A method for synthesizing chiral cyclic compounds by asymmetric hydrogenation of phenanthrene compounds catalyzed by rhodium

Abstract

The invention discloses a method for synthesizing a chiral cyclic compound by asymmetric hydrogenation of a phenanthrene compound catalyzed by rhodium. The method synthesizes a chiral cyclic compound by hydrogenation of a 9-substituted phenanthrene compound or a 9,10-disubstituted phenanthrene compound catalyzed by 2%-6% rhodium and a diphosphine ligand, and obtains a carbocyclic hydrogenated product with high yield and high enantioselectivity. The catalyst used in the invention is cheap and readily available, and the reaction conditions are relatively mild, and excellent yield and enantioselectivity can be obtained, which has potential practical value.

Description

Technical Field

[0001] The invention belongs to the field of asymmetric catalytic synthesis, relates to a method for synthesizing chiral cyclic compounds by asymmetric hydrogenation of phenanthrene compounds catalyzed by rhodium, and provides a method for synthesizing chiral cyclic compounds with high enantioselectivity. Background Art

[0002] Chiral compounds are important components of chiral substances and play a pivotal role and have broad application prospects in the fields of organic synthesis, medicinal chemistry, fine chemicals and material science. Chiral cyclic compounds are an important representative of chiral compounds.With the continuous innovation of new chiral catalysts and in-depth exploration of chiral catalytic systems, the synthesis of chiral cyclic compounds has made vigorous development. The main synthesis methods include asymmetric cycloaddition reaction, asymmetric cyclization reaction, asymmetric dearomatization reaction and asymmetric hydrogenation of aromatic compounds (Reference 1: (a) Takao, KI; Munakata, R.; Tadano, KI Chem. Rev. 2005, 105, 4779; (b) Moyano, A.; Rios, R. Chem. Rev. 2011, 111, 4703; (c) Jiang, X.; Wang, R. Chem. Rev. 2013, 113, 5515; (d) Masson, G.; Lalli, C.; Benohoud, M. Chem. Rev. 2014, 113, 5515; (e) Masson, G.; Lalli, C.; Benohoud, M. Chem. Rev. 2015, 113, 5515; (f) .;Dagousset,G.Chem.S℃.Rev.2013,42,902;(e)Chrzanowska,M.;Grajewska,A.;Rozwadowska,MDChem.Rev.2016,116,12369;(f)Shu,T.;Cossy,J.Chem.S℃.Rev .2021, 50,658. (g) Zhuo, C.-X.; Zhang, W.; You, S.-L. Angew. Chem. Int. Ed. 2012, 51, 12662; (h) Zheng, C.; 2008,76,909; (j) Zhou, Y.-G.Acc.Chem.Res.2007,40,1357; (k) Wang, D.-S.; Chen, Q.-A.; L u, S.-M.; Zhou, Y.-G.Chem.Rev.2012,112,2557; (l) Ye, Z.-S.; Shi, L.; Zhou, Y.-G.Synlett 2014,25,928;(f)Glorius,F.Org.Biomol.Chem.2005,3,4171;(m)Zhao,D.;Candish,L.;Paul,D.;Glorius,F.ACS Catal. 2016, 6, 5978; (n) Luo, Y.-E.; He, Y.-M.; Fan, Q.-H. Chem. Rec. 2016, 16, 2697; (o) Kim, AN; Stoltz, BMACS Catal. 2020, 10, 13834.).

[0003] Asymmetric hydrogenation of aromatic compounds with cyclic structural units is the simplest and most efficient way to construct chiral cyclic compounds. Its advantages are that aromatic compounds are easy to obtain, large in quantity, diverse in variety, stable in nature and easy to store, making them ideal chiral synthetic raw materials. Compared with aromatic heterocyclic compounds, the development of asymmetric hydrogenation of aromatic carbocyclic compounds is relatively slow, and only a few ruthenium-catalyzed hydrogenations of aromatic carbocyclic compounds have been reported. (Reference 2: (a) Urban, S.; Ortega, N.; Glorius, F. Angew. Chem. Int. Ed. 2011, 50, 3803-3806. (b) Kuwano, R.; Morioka, R.; Kashiwabara, M.; Kameyama, N. Angew. Chem. Int. Ed. 2012, 51, 4136-4139. (c) Kuwano, R.; Ikeda, R.; Hirasada, K. Chem. Com mun.2015,51,7558-7561.(d)Jin,Y.;Makida,Y.;Uchida,T.;Kuwano,R.J. Org.Chem.2018,83,3829-3839.(e)Yan,Z.;Xie,H.-P.;Shen,H.-Q.;Zhou,Y.-G.Org.Lett.2018,20,1094-1097.)Therefore, it is particularly important to develop a new and efficient catalytic system to realize the asymmetric hydrogenation of aromatic carbocyclic compounds for the construction of chiral cyclic compounds. Based on this, the present invention provides a method for asymmetric hydrogenation of 9-substituted phenanthrene compounds or 9,10-disubstituted phenanthrene compounds catalyzed by rhodium and chiral diphosphine ligands, and obtains chiral cyclic compounds with high yield and high enantioselectivity. Summary of the invention

[0004] The present invention discloses a method for synthesizing chiral cyclic compounds by asymmetric hydrogenation of phenanthrene compounds catalyzed by rhodium. The catalyst used in the present invention is cheap and readily available, and the reaction conditions are relatively mild, and excellent yield and enantioselectivity can be achieved, which has potential practical value.

[0005] The technical solution of the present invention is as follows:

[0006] A method for synthesizing chiral cyclic compounds by asymmetric hydrogenation of phenanthrene compounds catalyzed by rhodium is characterized in that the method uses a chiral diphosphine complex of rhodium as a catalyst and a 9-substituted phenanthrene compound or a 9,10-disubstituted phenanthrene compound as a substrate to synthesize the chiral cyclic compound after hydrogenation.

[0007] The reaction formula is as follows:

[0008]

[0009] Where:

[0010] R 1 It is hydrogen or C1-C10 alkyl or aryl, and C1-C10 alkyl includes one or more substituents of methoxy and halogen;

[0011] R 2 It is a C1-C10 alkyl or aryl group, and the C1-C10 alkyl group includes one or more substituents of methoxy and halogen;

[0012] R 3 It is a C1-C10 alkyl or aryl group, and the C1-C10 alkyl group includes one or more substituents of methoxy and halogen;

[0013] Ar and Ar' are benzene rings or aromatic rings containing substituents, wherein the substituents are C1-C10 alkyl groups, and the C1-C10 alkyl groups include methoxy and halogen or one or more substituents;

[0014] The catalyst is a complex of a metal rhodium precursor and a chiral diphosphine ligand.

[0015] Based on the above technical solution, preferably, the reaction solvent is an organic solvent, and the organic solvent is one or more of ethyl acetate, tetrahydrofuran, and toluene; preferably ethyl acetate.

[0016] Based on the above technical solution, preferably, the reaction temperature is 30-100° C., preferably 80° C., the reaction time is 48 minutes to 150 hours, preferably 120 hours, and the hydrogen pressure is 200-1200 psi, preferably 900 psi.

[0017] Based on the above technical scheme, the preferred molar ratio of 9-substituted phenanthrene compound or 9,10-disubstituted phenanthrene compound, metal rhodium precursor and chiral diphosphine ligand is 1:0.02:0.022-1:0.09:0.099, preferably 1:0.05:0.055; the amount of organic solvent used is 0.3-3mL, preferably 2mL; 9-substituted phenanthrene compound or 9,10-disubstituted phenanthrene compound 0.1-0.4mmol; preferably 0.2mmol.

[0018] Based on the above technical scheme, preferably, the metal rhodium precursor is one of bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt and bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; preferably bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt.

[0019] Based on the above technical scheme, preferably, the chiral bisphosphine ligand is (1R, 1′R, 2S, 2'S)-2,2'-di-tert-butyl-2,3,2'3'-tetrahydro-1H, 1'H-(1,1') diisophosphine, (R, R)-1,2-bis-2,5-diisopropylphosphine, 1,1-bis((2R, 5R)-2,5-di-propylphospho)ferrocene, (+)-1-[(R)-2-(2'-diphenylphosphinophenyl)ferrocene The invention further comprises one of (R)-(-)-1-[(S)-2-diphenylphosphino]ferrocenylethyldicyclohexylphosphine, (R)-(-)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine and (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldicyclohexylphosphine, and preferably (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldicyclohexylphosphine.

[0020] Based on the above technical scheme, preferably, the preparation method of the catalyst is: under the protection of nitrogen or argon, the metal rhodium precursor and the chiral diphosphine ligand are stirred in an organic solvent at room temperature for 10 minutes to 60 minutes, and the solvent used for the preparation of the catalyst is selected from one or more of trifluoroethanol, 1,2-dichloroethane, dichloromethane, ethyl acetate, tetrahydrofuran, 1,4-dioxane, toluene, benzene, trifluorotoluene, chlorobenzene, and methanol; preferably ethyl acetate.

[0021] Based on the above technical scheme, preferably, the specific reaction steps of the method are: adding a 9-substituted phenanthrene compound or a 9,10-disubstituted phenanthrene compound, an in-situ prepared catalyst and an organic solvent into a reaction bottle, placing the reaction bottle into an autoclave, introducing H2 to react to obtain a hydrogenated product, and purifying to obtain a pure product.

[0022] Based on the above technical scheme, preferably, the purification step is: after releasing hydrogen, the solvent is dried and separated by column chromatography to obtain a pure product.

[0023] The method of the present invention can realize asymmetric hydrogenation reaction of 9-substituted phenanthrene compounds or 9,10-disubstituted phenanthrene compounds as substrates catalyzed by rhodium, and obtain chiral cyclic compounds with high yield and high enantioselectivity (enantiomeric excess can reach 98%). The catalyst used in the invention is cheap and easy to obtain, and the reaction conditions are relatively mild, and excellent yield and enantioselectivity can be obtained, which has potential practical value.

[0024] Beneficial Effects

[0025] 1. The raw materials are simple and easy to obtain, the catalyst is easy to prepare, and the reaction operation is simple and practical.

[0026] 2. High reaction activity, complete conversion of raw materials, easy separation, and high-purity products can be obtained.

[0027] 3. Good stereoselectivity, and can obtain enantiomers with high enantioselectivity.

[0028] 4. The reaction conditions are mild and environmentally friendly. DETAILED DESCRIPTION

[0029] The present invention is described in detail below by examples, but the present invention is not limited to the following examples.

[0030] References for the synthesis of 9-substituted phenanthrene compounds or 9,10-disubstituted phenanthrene compounds in the following examples: (a) Palacios, SM; Asis, SE; Rossi, RA Bulletin de la S℃iete Chimique de France 1993, 130, 111-116. (b) Kiselyov, AS; Lee, H.; Harvey, RJO Org. Chem. 1995, 60, 6123-6128. (c) Zhu, C.; Wang, D.; Wang, D.; Zhao, Y. Sun, W.-Y.; Shi, Z. Angew. Chem. Int. Ed. 2018, 57, 8848-8853. (d) Hu, W.; Wang, H.; Bai, L.; Liu, J.; Luan, 5-768. (f) Beutner, GL; Young, IS; Davies, ML; Hickey, MR; Park, H.; Stevens, JM; Ye, Q. Org. Lett. 2018, 20, 4218-4222.

[0031] Examples 1-13

[0032] Condition optimization: changing the types of organic solvent, catalyst precursor and chiral ligand

[0033] Rhodium precursor (5.0 mol%) and chiral ligand (5.5 mol%) were added to the reaction bottle, and 1 mL of solvent was added after nitrogen replacement. The reaction bottle was stirred at room temperature for 10 minutes to prepare the catalyst in situ. The reaction bottle containing the substrate 9-substituted phenanthrene compound 1a (0.10 mmol) was added with the prepared catalyst and 1 mL of solvent in a glove box, and then placed in a high-pressure reactor, and hydrogen (900 psi) was introduced to react at 60°C for 65 hours. The hydrogen was slowly released, the solvent was removed by rotary evaporation, and the pure product was separated by column chromatography.

[0034] Types of organic solvent, catalyst precursor and chiral ligand. Specific results are shown in Table 1; ee is enantioselectivity.

[0035]

[0036] Table 1. Optimization of asymmetric hydrogenation conditions for 9-substituted phenanthrene compounds 1a

[0037]

[0038]

[0039] Examples 14-29

[0040] Asymmetric hydrogenation of 9-substituted phenanthrene compounds or 9,10-disubstituted phenanthrene compounds.

[0041] Add bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt (5.0 mol%) and (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldicyclohexylphosphine (5.5 mol%) into the reaction bottle, add 1 mL of ethyl acetate after nitrogen replacement, stir at room temperature for 10 minutes, and prepare the catalyst in situ. Add the catalyst and 1 mL of ethyl acetate to the reaction bottle containing the substrate 9-substituted phenanthrene compound (0.20 mmol) in advance in the glove box, put it into a high-pressure reactor, pass hydrogen (900 psi), and react at 60°C for 120 hours. Slowly release the hydrogen, remove the solvent by rotary evaporation, and separate by column chromatography to obtain the pure product.

[0042] The 9-substituted phenanthrene compound is 1, and only the type of 1 in the reaction is changed to obtain 10 different chiral cyclic compounds 2. The changed types are specifically as follows:

[0043]

[0044] In order to expand the substrate application scope of the reaction, 9,10-disubstituted phenanthrene compound 3 was also used in the reaction. Only the type of 3 in the reaction was changed to obtain 6 examples of different chiral cyclic compounds 4. The specific types of changes are as follows:

[0045]

[0046] (-)-2-(9,10-Dihydrophenanthren-9-yl)-N,N-diethylacetamide(2a):

[0047] 57.0mg,97%yield,60℃,65h,colorless oil,new compound,R f=0.35(hexanes / ethyl acetate 3 / 1), 127.7,127.4,127.1,123.9,123.5,41.9,40.3,36.2,35.5,33.7,14.1,13.2.HPLC:Chiralpak AD-Hcolumn,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time 13.4min and 14.5min(major).HRMS:Calculated for C 20 H 24 NO[M+H] + 294.1852,found:294.1854.

[0048] _____________________________________________________________________

[0049] (-)-2-(9,10-Dihydrophenanthren-9-yl)-N,N-dimethylacetamide(2b):

[0050] 50.0mg,94%yield,60℃,65h,colorless oil,new compound,R f =0.30(hexanes / ethyl acetate 3 / 1), 123.5,37.1,36.5,35.5,35.4,33.8.HPLC:Chiralcel OJ-H,254nm,30℃,n-Hexane / i-PrOH=80 / 20,flow=0.8mL / min,retention time 7.2min and 9.1min(major).HRMS:Calculated for C 18 H 20 NO[M+H] + 266.1539,found:266.1541.

[0051] _____________________________________________________________________

[0052] (-)-2-(9,10-Dihydrophenanthren-9-yl)-N,N-dipropylacetamide(2c):

[0053] 64.0mg,99%yield,60℃,65h,colorless oil,new compound,R f =0.20(hexanes / ethyl acetate 3 / 1),92%ee,[α] 20 D =-178.66(c 1.28,CHCl3). 1 H NMR(400MHz,CDCl3)δ7.75 129.4,128.3,127.8,127.7,127.4,127.1,123.9,123.5,49.5,47.9,36.2,35.6,33.6,22.1,21.0,11.5,10.9.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time 12.6min and 13.6min(major).HRMS:Calculated for C 22 H 28 NO[M+H] + 322.2165,found:322.2163.

[0054] _____________________________________________________________________

[0055] (-)-2-(9,10-Dihydrophenanthren-9-yl)-1-(pyrrolidin-1-yl)ethan-1-one(2d):

[0056] 56.0mg,96%yield,60℃,120h,colorless oil,new compound,R f =0.30(hexanes / ethyl acetate 1 / 1), 139.8,135.0,133.7,133.5,129.3,128.3,127.7,127.4,127.1,123.8,123.5,46.4,45.5,38.4,35.5,33.8,25.9,24.3.HPLC:Chiralcel OJ-H column,254nm,30℃,n-Hexane / i-PrOH=80 / 20,flow=0.8mL / min,retention time 6.6min and 8.6min(major).HRMS:Calculated for C 20 H 22 NO[M+H] + 292.1696,found:292.1695.

[0057] _____________________________________________________________________

[0058] (-)-2-(9,10-Dihydrophenanthren-9-yl)-1-(piperidin-1-yl)ethan-1-one(2e):

[0059] 60.0mg,98%yield,60℃,65h,colorless oil,new compound,R f =0.47(ethylacetate),86%ee,[α] 20 D CDCl3)δ170.0,139.8,135.0,133.5,133.6,129.4,128.5,127.8,127.7,127.5,127.1,123.9,123.4,46.7,42.7,36.0,35.6,33.9,26.1,25.6,24.4.HPLC:Chiralpak AD-Hcolumn,254 nm,30℃,n-Hexane / i-PrOH=95 / 5,flow=0.8mL / min,retention time17.8min(major)and 22.3min.HRMS:Calculated for C 21 H 24 NO[M+H] + 306.1852,found:306.1854.

[0060] _____________________________________________________________________

[0061] (-)-2-(9,10-Dihydrophenanthren-9-yl)-N-ethyl-N-phenylacetamide(2f):

[0062] 66.0mg,97%yield,80℃,120h,colorless oil,new compound,R f =0.45(hexanes / ethyl MHz,CDCl3)δ171.0,141.9,139.5,134.8,133.9,133.5,129.2,129.0,128.3,128.1,127.6,127.5,127.5,127.4,126.8,123.9,123.5,44.0,37.4,35.9,33.7,13.1.HPLC:ChiralcelOJ-H column,254 nm,30℃,n-Hexane / i-PrOH=70 / 30,flow=1.0mL / min,retention time5.4min and 8.8min(major).HRMS:Calculated for C 24 H 24 NO[M+H] + 342.1852,found:342.1855.

[0063] _____________________________________________________________________

[0064] (-)-N,N-Diethyl-2-(3-methyl-9,10-dihydrophenanthren-9-yl)acetamide(2g):

[0065] 60.0mg,98%yield,60℃,120h,colorless oil,new compound,R f =0.55(hexanes / ethyl acetate / 2.95-2.70(m,3H),2.41(s,3H),2.34(d,J=7.5Hz,2H),1.08(t,J=7.1Hz,3H),0.78(t,J=7.1Hz,3H). 13 C NMR(100MHz,CDCl3)δ170.8,140.0,136.4,133.7,133.5,132.0,129.2,128.5,128.4,127.7,127.3,124.2,123.8,41.9,40.3,36.2,35.7,33.3,21.5,14.1,13.2.HPLC:Chiralcel OJ-H column,254nm,30℃,n-Hexane / i-PrOH=90 / 10,flow=0.9mL / min,retention time 6.5min and 10.5min(major).HRMS:Calculated forC 21 H 26 NO[M+H] + 308.2009,found:308.2008.

[0066] _____________________________________________________________________

[0067] (-)-N,N-Diethyl-2-(4-methyl-9,10-dihydrophenanthren-9-yl)acetamide(2h):

[0068] 61.0mg,99%yield,60℃,120h,colorless oil,new compound,R f =0.50(hexanes / ethyl acetate 2 / 1), =7.1Hz,3H),0.75(t,J=7.1Hz,3H). 13C NMR(100MHz,CDCl3)δ170.9,141.9,137.1,134.2,134.0,133.6,130.7,128.4,127.8,127.0,127.0,126.9,126.2,41.9,40.3,36.1,35.3,34.9,23.0,14.0,13.1.HPLC:Chiralpak AD-3 column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=1.0mL / min,retentiontime 19.1min(major)and 21.9min.HRMS:Calculatedfor C 21 H 26 NO[M+H] + 308.2009,found:308.2010.

[0069] _____________________________________________________________________

[0070] (-)-N,N-Diethyl-2-(1-methyl-9,10-dihydrophenanthren-9-yl)acetamide(2i):

[0071] 60.0mg,98%yield,60℃,120h,colorless oil,new compound,R f =0.52(hexanes / ethyl acetate 2 / 1), 0.75(t,J=7.1Hz,3H). 13 C NMR(100MHz,CDCl3)δ170.8,139.8,136.4,134.1,133.7,133.5,129.6,128.0,127.6,127.3,126.4,124.3,121.5,41.9,40.4,36.3,35.4,29.1,19.8,14.0,13.2.HPLC:Chiralcel OJ-H column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=0.8mL / min,retention time 16.5min and 18.9min(major).HRMS:Calculated for C21 H 26 NO[M+H] + 308.2009,found:308.2011.

[0072] _____________________________________________________________________

[0073] (-)-N,N-Diethyl-2-(7-methyl-9,10-dihydrophenanthren-9-yl)acetamide(2j):

[0074] 60.0mg,98%yield,60℃,120h,colorless oil,new compound,R f =0.52(hexanes / ethyl acetate 2 / 1), 0.76(t,J=7.1Hz,3H). 13 C NMR(100MHz,CDCl3)δ170.8,139.8,137.6,134.7,133.8,130.8,129.3,129.0,128.2,127.3,127.0,123.8,123.2,41.9,40.3,36.3,35.7,33.8,21.2,14.0,13.2.HPLC:Chiralcel OJ-H column,254nm,30℃,n-Hexane / i-PrOH=90 / 10,flow=0.8mL / min,retention time 6.7min and 8.1min(major).HRMS:Calculated for C 21 H 26 NO[M+H] + 308.2009,found:308.2012.

[0075] _____________________________________________________________________

[0076] (-)-N,N-Diethyl-2-(10-methyl-9,10-dihydrophenanthren-9-yl)acetamide(4a):

[0077] 59.0mg,96%yield,80℃,120h,colorless oil,new compound,R f =0.20(hexanes / ethyl acetate 3 / 1), 6.3Hz,3H). 13 C NMR(100MHz,CDCl3)δ171.3,140.0,139.8,134.0,133.6,128.2,127.9,127.5,127.3,126.8,125.9,123.9,123.6,41.8,41.6,40.3,35.8,31.1,15.1,13.9,13.0.HPLC:Chiralpak AD-3 column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=1.0mL / min,retention time 12.8min(major)and 14.0min.HRMS:Calculated for C 21 H 26 NO[M+H] + 308.2009,found:308.2011.

[0078] _____________________________________________________________________

[0079] (-)-2-(10-Methyl-9,10-dihydrophenanthren-9-yl)-N,N-dipropylacetamide(4b):

[0080] 64.0mg,95%yield,80℃,120h,colorless oil,new compound,R f =0.50(hexanes / ethyl acetate / Hz,3H),0.52(t,J=7.2Hz,3H). 13C NMR(100MHz,CDCl3)δ171.8,140.0,139.8,134.1,133.7,128.2,127.9,127.5,127.4,126.8,125.8,123.8,123.6,49.6,48.0,41.7,35.8,31.0,22.0,20.9,15.1,11.5,10.9.HPLC:Chiralpak AD-3 column,254nm,30℃,n-Hexane / i-PrOH=98 / 2,flow=1.0mL / min,retention time 10.5min(major)and 11.9min.HRMS:Calculated for C 23 H 30 NO[M+H] + 336.2322,found:336.2324.

[0081] _____________________________________________________________________

[0082] (-)-2-(10-Methyl-9,10-dihydrophenanthren-9-yl)-1-(pyrrolidin-1-yl)ethan-1-one(4c):

[0083] 46.0mg,75%yield,80℃,120h,colorless oil,new compound,R f =0.40(hexanes / ethyl acetate / 1.57-1.46(m,1H),1.41(d,J=6.5Hz,3H). 13C NMR(100MHz,CDCl3)δ170.8,140.0,139.8,133.9,133.6,128.0,127.9,127.4,127.4,126.8,125.9,123.8,123.6,46.4,45.5,41.6,35.6,33.2,25.9,24.3,15.1.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-PrOH=80 / 20,flow=0.9mL / min,retention time 6.6min(major)and 8.3min.HRMS:Calculated for C 21 H 24 NO[M+H] + 306.1852,found:306.1857.

[0084] _____________________________________________________________________

[0085] (-)-2-(-10-Methyl-9,10-dihydrophenanthren-9-yl)-1-(piperidin-1-yl)ethan-1-one(4d):

[0086] 51.0mg,80%yield,80℃,120h,colorless oil,new compound,R f =0.45(hexanes / ethyl acetate /

[0087] 1.23-1.09(m,1H),0.88-0.68(s,1H). 13C NMR(100MHz,CDCl3)δ170.5,139.8,134.0,133.7,128.2,127.9,127.5,127.4,126.8,125.9,124.0,123.6,46.8,42.6,41.7,35.8,30.7,25.9,25.4,24.3,15.0.HPLC:Chiralpak AD-H column,254nm,30℃,n-Hexane / i-Pr-OH=80 / 20,flow=0.9mL / min,retention time 5.8min(major)and 8.1min.HRMS:Calculatedfor C 22 H 26 NO[M+H] + 320.2009,found:320.2012.

[0088] _____________________________________________________________________

Claims

1. A method for synthesizing chiral cyclic compounds by asymmetric hydrogenation of phenanthrene compounds catalyzed by rhodium, It is characterized in that The method uses a chiral diphosphine complex of rhodium as a catalyst and a 9-substituted phenanthrene compound or a 9,10-disubstituted phenanthrene compound as a substrate, and synthesizes a chiral cyclic compound after hydrogenation; The reaction formula is as follows: Where: R 1 is hydrogen or a C1-C10 alkyl group; R 2 It is a C1-C10 alkyl or aryl group, and the C1-C10 alkyl group includes one or more substituents of methoxy and halogen; R 3 It is a C1-C10 alkyl or aryl group, and the C1-C10 alkyl group includes one or more substituents of methoxy and halogen; Ar and Ar' are benzene rings or benzene rings containing substituents, and the substituents are methyl groups; The catalyst is a complex of a metal rhodium precursor and a chiral diphosphine ligand; The reaction solvent is an organic solvent, and the organic solvent is one or two of ethyl acetate and tetrahydrofuran; The metal rhodium precursor is bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt; the chiral diphosphine ligand is one of (R,R)-1,2-bis-2,5-diisopropylphosphine and (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldicyclohexylphosphine.

2. The method according to claim 1, It is characterized in that Reaction temperature: 30-100°C; reaction time: 48 minutes-150 hours; hydrogen pressure: 200-1200 psi.

3. The method according to claim 1, Features: The amount of organic solvent used is 1-4 mL per 0.1-0.4 mmol of 9-substituted phenanthrene compound or 9,10-disubstituted phenanthrene compound, and the molar ratio of 9-substituted phenanthrene compound or 9,10-disubstituted phenanthrene compound, metal rhodium precursor and chiral diphosphine ligand is 1:0.02:0.022-1:0.09:0.

099.

4. The method according to claim 1, Features: The preparation method of the catalyst comprises the following steps: under the protection of nitrogen or argon, stirring a metal rhodium precursor and a chiral diphosphine ligand in an organic solvent at room temperature for 10 minutes to 60 minutes; the solvent used in the preparation of the catalyst is selected from one or both of ethyl acetate and tetrahydrofuran.

5. The method according to claim 1, It is characterized in that The specific reaction steps of the method are: adding a 9-substituted phenanthrene compound or a 9,10-disubstituted phenanthrene compound, an in-situ prepared catalyst and an organic solvent into a reaction bottle, placing the reaction bottle into an autoclave, and introducing H 2 The reaction yields a hydrogenated product, which is then purified to obtain a pure product.

6. The method according to claim 5, It is characterized in that The purification step is: after releasing hydrogen, the solvent is dried by spin drying, and the pure product is separated by column chromatography.

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