An iridium complex, a preparation method thereof and application thereof in synthesis of chiral piperidine

Abstract

The application discloses an iridium complex, a preparation method thereof and application of the iridium complex in synthesis of chiral piperidines, and the preparation method of the iridium complex comprises the following steps: adding an indole compound, an iridium compound and an alkali into a first solvent, heating and stirring at 40-80 DEG C, lowering to room temperature after reaction, filtering, reducing pressure distillation, and separating by silica gel column chromatography to obtain the iridium complex; under the cooperation of the iridium complex as a catalyst and chiral phosphoric acid, 1,5-diol compounds and amine compounds can be directly reacted to obtain a series of chiral piperidine compounds, the method has the advantages of high reaction efficiency, simplicity and high yield, and the enantiomeric excess value of the chiral piperidine prepared by using the iridium catalyst is not less than 83%.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and in particular relates to an iridium complex and a preparation method thereof and application thereof in chiral piperidine synthesis. Background Art

[0002] Iridium complexes are widely used as catalysts in a variety of organic chemical reactions, such as allylic substitution reactions, hydrogenation reactions, and double bond isomerization reactions. Iridium complexes have also been widely used in hydrogen borrowing reactions. However, the limited variety of iridium complexes suitable for hydrogen borrowing reactions has severely restricted the development of hydrogen borrowing reactions. In particular, only a few iridium complexes have been proven to be effective in asymmetric hydrogen borrowing reactions. Therefore, the development of new iridium complexes for metal-catalyzed reactions, especially asymmetric catalytic reactions, is of far-reaching significance. Summary of the Invention

[0003] In view of the deficiencies in the prior art, the present invention aims to provide an iridium complex.

[0004] Another object of the present invention is to provide a method for preparing the iridium complex.

[0005] Another object of the present invention is to provide an application of an iridium complex in the synthesis of chiral piperidine.

[0006] The purpose of the present invention is achieved through the following technical solutions.

[0007] An iridium complex has the following general structural formula:

[0008] Wherein, R is methyl, ethyl, isopropyl or tert-butyl.

[0009] A method for preparing an iridium complex comprises the following steps:

[0010] Adding an indole compound, an iridium compound and a base to a first solvent, heating and stirring at 40-80° C., cooling to room temperature after the reaction is completed, filtering, distilling under reduced pressure, and separating by silica gel column chromatography to obtain an iridium complex;

[0011] The structural formula of the indole compound is

[0012] The general chemical formula of the iridium compound is Wherein, R is methyl, ethyl, isopropyl or tert-butyl;

[0013] Calculated by amount, the ratio of the indole compound, the iridium compound and the base is 0.25:(0.125-0.13):(0.3-0.4).

[0014] In the above technical solution, the ratio of the amount of the indole compound to the volume of the first solvent is 0.25:(4-6), the unit of the amount of the substance is mmol, and the unit of the volume is mL.

[0015] In the above technical solution, the base is a mixture of one or more of potassium acetate, sodium acetate, potassium carbonate, sodium carbonate, sodium bicarbonate and potassium bicarbonate.

[0016] In the above technical solution, the first solvent is one or a mixture of N,N-dimethylformamide, acetonitrile and dimethyl sulfoxide.

[0017] In the above technical solution, the stirring time is 4 to 12 hours.

[0018] Application of an iridium complex in the synthesis of chiral piperidine.

[0019] In the above technical solution, the chemical formula of the chiral piperidine is Wherein, R1 is phenyl, substituted phenyl or heteroaryl, the substituent on the substituted phenyl is meta- or para-substituted alkyl, halogen, alkoxy or aryl, and R2 is at least one of hydrogen, alkyl, haloalkyl, halogen, alkoxy and aryl.

[0020] In the above technical solution, the method for preparing chiral piperidine comprises: mixing the above iridium complex, diol compound, amine compound, chiral phosphoric acid, additive and second solvent, heating at 75-100° C. for reaction, and separating by silica gel column chromatography after the reaction is completed to obtain chiral piperidine;

[0021] The general chemical formula of the diol compound is Wherein, R1 is phenyl, substituted phenyl or heteroaryl, and the substituent on the substituted phenyl is an alkyl, halogen, alkoxy or aryl substituted at the meta or para position;

[0022] The general chemical formula of the amine compound is wherein R2 is at least one of hydrogen, alkyl, haloalkyl, halogen, alkoxy and aryl;

[0023] The general chemical formula of the chiral phosphoric acid is Wherein, R3 is isopropyl (i-Pr) or adamantyl (adamantyl).

[0024] In the above technical solution, the additive is a molecular sieve, and the pore size of the molecular sieve is

[0025] In the above technical solution, the second solvent is one or a mixture of n-hexane, cyclohexane and n-heptane.

[0026] In the above technical solution, the ratio of the iridium complex, the diol compound, the amine compound and the chiral phosphoric acid is (0.002-0.008):0.1:(0.1-0.12):(0.005-0.008) in terms of the amount of substances.

[0027] In the above technical solution, the ratio of the amount of the iridium complex, the mass of the additive and the volume of the second solvent is (0.002-0.008): (20-50): (0.3-0.6), the unit of the amount of the substance is mmol, the unit of the mass is mg, and the unit of the volume is mL.

[0028] In the above technical solution, the reaction time is 24 to 48 hours.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] The iridium complex of the present invention, when used as a catalyst and in combination with chiral phosphoric acid, can achieve the purpose of directly reacting a 1,5-diol compound with an amine compound to obtain a series of chiral piperidine compounds. The method has the advantages of high reaction efficiency, simplicity and high yield, and the enantiomeric excess (ee) value of the chiral piperidine prepared using the iridium catalyst is not less than 83%. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is the H NMR spectrum of the iridium complex prepared in Example 1;

[0032] Figure 2 This is the H NMR spectrum of the iridium complex prepared in Example 4;

[0033] Figure 3 This is the NMR carbon spectrum of the iridium complex prepared in Example 4;

[0034] Figure 4 This is the H NMR spectrum of the chiral piperidine prepared in Example 5. DETAILED DESCRIPTION

[0035] The technical solution of the present invention is further described in detail below with reference to the accompanying drawings and embodiments.

[0036] In the following embodiments, the structural formula of the indole compound is It was synthesized according to the literature (Condensation of Carboxylic Acids with Non-Nucleophilic N-Heterocycles and Anilides Using Boc2O, J. Org. Chem. 2016, 81, 11444-11453).

[0037] In the following examples, iridium compound 2a, iridium compound 2b, iridium compound 2c and iridium compound 2d were respectively used as iridium compounds and synthesized according to the literature (Extending the range of pentasubstituted cyclopentadienyl compounds:The synthesis of a series of tetramethyl(alkyl or aryl)cyclopentadienes(Cp*R), their iridium complexes and their catalytic activity for asymmetric transfer hydrogenation Polyhedron 2014, 84, 120-135; Development of Pseudo-C2-symmetric Chiral Binaphthyl Monocarboxylic Acids for Enantioselective C(sp3)–H Functionalization Reactions under Rh(III)Catalysis ACS Catal. 2021, 11, 7, 4271-4277).

[0038] In the following examples, diol compound 3a, diol compound 3b, diol compound 3c, diol compound 3d, diol compound 3e, diol compound 3f, diol compound 3g, and diol compound 3h were respectively used as diol compounds, and each was synthesized according to the literature (Stereoselective synthesis of alicyclic ketones: A hydrogen borrowing approach, Tetrahedron, 2019, 75, 130680; A phosphine-free iron complex-catalyzed synthesis of cycloalkanes via the borrowing hydrogen strategy, Chem. Commun. 2020, 56, 12909-12912);

[0039] The structural formulas of diol compound 3a, diol compound 3b, diol compound 3c, diol compound 3d, diol compound 3e, diol compound 3f, diol compound 3g and diol compound 3h are as follows:

[0040]

[0041] In the following examples, amine compound 4a and amine compound 4i were used as amine compounds, both purchased from Anhui Zesheng Technology Co., Ltd.;

[0042] The structural formulas of amine compound 4a and amine compound 4i are as follows:

[0043] In the following examples, chiral phosphoric acid was purchased from Shanghai Bid Pharmaceutical Technology Co., Ltd. The structural formula of chiral phosphoric acid is R3 is adamantyl group.

[0044] Example 1

[0045] A method for preparing an iridium complex comprises the following steps: adding an indole compound, an iridium compound, and a base to a first solvent, heating and stirring at 50°C, reacting for 6 hours, cooling the mixture to room temperature of 20-25°C, filtering with diatomaceous earth, distilling the filtrate under reduced pressure to remove the solvent, and separating the mixture by silica gel column chromatography (the eluent for the column chromatography is a mixture of n-hexane and ethyl acetate, with the ratio of n-hexane to ethyl acetate being 20:1 by volume), thereby obtaining an orange solid as the iridium complex ([Ir]-1a) with a yield of 88%. The iridium compound is iridium compound 2a, the base is sodium acetate, and the first solvent is acetonitrile. The ratio of the indole compound, the iridium compound, and the base is 0.25:0.126:0.3 by molar fraction, and the ratio of the indole compound to the first solvent by volume is 0.25:5. The units of molar fractions are mmol, and the units of volume fractions are mL.

[0046] The structure of the iridium complex prepared in Example 1 is as follows:

[0047]

[0048] The NMR data of the iridium complex prepared in Example 1 are as follows: 1 H NMR (500MHz, CDCl3): δ9.08 (dd, J=5.6, 1.6Hz, 1H), 8.57 (dd, J=8.1, 1.6Hz, 1H), 8.33 (d, J=8.0Hz, 1H), 7.99 (td, J=7.8, 1.6Hz, 1H), 7.48 (dd d,J=7.4,5.6,1.6Hz,1H),7.32(d,J=7.6Hz,1H),7.17(td,J=7.5,1.0Hz,1H),6.98(ddd,J=8.4,7.2,1.2Hz,1H),6.22(s,1H),1.46(s,15H). 13C NMR (126MHz, CDCl3): δ163.23,157.32,152.87,142.25,139.71,138.85,135 .93,128.47,128.07,123.61,121.26,117.98,117.15,115.15,90.21,8.71. Figure 1 This is the H-NMR spectrum of the iridium complex prepared in Example 1.

[0049] The structural formula of iridium compound 2a is as follows: R is methyl.

[0050] Example 2

[0051] The structure of the iridium complex prepared in this embodiment is as follows:

[0052] A method for preparing an iridium complex is substantially the same as the method of Example 1, except that the iridium compound is iridium compound 2b. The orange solid obtained by the method of Example 2 is the iridium complex ([Ir]-1b) in an 83% yield. The NMR data of the iridium complex prepared in Example 2 are as follows: 1 H NMR (500MHz, CDCl3): δ9.07 (ddd, J=5.6, 1.6, 0.6Hz, 1H), 8.56 (ddd, J=8.1, 1.6, 0.6Hz, 1H), 8.33 (d q, J=8.3, 0.8Hz, 1H), 7.97 (td, J=7.8, 1.6Hz, 1H), 7.47 (ddd, J=7.4, 5.6, 1.6Hz, 1H), 7.32 (ddd, J=7. 6,1.3,0.7Hz,1H),7.17(td,J=7.4,1.1Hz,1H),6.98(ddd,J=8.3,7.3,1.3Hz,1H),6.22(d,J=0.8Hz ,1H),1.91-1.74(m,2H),1.52(s,3H),1.51(s,3H),1.48(s,3H),1.44(s,3H),1.00(t,J=7.6Hz,3H). 13 C NMR (126MHz, CDCl3): δ163.26,157.37,152.88,141.97,139.69,138.86,135.89,128.41,128.02,123.60, 121.25,117.97,117.26,115.14,92.21,91.12,91.05,90.77,89.74,17.42,12.82,8.69,8.62,8.58,8.48.

[0053] The structural formula of iridium compound 2b is as follows: R is ethyl.

[0054] Example 3

[0055] The structure of the iridium complex prepared in this embodiment is as follows:

[0056] A method for preparing an iridium complex is substantially the same as that of Example 1, except that the iridium compound is iridium compound 2c. The method of Example 3 yields an orange solid, the iridium complex ([Ir]-1c), in 78% yield. The NMR data of the iridium complex prepared in Example 3 are as follows: 1 H NMR (500MHz, CDCl3): δ9.09 (ddd, J=5.7, 1.6, 0.6Hz, 1H), 8.58 (ddd, J=8.0, 1.7, 0.6Hz, 1H), 8.34 (dq, J=8. 4,0.8Hz,1H),7.99(td,J=7.8,1.6Hz,1H),7.48(ddd,J=7.4,5.7,1.7Hz,1H),7.32(ddd,J=7.6,1.2,0.7Hz, 1H), 7.16 (td, J=7.4, 1.1Hz, 1H), 6.98 (ddd, J=8.4, 7.2, 1.3Hz, 1H), 6.24 (d, J=0.8Hz, 1H), 2.41 (hept, J=7. 1Hz, 1H), 1.61 (s, 3H), 1.49 (s, 3H), 1.46 (s, 3H), 1.41 (s, 3H), 1.20 (d, J = 7.1Hz, 3H), 1.08 (d, J = 7.1Hz, 3H). 13 C NMR (126MHz, CDCl3): δ163.32,157.69,152.96,141.92,139.59,138.89,135.92,128.51,127.97,123.65,121 .32,117.98,117.53,115.26,95.89,94.20,90.31,89.97,89.79,25.97,21.40,21.35,9.77,9.47,8.67,8.64.

[0057] The structural formula of iridium compound 2c is as follows: R is isopropyl.

[0058] Example 4

[0059] The structure of the iridium complex prepared in this embodiment is as follows:

[0060] A method for preparing an iridium complex is substantially the same as the method of Example 1, except that the iridium compound is iridium compound 2d. The method of Example 4 produces a deep red solid, the iridium complex ([Ir]-1d), in a yield of 66%. The NMR data of the iridium complex prepared in Example 4 are as follows: 1 H NMR (500MHz, CDCl3): δ9.05 (dd, J=5.6, 1.7Hz, 1H), 8.58 (dd, J=8.0, 1.6Hz, 1H), 8.38 (d d,J=8.1,1.0Hz,1H),7.96(td,J=7.8,1.6Hz,1H),7.45(ddd,J=7.5,5.7,1.7Hz,1H),7. 33(dt,J=7.7,1.0Hz,1H),7.18(td,J=7.4,1.1Hz,1H),6.99(ddd,J=8.3,7.2,1.3Hz,1H ), 6.23 (d, J = 0.7Hz, 1H), 1.72 (s, 3H), 1.61 (d, J = 5.5Hz, 6H), 1.53 (s, 3H), 1.07 (s, 9H). 13 C NMR (126MHz, CDCl3): δ163.28,158.04,152.99,141.99,139.37,138.96,135.90,128.68,127.80,123.69,1 21.38,117.94,117.93,115.37,98.56,96.27,95.36,88.53,87.16,33.68,31.04,12.67,12.41,9.32,8.80. Figure 2 This is the H NMR spectrum of the iridium complex prepared in Example 4; Figure 3 This is the NMR carbon spectrum of the iridium complex prepared in Example 4.

[0061] The structural formula of iridium compound 2d is as follows: R is tert-butyl.

[0062] Chiral piperidine structural units are widely present in natural products and pharmaceuticals. For example, the migraine drug ubagepam and the antiviral drug lonafarnib are both chiral drugs containing piperidine structural units. Therefore, the development of new chiral synthetic strategies to efficiently prepare piperidine compounds with chiral structural units has a positive impact on drug development and the synthesis of related natural products.

[0063] Example 5

[0064] The structural formula of the chiral piperidine prepared in this embodiment is:

[0065] A method for preparing chiral piperidine comprises the following steps:

[0066] The iridium complex prepared in Example 4, the diol compound, the amine compound, the chiral phosphoric acid, the additive and the second solvent were mixed, heated at 80° C. for reaction, and the reaction was completed for 24 hours. The mixture was separated by silica gel column chromatography (the eluent for the column chromatography was a mixture of n-hexane and ethyl acetate, and the ratio of n-hexane to ethyl acetate was 20:1 by volume) to obtain a colorless transparent liquid chiral piperidine (5a) with a yield of 93% and an enantiomeric excess (ee) value of 90%. The diol compound was diol compound 3a, the amine compound was amine compound 4a, the additive was a molecular sieve, and the pore size of the molecular sieve was The second solvent is n-hexane. The ratio of the iridium complex, the diol compound, the amine compound, and the chiral phosphoric acid is 0.005:0.1:0.1:0.0075, based on the amount of substance. The ratio of the amount of substance of the iridium complex, the mass fraction of the additive, and the volume fraction of the second solvent is 0.005:30:0.5. The unit of the amount of substance is mmol, the unit of the mass fraction is mg, and the unit of the volume fraction is mL. The nuclear magnetic resonance data of the chiral piperidine prepared in this example are as follows:

[0067] 1 H NMR (500MHz, CDCl3): δ7.28(d,J=7.8Hz,2H),7.23(t,J=7.5Hz,2H),7.17–7.09(m,3H),6.90(d,J=8.1Hz,2H),6.76(t,J=7.3Hz,1H),4.54–4.47( m,1H),3.42(dt,J=11.8,5.6Hz,1H),3.27(dt,J=12.2,5.9Hz,1H),2.05– 1.90(m,2H),1.78(p,J=6.2,5.6Hz,2H),1.69(m,1H),1.61–1.51(m,1H).

[0068] 13 C NMR (126MHz, CDCl3): δ151.96,143.71,128.91,128.38,127.34,126.33,119.69,118.88,61.15,50.66,33.59,25.76,22.16. Figure 4 This is the H NMR spectrum of the chiral piperidine prepared in Example 5.

[0069] Example 6

[0070] The structural formula of the chiral piperidine prepared in this embodiment is:

[0071] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the diol compound is diol compound 3b. The method of Example 6 yields a colorless, transparent chiral piperidine (5b) in 76% yield and 86% enantiomeric excess (ee). The NMR data of the chiral piperidine prepared in this example are as follows:

[0072] 1 H NMR (500MHz, CDCl3): δ7.21–7.10(m,4H),7.05(d,J=7.9Hz,2H),6.90(d,J=7.5Hz,2H),6.80–6.72(m,1H),4.51(t,J=5.6Hz,1H) ,3.48–3.34(m,1H),3.34–3.20(m,1H),2.28(s,3H),2.05–1.88(m,2H),1.82–1.73(m,2H),1.73–1.63(m,1H),1.60–1.50(m,1H).

[0073] 13 C NMR (126MHz, CDCl3): δ151.99,140.54,135.76,129.10,128.91,127.23,119.49,118.65,60.69,50.36,33.48,25.75,22.05,21.13.

[0074] Example 7

[0075] The structural formula of the chiral piperidine prepared in this embodiment is:

[0076] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the diol compound is diol compound 3c. The method of Example 7 yields chiral piperidine (5c) as a white solid in 82% yield and 83% enantiomeric excess (ee). The NMR data of the chiral piperidine prepared in this example are as follows:

[0077] 1H NMR (500MHz, CDCl3): δ7.62–7.52(m,2H),7.53–7.45(m,2H),7.46–7.38(m,2H),7.39–7.28(m,3H),7.22–7.13(m,2H),6.95(d,J=7.8H z,2H),6.79(t,J=7.3Hz,1H),4.60(t,J=5.6Hz,1H),3.51–3.39(m,1H),3.37–3.24(m,1H),2.10–1.97(m,2H),1.85–1.77(m,2H),1.77 -1.68(m,1H),1.64–1.56(m,1H).

[0078] 13 C NMR (126MHz, CDCl3): δ151.92,142.80,141.05,139.12,128.99,128.79,127.7 6,127.14,127.10,127.08,119.64,118.69,60.74,50.41,33.44,25.73,22.07.

[0079] Example 8

[0080] The structural formula of the chiral piperidine prepared in this embodiment is:

[0081] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the diol compound is diol compound 3d. The method of Example 8 yields a colorless, transparent chiral piperidine (5d) in 85% yield and 83% enantiomeric excess (ee). The NMR data of the chiral piperidine prepared in this example are as follows:

[0082] 1 H NMR (500MHz, CDCl3): δ7.22–7.12(m,4H),6.90(d,J=7.8Hz,2H),6.80–6.74(m,3H),4.47(dd,J=6.4,4.7Hz,1H),3.75(s ,3H),3.43–3.34(m,1H),3.29–3.22(m,1H),2.02–1.88(m,2H),1.82–1.74(m,2H),1.74–1.64(m,1H),1.59–1.51(m,1H).

[0083] 13C NMR (126MHz, CDCl3): δ158.01,152.02,135.61,128.89,128.35,119.66,118.95,113.74,60.54,55.25,50.60,33.59,25.80,22.15.

[0084] Example 9

[0085] The structural formula of the chiral piperidine prepared in this embodiment is:

[0086] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the diol compound is diol compound 3e. The method of Example 9 yields a colorless, transparent chiral piperidine (5e) in a yield of 61% and an enantiomeric excess (ee) of 95%. The NMR data of the chiral piperidine prepared in this example are as follows:

[0087] 1 H NMR (500MHz, CDCl3): δ7.39–7.30(m,2H),7.19–7.08(m,4H),6.88(d,J=7.6Hz,2H),6.79(t,J=7.3Hz,1H),4.38(dd,J=7.6,4.1Hz,1H),3.39 (dt,J=12.5,5.5Hz,1H),3.22–3.11(m,1H),2.00–1.92(m,1H),1.88–1.81(m,1H),1.80–1.74(m,2H),1.73–1.64(m,1H),1.59–1.47(m,1H).

[0088] 13 C NMR (126MHz, CDCl3): δ151.88,143.11,131.48,129.13,128.96,120.43,119.99,119.70,61.15,51.78,34.10,25.82,22.45.

[0089] Example 10

[0090] The structural formula of the chiral piperidine prepared in this embodiment is:

[0091] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the diol compound is diol compound 3f. The method of Example 10 yields a chiral piperidine (5f) as a colorless, transparent liquid in 76% yield with an enantiomeric excess (ee) of 86%. The NMR data of the chiral piperidine prepared in this example are as follows:

[0092] 1 H NMR (500MHz, CDCl3): δ7.21–7.09(m,4H),7.08(d,J=7.9Hz,1H),6.96(d,J=7.4Hz,1H),6.94–6.86(m,2H),6.80–6.73(m,1H),4.50(t,J=5.5Hz 1H),3.49–3.36(m,1H),3.35–3.23(m,1H),2.30(s,3H),2.05–1.91(m,2H),1.78(p,J=5.9Hz,2H),1.76–1.64(m,1H),1.61–1.52(m,1H).

[0093] 13 C NMR (126MHz, CDCl3): δ151.95,143.63,137.87,128.92,128.24,127.99,1 27.11,124.39,119.46,118.56,61.02,50.25,33.33,25.63,22.03,21.69.

[0094] Example 11

[0095] The structural formula of the chiral piperidine prepared in this embodiment is:

[0096] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the diol compound is 3 g. The method of Example 11 yields a chiral piperidine (5 g) as a colorless, transparent liquid in a yield of 56% and an enantiomeric excess (ee) of 93%. The NMR data of the chiral piperidine prepared in this example are as follows:

[0097] 1 H NMR (500MHz, CDCl3): δ7.21–7.11(m,3H),7.04(d,J=7.7Hz,1H),6.99(dt,J=10.4,2.2Hz,1H),6.89(d,J=8.0Hz,2H),6.84–6.75(m,2H),4.45(dd,J=7 .3,4.2Hz,1H),3.44–3.34(m,1H),3.26–3.16(m,1H),2.03–1.95(m,1H),1 .92–1.84(m,1H),1.82–1.74(m,2H),1.74–1.64(m,1H),1.60–1.50(m,1H).

[0098] 13C NMR (126MHz, CDCl3): δ163.15 (d, J = 245.0Hz), 151.80, 146.84 (d, J = 6.7Hz), 129.78 (d, J = 8.2Hz), 128.98, 122.9 2(d,J=2.7Hz),120.19,119.25,114.25(d,J=21.7Hz),113.26(d,J=21.3Hz),61.09,51.16,33.72,25.70,22.24.

[0099] Example 12

[0100] The structural formula of the chiral piperidine prepared in this embodiment is:

[0101] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the diol compound is diol compound 3h. The method of Example 12 yields a colorless, transparent chiral piperidine (5h) in a yield of 69% and an enantiomeric excess (ee) of 84%. The NMR data of the chiral piperidine prepared in this example are as follows:

[0102] 1 H NMR (500MHz, CDCl3): δ7.24–7.16(m,3H), 6.99–6.87(m,4H), 6.76(t,J=7.3Hz,1H), 4.90(t,J=4.7Hz,1H), 3.46(dt,J=12. 7, 4.6Hz, 1H), 3.28–3.19 (m, 1H), 2.15–2.07 (m, 1H), 2.07–1.97 (m, 1H), 1.72 (p, J = 6.1Hz, 2H), 1.63 (h, J = 5.3, 4.7Hz, 2H).

[0103] 13 C NMR (126MHz, CDCl3): δ151.34,143.67,129.20,127.47,125.34,121.43,118.66,116.61,56.45,46.54,31.52,25.61,20.92.

[0104] HRMS(ESI):m / z Calcd.for[C 15 H 18 NS,M+H] + :244.1154;Found:244.1156.

[0105] Example 13

[0106] The structural formula of the chiral piperidine prepared in this embodiment is:

[0107] A method for preparing a chiral piperidine is substantially the same as that of Example 5, except that the amine compound is amine compound 4i. The method of Example 13 yields a chiral piperidine product (5i) as a colorless, transparent liquid in 71% yield with an enantiomeric excess (ee) of 89%. The NMR data of the chiral piperidine prepared in this example are as follows:

[0108] 1 H NMR (500MHz, CDCl3): δ7.25–7.14(m,5H),7.14–7.06(m,1H),7.01(dd,J=8.9,2.8Hz,1H),6.72(d,J=8.8Hz,1H),4.05(dd,J=9.3,3 .4Hz,1H),3.76(s,3H),3.38(dt,J=11.8,4.3Hz,1H),2.95-2.85(m,1H),1.99–1.90(m,1H),1.88–1.72(m,4H),1.57–1.47(m,1H).

[0109] 13 C NMR (126MHz, CDCl3): δ152.32,145.70,144.09,128.35,127.49,126.78,126.58,123.76(q,J=272.4 Hz), 121.70 (q, J = 5.2Hz), 118.62 (q, J = 30.5Hz), 112.48, 64.28, 56.16, 55.97, 35.90, 26.44, 23.98.

[0110] The above is an exemplary description of the present invention. It should be noted that, without departing from the core of the present invention, any simple deformation, modification or other equivalent replacement that can be made by other skilled in the art without expending creative labor falls within the scope of protection of the present invention.

Claims

1. An iridium complex, characterized in that Its general structural formula is as follows: Wherein, R is methyl, ethyl, isopropyl or tert-butyl.

2. A method for preparing an iridium complex, characterized in that: The method comprises the following steps: adding an indole compound, an iridium compound and a base to a first solvent, heating and stirring at 40-80° C., cooling to room temperature after the reaction is completed, filtering, distilling under reduced pressure, and separating by silica gel column chromatography to obtain an iridium complex; The structural formula of the indole compound is The general chemical formula of the iridium compound is Wherein, R is methyl, ethyl, isopropyl or tert-butyl; Calculated by amount, the ratio of the indole compound, the iridium compound and the base is 0.25:(0.125-0.13):(0.3-0.4).

3. The preparation method according to claim 2, characterized in that The ratio of the amount of the indole compound to the volume of the first solvent is 0.25:(4-6), the unit of the amount of the substance is mmol, and the unit of the volume is mL.

4. The preparation method according to claim 2 or 3, characterized in that The base is a mixture of one or more of potassium acetate, sodium acetate, potassium carbonate, sodium carbonate, sodium bicarbonate and potassium bicarbonate; The first solvent is one or a mixture of N,N-dimethylformamide, acetonitrile and dimethyl sulfoxide; The stirring time is 4 to 12 hours.

5. The use of the iridium complex as claimed in claim 1 in the synthesis of chiral piperidine, characterized in that: The general chemical formula of the chiral piperidine is wherein R1 is phenyl, substituted phenyl or heteroaryl, the substituent on the substituted phenyl is an alkyl, halogen, alkoxy or aryl substituted at the meta or para position, and R2 is at least one of hydrogen, alkyl, haloalkyl, halogen, alkoxy and aryl; The preparation method of the chiral piperidine comprises: mixing the iridium complex, a diol compound, an amine compound, chiral phosphoric acid, an additive and a second solvent, heating at 75-100° C. for reaction for 24-48 hours, and separating by silica gel column chromatography after the reaction is completed to obtain the chiral piperidine; The general chemical formula of the diol compound is Wherein, R1 is phenyl, substituted phenyl or heteroaryl, and the substituent on the substituted phenyl is an alkyl, halogen, alkoxy or aryl substituted at the meta or para position; The general chemical formula of the amine compound is wherein R2 is at least one of hydrogen, alkyl, haloalkyl, halogen, alkoxy and aryl; The general chemical formula of the chiral phosphoric acid is Wherein, R3 is isopropyl or adamantyl, and the ratio of the iridium complex, the diol compound, the amine compound and the chiral phosphoric acid is (0.002-0.008):0.1:(0.1-0.12):(0.005-0.008) in terms of the amount of substances.

6. The use according to claim 5, characterized in that The additive is a molecular sieve, and the pore size of the molecular sieve is 7. The use according to claim 5, characterized in that The second solvent is one or a mixture of n-hexane, cyclohexane and n-heptane.

8. The use according to claim 5, characterized in that The ratio of the amount of the iridium complex, the mass of the additive and the volume of the second solvent is (0.002-0.008): (20-50): (0.3-0.6), the unit of the amount of the substance is mmol, the unit of the mass is mg, and the unit of the volume is mL.

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