hz, 2H), 7.31 - 7.22 (m, 2H), 6.98 (td, J = 7.5, 0.9 Hz, 2H), 6.91 (d, J = 8.2 Hz, 2H), 3.79 (s, 6H), 3.44 - 3.31 (m, 2H), 3.04 - 2.90 (m, 2H), 2.79 - 2.67 (m, 2H), 2.35 - 2.23 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 169.0, 157.0, 154.0, 134.8, 131.7, 131.5, 129.8, 129.2, 122.9, 121.0, 111.4, 60.6, 55.6, 37.8, 28.9. [α] 25 D = 310.769 (c = 0.130, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 29 H 27 N2O2 + 435.2067; found 435.2060. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 220 nm, Rt = 11.309 min (minor) and 14.874 min (major), 98% ee.

[0161] Example 12

[0162] In this example, (R)-2,2'-bis(3-hydroxyphenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0163]

[0164] White solid (62.6 mg, 77% yield), m.p. 191.9 °C - 192.5 °C. 11H NMR (400 MHz, CDCl3) δ 9.51 (s, 2H), 7.24 - 7.10 (m, 4H), 7.01 (t, J = 7.8 Hz, 2H), 6.83 (d, J = 7.9 Hz, 2H), 6.72 (d, J = 7.6 Hz, 2H), 6.47 (dd, J = 8.0, 1.8 Hz, 2H), 3.17 - 2.92 (m, 4H), 2.69 - 2.55 (m, 2H), 2.42 - 2.25 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 168.1, 158.3, 157.3, 141.0, 137.4, 133.1, 129.0, 119.8, 117.3, 115.2, 114.6, 61.4, 37.9, 28.3. [α] 25 D = 1000.000 (c = 0.065, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 27 H 23 N2O2 + 407.1754; found 407.1752. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 220 nm, Rt = 33.032 min (major) and 37.718 min (minor), 98% ee.

[0165] Example 13

[0166] In this example, (R)-2,2'-bis(4-(N,N-dimethylamino)phenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0167]

[0168] Brown solid (68.2 mg, 74% yield), m.p. 207.7 °C - 207.9 °C. 11H NMR (400 MHz, CDCl3) δ 7.91 - 7.74 (m, 4H), 7.52 (d, J = 7.9 Hz, 2H), 7.39 (d, J = 7.9 Hz, 2H), 6.80 - 6.67 (m, 4H), 3.57 - 3.45 (m, 2H), 3.12 - 2.86 (m, 14H), 2.84 - 2.75 (m, 2H), 2.33 - 2.21 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.4, 155.8, 150.7, 133.6, 132.5, 128.5, 127.6, 117.0, 112.4, 60.3, 40.6, 38.0, 29.0. [α] 25 25 D = 801.667 (c = 0.060, CHCl3). HRMS (ESI) m / z: [M + H] + + calcd. for C 31 31 H 33 33 N4 + + 461.2700; found 461.2696. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 5:95, 1 mL / min), 40 °C, 220 nm, Rt = 10.361 min (minor) and 14.189 min (major), 92% ee.

[0169]

[0169] Example 14

[0170] In this example, (R)-2,2'-bis(2-naphthyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0171]

[0172] White solid (75.0 mg, 79% yield), m.p. 224.6 °C - 224.9 °C. 1 11H NMR (400 MHz, CDCl3) δ 8.38 (s, 2H), 8.12 (dd, J = 8.6, 1.7 Hz, 2H), 7.94 - 7.85 (m, 3H), 7.85 - 7.77 (m, 3H), 7.72 - 7.63 (m, 4H), 7.51 - 7.41 (m, 4H), 3.72 - 3.55 (m, 2H), 3.17 - 3.02 (m, 2H), 2.96 - 2.85 (m, 2H), 2.47 - 2.32 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.6, 155.6, 137.4, 135.4, 133.6, 133.4, 132.9, 128.6, 128.1, 127.6, 126.1, 126.0, 125.8, 125.0, 118.8, 60.4, 38.0, 29.1. [α] 25 D = 837.273 (c = 0.110, CHCl3). HRMS (ESI) m / z: [M+H] + calcd. for C 35 H 26 N2 + 475.2169; found 475.2163. HPLC (Shimadzu LC - 2030) (Daicel Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 32.392 min (major) and 37.209 min (minor), 96% ee.

[0173] Example 15

[0174] In this example, (R)-2,2'-bis(2-thienyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0175]

[0176] Yellow solid (64.0 mg, 83% yield), m.p. 107.4 °C - 107.8 °C. 11H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.9 Hz, 2H), 7.42 (dd, J = 3.6, 0.9 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.24 - 7.19 (m, 2H), 6.99 (dd, J = 5.0, 3.7 Hz, 2H), 3.63 - 3.48 (m, 2H), 3.01 - 2.87 (m, 2H), 2.83 - 2.70 (m, 2H), 2.34 - 2.19 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.3, 150.9, 146.0, 135.1, 132.8, 127.7, 126.4, 123.5, 116.9, 59.8, 37.7, 29.1. [α] 25 D = 442.105 (c = 0.095, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 23 H 19 N2S2 + 387.0984; found 387.0974. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 220 nm, Rt = 8.887 min (major) and 11.499 min (minor), 94% ee.

[0177] Example 16

[0178] In this example, (R)-2,2'-bis(3-thienyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0179]

[0180] Yellow solid (67.9 mg, 88% yield), m.p. 121.6 °C - 121.8 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 2H), 7.55 - 7.40 (m, 4H), 7.29 (d, J = 7.8 Hz, 2H), 7.24 - 7.14 (m, 2H), 3.52 - 3.32 (m, 2H), 3.02 - 2.82 (m, 2H), 2.83 - 2.61 (m, 2H), 2.31 - 2.13 (m, 2H).13 CNMR(101MHz,CDCl3)δ169.4,151.9,142.9,134.8,132.7,126.4,125.7,122.4,118.2,60.1,37.8,29.0.[α] 25 D =340.146(c=0.135,CHCl3).HRMS(ESI)m / z:[M+H] + calcd.for C 23 H 19 N2S2 + 387.0984;found387.0989.HPLC(Shimadzu LC-2030)(Daicel AD-H Column, i PrOH:Hexane=1:99,1mL / min),40℃,220nm,Rt=11.609min(major)and 15.496min(minor),98%ee.

[0181] Example 17

[0182] In this example, (R)-2,2'-bis(3-benzofuranyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0183]

[0184] Red-brown solid (65.5 mg, 72% yield), m.p. 93.0 °C - 93.5 °C. 1 H NMR(400MHz,CDCl3)δ8.01(d,J=7.5Hz,2H),7.90(s,2H),7.52(d,J=7.9Hz,2H),7.41-7.27(m,4H),7.21-7.10(m,4H),3.49-3.35(m,2H),3.04-2.90(m,2H),2.84-2.71(m,2H),2.35-2.21(m,2H). 13 C NMR(101MHz,CDCl3)δ169.4,156.0,150.5,143.2,134.7,132.8,126.1,124.4,123.0,122.5,122.3,119.1,111.4,60.4,37.7,29.1.[α] 25 D= 346.667 (c = 0.090, CHCl3). HRMS (ESI) m / z: [M+H] + calcd. for C 31 H 23 N2O2 + 455.1754; found 455.1747. HPLC (Shimadzu LC-2030) (Daicel AD-H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 220 nm, Rt = 18.975 min (minor) and 23.566 min (major), 99% ee.

[0185] Example 18

[0186] In this example, (R)-2,2'-bis(ferrocenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0187]

[0188] Yellow solid (88.7 mg, 75% yield), m.p. 123.8 °C - 124.2 °C. 1 H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 7.8 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 4.88 - 4.81 (m, 2H), 4.76 - 4.70 (m, 2H), 4.28 - 4.23 (m, 4H), 3.95 - 3.82 (m, 10H), 3.57 - 3.43 (m, 2H), 3.02 - 2.90 (m, 2H), 2.82 - 2.72 (m, 2H), 2.37 - 2.24 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 169.4, 156.9, 133.1, 131.9, 117.7, 85.5, 69.5, 69.2, 69.1, 67.7, 67.1, 60.0, 37.3, 29.1. [α] 25 D = 167.879 (c = 0.330, CHCl3). HRMS (ESI) m / z: [M+H] + calcd. for C 35 H 31 Fe2N2 +591.1181; found 591.1184. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 220 nm, Rt = 7.128 min (major) and 11.303 min (minor), 93% ee.

[0189] Example 19

[0190] In this example, (R)-2,2'-bis(1-cyclohexenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0191]

[0192] Colorless oily liquid (50.1 mg, 66% yield). 1 H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 7.8 Hz, 2H), 7.08 (d, J = 7.9 Hz, 2H), 6.63 (t, J = 4.0 Hz, 2H), 3.53 - 3.36 (m, 2H), 3.00 - 2.83 (m, 2H), 2.80 - 2.63 (m, 2H), 2.49 - 2.31 (m, 4H), 2.28 - 2.08 (m, 6H), 1.79 - 1.66 (m, 4H), 1.67 - 1.54 (m, 4H). 13 C NMR (101 MHz, CDCl3) δ 168.7, 157.0, 136.6, 134.2, 132.2, 126.7, 116.5, 60.0, 37.9, 29.0, 25.9, 23.0, 22.3. [α] 25 D = 194.400 (c = 0.125, CHCl3). HRMS (ESI) m / z: [M + H] + calcd. for C 27 H 31 N2 + 383.2482; found 383.2477. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, iPrOH:Hexane = 0.5:99.5, 1 mL / min), 40 °C, 254 nm, Rt = 4.174 min (minor) and 4.708 min (major), 99% ee.

[0193] Example 20

[0194] In this example, (R)-2,2'-bis(2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0195]

[0196] White solid (26.3 mg, 70% yield), m.p. 180 °C - 185 °C. 1 H NMR (400 MHz, CDCl3) δ 8.66 - 8.52 (m, 2H), 8.26 (d, J = 8.0 Hz, 2H), 8.20 (d, J = 7.9 Hz, 2H), 7.75 - 7.62 (m, 4H), 7.23 - 7.12 (m, 2H), 3.60 - 3.45 (m, 2H), 3.14 - 2.96 (m, 2H), 2.91 - 2.77 (m, 2H), 2.42 - 2.27 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 169.1, 156.8, 154.6, 148.8, 137.1, 136.7, 133.0, 123.1, 121.0, 119.1, 60.0, 37.9, 29.1. [α] 25 D = 439.167 (c = 0.36, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 25 H 20 N4Na + 399.1580; found 399.1580. HPLC (Shimadzu LC-2030) (Daicel AD-H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 21.693 min (major) and 19.854 min (minor), 99% ee.

[0197] Example 21

[0198] In this example, (R)-2,2'-bis(3-methyl-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0199]

[0200] Brown solid (27.0 mg, 67% yield), m.p. 102.8 °C to 103.2 °C. 1 H NMR (400 MHz, CDCl3) δ 8.45 (dd, J = 4.6, 1.0 Hz, 2H), 7.69 - 7.60 (m, 4H), 7.47 (dd, J = 7.6, 0.7 Hz, 2H), 7.16 - 7.05 (m, 2H), 3.45 - 3.30 (m, 2H), 3.10 - 2.96 (m, 2H), 2.84 - 2.73 (m, 2H), 2.39 - 2.31 (m, 2H), 2.28 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 168.0, 157.5, 156.4, 146.4, 139.3, 135.6, 132.7, 122.6, 122.2, 60.2, 37.7, 28.9, 20.5. [α] 25 D = 310.000 (c = 0.120, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 27 H 25 N4 + 405.2074; found 405.2073. HPLC (Shimadzu LC-2030) (Daicel AD-H Column, i PrOH:Hexane = 3:97, 1 mL / min), 40 °C, 254 nm, Rt = 15.572 min (minor) and 20.960 min (major), 97% ee.

[0201] Example 22

[0202] In this example, (R)-2,2'-bis(4-methyl-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0203]

[0204] White solid (21.9 mg, 54% yield), m.p. 172.6 °C - 172.8 °C. 1 H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 4.9 Hz, 2H), 8.19 (d, J = 7.9 Hz, 2H), 8.06 (s, 2H), 7.70 (d, J = 7.9 Hz, 2H), 7.01 (dd, J = 4.9, 0.9 Hz, 2H), 3.56 - 3.45 (m, 2H), 3.12 - 3.00 (m, 2H), 2.89 - 2.79 (m, 2H), 2.42 - 2.27 (m, 8H). 13 C NMR (101 MHz, CDCl3) δ 168.9, 156.6, 154.8, 148.7, 147.7, 137.0, 133.0, 124.2, 121.8, 119.3, 60.1, 38.0, 29.0, 21.3. [α] 25 D = 480.000 (c = 0.125, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 27 H 25 N4 + 405.2074; found 405.2077. HPLC (Shimadzu LC - 2030) (Daicel IGColumn, i PrOH:Hexane = 15:85, 1 mL / min), 40 °C, 254 nm, Rt = 9.546 min (minor) and 10.901 min (major), 99% ee.

[0205] Example 23

[0206] In this example, (R)-2,2'-bis(5-methyl-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0207]

[0208] White solid (17.6 mg, 44% yield), m.p. 195.7 °C - 196.0 °C. 11H NMR (400 MHz, CDCl3) δ 8.40 (dd, J = 1.4, 0.6 Hz, 2H), 8.14 (dd, J = 8.0, 2.9 Hz, 4H), 7.67 (d, J = 7.9 Hz, 2H), 7.47 (dd, J = 8.1, 1.7 Hz, 2H), 3.61 - 3.45 (m, 2H), 3.13 - 2.96 (m, 2H), 2.90 - 2.78 (m, 2H), 2.39 - 2.24 (m, 8H). 13 13C NMR (101 MHz, CDCl3) δ 169.0, 154.7, 154.3, 149.2, 137.2, 136.7, 132.9, 132.7, 120.6, 118.7, 60.0, 37.92, 29.1, 18.4. [α] 25 D = 550.769 (c = 0.065, CHCl3). HRMS (ESI) m / z: [M+H] + calcd for C 27 H 25 N4 + 405.2074; found 405.2073. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 254 nm, Rt = 11.691 min (minor) and 13.411 min (major), 99% ee.

[0209] Example 24

[0210] In this example, (R)-2,2'-bis(6-methyl-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0211]

[0212] White solid (28.5 mg, 71% yield), m.p. 94.4 °C - 94.8 °C. 11H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 7.9 Hz, 2H), 8.03 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 7.9 Hz, 2H), 7.55 (t, J = 7.7 Hz, 2H), 7.04 (d, J = 7.6 Hz, 2H), 3.59 - 3.43 (m, 2H), 3.12 - 2.97 (m, 2H), 2.89 - 2.78 (m, 2H), 2.57 (s, 6H), 2.38 - 2.27 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.0, 157.4, 156.3, 154.9, 136.8, 136.8, 132.9, 122.6, 119.1, 118.0, 60.0, 37.9, 29.0, 24.7.

[0213] [α] 25 D = 348.333 (c = 0.180, CHCl3). HRMS (ESI) m / z: [M+H] + calcd for C 27 H 25 N4 + 405.2074; found 405.2071. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 5.693 min (minor) and 7.284 min (major), 99% ee.

[0214] Example 25

[0215] In this example, (R)-2,2'-bis(6-phenyl-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0216]

[0217] White solid (42.3 mg, 80% yield), m.p. 236.1 °C - 236.5 °C. 11H NMR (400 MHz, CDCl3) δ 8.43 (d, J = 7.9 Hz, 2H), 8.22 (d, J = 7.7 Hz, 2H), 8.17 - 8.05 (m, 4H), 7.82 - 7.70 (m, 4H), 7.66 (d, J = 7.7 Hz, 2H), 7.55 - 7.44 (m, 4H), 7.45 - 7.35 (m, 2H), 3.66 - 3.48 (m, 2H), 3.16 - 3.01 (m, 2H), 2.96 - 2.76 (m, 2H), 2.45 - 2.28 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.0, 156.5, 156.1, 154.9, 139.7, 137.4, 137.1, 132.9, 128.9, 128.7, 127.0, 119.7, 119.3, 119.3, 60.0, 38.0, 29.1. [α] 25 D = 90.588 (c = 0.170, CHCl3). HRMS (ESI) m / z: [M+H] + calcd for C 37 H 29 N4 + 529.2387; found 529.2394. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 3:97, 1 mL / min), 40 °C, 254 nm, Rt = 8.928 min (minor) and 11.062 min (major), 97% ee.

[0218] Example 26

[0219] In this example, (R)-2,2'-bis(4-trifluoromethylphenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0220]

[0221] White solid (22.9 mg, 47% yield), m.p. 140.7 °C - 141.2 °C. 11H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 7.9 Hz, 2H), 8.05 (dd, J = 7.8, 0.8 Hz, 2H), 7.67 (d, J = 7.9 Hz, 2H), 7.59 (t, J = 7.8 Hz, 2H), 7.23 (dd, J = 7.8, 0.8 Hz, 2H), 3.62 - 3.47 (m, 2H), 3.10 - 2.97 (m, 2H), 2.90 - 2.78 (m, 2H), 2.40 - 2.26 (m, 2H), 1.39 (s, 18H). 13 13C NMR (101 MHz, CDCl3) δ 168.9, 168.1, 155.4, 155.2, 136.7, 136.6, 132.8, 119.2, 118.3, 117.5, 59.98, 38.0, 37.6, 30.3, 29.1. [α] 25 D + = 349.600 (c = 0.125, CHCl3). HRMS (ESI) m / z: [M + H] 33 37 calcd for C + R H R 37 N4 + R 489.3013; found 489.3012. SFC (Daicel OD - 3, 15% MeOH in CO2, 2000 psi, 0.8 mL / min, 296 nm, 35 °C): t R R (minor) = 6.203 min, t R R (major) = 5.171 min, 99% ee.

[0222] Example 27

[0223] In this example, (R)-2,2'-bis(6-methoxy-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0224]

[0225] White solid (37.5 mg, 86% yield), m.p. 101.6 °C - 102.0 °C. 1 11H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 7.9 Hz, 2H), 7.86 (d, J = 7.4 Hz, 2H), 7.67 (d, J = 7.9 Hz, 2H), 7.57 (t, J = 7.8 Hz, 2H), 6.66 (d, J = 8.1 Hz, 2H), 4.00 (s, 6H), 3.62 - 3.46 (m, 2H), 3.12 - 2.97 (m, 2H), 2.91 - 2.77 (m, 2H), 2.40 - 2.26 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.0, 163.3, 154.6, 154.2, 139.2, 136.9, 132.8, 119.0, 113.6, 110.2, 59.9, 53.2, 37.9, 29.1. [α] 25 D = 288.065 (c = 0.310, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 27 H 25 N4O2 + 437.1972; found 437.1966. HPLC (Shimadzu LC - 2030) (Daicel IC Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 7.355 min (major) and 8.209 min (minor), 94% ee.

[0226] Example 28

[0227] In this example, (R)-2,2'-bis[6-((4-methoxybenzyl)oxy)-2-pyridyl]-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0228]

[0229] White solid (30.2 mg, 47% yield), m.p. 87.4 °C - 87.8 °C. 11H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 7.9 Hz, 2H), 7.88 (d, J = 7.4 Hz, 2H), 7.69 (d, J = 7.9 Hz, 2H), 7.58 (t, J = 7.8 Hz, 2H), 7.42 (d, J = 8.6 Hz, 4H), 6.90 (d, J = 8.6 Hz, 4H), 6.70 (d, J = 8.1 Hz, 2H), 5.42 (s, 4H), 3.80 (s, 6H), 3.63 - 3.49 (m, 2H), 3.11 - 2.98 (m, 2H), 2.92 - 2.78 (m, 2H), 2.43 - 2.26 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.1, 162.9, 159.4, 154.6, 154.1, 139.3, 136.9, 132.8, 129.9, 129.9, 119.0, 113.9, 113.7, 110.7, 67.2, 59.9, 55.3, 37.9, 29.1. [α] 25 D = 180.000 (c = 0.125, CHCl3). HRMS (ESI) m / z: [M + Na] + calcd for C 41 H 36 N4NaO4 + 671.2629; found 671.2615. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 3:97, 1 mL / min), 40 °C, 254 nm, Rt = 27.780 min (major) and 41.989 min (minor), 97% ee.

[0230] Example 29

[0231] In this example, (R)-2,2'-bis(5 - methoxy - 2 - pyridyl)-5,5',6,6'-tetrahydro - 7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0232]

[0233] White solid (25.0 mg, 57% yield), m.p. 156.6 °C - 156.8 °C. 11H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 2.9 Hz, 2H), 8.20 (d, J = 8.8 Hz, 2H), 8.09 (d, J = 7.9 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.18 (dd, J = 8.8, 3.0 Hz, 2H), 3.84 (s, 6H), 3.58 - 3.42 (m, 2H), 3.11 - 2.95 (m, 2H), 2.89 - 2.76 (m, 2H), 2.40 - 2.25 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 168.9, 155.6, 154.5, 149.8, 136.3, 136.1, 132.9, 121.6, 121.0, 118.3, 60.0, 55.6, 37.9, 29.0. [α] 25 D = 12.381 (c = 0.105, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 27 H 25 N4O2 + 437.1972; found 437.1971. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i PrOH:Hexane = 15:85, 1 mL / min), 40 °C, 254 nm, Rt = 14.566 min (minor) and 18.579 min (major), 99% ee.

[0234] Example 30

[0235] In this example, dimethyl (R)-6,6'-[(5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-2,2'-diyl)]dinicotinate was prepared, and its structural formula is as follows:

[0236]

[0237] White solid (26.5 mg, 54% yield), m.p. 128.4 °C - 128.6 °C. 11H NMR (400 MHz, CDCl3) δ 9.16 (dd, J = 2.1, 0.8 Hz, 2H), 8.39 - 8.19 (m, 6H), 7.72 (d, J = 7.9 Hz, 2H), 3.92 (s, 6H), 3.61 - 3.47 (m, 2H), 3.16 - 3.02 (m, 2H), 2.92 - 2.78 (m, 2H), 2.43 - 2.27 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.2, 166.0, 160.1, 153.6, 150.3, 138.1, 137.7, 133.2, 125.0, 120.3, 120.1, 60.0, 52.3, 37.8, 29.1. [α] 25 25 D = 610.204 (c = 0.245, CHCl3). HRMS (ESI) m / z: [M + Na] + + calcd for C 29 29 H 24 24 N4NaO4 + + 515.1690; found 515.1694. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i i PrOH:Hexane = 20:80, 1 mL / min), 40 °C, 254 nm, Rt = 6.859 min (minor) and 12.936 min (major), 97% ee.

[0238] Example 31

[0239] In this example, (R)-2,2'-bis(6-fluoro-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0240]

[0241] White solid (15.9 mg, 39% yield), m.p. 93.6 °C - 93.8 °C. 1 11H NMR (400 MHz, CDCl3) δ 8.14 (dd, J = 7.7, 3.1 Hz, 4H), 7.76 (q, J = 8.0 Hz, 2H), 7.69 (d, J = 7.9 Hz, 2H), 6.82 (dd, J = 8.0, 2.8 Hz, 2H), 3.60 - 3.43 (m, 2H), 3.16 - 2.98 (m, 2H), 2.91 - 2.77 (m, 2H), 2.46 - 2.28 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.1, 163.0 (d, J = 238.4 Hz, 1C), 155.5 (d, J = 13.2 Hz, 1C), 153.1, 141.6 (d, J = 7.7 Hz, 1C), 137.7, 133.1, 119.5, 118.0 (d, J = 4.0 Hz, 1C), 108.7 (d, J = 37.7 Hz, 1C), 59.9, 37.8, 29.1. 19 19F NMR (377 MHz, CDCl3) δ -68.05. [α] 25 D = 442.857 (c = 0.140, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 25 H 18 F2N4Na + 435.1392; found 435.1389. HPLC (Shimadzu LC - 2030) (Daicel IC Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 13.651 min (minor) and 14.440 min (major), 99% ee.

[0242] Example 32

[0243] In this example, (R)-2,2'-bis(4-tert-butyl-2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0244]

[0245] White solid (19.7 mg, 40% yield), m.p. 221.5 °C - 221.8 °C. 11H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 5.2 Hz, 2H), 8.33 (d, J = 1.5 Hz, 2H), 8.17 (d, J = 7.9 Hz, 2H), 7.69 (d, J = 7.9 Hz, 2H), 7.19 (dd, J = 5.2, 2.0 Hz, 2H), 3.66 - 3.49 (m, 2H), 3.13 - 3.00 (m, 2H), 2.96 - 2.83 (m, 2H), 2.42 - 2.30 (m, 2H), 1.31 (s, 18H). 13 13C NMR (101 MHz, CDCl3) δ 169.0, 160.5, 156.6, 154.8, 148.8, 136.8, 132.9, 120.4, 119.2, 117.9, 59.9, 37.8, 34.9, 30.6, 29.1. [α] 25 D = 423.333 (c = 0.210, CHCl3). HRMS (ESI) m / z: [M+H] + calcd for C 33 H 37 N4 + 489.3013; found 489.3010. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 254 nm, Rt = 8.425 min (minor) and 14.445 min (major), 99% ee.

[0246] Example 33

[0247] In this example, (R)-2,2'-bis(quinolin-2-yl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0248]

[0249] White solid (23.8 mg, 50% yield), m.p. 225.5 °C - 225.8 °C. 11H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 7.9 Hz, 2H), 8.43 (d, J = 8.6 Hz, 2H), 8.12 (d, J = 8.6 Hz, 4H), 7.85 - 7.72 (m, 4H), 7.72 - 7.61 (m, 2H), 7.54 - 7.41 (m, 2H), 3.69 - 3.51 (m, 2H), 3.19 - 3.04 (m, 2H), 3.00 - 2.83 (m, 2H), 2.50 - 2.32 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.0, 156.9, 154.9, 147.9, 137.5, 136.4, 133.1, 129.7, 129.3, 128.1, 127.6, 126.3, 119.9, 119.3, 60.1, 37.9, 29.2. [α] 25 D = 462.857 (c = 0.140, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 33 H 25 N4 + 477.2074; found 477.2072. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i PrOH:Hexane = 2:98, 1 mL / min), 40 °C, 254 nm, Rt = 22.413 min (minor) and 36.990 min (major), 99% ee.

[0250] Example 34

[0251] In this example, (R)-2,2'-bis(isoquinolin-1-yl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0252]

[0253] Yellow solid (23.4 mg, 49% yield), m.p. 156.1 °C - 156.5 °C. 11H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 5.6 Hz, 2H), 8.50 (dd, J = 8.6, 0.8 Hz, 2H), 7.83 (d, J = 7.8 Hz, 2H), 7.80 - 7.69 (m, 4H), 7.62 (d, J = 5.3 Hz, 2H), 7.60 - 7.52 (m, 2H), 7.29 - 7.24 (m, 2H), 3.43 - 3.30 (m, 2H), 3.16 - 3.04 (m, 2H), 2.91 - 2.78 (m, 2H), 2.54 - 2.41 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 168.3, 157.9, 157.0, 141.7, 137.2, 136.6, 133.2, 129.8, 128.6, 127.2, 127.0, 126.6, 123.4, 121.0, 60.5, 37.5, 28.9. [α] 25 D = 335.676 (c = 0.185, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 33 H 24 N4Na + 499.1893; found 499.1887. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i PrOH:Hexane = 15:85, 1 mL / min), 40 °C, 254 nm, Rt = 21.405 min (minor) and 25.312 min (major), 99% ee.

[0254] Example 35

[0255] In this example, (R)-3,3'-di-n-octyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0256]

[0257] Colorless oily liquid (78.5 mg, 88% yield). 11H NMR (400 MHz, CDCl3) δ 8.16 (s, 2H), 7.36 (s, 2H), 3.21 - 3.09 (m, 2H), 3.02 - 2.89 (m, 2H), 2.61 - 2.48 (m, 6H), 2.31 - 2.21 (m, 2H), 1.64 - 1.50 (m, 4H), 1.36 - 1.20 (m, 20H), 0.87 (t, J=6.8 Hz, 6H). 13 13C NMR (101 MHz, CDCl3) δ 166.3, 148.7, 136.5, 135.9, 132.5, 59.7, 37.9, 33.0, 31.9, 31.5, 29.5, 29.3, 29.3, 28.5, 22.7, 14.1. [α]< 25 D = - 14.098 (c=0.305, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 31 H 47 N4 + 447.3734; found 447.3737. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane=3:97, 1 mL / min), 40 °C, 220 nm, Rt=3.993 min (major) and 7.599 min (minor), 95% ee.

[0258] Example 36

[0259] In this example, ((R)-3,3'-diphenylethyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]) was prepared, and its structural formula is as follows:

[0260]

[0261] White solid (68.2 mg, 79% yield), m.p. 131.6 °C - 132.0 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 2H), 7.39 (s, 2H), 7.35 - 7.25 (m, 4H), 7.23 - 7.12 (m, 6H), 3.20 - 3.09 (m, 2H), 3.04 - 2.93 (m, 2H), 2.93 - 2.79 (m, 8H), 2.64 - 2.51 (m, 2H), 2.34 - 2.22 (m, 2H). 1313C NMR (101 MHz, CDCl3) δ 166.6, 148.6, 141.4, 136.7, 135.0, 132.6, 128.5, 128.4, 126.1, 59.8, 37.8, 37.8, 35.0, 28.5. [α] 25 D = -3.333 (c = 0.180, CHCl3). HRMS (ESI) m / z: [M+H] + calcd for C 31 H 31 N2 + 431.2482; found 431.2482. HPLC (Shimadzu LC-2030) (Daicel OD-H Column, i PrOH:Hexane = 5:95, 1 mL / min), 40 °C, 220 nm, Rt = 12.210 min (minor) and 23.185 min (major), 95% ee.

[0262] Example 37

[0263] In this example, (R)-3,3'-dibenzyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0264]

[0265] Yellow solid (40.9 mg, 51% yield), m.p. 80.1 °C - 80.4 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 2H), 7.38 - 7.24 (m, 6H), 7.23 - 7.11 (m, 6H), 3.90 (s, 4H), 3.19 - 3.04 (m, 2H), 2.99 - 2.84 (m, 2H), 2.63 - 2.48 (m, 2H), 2.32 - 2.17 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 166.9, 148.8, 140.3, 136.8, 134.5, 132.9, 129.0, 128.6, 126.4, 59.7, 39.0, 37.9, 28.5. [α] 25 D = -35.909 (c = 0.220, CHCl3). HRMS (ESI) m / z: [M+H] + calcd for C 29H 27 N2 + 403.2169; found 403.2170. HPLC (Shimadzu LC-2030) (Daicel OD-H Column, i PrOH:Hexane = 6:94, 1 mL / min), 40 °C, 220 nm, Rt = 11.620 min (minor) and 23.196 min (major), 95% ee.

[0266] Example 38

[0267] In this example, (R)-3,3'-dicyclopropyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0268]

[0269] White solid (38.9 mg, 57% yield), m.p. 80.8 °C - 81.2 °C. 1 H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 1.4 Hz, 2H), 7.16 (s, 2H), 3.23 - 3.07 (m, 2H), 2.99 - 2.88 (m, 2H), 2.61 - 2.49 (m, 2H), 2.31 - 2.19 (m, 2H), 1.89 - 1.79 (m, 2H), 1.01 - 0.88 (m, 4H), 0.70 - 0.58 (m, 4H). 13 C NMR (101 MHz, CDCl3) δ 166.2, 147.4, 137.1, 136.5, 129.3, 59.6, 37.9, 28.5, 13.0, 8.7, 8.6. [α] 25 D = 5.333 (c = 0.150, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 21 H 23 N2 + 303.1856; found 303.1851. HPLC (Shimadzu LC-2030) (Daicel Chiralpak OD-H Column, i PrOH:Hexane = 2:98, 1 mL / min), 40 °C, 254 nm, Rt = 8.089 min (major) and 13.096 min (minor), 93% ee.

[0270] Example 39

[0271] In this example, (R)-3,3'-bis(trimethylsilyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0272]

[0273] White solid (50.5 mg, 69% yield), m.p. 217.2 °C - 217.5 °C. 1 H NMR (400 MHz, CDCl3) δ 8.44 (s, 2H), 7.68 (s, 2H), 3.31 - 3.16 (m, 2H), 3.06 - 2.95 (m, 2H), 2.68 - 2.53 (m, 2H), 2.34 - 2.20 (m, 2H), 0.25 (s, 18H). 13 C NMR (101 MHz, CDCl3) δ 169.3, 152.8, 137.6, 136.1, 132.3, 60.6, 37.5, 28.8, -1.1. [α] 25 D = -20.583 (c = 0.515, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 21 H 31 N2Si2 + 367.2020; found 367.2016. HPLC (Shimadzu LC - 2030) (Daicel ID Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 220 nm, Rt = 4.382 min (major) and 8.015 min (minor), 94% ee.

[0274] Example 40

[0275] In this example, (R)-bis(tert-butyl) ((5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-3,3'-dimethylene) dicarbamate) was prepared, and its structural formula is as follows:

[0276]

[0277] White solid (88.7 mg, 92% yield), m.p. 80.1 °C - 80.6 °C.1 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 2H), 7.49 (s, 2H), 4.94 (s, 2H), 4.23 (d, J = 5.5 Hz, 4H), 3.21 - 3.09 (m, 2H), 3.05 - 2.91 (m, 2H), 2.62 - 2.49 (m, 2H), 2.33 - 2.20 (m, 2H), 1.43 (s, 18H). 13 13C NMR (101 MHz, CDCl3) δ 168.1, 155.9, 147.9, 137.1, 132.6, 132.1, 79.7, 59.9, 42.2, 37.7, 28.5, 28.4. [α] 25 D = -27.586 (c = 0.145, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 27 H 36 N4NaO4 + 503.2629; found 503.2628. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 220 nm, Rt = 28.807 min (major) and 34.892 min (minor), 93% ee.

[0278] Example 41

[0279] In this example, (R)-3,3'-bis[(benzyloxy)methyl]-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0280]

[0281] Colorless oily liquid (62.0 mg, 67% yield). 1 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 2H), 7.60 (s, 2H), 7.41 - 7.22 (m, 10H), 4.55 (s, 4H), 4.51 (s, 4H), 3.27 - 3.14 (m, 2H), 3.07 - 2.94 (m, 2H), 2.67 - 2.54 (m, 2H), 2.36 - 2.24 (m, 2H). 1313C NMR (101 MHz, CDCl3) δ 168.5, 148.2, 138.0, 136.9, 132.4, 131.7, 128.5, 127.8, 127.8, 72.3, 69.8, 60.0, 37.8, 28.5. [α] 25 D = -22.564 (c = 0.195, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 31 H 30 N2NaO2 + 485.2199; found 485.2188. HPLC (Shimadzu LC-2030) (Daicel OD-H Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 220 nm, Rt = 10.643 min (major) and 25.777 min (minor), 96% ee.

[0282] Example 42

[0283] In this example, (R)-2,2'-[(5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-3,3'-diyl)diethylidene]diol was prepared, and its structural formula is as follows:

[0284]

[0285] White solid (38.6 mg, 62% yield), m.p. 156.2 °C - 156.9 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 2H), 7.43 (s, 2H), 3.66 - 3.51 (m, 4H), 3.15 - 2.94 (m, 6H), 2.71 (t, J = 6.7 Hz, 4H), 2.59 - 2.48 (m, 2H), 2.32 - 2.24 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 166.6, 148.7, 137.2, 133.6, 132.6, 62.9, 59.8, 37.8, 36.2, 28.4. [α] 25 D = -22.000 (c = 0.250, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 19 H22 N2NaO2 + 333.1573; found 333.1568. HPLC (Shimadzu LC-2030) (Daicel AD-H Column, i PrOH:Hexane = 15:85, 0.8 mL / min), 40 °C, 220 nm, Rt = 10.791 min (major) and 12.148 min (minor), 96% ee.

[0286] Example 43

[0287] In this example, (R)-3,3'-bis(ethyl propionate)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0288]

[0289] Brown oily liquid (41.0 mg, 49% yield). 1 H NMR (400 MHz, CDCl3) δ 8.18 (s, 2H), 7.40 (s, 2H), 4.12 (q, J = 7.1 Hz, 4H), 3.21 - 3.07 (m, 2H), 3.02 - 2.91 (m, 2H), 2.92 - 2.82 (m, 4H), 2.64 - 2.48 (m, 6H), 2.32 - 2.21 (m, 2H), 1.23 (t, J = 7.1 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 172.6, 166.9, 148.6, 136.8, 133.9, 132.6, 60.6, 59.8, 37.8, 35.7, 28.5, 28.1, 14.2. [α] 25 D = -18.750 (c = 0.320, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 25 H 30 N2NaO4 + 445.2098; found 445.2097. HPLC (Shimadzu LC-2030) (Daicel OD-H Column, iPrOH:Hexane = 15:85, 1 mL / min), 40 °C, 220 nm, Rt = 6.491 min (minor) and 10.253 min (major), 96% ee.

[0290] Example 44

[0291] In this example, (R)-3,3'-bis(3-chloropropyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0292]

[0293] White solid (39.2 mg, 52% yield), m.p. 61.5 °C to 61.8 °C. 1 H NMR (400 MHz, CDCl3) δ 8.19 (s, 2H), 7.42 (s, 2H), 3.53 (t, J = 6.4 Hz, 4H), 3.25 - 3.12 (m, 2H), 3.05 - 2.92 (m, 2H), 2.73 (t, J = 7.5 Hz, 4H), 2.64 - 2.52 (m, 2H), 2.34 - 2.24 (m, 2H), 2.05 (dt, J = 13.4, 6.5 Hz, 4H). 13 C NMR (101 MHz, CDCl3) δ 166.9, 148.8, 136.8, 133.9, 132.8, 59.8, 44.1, 37.8, 33.9, 29.9, 28.5. [α] 25 D = -33.488 (c = 0.215, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 21 H 25 Cl2N2 + 375.1389; found 375.1389. HPLC (Shimadzu LC-2030) (Daicel OD-H Column, i PrOH:Hexane = 5:95, 1 mL / min), 40 °C, 220 nm, Rt = 12.339 min (minor) and 36.114 min (major), 97% ee.

[0294] Example 45

[0295] In this example, (R)-3,3'-bis(2-bromoethyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0296]

[0297] Red-brown oily liquid (53.7 mg, 62% yield). 1 H NMR (400 MHz, CDCl3) δ 8.19 (s, 2H), 7.43 (s, 2H), 3.51 (t, J = 7.5 Hz, 4H), 3.24 - 3.07 (m, 6H), 3.03 - 2.93 (m, 2H), 2.65 - 2.50 (m, 2H), 2.36 - 2.24 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 167.5, 148.8, 136.9, 132.9, 132.3, 59.9, 37.8, 36.5, 32.5, 28.5. [α] 25 D = 14.063 (c = 0.320, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 19 H 21 Br2N2 + 435.0066; found 435.0064. HPLC (Shimadzu LC-2030) (Daicel OJ-H Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 220 nm, Rt = 13.048 min (major) and 15.832 min (minor), 95% ee.

[0298] Example 46

[0299] In this example, (R)-2,2'-bis(4-trifluoromethylphenyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0300]

[0301] Colorless oily liquid (47.7 mg, 40% yield). 11H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 1.2 Hz, 2H), 7.90 - 7.77 (m, 4H), 7.77 - 7.63 (m, 4H), 7.40 (s, 2H), 3.73 (t, J = 7.1 Hz, 4H), 3.19 - 3.05 (m, 2H), 2.98 - 2.85 (m, 2H), 2.68 - 2.56 (m, 4H), 2.54 - 2.42 (m, 2H), 2.28 - 2.14 (m, 2H), 2.04 - 1.92 (m, 4H). 13 13C NMR (101 MHz, CDCl3) δ 168.4, 166.7, 148.6, 136.6, 134.2, 134.0, 132.4, 132.1, 123.3, 59.7, 37.80, 37.8, 30.3, 29.9, 28.5. [α] 25 25 D = 43.000 (c = 0.100, CHCl3). HRMS (ESI) m / z: [M+Na] + + calcd for C 37 37 H 32 32 N2NaO4 + + 619.2316; found 619.2312. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i i PrOH:Hexane = 20:80, 1 mL / min), 40 °C, 220 nm, Rt = 28.981 min (minor) and 45.790 min (major), 99% ee.

[0302] Example 47

[0303] In this example, (R)-2-(2-bromophenyl)-2'-phenyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0304]

[0305] Brown oily liquid (23.7 mg, 52% yield). 1 11H NMR (400 MHz, CDCl3) δ 7.98 - 7.87 (m, 2H), 7.67 - 7.53 (m, 3H), 7.48 (d, J = 7.9 Hz, 1H), 7.44 (dd, J = 7.7, 1.7 Hz, 1H), 7.42 - 7.26 (m, 5H), 7.19 - 7.11 (m, 1H), 3.54 - 3.31 (m, 2H), 3.10 - 2.93 (m, 2H), 2.87 - 2.69 (m, 2H), 2.44 - 2.27 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.2, 169.0, 156.5, 155.8, 141.7, 140.1, 135.8, 135.4, 133.4, 132.8, 132.0, 131.8, 129.2, 128.5, 128.3, 127.4, 126.8, 122.5, 122.2, 118.5, 60.5, 37.9, 37.8, 29.0, 28.8. [α] 25 25 D = 330.833 (c = 0.120, CHCl3). HRMS (ESI) m / z: [M + Na] + + calcd for C 27 27 H 21 21 BrN2Na + + 475.0780; found 475.0769. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 6.193 min (minor) and 8.323 min (major), 98% ee.

[0306] Example 48

[0307] In this example, (R)-2-phenyl-2'-(2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0308]

[0309] Yellow solid (21.3 mg, 57% yield), m.p. 121.2 °C - 121.7 °C. 1 11H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 4.2 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.16 (d, J = 7.9 Hz, 1H), 7.88 - 7.78 (m, 2H), 7.69 - 7.59 (m, 2H), 7.55 (d, J = 7.9 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.35 - 7.26 (m, 2H), 7.26 - 7.19 (m, 1H), 7.18 - 7.09 (m, 1H), 3.57 - 3.37 (m, 2H), 3.04 - 2.90 (m, 2H), 2.83 - 2.68 (m, 2H), 2.39 - 2.18 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 169.5, 169.1, 156.9, 155.7, 154.5, 148.9, 139.9, 137.2, 136.6, 135.1, 133.0, 132.8, 128.5, 128.3, 126.8, 123.1, 121.0, 119.1, 118.4, 60.1, 38.0, 37.8, 29.1, 29.0. [α] 25 D = 373.333 (c = 0.195, CHCl3). HRMS (ESI) m / z: [M + Na] + calcd for C 26 H 21 N3Na + 398.1628; found 398.1628. HPLC (Shimadzu LC - 2030) (Daicel IC Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 15.768 min (minor) and 18.640 min (major), 99% ee.

[0310] Example 49

[0311] In this example, tert - butyl (S)-((2'-phenyl - 5,5',6,6'-tetrahydro - 7,7'-spirobi[cyclopenta[b]pyridine]-3-yl)methyl)carbamate was prepared, and its structural formula is as follows:

[0312]

[0313] Colorless oily liquid (41.0 mg, 96% yield). 11H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.96 - 7.82 (m, 2H), 7.59 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 7.9 Hz, 2H), 7.36 (t, J = 7.3 Hz, 2H), 7.33 - 7.27 (m, 1H), 4.92 (s, 1H), 4.24 (d, J = 5.6 Hz, 2H), 3.43 - 3.23 (m, 2H), 3.05 - 2.93 (m, 2H), 2.83 - 2.72 (m, 1H), 2.72 - 2.60 (m, 1H), 2.39 - 2.22 (m, 2H), 1.45 (s, 9H). 13 13C NMR (101 MHz, CDCl3) δ 168.8, 156.1, 155.9, 147.5, 139.9, 137.1, 135.1, 133.0, 132.3, 132.0, 128.5, 128.3, 126.8, 118.7, 79.7, 60.1, 42.3, 38.1, 37.6, 28.8, 28.6, 28.4. [α]< 25 D = 81.724 (c = 0.290, CHCl3). HRMS (ESI) m / z: [M + Na] + calcd for C 27 H 29 N3NaO2 + 450.2152; found 450.2150. HPLC (Shimadzu LC - 2030) (Daicel IG Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 254 nm, Rt = 14.304 min (major) and 19.773 min (minor), 99% ee.

[0314] Example 50

[0315] In this example, the first [2 + 2 + 2] cycloaddition product (S)-7-(but-3-yn-1-yl)-3-(trimethylsilyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-7-carbonitrile was prepared, and its structural formula is as follows:

[0316]

[0317] Brown oily liquid (187.5 mg, 70% yield). 11H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.69 (s, 1H), 3.12 - 2.92 (m, 2H), 2.72 - 2.57 (m, 2H), 2.54 - 2.43 (m, 1H), 2.42 - 2.28 (m, 2H), 2.10 - 1.99 (m, 1H), 1.96 (t, J = 2.5 Hz, 1H), 0.28 (s, 9H). 13 13C NMR (101 MHz, CDCl3) δ 161.0, 153.0, 138.5, 135.3, 135.0, 121.3, 82.7, 69.3, 47.0, 36.1, 35.7, 27.9, 15.0, -1.3. [α] 25 D = 3.182 (c = 0.220, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 16 H 21 N2Si + 269.1469; found 269.1467. HPLC (Shimadzu LC - 2030) (Daicel IC Column, i PrOH:Hexane = 2:98, 1 mL / min), 40 °C, 220 nm, Rt = 20.983 min (minor) and 23.110 min (major), 82% ee.

[0318] The second [2 + 2 + 2] cycloaddition product (S)-2-(4-methoxyphenyl)-3'-(trimethylsilyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0319]

[0320] Yellow solid (25.3 mg, 63% yield), m.p. 122.4 °C - 122.6 °C. 11H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 0.6 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.70 - 7.64 (m, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 6.99 - 6.86 (m, 2H), 3.81 (s, 3H), 3.48 - 3.22 (m, 2H), 3.07 - 2.91 (m, 2H), 2.85 - 2.75 (m, 1H), 2.71 - 2.62 (m, 1H), 2.36 - 2.20 (m, 2H), 0.26 (s, 9H). 13 13C NMR (101 MHz, CDCl3) δ 170.0, 168.7, 160.0, 155.8, 152.4, 137.4, 136.0, 134.4, 133.0, 132.8, 132.1, 128.1, 118.0, 113.9, 60.5, 55.4, 37.8, 37.7, 29.1, 28.7, -1.1. [α] 25 D = 193.600 (c = 0.125, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 25 H 29 N2OSi + 401.2044; found 401.2037. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 7.584 min (minor) and 9.626 min (major), 97% ee.

[0321] Example 51

[0322] In this example, (S)-2-(2-pyridyl)-3'-(trimethylsilyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0323]

[0324] White solid (24.3 mg, 65% yield), m.p. 146.8 °C - 147.0 °C. 11H NMR (400 MHz, CDCl3) δ 8.66 - 8.55 (m, 1H), 8.46 - 8.35 (m, 1H), 8.31 - 8.22 (m, 1H), 8.19 (d, J = 7.9 Hz, 1H), 7.73 - 7.58 (m, 3H), 7.23 - 7.14 (m, 1H), 3.48 - 3.31 (m, 2H), 3.09 - 2.96 (m, 2H), 2.82 - 2.63 (m, 2H), 2.38 - 2.22 (m, 2H), 0.27 (s, 9H). 13 13C NMR (101 MHz, CDCl3) δ 169.9, 168.5, 156.8, 154.9, 152.5, 148.9, 137.4, 137.2, 136.6, 136.0, 133.2, 132.2, 123.1, 121.1, 119.3, 60.3, 37.8, 37.7, 29.1, 28.84, -1.1. [α] 25 D = 148.462 (c = 0.130, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 23 H 26 N3Si + 372.1891; found 372.1886. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 5:95, 1 mL / min), 40 °C, 254 nm, Rt = 4.668 min (minor) and 5.305 min (major), 97% ee.

[0325] Example 52

[0326] In this example, tert - butyl (R)-((3'-(trimethylsilyl)-5,5',6,6'-tetrahydro - 7,7'-spirobi[cyclopenta[b]pyridine]-3 - yl)methyl)carbamate was prepared, and its structural formula is as follows:

[0327]

[0328] Colorless oily liquid (36.3 mg, 86% yield). 11H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 8.24 (s, 1H), 7.67 (s, 1H), 7.51 (s, 1H), 4.89 (s, 1H), 4.26 (t, J = 10.5 Hz, 2H), 3.26 - 3.12 (m, 2H), 3.07 - 2.92 (m, 2H), 2.67 - 2.49 (m, 2H), 2.35 - 2.20 (m, 2H), 1.44 (s, 9H), 0.25 (s, 9H). 13 13C NMR (101 MHz, CDCl3) δ 169.1, 168.3, 155.9, 152.8, 148.0, 137.6, 137.1, 136.0, 132.5, 132.4, 132.1, 79.7, 60.3, 42.3, 37.8, 37.4, 28.7, 28.6, 28.4, -1.1. [α] 25 D = -21.351 (c = 0.370, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 24 H 33 N3NaO2Si + 446.2234; found 446.2232. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 5:95, 1 mL / min), 40 °C, 254 nm, Rt = 6.563 min (minor) and 13.564 min (major), 91% ee.

[0329] Example 53

[0330] In this example, the first [2 + 2 + 2] cycloaddition product (S)-7-(but-3-yn-1-yl)-3-octyl-6,7-dihydro-5H-cyclopenta[b]pyridine-7-carbonitrile was prepared, and its structural formula is as follows:

[0331]

[0332] Colorless oily liquid (237.0 mg, 77% yield). 11H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.39 (s, 1H), 3.11 - 2.89 (m, 2H), 2.74 - 2.54 (m, 4H), 2.54 - 2.43 (m, 1H), 2.44 - 2.29 (m, 2H), 2.11 - 1.99 (m, 1H), 1.96 (t, J = 2.6 Hz, 1H), 1.68 - 1.51 (m, 2H), 1.34 - 1.20 (m, 10H), 0.87 (t, J = 6.8 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 158.1, 149.2, 138.4, 135.6, 133.3, 121.5, 82.8, 69.2, 46.7, 36.3, 36.1, 33.0, 31.9, 31.4, 29.4, 29.2, 29.2, 27.8, 22.7, 15.1, 14.1. [α] 25 D = 4.337 (c = 0.415, CHCl3). HRMS (ESI) m / z: [M + Na] + calcd for C 21 H 28 N2Na + 331.2145; found 331.2145. HPLC (Shimadzu LC - 2030) (Daicel OJ - H Column, i PrOH:Hexane = 2:98, 1 mL / min), 40 °C, 220 nm, Rt = 8.625 min (minor) and 10.560 min (major), 91% ee.

[0333] In this example, the second [2 + 2 + 2] cycloaddition product (S)-3'-octyl-2-(thiophen-2-yl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0334]

[0335] Colorless oily liquid (35.4 mg, 85% yield). 11H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.45 (dd, J = 3.6, 0.9 Hz, 1H), 7.42 - 7.35 (m, 2H), 7.23 (dd, J = 5.0, 0.9 Hz, 1H), 7.00 (dd, J = 5.0, 3.7 Hz, 1H), 3.50 - 3.26 (m, 2H), 3.03 - 2.89 (m, 2H), 2.80 - 2.63 (m, 2H), 2.59 - 2.49 (m, 2H), 2.33 - 2.20 (m, 2H), 1.63 - 1.53 (m, 2H), 1.34 - 1.21 (m, 10H), 0.87 (t, J = 6.8 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 168.9, 166.7, 151.2, 148.1, 146.0, 136.6, 135.9, 134.9, 132.9, 132.5, 127.7, 126.4, 123.7, 117.0, 59.7, 38.3, 37.4, 33.1, 31.9, 31.5, 29.5, 29.3, 29.3, 28.8, 28.8, 22.7, 14.2. [α] 25 D = 130.000 (c = 0.170, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 27 H 33 N2S + 417.2359; found 417.2359. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 1:99, 1 mL / min), 40 °C, 254 nm, Rt = 8.637 min (minor) and 11.887 min (major), 96% ee.

[0336] Example 54

[0337] In this example, (S)-3'-octyl-2-(2-pyridyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine] was prepared, and its structural formula is as follows:

[0338]

[0339] Colorless oily liquid (27.2 mg, 66% yield). 11H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 4.0 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 8.18 (d, J = 7.9 Hz, 1H), 8.14 (s, 1H), 7.76 - 7.60 (m, 2H), 7.40 (s, 1H), 7.22 - 7.14 (m, 1H), 3.42 - 3.26 (m, 2H), 3.07 - 2.92 (m, 2H), 2.79 - 2.64 (m, 2H), 2.60 - 2.48 (m, 2H), 2.37 - 2.23 (m, 2H), 1.65 - 1.53 (m, 2H), 1.34 - 1.21 (m, 10H), 0.87 (t, J = 6.8 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 168.7, 166.8, 156.9, 154.9, 148.8, 148.3, 137.0, 136.6, 136.5, 135.9, 133.2, 132.4, 123.1, 121.1, 119.2, 59.9, 38.3, 37.6, 33.1, 31.9, 31.5, 29.5, 29.3, 29.3, 28.8, 28.8, 22.7, 14.2. [α] 25 D = 115.385 (c = 0.130, CHCl3). HRMS (ESI) m / z: [M + H] + calcd for C 28 H 34 N3 + 412.2747; found 412.2746. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 5:95, 1 mL / min), 40 °C, 254 nm, Rt = 4.797 min (minor) and 7.308 min (major), 98% ee.

[0340] Example 55

[0341] In this example, tert - butyl (R)-((3'-octyl-5,5',6,6'-tetrahydro-7,7'-spiro[cyclopenta[b]pyridine]-3-yl)methyl)carbamate was prepared, and its structural formula is as follows:

[0342]

[0343] Colorless oily liquid (39.1 mg, 84% yield). 11H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 8.14 (s, 1H), 7.50 (s, 1H), 7.37 (s, 1H), 4.91 (s, 1H), 4.24 (d, J = 4.2 Hz, 2H), 3.25 - 3.07 (m, 2H), 3.05 - 2.89 (m, 2H), 2.62 - 2.47 (m, 4H), 2.32 - 2.22 (m, 2H), 1.62 - 1.53 (m, 2H), 1.44 (s, 9H), 1.33 - 1.21 (m, 10H), 0.87 (t, J = 6.8 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 168.3, 166.0, 155.9, 148.6, 147.9, 137.2, 136.6, 136.2, 132.7, 132.5, 132.1, 59.8, 42.3, 37.9, 37.8, 33.0, 31.9, 31.5, 29.5, 29.3, 29.3, 28.5, 28.5, 28.3, 28.0, 22.7, 14.2. [α] 25 D = 16.774 (c = 0.155, CHCl3). HRMS (ESI) m / z: [M + Na] + calcd for C 29 H 41 N3NaO2 + 486.3091; found 486.3090. HPLC (Shimadzu LC - 2030) (Daicel OD - H Column, i PrOH:Hexane = 10:90, 1 mL / min), 40 °C, 254 nm, Rt = 5.030 min (minor) and 12.075 min (major), 96% ee.

[0344] Example 56

[0345] In this example, (R)-2,2'-diphenyl-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-1,1'-dioxide was prepared, and its structural formula is as follows:

[0346]

[0347] White solid (37.0 mg, 91% yield), m.p. 302.2 °C - 302.8 °C. 11H NMR (400 MHz, CDCl3) δ 7.80 - 7.67 (m, 4H), 7.43 - 7.31 (m, 6H), 7.24 (d, J = 7.8 Hz, 2H), 7.16 (d, J = 7.8 Hz, 2H), 3.45 - 3.29 (m, 2H), 3.20 - 3.07 (m, 2H), 3.07 - 2.93 (m, 2H), 2.29 - 2.18 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 153.2, 147.3, 141.0, 133.2, 129.6, 128.8, 128.1, 126.1, 122.6, 58.3, 34.6, 29.9. [α] 25 25 D = 24.545 (c = 0.220, CHCl3). HRMS (ESI) m / z: [M+Na] + + calcd for C 27 27 H 22 22 N2NaO2 + + 429.1573; found 429.1570. HPLC (Shimadzu LC - 2030) (Daicel ID Column, i PrOH:Hexane = 15:85, 1 mL / min), 40 °C, 254 nm, Rt = 5.124 min (major) and 5.908 min (minor), 95% ee.

[0348]

[0348] Example 57

[0349] In this example, (R)-2,2'-bis(2-naphthyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-1,1'-dioxide was prepared, and its structural formula is as follows:

[0350]

[0351] White solid product (96.1 mg, 95% yield), m.p. 304.5 °C - 304.9 °C. 1 1 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 2H), 7.92 - 7.79 (m, 8H), 7.51 - 7.43 (m, 4H), 7.36 (d, J = 7.8 Hz, 2H), 7.22 (d, J = 7.8 Hz, 2H), 3.45 - 3.34 (m, 2H), 3.22 - 3.12 (m, 2H), 3.12 - 3.01 (m, 2H), 2.32 - 2.24 (m, 2H).13 13C NMR (101 MHz, DMSO) δ 153.2, 145.6, 140.3, 132.8, 132.5, 130.6, 128.7, 128.4, 127.5, 126.9, 126.8, 126.8, 126.3, 126.3, 122.6, 57.4, 32.2, 28.9. [α] 25 D = 229.474 (c = 0.095, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 35 H 26 N2NaO2 + 529.1886; found 529.1879. 96% ee.

[0352] Example 58

[0353] In this example, (R)-3,3'-bis(trimethylsilyl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-1,1'-dioxide was prepared, and its structural formula is as follows:

[0354]

[0355] Yellow solid product (66.8 mg, 84% yield), m.p. 250.5 °C - 250.8 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.92 (s, 2H), 7.22 (d, J = 0.5 Hz, 2H), 3.45 - 3.29 (m, 2H), 3.13 - 3.01 (m, 2H), 2.90 - 2.81 (m, 2H), 2.19 - 2.10 (m, 2H), 0.26 (s, 18H). 13 13C NMR (101 MHz, CDCl3) δ 152.3, 142.2, 140.9, 137.2, 127.7, 57.2, 34.4, 29.9, -1.4. [α] 25 D = -86.067 (c = 0.445, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 21 H 30 N2NaO2 + 421.1738; found 421.1737. HPLC (Shimadzu LC - 2030) (Daicel ID Column,i PrOH:Hexane = 30:70, 1 mL / min), 40 °C, 220 nm, Rt = 11.416 min (major) and 25.970 min (minor), 96% ee.

[0356] Example 59

[0357] In this example, (R)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]-1,1'-dioxide was prepared, and its structural formula is as follows:

[0358]

[0359] White solid product (17.3 mg, 68% yield), m.p. 225.2 °C - 225.6 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 6.3, 0.6 Hz, 2H), 7.17 (dd, J = 7.6, 0.9 Hz, 2H), 7.09 (dd, J = 7.5, 6.4 Hz, 2H), 3.43 - 3.31 (m, 2H), 3.16 - 3.04 (m, 2H), 2.94 - 2.83 (m, 2H), 2.24 - 2.13 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 152.4, 142.9, 137.7, 124.8, 123.1, 57.3, 34.6, 30.1. [α] 25 D = -168.947 (c = 0.190, CHCl3). HRMS (ESI) m / z: [M+Na] + calcd for C 15 H 14 N2NaO2 + 277.0947; found 277.0944. HPLC (Shimadzu LC - 2030) (Daicel AD - H Column, i PrOH:Hexane = 20:80, 1 mL / min), 40 °C, 220 nm, Rt = 13.546 min (major) and 22.474 min (minor), 95% ee.

[0360] Example 60

[0361] In this example, hydrated-[2,2'-bis(pyridin-2-yl)-5,5',6,6'-tetrahydro-7,7'-spirobi[cyclopenta[b]pyridine]]-(trifluoromethanesulfonic acid)-iron trifluoromethanesulfonate dichloromethane solvate was prepared. A solution of Example 20 (37.6 mg, 0.1 mmol) and Fe(OTf)2 (35.3 mg, 0.1 mmol, 1.0 equiv) in THF (1.0 mL) was stirred at room temperature for 24 hours. After the reaction was completed, the resulting yellow solid (63.3 mg, 85% yield) was washed several times with n-hexane solution. Crystals were obtained in dichloromethane solution and characterized by X-ray single crystal diffractometer, CCDC: 2403729.

[0362] Its structural formula is as follows:

[0363]

[0364] Example 61

[0365] In this example, (S)-1-(4-methoxyphenyl)-3-buten-1-ol was prepared, and its structural formula is as follows:

[0366]

[0367] Colorless oily liquid, 1 1H NMR (400 MHz, CDCl3) δ 7.32 - 7.21 (m, 2H), 6.93 - 6.82 (m, 2H), 5.89 - 5.69 (m, 1H), 5.18 - 5.07 (m, 2H), 4.65 (t, J = 6.5 Hz, 1H), 3.78 (s, 3H), 2.55 - 2.42 (m, 2H), 2.22 (s, 1H).

[0368] Spirobipyridine N-oxides with 2,2′-diaryl or 3,3′-disilyl groups give higher enantioselectivity than spirobipyridine N-oxides without substituents, and absolute configuration inversion can be achieved under the condition of maintaining the configuration of the spiro atom while changing the substituents, reflecting the key role of the 2,2′- or 3,3′-substituents.

[0369] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various deformations or modifications within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A chiral spirocyclic bipyridine compound, characterized in that: The compound has a chiral spirocyclic bipyridine structure, and the substituents are at the 2,2' position, the 3,3' position or the 2,3' position.

2. The chiral spirocyclic bipyridine compound according to claim 1, characterized in that: The structural formula of the chiral 2,2′-substituted spiro bipyridine compound is shown in Formula 1 or 2; the structural formula of the chiral 3,3′-substituted spiro bipyridine compound is shown in Formula 3 or 4; the structural formula of the chiral 2,3′-substituted spiro bipyridine compound is shown in Formula 5: Among them, R 1 , R 2 are selected from C6-C20 aryl, C4-C20 heterocyclic aryl, C6-C20 substituted aryl containing nitrogen, oxygen or halogen, C2-C20 alkenyl; and R 1 , R 2 different; R 3 , R 4 are selected from C1-C20 alkyl, trisubstituted silicon, C3-C20 cycloalkyl, C1-C14 alkyl containing phenyl or C1-C20 alkyl containing heteroatoms; the heteroatoms are one or more of silicon, nitrogen, oxygen and halogen; the substituent of the trisubstituted silicon is C1-C6 alkyl or phenyl; and R 3 , R 4 different.

3. The chiral spirocyclic bipyridine compound according to claim 2, characterized in that: Include at least one of the following technical features: A. The C6-C20 aryl group is a phenyl group, a substituted phenyl group or a naphthyl group; the substituent in the substituted phenyl group is a C1-C10 alkyl group, a C6-C10 aryl group, or a substituent containing nitrogen, sulfur, oxygen or halogen atoms; B. The C4-C20 heterocyclic aromatic group is benzofuranyl, thienyl, substituted or unsubstituted pyridyl, quinolyl, isoquinolyl or ferrocenyl; the substituted pyridyl is C1-C6 alkyl, phenyl or pyridyl substituted with nitrogen, oxygen or halogen; C. The C1-C20 alkyl group is an n-octyl group or a C1-C14 alkyl group containing a phenyl group; D. The trisubstituted silyl group is trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl or triisopropylsilyl; E. The C2-C20 alkenyl group contains a C3-C20 cycloalkyl group; the C3-C20 cycloalkyl group contains a cyclopropyl group.

4. A method for preparing a chiral spirocyclic bipyridine compound as claimed in claim 2 or 3, characterized in that: S1, the preparation method of the chiral spirocyclic bipyridine compound represented by Formula 1 or Formula 3 comprises the following steps: S11, using a cobalt catalyst and a ligand as catalysts, in the presence of an organic solvent, an additive and a reducing agent, the raw material 7-1 or 7-3 and the raw material 6 undergo a double [2+2+2] cycloaddition reaction; S12, after the reaction is completed, separation and purification are performed to obtain a chiral spirocyclic bipyridine compound represented by Formula 1 or Formula 3; The reaction equation is as follows S1: The preparation method of the chiral spirocyclic bipyridine compound represented by S2, Formula 2, Formula 4 or Formula 5 comprises the following steps: S21, using a cobalt catalyst and a ligand as catalysts, in the presence of an organic solvent and a reducing agent, the raw material 7-1 or 7-3 and the raw material 6 undergo a first [2+2+2] cycloaddition reaction; S22, after the reaction is completed, separation and purification are performed to obtain a 2- or 3-substituted pyridine compound 8 or 9 containing a quaternary carbon chiral center of a cyano group; S23, using a cobalt catalyst and a ligand as catalysts, in the presence of an organic solvent, an additive and a reducing agent, the intermediate 8 or 9 undergoes a second [2+2+2] cycloaddition reaction with the raw material 7-2 or 7-4; S24, after the reaction is completed, separation and purification are performed to obtain a chiral spirocyclic bipyridine compound represented by Formula 2, Formula 4 or Formula 5; The reaction equation is as follows S2:

5. The method for preparing a chiral spirocyclic bipyridine compound according to claim 4, characterized in that: Include at least one of the following technical features: A. The cobalt catalyst (Co catalyst) is a monovalent cobalt or a divalent cobalt catalyst; the monovalent cobalt catalyst comprises tri(triphenylphosphine)cobalt chloride or chiral bisoxazoline-phosphine cobalt iodide, and the divalent cobalt catalyst comprises cobalt iodide, cobalt tetrafluoroborate, cobalt acetate, cobalt trifluoromethanesulfonate or cobalt bromide; B. The ligand is a chiral bisoxazoline-phosphine tridentate ligand, and its structural formula is as follows: Among them, R 5 is selected from C6-C20 aryl, C4-C20 heterocyclic aryl containing oxygen, nitrogen or sulfur atoms, C1-C20 alkyl, C6-C20 substituted aryl, wherein the substituent is C1-C8 alkyl or methoxy; R 6 is methyl, ethyl, isopropyl, isobutyl, cyclohexyl, benzyl or phenyl; C. The reducing agent is one of silane, borane, zinc powder, indium powder and manganese powder; D. The additive is one of sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, zinc trifluoromethanesulfonate, scandium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, and indium trifluoromethanesulfonate; E. The organic solvent is one of dichloroethane, acetonitrile, dichloromethane, toluene, benzonitrile, trifluorotoluene, hexafluoroisopropanol, trifluoroethanol, and N,N′-dimethylformamide. In F and S11, the molar ratio of the cobalt catalyst to the ligand is 1:(1-2); the molar ratio of the raw material 7-1 or 7-3 to the raw material 6 is (2.5-4):1; the molar ratio of the cobalt catalyst to the raw material 6 is 1:(10-1000); the molar ratio of the reducing agent to the raw material 6 is 1:(2.5-1000); the molar ratio of the additive to the cobalt catalyst is (1-2):1; the reaction temperature is 0-100°C; In G and S21, the molar ratio of the cobalt catalyst to the ligand is 1:(1-2); the molar ratio of the raw material 7-1 or 7-3 to the raw material 6 is (1-2):1; the molar ratio of the cobalt catalyst to the raw material 6 is 1:(10-1000); the molar ratio of the reducing agent to the raw material 6 is 1:(2.5-1000); the reaction temperature is 0-100°C; In H and S23, the molar ratio of the cobalt catalyst to the ligand is 1:(1-2); the molar ratio of the additive to the cobalt catalyst is (1-2):1; the molar ratio of the intermediate product 8 or 9 to the raw material 7-2 or 7-4 is 1:2; the molar ratio of the cobalt catalyst to the intermediate product 8 or 9 is 1:(10-1000); the molar ratio of the reducing agent to the intermediate product 8 or 9 is 1:(2.5-1000); the reaction temperature is 0-100°C.

6. A 2,2′- or 3,3′-substituted chiral spirocyclic bipyridine nitrogen oxide compound, the structural formula of which is shown in Formula 10 and 11: in, R 1 R is selected from C6-C20 aryl, C4-C20 heterocyclic aryl, C6-C20 substituted aryl containing nitrogen, oxygen or halogen, C2-C20 alkenyl; 3 They are respectively selected from hydrogen atoms, C1-C20 alkyl groups, C3-C20 trialkylsilyl groups, C3-C20 cycloalkyl groups, C1-C14 alkyl groups containing phenyl groups, or C1-C20 alkyl groups containing heteroatoms; the heteroatoms are one or more of silicon, nitrogen, oxygen, and halogen.

7. A method for preparing a 2,2′- or 3,3′-substituted chiral spirocyclic bipyridine nitrogen oxide compound as claimed in claim 6, characterized in that: The method comprises the following steps: S1, adding an equivalent amount of an oxidizing agent, and reacting the raw material 1 or 3 in an organic solvent; S2. After the reaction is completed, separation and purification are performed to obtain the 2,2′- or 3,3′-substituted chiral spirocyclic bipyridine nitrogen oxide compound 10 or 11; The reaction equation is as follows:

8. The method for preparing the 2,2′- or 3,3′-substituted chiral spirocyclic bipyridine nitrogen oxide compound according to claim 7, characterized in that: Include at least one of the following technical features: A. The oxidizing agent is one of m-chloroperbenzoic acid, hydrogen peroxide, perbenzoic acid, peracetic acid, peroxytrifluoroacetic acid, tert-butyl hydroperoxide, and acetone peroxide; B. The organic solvent is one of dichloromethane and dichloroethane; C. The molar ratio of raw material 1 or 3 to the oxidizing agent is 1:2-4; D. The reaction temperature is 0℃~100℃.

9. Use of a chiral 2,2′-substituted spirocyclic bipyridine compound as shown in Formula 1 or 2 as a ligand for coordination with a transition metal; in, R 1 , R 2 are selected from C6-C20 aryl, C4-C20 heterocyclic aryl, C6-C20 substituted aryl containing nitrogen, oxygen or halogen, C2-C20 alkenyl; and R 1 , R 2 different.

10. Use of the 2,2'- or 3,3'-substituted chiral spirocyclic bipyridine nitrogen oxide compound as claimed in claim 6 as an organic catalyst in asymmetric synthesis.

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