Iridium complex as well as preparation method and application thereof in chiral piperidine synthesis

Abstract

The preparation method of the iridium complex comprises the following steps: adding an indole compound, an iridium compound and alkali into a first solvent, heating and stirring at 40-80 DEG C, after the reaction is finished, cooling to room temperature, filtering, carrying out reduced pressure distillation, and carrying out silica gel column chromatography separation to obtain the iridium complex; the iridium complex is used as a catalyst, under the combined action of the iridium complex and chiral phosphoric acid, the purpose that a 1, 5-diol compound and an amine compound directly react to obtain a series of chiral piperidine compounds can be achieved, and the method has the advantages of being high in reaction efficiency, simple, convenient and high in yield; and the enantiomer excess value of the chiral piperidine prepared by adopting the iridium catalyst is not less than 83%.

Description

Technical Field

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

[0002] Iridium complexes are widely used as catalysts in many types of organic chemical reactions, such as allylic substitution reactions, hydrogenation reactions, and double bond isomerization reactions. At the same time, iridium complexes have also been widely used in hydrogen borrowing reactions. However, the limited types of iridium complexes suitable for hydrogen borrowing reactions have severely restricted the development of hydrogen borrowing reactions, especially in the study of asymmetric hydrogen borrowing reactions, where only a few iridium complexes have been proven to be effective. Therefore, the development of new iridium complexes for metal-catalyzed reactions, especially asymmetric catalytic reactions, has far-reaching significance in research and application. Summary of the invention

[0003] In view of the deficiencies in the prior art, the object of the present invention is 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 to 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 Among them, 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 scheme, 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 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 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 the 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 is used as a catalyst and, under the action of 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 by using the iridium catalyst is not less than 83%. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 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 in conjunction with the accompanying drawings and embodiments.

[0036] In the following examples, the structural formula of the indole compound is 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 embodiments, iridium compound 2a, iridium compound 2b, iridium compound 2c and iridium compound 2d are 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 are respectively used as diol compounds, and each is 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, and both were 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 to room temperature of 20-25°C, filtering with diatomaceous earth, distilling the filtrate under reduced pressure to remove the solvent, and separating by silica gel column chromatography (the eluent of the column chromatography is a mixed solution of n-hexane and ethyl acetate, and the ratio of n-hexane to ethyl acetate is 20:1 by volume), and obtaining an orange solid as an iridium complex ([Ir]-1a) with a yield of 88%, wherein the iridium compound is iridium compound 2a, the base is sodium acetate, and the first solvent is acetonitrile. By molar fraction, the ratio of the indole compound, the iridium compound and the base is 0.25:0.126:0.3, and the ratio of the molar fraction of the indole compound to the volume fraction of the first solvent is 0.25:5. The unit of the molar fraction is mmol, and the unit of the volume fraction is 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 basically the same as the method for preparing Example 1, except that the iridium compound is iridium compound 2b, and the orange solid obtained by the preparation method of Example 2 is an iridium complex ([Ir]-1b) with a yield of 83%. 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 basically the same as the method for preparing Example 1, except that the iridium compound is iridium compound 2c, and the orange solid obtained by the preparation method of Example 3 is an iridium complex ([Ir]-1c) with a yield of 78%. 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 basically the same as the method for preparing Example 1, except that the iridium compound is iridium compound 2d, and the preparation method of Example 4 obtains a dark red solid as an iridium complex ([Ir]-1d) with 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 drugs. For example, the migraine drug ubegepant and the antiviral drug lonafarnib are both chiral drugs containing piperidine structural units. Therefore, the development of new chiral synthesis strategies to efficiently prepare piperidine compounds with chiral structural units has a very positive effect 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 terminated after 24 hours. The mixture was separated by silica gel column chromatography (the eluent of 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), and a colorless transparent liquid was obtained as 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, and 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 in terms of the amount of substance, and 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 chiral piperidine is basically the same as that of Example 5, except that the diol compound is diol compound 3b, and the method of Example 6 obtains chiral piperidine (5b) as a colorless transparent liquid with a yield of 76% and an enantiomeric excess (ee) value of 86%. 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 chiral piperidine is basically the same as that of Example 5, except that the diol compound is diol compound 3c, and the method of Example 7 obtains chiral piperidine (5c) as a white solid with a yield of 82% and an enantiomeric excess (ee) value of 83%. 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 chiral piperidine is basically the same as that of Example 5, except that the diol compound is diol compound 3d, and the method of Example 8 obtains a colorless transparent liquid chiral piperidine (5d) with a yield of 85% and an enantiomeric excess (ee) value of 83%. 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 chiral piperidine is basically the same as that of Example 5, except that the diol compound is diol compound 3e, and the method of Example 9 obtains chiral piperidine (5e) as a colorless transparent liquid with a yield of 61% and an enantiomeric excess (ee) value 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 chiral piperidine is basically the same as that of Example 5, except that the diol compound is diol compound 3f, and the method of Example 10 obtains a colorless transparent liquid chiral piperidine (5f) with a yield of 76% and an enantiomeric excess (ee) value 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] Embodiment 11

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

[0096] A method for preparing chiral piperidine is basically the same as that of Example 5, except that: the diol compound is 3g of the diol compound, and the method of Example 11 obtains chiral piperidine (5g) as a colorless transparent liquid, with a yield of 56% and an enantiomeric excess (ee) value 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 chiral piperidine is basically the same as that of Example 5, except that the diol compound is diol compound 3h, and the method of Example 12 obtains chiral piperidine (5h) as a colorless transparent liquid with a yield of 69% and an enantiomeric excess (ee) value 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] Embodiment 13

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

[0107] A method for preparing chiral piperidine is basically the same as that of Example 5, except that the amine compound is amine compound 4i, and the method of Example 13 obtains a colorless transparent liquid as a chiral piperidine product (5i), with a yield of 71% and an enantiomeric excess (ee) value 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 present invention is described above by way of example. 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 those skilled in the art without inventive effort falls within the protection scope of the present invention.

Claims

1. An iridium complex, characterized in that Its general structure 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. Use of the iridium complex as claimed in claim 1 in the synthesis of chiral piperidine.

6. The use according to claim 5, characterized in that: The general chemical formula of the chiral piperidine is Among them, 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.

7. The use according to claim 6, characterized in that: A method for preparing chiral piperidine, comprising: mixing the iridium complex according to claim 1, a diol compound, an amine compound, chiral phosphoric acid, an additive and a 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; The 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 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 molar fractions.

8. The use according to claim 7, characterized in that: The additive is a molecular sieve, and the pore size of the molecular sieve is 9. The use according to claim 6, characterized in that: The second solvent is one or a mixture of n-hexane, cyclohexane and n-heptane.

10. The use according to claim 6, 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; The reaction time is 24 to 48 hours.

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