铱催化酮不对称氢化及其在药物绿色合成中的应用

Ir-CATALYZED ASYMMETRIC HYDROGENATION OF KETONES AND ITS APPLICATIONS IN THE GREEN SYNTHESIS OF DRUGS

宋静远

SONG Jingyuan

11949016

博士

085274 能源与环保

0852 工程博士

张绪穆

理学院

2023-04-17

2023-06-26

哈尔滨工业大学

哈尔滨

手性存在于世界的方方面面，手性醇是许多重要药物分子的关键合成砌块。手性拆分、CBS硼氢化反应、酶催化等方法可获得单一手性的醇类化合物，但这些方法往往效率低、催化剂负载高、反应条件苛刻。过渡金属催化的酮不对称氢化反应具有高效、高立体选择性、高原子经济性、绿色环保等优势，是制备这类手性化合物最为高效和便捷的方法之一。目前还有一些挑战性底物的氢化难以实现。另外，一些反应所需要的高催化剂负载，将非常不利于大规模工业化应用。金属催化剂的核心在于手性配体，发展新型高效的手性配体是解决现有问题的利器。

本论文以铱催化的酮不对称氢化反应作为研究对象，通过对实验条件的筛选，高效且高立体选择性地构建了手性二醇、手性内酯、手性芳基醇等手性化合物。通过对配体的结构进行了改造，设计合成了系列以氧杂螺环为骨架的手性膦配体，实现环状二芳基醇的对映选择性构建。具体内容如下：

以1,4-丁二酮作为底物，应用金属铱催化剂，在S/C = 1 000的条件下，甲基叔丁基醚作为溶剂，辅以10 mol%的氢氧化钾，实现了20例1,4-丁二醇的手性合成，产物收率高达99%，dr值高达100:1，ee值高达99%以上，模型底物的转化数高达40 000。随后用这一方法实现了手性1,2-乙二醇和1,5-戊二醇的构建。实验的过程中捕获到手性单醇中间体，帮助提出分步氢化的反应机理。

手性内酯广泛存在于天然产物及药物分子中，其高效合成方法的发展具有重要的应用价值。以酮酯作为底物，应用金属铱催化剂，在S/C = 200下，四氢呋喃或二氯甲烷作为溶剂，辅以氢氧化钾或甲醇钾，先氢化后串联内酯化，实现了苯基内酯、γ-内酯、联苯七元环内酯共计24个手性内酯的构建，产率最高可达99%，ee值高达99%，与之前的方法相比具有室温反应、催化负载低至0.5 mol%、底物范围广等优势。该方法不仅将铱催化的氢化体系应用于的苯基内酯和γ-内酯的手性合成，更是实现了具有轴手性的联芳基内酯的构建。

邻位无取代的二芳基酮不对称氢化仍难以实现，瞄准环状二芳基酮，在尝试了诸多铱金属的络合物后，仍不能以高对映选择性得到相应的手性醇。经过对手性氧杂螺环为骨架的配体不断设计、合成、优化，最终发现氮上连有苯并喹啉的O-SpiroPABQ是该反应的优势配体，令模型产物具有96%的ee值，所拓展的手性醇的ee值几乎都在90%以上，最高可达99%。发现该手性螺环配体的铱络合物是一种新型的膦-氮-氮-碳（PNNC）络合模式。所构建的Ir/O-SpiroPABQ催化体系高效且高对映选择性地实现了环状二芳基醇的手性合成，为最新一代抗流感药物巴洛沙韦的关键中间体的合成提供了一种有效的方法。

目前高昂的成本制约着金属催化剂在工业中广泛应用，除了应用廉价金属、缩短配体合成的步骤、提高合成效率等方法外，降低催化剂负载也将大大有利于提升金属络合物的应用空间。应用铱金属与手性氧杂螺环三齿配体O-SpiroPAP的络合物作为催化剂，以低催化剂负载实现了药物克唑替尼、劳拉替尼以及哌仑他韦醇类中间体的手性合成，反应的转化数均在5 000以上，ee值高达99%，dr值大于20:1。为这些药物中间体的工业化合成提供了一种高效的新方法。

Chirality exists in all aspects of the world. Chiral alcohols being a key synthetic building block for many important drug molecules. They are obtained by chiral resolution, CBS borohydride reactions and enzyme catalysis. However, these methods often suffer from low efficiency, high catalyst loading and harsh reaction conditions. Transition metal-catalyzed asymmetric hydrogenation of ketones has the advantages of high efficiency, high stereoselectivity, high atomic economy and greenness. It is one of the most efficient and convenient methods for the preparation of such chiral compounds. There are still some challenging substrates for which hydrogenation is difficult to achieve. In addition, the high catalyst loading required for some reactions would be very detrimental to large-scale industrial applications. The key to metal catalysts lies in chiral ligands. The development of new efficient chiral ligands is a powerful tool to solve existing problems.

In this thesis, asymmetric hydrogenation of ketones catalyzed by iridium was explored, and chiral compounds such as chiral diols, chiral lactones and chiral aryl alcohols were constructed efficiently and with high stereoselectivity through the screening of experimental conditions. Several chiral phosphine ligands with an oxa-spirocyclic backbone have been designed and synthesized to achieve the enantioselective construction of cyclic diaryl alcohols. The details are as follows:

The chiral synthesis of 20 examples of 1,4-diols was achieved using 1,4-diones as substrate, an iridium complex as metal catalyst, methyl tert-butyl ether as solvent and 10 mol% KOH at S/C = 1 000, with product yields up to 99%, dr values up to 100:1, ee values up to >99% and turnover numbers of model substrates up to 40 000. This method was subsequently applied to the construction of chiral 1,2-ethanediols and 1,5-pentanediols. Chiral mono-alcohol intermediate was captured during the experiment, which helped to suggest the reaction mechanism of stepwise hydrogenation.

Chiral lactones are widely found in natural products and pharmaceutical molecules, and the development of efficient synthetic methods for their synthesis is of great application. In this paper, the construction of a total of 24 chiral lactones, including benzo-fused lactones, γ-lactones and biaryl-bridged lactones, were achieved by hydrogenation and lactonization using ketoesters as substrates, metal iridium complex as catalyst at S/C = 200, tetrahydrofuran or dichloromethane as solvents, supplemented with KOH or MeOK. The yields of lactones up to 99% and ee values up to 99%. Compared to previous methods, the reaction is carried out at room temperature, the catalytic loading is as low as 0.5 mol% and the substrate range is wide. The method not only applies the iridium-catalyzed hydrogenation system to the chiral synthesis of benzo-fused lactones and γ-lactones, which are widely found in natural products and pharmaceuticals, but also, achieves the construction of chiral biaryl-bridged lactones with atropisomerism.

Asymmetric hydrogenation of diaryl ketones without substitution at the ortho-position is still difficult to achieve. We aimed at cyclic diaryl ketone substrates. After trying numerous complexes of iridium metals, the corresponding chiral alcohols could not be obtained with high enantioselectivity. After continuous design, synthesis and optimization of chiral oxa-spirocyclic phosphine ligands, O-SpiroPABQ with a benzoquinoline was eventually found to be a superior ligand for this reaction, resulting in a model product with an ee value of 96%, and the ee values of the expanded chiral alcohols were almost always above 90% and up to 99%. The iridium complex was found to be a novel phosphine-nitrogen-nitrogen-carbon (PNNC) complexation mode. This efficient and highly enantioselective hydrogenation method achieves the chiral synthesis of cyclic diaryl alcohols and provides an efficient method for the synthesis of key intermediates of the latest generation of anti-influenza drugs, baloxavir.

The high cost of metal catalysts is a constraint to their widespread use in industry. In addition to the application of inexpensive metals, shortening the steps of ligand synthesis and improving the efficiency of synthesis, reducing the catalyst loading would also help to greatly enhance the application of metal complexes. We applied the complexes of iridium metal and the chiral oxa-spiro ligand O-SpiroPAP as catalysts to achieve the chiral synthesis of three important intermediates of crizotinib, lorlatinib and pibrentasvir with low catalyst loadings, good reactivity and stereoselectivity (TON above 5 000, ee values up to 99% and dr values >20:1). It provides a new and efficient method for the industrial synthesis of these drug intermediates.

不对称氢化 铱催化 手性膦配体 手性醇 药物合成

Asymmetric Hydrogenation Ir Catalyst Chiral Phosphine Ligand Chiral Alcohol Synthesis Of Drug

中文

联合培养

2019

2023-06

[1] 戴立信，陆熙炎，朱光美. 手性技术的兴起[J]. 化学通报, 1995, 6, 15-22.
[2] 孟庆华. 新型手性双膦配体的合成及其在官能化酮的不对称催化氢化中的应用[D]. 上海：上海交通大学, 2008：1-3.
[3] NUNEZ M C, GARCIA-RUBINO M E, CONEJO-GARCIA A, et al. Homochiral Drugs: A Demanding Tendency of the Pharmaceutical Industry[J]. Current Medicinal Chemistry, 2009, 16(16): 2064-2074.
[4] CALVIN M. Homogeneous Catalytic Hydrogenation.[J]. Transactions of the Faraday Society, 1938, 34(2): 1180-1190.
[5] OSBORN J A, JARDINE F H, YOUNG J F, et al. The Preparation and Properties of Tris(Triphenylphosphine)Halogenorhodium(I) and Some Reactions Thereof Including Catalytic Homogeneous Hydrogenation of Olefins and Acetylenes and Their Derivatives[J]. Journal of the Chemical Society A: Inorganic, Physical, Theoretical, 1966, 1711-1732.
[6] KNOWLES W S, SABACKY M J. Catalytic Asymmetric Hydrogenation Employing a Soluble Optically Active Rhodium Complex[J]. Chemical Communications, 1968, 1445-1446.
[7] HORNER L, SIEGEL H, BUTHE H. Asymmetric Catalytic Hydrogenation with an Optically Active Phosphinerhodium Complex in Homogeneous Solution[J]. Angewandte Chemie International Edition, 1968, 7(12): 942-942.
[8] VINEYARD B D, KNOWLES W S, SABACKY M J, et al. Asymmetric Hydrogenation. Rhodium Chiral Bisphosphine Catalyst[J]. Journal of the American Chemical Society, 1977, 99(18): 5946-5952.
[9] KNOWLES W S. Asymmetric Hydrogenations (Nobel Lecture)[J]. Angewandte Chemie International Edition, 2002, 41(12): 1998-2007.
[10] NOYORI R. Asymmetric Catalysis: Science and Opportunities (Nobel Lecture)[J]. Angewandte Chemie International Edition, 2002, 41(12): 2008-2022.
[11] TANG W J, ZHANG X M. New Chiral Phosphorus Ligands for Enantioselective Hydrogenation[J]. Chemical Reviews, 2003, 103(8): 3029-3069.
[12] 谢建华，周其林. 金属催化的不对称氢化反应研究进展与展望[J]. 化学学报, 2012, 70(13): 1427-1438.
[13] XU Y J, ALCOCK N W, CLARKSON G J, et al. Asymmetric Hydrogenation of Ketones Using a Ruthenium(II) Catalyst Containing Binol-Derived Monodonor Phosphorus-Donor Ligands[J]. Organic Letters, 2004, 6(22): 4105-4107.
[14] JING Q, ZHANG X, SUN H, et al. Bulky Achiral Triarylphosphines Mimic Binap in Ru(II)-Catalyzed Asymmetric Hydrogenation of Ketones[J]. Advanced Synthesis & Catalysis, 2005, 347(9): 1193-1197.
[15] BERKESSEL A, REICHAU S, VON DER HOH A, et al. Light-Induced Enantioselective Hydrogenation Using Chiral Derivatives of Casey's Iron-Cyclopentadienone Catalyst[J]. Organometallics, 2011, 30(14): 3880-3887.
[16] JUNGE K, WENDT B, ADDIS D, et al. Copper-Catalyzed Enantioselective Hydrogenation of Ketones[J]. Chemistry – A European Journal, 2011, 17(1): 101-105.
[17] 高安丽，叶青松，余娟，刘伟平. 手性binap-Ru(II)催化剂用于不对称加氢反应的研究进展[J]. 有机化学, 2017, 37(1): 47-78.
[18] NOYORI R, OHKUMA T, KITAMURA M, et al. Asymmetric Hydrogenation Of .Beta.-Keto Carboxylic Esters. A Practical, Purely Chemical Access To .Beta.-Hydroxy Esters in High Enantiomeric Purity[J]. Journal of the American Chemical Society, 1987, 109(19): 5856-5858.
[19] KITAMURA M, OHKUMA T, TOKUNAGA M, et al. Dynamic Kinetic Resolution in Binap—Ruthenium(II) Catalyzed Hydrogenation of 2-Substituted 3-Oxo Carboxylic Esters[J]. Tetrahedron: Asymmetry, 1990, 1(1): 1-4.
[20] MASHIMA K, KUSANO K H, SATO N, et al. Cationic Binap-Ru(II) Halide-Complexes - Highly Efficient Catalysts for Stereoselective Asymmetric Hydrogenation of Alpha-Functionalized and Beta-Functionalized Ketones[J]. Journal of Organic Chemistry, 1994, 59(11): 3064-3076.
[21] NOYORI R, IKEDA T, OHKUMA T, et al. Stereoselective Hydrogenation Via Dynamic Kinetic Resolution[J]. Journal of the American Chemical Society, 1989, 111(25): 9134-9135.
[22] OHKUMA T, KITAMURA M, NOYORI R. Enantioselective Synthesis of 4-Substituted Γ-Lactones[J]. Tetrahedron Letters, 1990, 31(38): 5509-5512.
[23] OHKUMA T, OOKA H, HASHIGUCHI S, et al. Practical Enantioselective Hydrogenation of Aromatic Ketones[J]. Journal of the American Chemical Society, 1995, 117(9): 2675-2676.
[24] DOUCET H, OHKUMA T, MURATA K, et al. Trans-[RuCl2(Phosphane)2(1,2-Diamine)] and Chiral Trans-[RuCl2(Diphosphane)(1,2-Diamine]): Shelf-Stable Precatalysts for the Rapid, Productive, and Stereoselective Hydrogenation of Ketones[J]. Angewandte Chemie International Edition, 1998, 37(12): 1703-1707.
[25] OHKUMA T, KOIZUMI M, DOUCET H, et al. Asymmetric Hydrogenation of Alkenyl, Cyclopropyl, and Aryl Ketones. RuCl2(Xylbinap)(1,2-Diamine) as a Precatalyst Exhibiting a Wide Scope[J]. Journal of the American Chemical Society, 1998, 120(51): 13529-13530.
[26] OHKUMA T, ISHII D, TAKENO H, et al. Asymmetric Hydrogenation of Amino Ketones Using Chiral RuCl2(Diphophine)(1,2-Diamine) Complexes[J]. Journal of the American Chemical Society, 2000, 122(27): 6510-6511.
[27] OHKUMA T, KOIZUMI M, YOSHIDA M, et al. General Asymmetric Hydrogenation of Hetero-Aromatic Ketones[J]. Organic Letters, 2000, 2(12): 1749-1751.
[28] NOYORI R, OHKUMA T. Asymmetric Catalysis by Architectural and Functional Molecular Engineering: Practical Chemo- and Stereoselective Hydrogenation of Ketones[J]. Angewandte Chemie International Edition, 2001, 40(1): 40-73.
[29] SANDOVAL C A, OHKUMA T, MUNIZ K, et al. Mechanism of Asymmetric Hydrogenation of Ketones Catalyzed by Binap/1,2-Diamine-Ruthenium(II) Complexes[J]. Journal of the American Chemical Society, 2003, 125(44): 13490-13503.
[30] BURK M J. C2-Symmetrical Bis(Phospholanes) and Their Use in Highly Enantioselective Hydrogenation Reactions[J]. Journal of the American Chemical Society, 1991, 113(22): 8518-8519.
[31] BURK M J. Modular Phospholane Ligands in Asymmetric Catalysis[J]. Accounts of Chemical Research, 2000, 33(6): 363-372.
[32] TOGNI A, BREUTEL C, SCHNYDER A, et al. A Novel Easily Accessible Chiral Ferrocenyldiphosphine for Highly Enantioselective Hydrogenation, Allylic Alkylation, and Hydroboration Reactions[J]. Journal of the American Chemical Society, 1994, 116(9): 4062-4066.
[33] BENINCORI T, BRENNA E, SANNICOLò F, et al. New Class of Chiral Diphosphine Ligands for Highly Efficient Transition Metal-Catalyzed Stereoselective Reactions:  The Bis(Diphenylphosphino) Five-Membered Biheteroaryls[J]. The Journal of Organic Chemistry, 1996, 61(18): 6244-6251.
[34] KAGAN H B, DANG T-P. Asymmetric Catalytic Reduction with Transition Metal Complexes. I. Catalytic System of Rhodium(I) with (-)-2,3-0-Isopropylidene-2,3-Dihydroxy-1,4-Bis(Diphenylphosphino)Butane, a New Chiral Diphosphine[J]. Journal of the American Chemical Society, 1972, 94(18): 6429-6433.
[35] ZHU G, CAO P, JIANG Q, et al. Highly Enantioselective Rh-Catalyzed Hydrogenations with a New Chiral 1,4-Bisphosphine Containing a Cyclic Backbone[J]. Journal of the American Chemical Society, 1997, 119(7): 1799-1800.
[36] ZHU G, CASALNUOVO A L, ZHANG X. Practical Syntheses of Β-Amino Alcohols Via Asymmetric Catalytic Hydrogenation[J]. The Journal of Organic Chemistry, 1998, 63(23): 8100-8101.
[37] CAO P, ZHANG X. Ru-Bicp-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones[J]. The Journal of Organic Chemistry, 1999, 64(6): 2127-2129.
[38] ZHU G, ZHANG X. Additive Effects in Ir–Bicp Catalyzed Asymmetric Hydrogenation of Imines[J]. Tetrahedron: Asymmetry, 1998, 9(14): 2415-2418.
[39] ZHANG Z, QIAN H, LONGMIRE J, et al. Synthesis of Chiral Bisphosphines with Tunable Bite Angles and Their Applications in Asymmetric Hydrogenation of Β-Ketoesters[J]. The Journal of Organic Chemistry, 2000, 65(19): 6223-6226.
[40] WU S L, WANG W M, TANG W J, et al. Highly Enantioselective Hydrogenation of Enol Acetates Catalyzed by Ru-Tunaphos Complexes[J]. Organic Letters, 2002, 4(25): 4495-4497.
[41] TANG W, WU S, ZHANG X. Enantioselective Hydrogenation of Tetrasubstituted Olefins of Cyclic Β-(Acylamino)Acrylates[J]. Journal of the American Chemical Society, 2003, 125(32): 9570-9571.
[42] LEI A, WU S, HE M, et al. Highly Enantioselective Asymmetric Hydrogenation of Α-Phthalimide Ketone:  An Efficient Entry to Enantiomerically Pure Amino Alcohols[J]. Journal of the American Chemical Society, 2004, 126(6): 1626-1627.
[43] LI W, SUN X, ZHOU L, et al. Highly Efficient and Highly Enantioselective Asymmetric Hydrogenation of Ketones with Tunesphos/1,2-Diamine−Ruthenium(II) Complexes[J]. The Journal of Organic Chemistry, 2009, 74(3): 1397-1399.
[44] SAITO T, YOKOZAWA T, ISHIZAKI T, et al. New Chiral Diphosphine Ligands Designed to Have a Narrow Dihedral Angle in the Biaryl Backbone[J]. Advanced Synthesis & Catalysis, 2001, 343(3): 264-267.
[45] FRIEDFELD M R, ZHONG H, RUCK R T, et al. Cobalt-Catalyzed Asymmetric Hydrogenation of Enamides Enabled by Single-Electron Reduction[J]. Science, 2018, 360(6391): 888-893.
[46] YANG P, LIM L H, CHUANPRASIT P, et al. Nickel-Catalyzed Enantioselective Reductive Amination of Ketones with Both Arylamines and Benzhydrazide[J]. Angewandte Chemie International Edition, 2016, 55(39): 12083-12087.
[47] YANG Y, PERRY I B, LU G, et al. Copper-Catalyzed Asymmetric Addition of Olefin-Derived Nucleophiles to Ketones[J]. Science, 2016, 353(6295): 144-150.
[48] BANDAR J S, ASCIC E, BUCHWALD S L. Enantioselective Cuh-Catalyzed Reductive Coupling of Aryl Alkenes and Activated Carboxylic Acids[J]. Journal of the American Chemical Society, 2016, 138(18): 5821-5824.
[49] ZHENG X, GUO R, ZHANG G, et al. Rhodium(I)-Catalyzed Asymmetric
[4 + 2] Cycloaddition Reactions of 2-Alkylenecyclobutanols with Cyclic Enones through C–C Bond Cleavage: Efficient Access to Trans-Bicyclic Compounds[J]. Chemical Science, 2018, 9(7): 1873-1877.
[50] ITOH T, KANZAKI Y, SHIMIZU Y, et al. Copper(I)-Catalyzed Enantio- and Diastereodivergent Borylative Coupling of Styrenes and Imines[J]. Angewandte Chemie International Edition, 2018, 57(27): 8265-8269.
[51] CHAN A S C, HU W, PAI C-C, et al. Novel Spiro Phosphinite Ligands and Their Application in Homogeneous Catalytic Hydrogenation Reactions[J]. Journal of the American Chemical Society, 1997, 119(40): 9570-9571.
[52] HU A-G, FU Y, XIE J-H, et al. Monodentate Chiral Spiro Phosphoramidites: Efficient Ligands for Rhodium-Catalyzed Enantioselective Hydrogenation of Enamides[J]. Angewandte Chemie International Edition, 2002, 41(13): 2348-2350.
[53] XIE J-H, WANG L-X, FU Y, et al. Synthesis of Spiro Diphosphines and Their Application in Asymmetric Hydrogenation of Ketones[J]. Journal of the American Chemical Society, 2003, 125(15): 4404-4405.
[54] CHENG X, ZHANG Q, XIE J-H, et al. Highly Rigid Diphosphane Ligands with a Large Dihedral Angle Based on a Chiral Spirobifluorene Backbone[J]. Angewandte Chemie International Edition, 2005, 44(7): 1118-1121.
[55] ZHU S-F, XIE J-B, ZHANG Y-Z, et al. Well-Defined Chiral Spiro Iridium/Phosphine−Oxazoline Cationic Complexes for Highly Enantioselective Hydrogenation of Imines at Ambient Pressure[J]. Journal of the American Chemical Society, 2006, 128(39): 12886-12891.
[56] XIE J-B, XIE J-H, LIU X-Y, et al. Highly Enantioselective Hydrogenation of Α-Arylmethylene Cycloalkanones Catalyzed by Iridium Complexes of Chiral Spiro Aminophosphine Ligands[J]. Journal of the American Chemical Society, 2010, 132(13): 4538-4539.
[57] HUANG J, HONG M, WANG C-C, et al. Asymmetric Synthesis of Chiral Spiroketal Bisphosphine Ligands and Their Application in Enantioselective Olefin Hydrogenation[J]. The Journal of Organic Chemistry, 2018, 83(20): 12838-12846.
[58] CHEN G-Q, HUANG J-M, LIN B-J, et al. Highly Enantioselective Hydrogenation of Tetra- and Tri-Substituted Α,Β-Unsaturated Carboxylic Acids with Oxa-Spiro Diphosphine Ligands[J]. CCS Chemistry, 2020, 2(6): 468-477.
[59] XIE J-B, XIE J-H, LIU X-Y, et al. Chiral Iridium Spiro Aminophosphine Complexes: Asymmetric Hydrogenation of Simple Ketones, Structure, and Plausible Mechanism[J]. Chemistry – An Asian Journal, 2011, 6(3): 899-908.
[60] JIANG Y, JIANG Q, ZHANG X. A New Chiral Bis(Oxazolinylmethyl)Amine Ligand for Ru-Catalyzed Asymmetric Transfer Hydrogenation of Ketones[J]. Journal of the American Chemical Society, 1998, 120(15): 3817-3818.
[61] CLARKE M L, DíAZ-VALENZUELA M B, SLAWIN A M Z. Hydrogenation of Aldehydes, Esters, Imines, and Ketones Catalyzed by a Ruthenium Complex of a Chiral Tridentate Ligand[J]. Organometallics, 2007, 26(1): 16-19.
[62] LI W, HOU G, WANG C, et al. Asymmetric Hydrogenation of Ketones Catalyzed by a Ruthenium(II)-Indan–Ambox Complex[J]. Chemical Communications, 2010, 46(22): 3979-3981.
[63] XIE J-H, LIU X-Y, XIE J-B, et al. An Additional Coordination Group Leads to Extremely Efficient Chiral Iridium Catalysts for Asymmetric Hydrogenation of Ketones[J]. Angewandte Chemie International Edition, 2011, 50(32): 7329-7332.
[64] YANG X-H, WANG K, ZHU S-F, et al. Remote Ester Group Leads to Efficient Kinetic Resolution of Racemic Aliphatic Alcohols Via Asymmetric Hydrogenation[J]. Journal of the American Chemical Society, 2014, 136(50): 17426-17429.
[65] YANG X-H, XIE J-H, ZHOU Q-L. Chiral Spiro Iridium Catalysts with Spiropap Ligands: Highly Efficient for Asymmetric Hydrogenation of Ketones and Ketoesters[J]. Organic Chemistry Frontiers, 2014, 1(2): 190-193.
[66] YUAN M-L, XIE J-H, YANG X-H, et al. Enantioselective Synthesis of Chiral 1,2-Amino Alcohols Via Asymmetric Hydrogenation of Α-Amino Ketones with Chiral Spiro Iridium Catalysts[J]. Synthesis, 2014, 46(21): 2910-2916.
[67] ZHANG Q-Q, XIE J-H, YANG X-H, et al. Iridium-Catalyzed Asymmetric Hydrogenation of Α-Substituted Α,Β-Unsaturated Acyclic Ketones: Enantioselective Total Synthesis of (−)-Mesembrine[J]. Organic Letters, 2012, 14(24): 6158-6161.
[68] BAO D-H, WU H-L, LIU C-L, et al. Development of Chiral Spiro P-N-S Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Β-Alkyl-Β-Ketoesters[J]. Angewandte Chemie International Edition, 2015, 54(30): 8791-8794.
[69] GU G, HU Y, LIU S, et al. Indan-F-Amphox: An Efficient Pnn Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of Β-Aryl Β-Ketoesters[J]. Chinese Journal of Organic Chemistry, 2020, 40(4): 997-1002.
[70] WU W, LIU S, DUAN M, et al. Iridium Catalysts with F-Amphox Ligands: Asymmetric Hydrogenation of Simple Ketones[J]. Organic Letters, 2016, 18(12): 2938-2941.
[71] YU J, LONG J, YANG Y, et al. Iridium-Catalyzed Asymmetric Hydrogenation of Ketones with Accessible and Modular Ferrocene-Based Amino-Phosphine Acid (F-Ampha) Ligands[J]. Organic Letters, 2017, 19(3): 690-693.
[72] YU J, DUAN M, WU W, et al. Readily Accessible and Highly Efficient Ferrocene-Based Amino-Phosphine-Alcohol (F-Amphol) Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Simple Ketones[J]. Chemistry–A European Journal, 2017, 23(4): 970-975.
[73] LIANG Z Q, YANG T L, GU G X, et al. Scope and Mechanism on Iridium-F-Amphamide Catalyzed Asymmetric Hydrogenation of Ketones[J]. Chinese Journal of Chemistry, 2018, 36(9): 851-856.
[74] CHEN G-Q, LIN B-J, HUANG J-M, et al. Design and Synthesis of Chiral Oxa-Spirocyclic Ligands for Ir-Catalyzed Direct Asymmetric Reduction of Bringmann’s Lactones with Molecular H2[J]. Journal of the American Chemical Society, 2018, 140(26): 8064-8068.
[75] ZHANG F-H, ZHANG F-J, LI M-L, et al. Enantioselective Hydrogenation of Dialkyl Ketones[J]. Nature Catalysis, 2020, 3(8): 621-627.
[76] ZHANG G, SCOTT B L, HANSON S K. Mild and Homogeneous Cobalt-Catalyzed Hydrogenation of C=C, C=O and C=N Bonds[J]. Angewandte Chemie International Edition, 2012, 51(48): 12102-12106.
[77] LAGADITIS P O, SUES P E, SONNENBERG J F, et al. Iron(II) Complexes Containing Unsymmetrical P–N–P′ Pincer Ligands for the Catalytic Asymmetric Hydrogenation of Ketones and Imines[J]. Journal of the American Chemical Society, 2014, 136(4): 1367-1380.
[78] WIDEGREN M B, HARKNESS G J, SLAWIN A M Z, et al. A Highly Active Manganese Catalyst for Enantioselective Ketone and Ester Hydrogenation[J]. Angewandte Chemie International Edition, 2017, 56(21): 5825-5828.
[79] ZHANG L, TANG Y, HAN Z, et al. Lutidine-Based Chiral Pincer Manganese Catalysts for Enantioselective Hydrogenation of Ketones[J]. Angewandte Chemie International Edition, 2019, 58(15): 4973-4977.
[80] ZHANG L, WANG Z, HAN Z, et al. Manganese-Catalyzed Anti-Selective Asymmetric Hydrogenation of Α-Substituted Β-Ketoamides[J]. Angewandte Chemie International Edition, 2020, 59(36): 15565-15569.
[81] HUANG H, OKUNO T, TSUDA K, et al. Enantioselective Hydrogenation of Aromatic Ketones Catalyzed by Ru Complexes of Goodwin−Lions-Type Sp2N/Sp3N Hybrid Ligands R-Binan-R‘-Py[J]. Journal of the American Chemical Society, 2006, 128(27): 8716-8717.
[82] PATCHETT R, MAGPANTAY I, SAUDAN L, et al. Asymmetric Hydrogenation of Ketones with H2 and Ruthenium Catalysts Containing Chiral Tetradentate S2n2 Ligands[J]. Angewandte Chemie International Edition, 2013, 52(39): 10352-10355.
[83] CETTOLIN M, PUYLAERT P, PIGNATARO L, et al. Use of the Trost Ligand in the Ruthenium-Catalyzed Asymmetric Hydrogenation of Ketones[J]. ChemCatChem, 2017, 9(16): 3125-3130.
[84] SUI-SENG C, FREUTEL F, LOUGH A J, et al. Highly Efficient Catalyst Systems Using Iron Complexes with a Tetradentate Pnnp Ligand for the Asymmetric Hydrogenation of Polar Bonds[J]. Angewandte Chemie International Edition, 2008, 47(5): 940-943.
[85] ZUO W W, LOUGH A J, LI Y F, et al. Amine(Imine)Diphosphine Iron Catalysts for Asymmetric Transfer Hydrogenation of Ketones and Imines[J]. Science, 2013, 342(6162): 1080-1083.
[86] ZHANG D, ZHU E-Z, LIN Z-W, et al. Enantioselective Hydrogenation of Ketones Catalyzed by Chiral Cobalt Complexes Containing Pnnp Ligand[J]. Asian Journal of Organic Chemistry, 2016, 5(11): 1323-1326.
[87] YU J, HUANG F, FANG W, et al. Discovery and Development of Ferrocene-Based Tetradentate Ligands for Ir-Catalysed Asymmetric Hydrogenation of Ketone[J]. Green Synthesis and Catalysis, 2022, 3(2): 175-178.
[88] LIANG Y, JING Q, LI X, et al. Programmed Assembly of Two Different Ligands with Metallic Ions:  Generation of Self-Supported Noyori-Type Catalysts for Heterogeneous Asymmetric Hydrogenation of Ketones[J]. Journal of the American Chemical Society, 2005, 127(21): 7694-7695.
[89] 张树辛，冯宇，范青华. 过渡金属催化的不对称氢化反应的国内研究进展[J]. 高等学校化学学报, 2020, 41(10): 2107-2136.
[90] DUB P A, GORDON J C. The Mechanism of Enantioselective Ketone Reduction with Noyori and Noyori–Ikariya Bifunctional Catalysts[J]. Dalton Transactions, 2016, 45(16): 6756-6781.
[91] 陈才友，董秀琴，张绪穆. 不对称氢化反应在手性药物合成中的应用[J]. 中国医药工业杂志, 2017, 48(7): 943-964.
[92] DEGOEY D A, RANDOLPH J T, LIU D, et al. Discovery of Abt-267, a Pan-Genotypic Inhibitor of HCV NS5A[J]. Journal of Medicinal Chemistry, 2014, 57(5): 2047-2057.
[93] WAGNER R, RANDOLPH J T, PATEL S V, et al. Highlights of the Structure-Activity Relationships of Benzimidazole Linked Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor Pibrentasvir (Abt-530)[J]. Journal of Medicinal Chemistry, 2018, 61(9): 4052-4066.
[94] HALLAND N, BRAUNTON A, BACHMANN S, et al. Direct Organocatalytic Asymmetric Alpha-Chlorination of Aldehydes[J]. Journal of the American Chemical Society, 2004, 126(15): 4790-4791.
[95] O'REILLY M C, LINDSLEY C W. A General, Enantioselective Synthesis of Protected Morpholines and Piperazines[J]. Organic Letters, 2012, 14(11): 2910-2913.
[96] PERIASAMY M, SEENIVASAPERUMAL M, RAO V D. Convenient Procedures for the Asymmetric Reduction of 1,4-Diphenylbutane-1,4-Dione and Synthesis of 2,5-Diphenylpyrrolidine Derivatives[J]. Synthesis, 2003, 16(16): 2507-2510.
[97] SENTER T J, O'REILLY M C, CHONG K M, et al. A General, Enantioselective Synthesis of N-Alkyl Terminal Aziridines and C2-Functionalized Azetidines Via Organocatalysis[J]. Tetrahedron Letters, 2015, 56(10): 1276-1279.
[98] LI C Y, SUN X L, JING Q, et al. Enantioselective Synthesis of Allenic Esters Via an Ylide Route[J]. Chemical Communications, 2006, 28: 2980-2982.
[99] REZAZADEH KHALKHALI M, WILDE M M D, GRAVEL M. Enantioselective Stetter Reactions Catalyzed by Bis(Amino)Cyclopropenylidenes: Important Role for Water as an Additive[J]. Organic Letters, 2021, 23(1): 155-159.
[100] LASSALETTA J M, ALCARAZO M, FERNANDEZ R. Glyoxal Bis-Hydrazones: A New Family of Nitrogen Ligands for Asymmetric Catalysis[J]. Chemical Communications, 2004, 3: 298-299.
[101] BERMEJO A, ROS A, FERNáNDEZ R, et al. C2-Symmetric Bis-Hydrazones as Ligands in the Asymmetric Suzuki−Miyaura Cross-Coupling[J]. Journal of the American Chemical Society, 2008, 130(47): 15798-15799.
[102] BURK M J, FEASTER J E, HARLOW R L. New Electron-Rich Chiral Phosphines for Asymmetric Catalysis[J]. Organometallics, 1990, 9(10): 2653-2655.
[103] BURK M J, FEASTER J E, NUGENT W A, et al. Preparation and Use of C2-Symmetrical Bis(Phospholanes)-Production of Alpha-Amino-Acid Derivatives Via Highly Enantioselective Hydrogenation Reactions[J]. Journal of the American Chemical Society, 1993, 115(22): 10125-10138.
[104] EDELSTEIN E K, RANKIC D A, DUDLEY C C, et al. Synthesis of Proline Analogues Via Rh-Catalyzed Asymmetric Conjugate Addition[J]. ACS Catalysis, 2021, 11(2): 743-749.
[105] SAWANO T, ASHOURI A, NISHIMURA T, et al. Cobalt-Catalyzed Asymmetric 1,6-Addition of (Triisopropylsilyl)-Acetylene to Alpha,Beta,Gamma,Delta-Unsaturated Carbonyl Compounds[J]. Journal of the American Chemical Society, 2012, 134(46): 18936-18939.
[106] BURK M J, FEASTER J E, HARLOW R L. New Chiral Phospholanes-Synthesis, Characterization, and Use in Asymmetric Hydrogenation Reactions[J]. Tetrahedron: Asymmetry, 1991, 2(7): 569-592.
[107] ALDOUS D J, DUTTON W M, STEEL P G. A Simple Enantioselective Preparation of (2S,5S)-2,5-Diphenylpyrrolidine and Related Diaryl Amines[J]. Tetrahedron: Asymmetry, 2000, 11(12): 2455-2462.
[108] BALLISTRERI F P, PATTI A, PEDOTTI S, et al. Synthesis of Novel Chiral ‘Salen-Type’ Ferrocenyl Ligands[J]. Tetrahedron: Asymmetry, 2007, 18(20): 2377-2380.
[109] FADEYI O O, SCHULTE M L, LINDSLEY C W. General Access to Chiral N-Alkyl Terminal Aziridines Via Organocatalysis[J]. Organic Letters, 2010, 12(14): 3276-3278.
[110] YAMADA T, SATO M, GUNJI Y, et al. Efficient Preparation of Optically Pure C2-Symmetrical Cyclic Amines for Chiral Auxiliary[J]. Synthesis, 2004, 9: 1434-1438.
[111] ECHEVERRIA P G, FéRARD C, PHANSAVATH P, et al. Synthesis, Characterization and Use of a New Tethered Rh(III) Complex in Asymmetric Transfer Hydrogenation of Ketones[J]. Catalysis Communications, 2015, 62: 95-99.
[112] ZHENG L S, LLOPIS Q, ECHEVERRIA P G, et al. Asymmetric Transfer Hydrogenation of (Hetero)Arylketones with Tethered Rh(III)-N-(P-Tolylsulfonyl)-1,2-Diphenylethylene-1,2-Diamine Complexes: Scope and Limitations[J]. Journal of Organic Chemistry, 2017, 82(11): 5607-5615.
[113] MOURELLE-INSUA A, DE GONZALO G, LAVANDERA I, et al. Stereoselective Enzymatic Reduction of 1,4-Diaryl-1,4-Diones to the Corresponding Diols Employing Alcohol Dehydrogenases[J]. Catalysts, 2018, 8(4): 150-161.
[114] ZHOU J, XU G, NI Y. Stereochemistry in Asymmetric Reduction of Bulky–Bulky Ketones by Alcohol Dehydrogenases[J]. ACS Catalysis, 2020, 10(19): 10954-10966.
[115] TAN X F, ZENG W J, WEN J L, et al. Iridium-Catalyzed Asymmetric Hydrogenation of A-Fluoro Ketones Via a Dynamic Kinetic Resolution Strategy[J]. Organic Letters, 2020, 22(18): 7230-7233.
[116] WANG J, SHAO P L, LIN X, et al. Facile Synthesis of Enantiopure Sugar Alcohols: Asymmetric Hydrogenation and Dynamic Kinetic Resolution Combined[J]. Angewandte Chemie International Edition, 2020, 59(41): 18166-18171.
[117] YIN C C, DONG X Q, ZHANG X M. Iridium/F-Amphol-Catalyzed Efficient Asymmetric Hydrogenation of Benzo-Fused Cyclic Ketones[J]. Advanced Synthesis & Catalysis, 2018, 360(22): 4319-4324.
[118] ZHU T Z, SHAO P L, ZHANG X M. Asymmetric Hydrogenation of Trifluoromethyl Ketones: Application in the Synthesis of Odanacatib and Lx-1031[J]. Organic Chemistry Frontiers, 2021, 8(14): 3705-3711.
[119] ALNABULSI S, SANTINA E, RUSSO I, et al. Non-Symmetrical Furan-Amidines as Novel Leads for the Treatment of Cancer and Malaria[J]. European Journal of Medicinal Chemistry, 2016, (111): 33-45.
[120] NEVAR N M, KEL'IN A V, KULINKOVICH O G. One Step Preparation of 1,4-Diketones from Methyl Ketones and Alpha-Bromomethyl Ketones in the Presence of ZnCl2 Center Dot T-BuOH Center Dot Et2NR as a Condensation Agent[J]. Synthesis, 2000, 9: 1259-1262.
[121] HUA G, HENRY J B, LI Y, et al. Synthesis of Novel 2,5-Diarylselenophenes from Selenation of 1,4-Diarylbutane-1,4-Diones or Methanol/Arylacetylenes[J]. Organic & Biomolecular Chemistry, 2010, 8(7): 1655-1660.
[122] MATTSON A E, BHARADWAJ A R, ZUHL A M, et al. Thiazolium-Catalyzed Additions of Acylsilanes: A General Strategy for Acyl Anion Addition Reactions[J]. Journal of Organic Chemistry, 2006, 71(15): 5715-5724.
[123] VERMA R S, MISHRA M, PANDEY C B, et al. Global Access to 3/4-Phosphorylated Heterocycles Via a Carbene-Catalyzed Stetter Reaction of Vinylphosphonates and Aldehydes[J]. Journal of Organic Chemistry, 2020, 85(12): 8166-8175.
[124] XIA Y, LIN L L, CHANG F Z, et al. Asymmetric Ring-Opening of Cyclopropyl Ketones with Thiol, Alcohol, and Carboxylic Acid Nucleophiles Catalyzed by a Chiral N,N'-Dioxide-Scandium(III) Complex[J]. Angewandte Chemie International Edition, 2015, 54(46): 13748-13752.
[125] GASTON M S, CID M P, SALVATIERRA N A. Bicuculline, a Gaba(a)-Receptor Antagonist, Blocked Hpa Axis Activation Induced by Ghrelin under an Acute Stress[J]. Behavioural Brain Research, 2017, 320: 464-472.
[126] KARMAKAR R, PAHARI P, MAL D. Phthalides and Phthalans: Synthetic Methodologies and Their Applications in the Total Synthesis[J]. Chemical Reviews, 2014, 114(12): 6213-6284.
[127] WITULSKI B, ZIMMERMANN A, GOWANS N D. First Total Synthesis of the Marine Illudalane Sesquiterpenoid Alcyopterosin E[J]. Chemical Communications, 2002, 24: 2984-2985.
[128] DU C, LI L Q, DA S J, et al. A Versatile Approach for the Total Syntheses of Fuscinarin and Fuscins[J]. Chinese Journal of Chemistry, 2008, 26(4): 693-698.
[129] JADULCO R, BRAUERS G, EDRADA R A, et al. New Metabolites from Sponge-Derived Fungi Curvularia Lunata and Cladosporium Herbarum[J]. Journal of Natural Products, 2002, 65(5): 730-733.
[130] BRAUN G H, RAMOS H P, CANDIDO A C B B, et al. Evaluation of Antileishmanial Activity of Harzialactone a Isolated from the Marine-Derived Fungus Paecilomyces Sp[J]. Natural Product Research, 2021, 35(10): 1644-1647.
[131] DUAN S, LI B, DUGGER R W, et al. Developing an Asymmetric Transfer Hydrogenation Process for (S)-5-Fluoro-3-Methylisobenzofuran-1(3H)-One, a Key Intermediate to Lorlatinib[J]. Organic Process Research & Development, 2017, 21(9): 1340-1348.
[132] PHAN D H T, KIM B, DONG V M. Phthalides by Rhodium-Catalyzed Ketone Hydroacylation[J]. Journal of the American Chemical Society, 2009, 131(43): 15608-15609.
[133] ZHANG B, XU M H, LIN G Q. Catalytic Enantioselective Synthesis of Chiral Phthalides by Efficient Reductive Cyclization of 2-Acylarylcarboxylates under Aqueous Transfer Hydrogenation Conditions[J]. Organic Letters, 2009, 11(20): 4712-4715.
[134] GE Y, HAN Z, WANG Z, et al. Ir-Spinphox Catalyzed Enantioselective Hydrogenation of 3-Ylidenephthalides[J]. Angewandte Chemie International Edition, 2018, 57(40): 13140-13144.
[135] MANGAS-SANCHEZ J, BUSTO E, GOTOR-FERNANDEZ V, et al. Highly Stereoselective Chemoenzymatic Synthesis of the 3H-Isobenzofuran Skeleton. Access to Enantiopure 3-Methylphthalides[J]. Organic Letters, 2012, 14(6): 1444-1447.
[136] HILBORN J W, LU Z H, JURGENS A R, et al. A Practical Asymmetric Synthesis of (R)-Fluoxetine and Its Major Metabolite (R)-Norfluoxetine[J]. Tetrahedron Letters, 2001, 42(51): 8919-8921.
[137] SU Y, TU Y Q, GU P. Preparation of Enantioenriched Gamma-Substituted Lactones Via Asymmetric Transfer Hydrogenation of Beta-Azidocyclopropane Carboxylates Using the Ru-TsDEPN Complex[J]. Organic Letters, 2014, 16(16): 4204-4207.
[138] LI M-L, LI Y, PAN J-B, et al. Carboxyl Group-Directed Iridium-Catalyzed Enantioselective Hydrogenation of Aliphatic Γ-Ketoacids[J]. ACS Catalysis, 2020, 10(17): 10032-10039.
[139] ZHANG K, ZHANG X, CHEN J, et al. Palladium/Zinc Co-Catalyzed Asymmetric Hydrogenation of Gamma-Keto Carboxylic Acids[J]. Chemistry-An Asian Journal, 2021, 16(10): 1229-1232.
[140] DENG C Q, DENG J. Ni-Catalyzed Asymmetric Hydrogenation of Aromatic Ketoacids for the Synthesis of Chiral Lactones[J]. Organic Letters, 2022, 24(13): 2494-2498.
[141] PETRIGNET J, NGI S I, ABARBRI M, et al. Short and Convenient Synthesis of Two Natural Phthalides by a Copper(I) Catalysed Sonogashira/Oxacyclisation Copper(I) Process[J]. Tetrahedron Letters, 2014, 55(5): 982-984.
[142] SHI Y, TAN X, GAO S, et al. Direct Synthesis of Chiral NH Lactams Via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters[J]. Organic Letters, 2020, 22(7): 2707-2713.
[143] ZHANG Y, LIU Y Q, HU L, et al. Asymmetric Reductive Amination/Ring-Closing Cascade: Direct Synthesis of Enantioenriched Biaryl-Bridged NH Lactams[J]. Organic Letters, 2020, 22(16): 6479-6483.
[144] 张瑶. 串联不对称还原胺化-分子内环化直接合成手性NH内酰胺[D]. 哈尔滨：哈尔滨工业大学, 2020：27-38.
[145] NICHOLSON K G, AOKI F Y, OSTERHAUS A, et al. Efficacy and Safety of Oseltamivir in Treatment of Acute Influenza: A Randomised Controlled Trial[J]. The Lancet, 2000, 355(9218): 1845-1850.
[146] HAYDEN F G, SUGAYA N, HIROTSU N, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents[J]. The New England Journal of Medicine, 2018, 379(10): 913-923.
[147] 郑旭春, 张一平, 付晨晨, et al. 一种新型抗流感药物的合成方法, CN109504721A [P/OL]. 2019-03-22.
[148] 张福利, 江锣斌, 邱友春, et al. 一种手性二苯并[B,E]硫杂䓬-11-醇的制备方法, CN110143944A[P/OL]. 2019-08-20.
[149] 资春鹏, 曾亮, 王云春. 一种巴洛沙韦酯中间体的合成方法, CN112812095A[P/OL]. 2021-05-18.
[150] NISHIYAMA Y, HOSOYA T, YOSHIDA S. Synthesis of Benzyl Sulfides Via Substitution Reaction at the Sulfur of Phosphinic Acid Thioesters[J]. Chemical Communications, 2020, 56(43): 5771-5774.
[151] ZHOU Z, WANG Z, KOU J, et al. Development of a Quality Controllable and Scalable Process for the Preparation of 7,8-Difluoro-6,11-Dihydrodibenzo[B,E]Thiepin-11-Ol: A Key Intermediate for Baloxavir Marboxil[J]. Organic Process Research & Development, 2019, 23(12): 2716-2723.
[152] KWAK E L, BANG Y J, CAMIDGE D R, et al. Anaplastic Lymphoma Kinase Inhibition in Non-Small-Cell Lung Cancer[J]. New England Journal of Medicine, 2010, 363(18): 1693-1703.
[153] KRIS M G, JOHNSON B E, BERRY L D, et al. Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs[J]. Jama-Journal of the American Medical Association, 2014, 311(19): 1998-2006.
[154] HORN L, INFANTE J R, RECKAMP K L, et al. Ensartinib (X-396) in Alk-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study[J]. Clinical Cancer Research, 2018, 24(12): 2771-2779.
[155] QIAN J-Q, YAN P-C, CHE D-Q, et al. A Novel Approach for the Synthesis of Crizotinib through the Key Chiral Alcohol Intermediate by Asymmetric Hydrogenation Using Highly Active Ir-SpiroPAP Catalyst[J]. Tetrahedron Letters, 2014, 55(9): 1528-1531.
[156] LING F, CHEN J, NIAN S, et al. Manganese-Catalyzed Enantioselective Hydrogenation of Simple Ketones Using an Imidazole-Based Chiral Pnn Tridentate Ligand[J]. Synlett, 2020, 31(03): 285-289.
[157] JOHNSON T W, RICHARDSON P F, BAILEY S, et al. Discovery of (10R)-7-Amino-12-Fluoro-2,10,16-Trimethyl-15-Oxo-10,15,16,17-Tetrahydro-2H-8,4-(Metheno)Pyrazolo
[4,3-H]
[2,5,11]-Benzoxadiazacyclotetradecine-3-Carbonitrile (Pf-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and C-Ros Oncogene 1 (Ros1) with Preclinical Brain Exposure and Broad-Spectrum Potency against Alk-Resistant Mutations[J]. Journal of Medicinal Chemistry, 2014, 57(11): 4720-4744.
[158] MOHD HANAFIAH K, GROEGER J, FLAXMAN A D, et al. Global Epidemiology of Hepatitis C Virus Infection: New Estimates of Age-Specific Antibody to Hcv Seroprevalence[J]. Hepatology, 2013, 57(4): 1333-1342.
[159] SONG J, SHAO P-L, WANG J, et al. Asymmetric Hydrogenation of 1,4-Diketones: Facile Synthesis of Enantiopure 1,4-Diarylbutane-1,4-Diols[J]. Chemical Communications, 2022, 58(2): 262-265.

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宋静远. 铱催化酮不对称氢化及其在药物绿色合成中的应用[D]. 哈尔滨. 哈尔滨工业大学,2023.