CN115477672A - 一种含有轴手性和膦中心手性化合物及其制备方法 - Google Patents
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- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims abstract description 26
- 150000001875 compounds Chemical class 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 57
- 239000003446 ligand Substances 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 21
- 150000004714 phosphonium salts Chemical group 0.000 claims abstract description 17
- 239000004327 boric acid Chemical group 0.000 claims abstract description 12
- 150000008300 phosphoramidites Chemical class 0.000 claims abstract description 11
- -1 aryl/alkenyl boric acid Chemical group 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 9
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical group OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000654 additive Substances 0.000 claims abstract description 7
- 230000000996 additive effect Effects 0.000 claims abstract description 7
- 239000002904 solvent Chemical group 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 239000011593 sulfur Substances 0.000 claims abstract description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 4
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000004440 column chromatography Methods 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 239000011261 inert gas Substances 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical group Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- 229940045803 cuprous chloride Drugs 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 claims description 2
- 229940112669 cuprous oxide Drugs 0.000 claims description 2
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- 229910052763 palladium Inorganic materials 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
- 238000005481 NMR spectroscopy Methods 0.000 description 51
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
- 238000012512 characterization method Methods 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 9
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000003003 phosphines Chemical class 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- QKZWXPLBVCKXNQ-UHFFFAOYSA-N (2-methoxyphenyl)-[2-[(2-methoxyphenyl)-phenylphosphanyl]ethyl]-phenylphosphane Chemical compound COC1=CC=CC=C1P(C=1C=CC=CC=1)CCP(C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102220305863 rs1015663503 Human genes 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
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- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
- C07F9/655354—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0255—Phosphorus containing compounds
- B01J31/0267—Phosphines or phosphonium compounds, i.e. phosphorus bonded to at least one carbon atom, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, the other atoms bonded to phosphorus being either carbon or hydrogen
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Abstract
本发明公开了一种含有轴手性和膦中心手性化合物及其制备方法，所述制备方法包括：将碱、催化剂、手性亚磷酰胺配体、添加剂、季鏻盐、硼酸和溶剂混合反应；在惰性气体保护下反应结束后，加入硫或硼烷二甲硫醚，常温下惰性气体保护继续反应；过滤、浓缩、柱层析得到含有轴手性和膦中心手性化合物；本方法采用季鏻盐、芳基/烯基硼酸为原料，以钯和手性亚磷酰胺配体为催化体系，在温和的条件下以较高的产率和对映选择性得到P‑中心手性膦化合物，实现了碳膦键的不对称反应。
Description
技术领域
本发明涉及手性膦化合物制备领域，具体地，涉及一种含有轴手性和膦中心手性化合物及其制备方法。
背景技术
手性膦化合物在金属催化不对称合成中是一类非常重要的手性配体，也是一类非常重要的手性有机催化剂。目前应用最广泛的主要是基于轴手性、碳中心手性、螺环手性的膦配体，如常见的联萘类、联苯类、螺环类及碳中心手性膦配体，在手性药物及材料合成中表现出了重要的研究意义和经济价值。
不同于传统的手性膦配体，P-手性膦配体以膦为手性中心，其手性中心直接与过渡金属配位，所形成的配合物中手性环境更靠近底物和反应中心，理论上会表现出更好的手性控制能力。早在1975年，Knowles就合成了P- 手性膦配体DIPAMP，成功地应用于烯烃的不对称氢化反应中，并应用于治疗帕金森氏症的药L-DOPA的工业制备，因此荣获了2001年诺贝尔奖。然而由于合成方法和操作条件的限制，在之后的十几年里，P-手性膦配体的发展较为缓慢。1990年以来，P-手性膦配体又重新得到了关注，张绪穆、汤文军、Imamoto等小组做出了非常出色的工作，发展出BisP*,MiniPhos, TangPhos,DuanPhos,QuinoxP*等P-手性膦配体，在不对称合成特别是不对称氢化方面，表现出了非常优异的活性和立体控制能力，但是目前，这些配体的合成主要是通过对映体拆分的手段获得，一般需要当量的手性试剂，因此发展手性催化的方法来合成P-手性膦配体具有挑战性和重要的研究意义。
发明内容
本发明的目的是提供一种含有轴手性和膦中心手性化合物及其制备方法，采用季鏻盐、芳基/烯基硼酸为原料，以钯和手性亚磷酰胺配体为催化体系，在温和的条件下以较高的产率和对映选择性得到P-中心手性膦化合物，实现了碳膦键的不对称反应。
为了实现上述目的，本发明提供了一种含有轴手性和膦中心手性化合物，所述含有轴手性和膦中心手性化合物的结构式为：
其中，R为H、烷基、芳基、或带有官能团的烷基；
R1和R2分别为烷基；
X为S或BH3；
R3为含取代基团的芳基或烯基。
优选地，R1和R2为甲基、乙基、异丙基、叔丁基或环己基。
优选地，R3的结构式为：
本发明还提供了一种含有轴手性和膦中心手性化合物的制备方法，所述制备方法包括：
(1)将碱、催化剂、手性亚磷酰胺配体、添加剂、季鏻盐、硼酸和溶剂混合反应；
(2)加入硫或硼烷二甲硫醚，在惰性气体保护下混合反应；
(3)过滤、浓缩、柱层析得到含有轴手性和膦中心手性化合物；其中，反应路线如下：
优选地，在步骤(1)中，混合反应的条件包括温度为38-42℃；和/或
时间为35-37h；
优选地，在步骤(2)中，混合反应的条件包括温度为24-26℃；和/或
时间为110-130min。
优选地，季鏻盐中R为H、烷基、芳基或带有官能团的烷基；
R1和R2分别为烷基；
优选地，R1和R2分别为甲基、乙基、异丙基、叔丁基或环己基。
优选地，硼酸为包含取代基的芳基硼酸或烯基硼酸。
优选地，催化剂为烯丙基氯化钯二聚体、肉桂基氯化钯二聚体、醋酸钯、三氟乙酸钯、氯化钯、Pd(dba)2或Pd2(dba)3中的一种。
优选地，碱为碳酸盐或磷酸盐；
优选地，碱为碳酸铯、碳酸钾或磷酸钾；
优选地，添加剂为氯化亚铜、溴化亚铜、碘化亚铜或氧化亚铜中的一种。
优选地，溶剂为2-甲基四氢呋喃、THF、DME、乙醚或叔丁醇甲醚中的一种。
优选地，手性亚磷酰胺配体的结构式为：
其中，R4为异丙基或环己基。
优选地，各原料按以下配比混合：
季鏻盐：硼酸：催化剂：手性亚磷酰胺配体：添加剂：碱：溶剂＝1毫摩尔:0.1～10毫摩尔:0.01～1毫摩尔:0.01～1毫摩尔:0.1～5毫摩尔:0.1～5毫摩尔:0-100毫升。
在上述技术方案中，首次采用钯催化碳膦键不对称断裂的方式，实现了季鏻盐和芳基硼酸的偶联反应，反应具有较高的对映选择性和较高的产率，且产物可以作为手性催化剂催化不对称反应。
本发明还具有以下优点：1)反应条件简单温和；2)产物易分离纯化；3) 反应具有良好的产率，较高的对映选择性和非对映选择性；4)产物同时含有轴手性和膦中心手性。本发明所得到的相应P-手性膦化合物的产率为 41-83％，最高98％ee，>25:1dr。
本发明的其他特征和优点将在随后的具体实施方式部分予以详细说明。
附图说明
附图是用来提供对本发明的进一步理解，并且构成说明书的一部分，与下面的具体实施方式一起用于解释本发明，但并不构成对本发明的限制。在附图中：
图1是本发明中实施例1的反应路线图；
图2是本发明中实施例2的反应路线图；
图3是本发明中实施例3的反应路线图；
图4是本发明中实施例4的反应路线图；
图5是本发明中实施例5的反应路线图；
图6是本发明中实施例6的反应路线图；
图7是本发明中实施例7的反应路线图；
图8是本发明中实施例8的反应路线图；
图9是本发明中实施例9的反应路线图；
图10是本发明中实施例10的反应路线图；
图11是本发明中实施例11的反应路线图；
图12是本发明中实施例12的反应路线图；
图13是本发明中实施例13的反应路线图；
图14是本发明中实施例14的反应路线图；
图15是本发明中实施例15的反应路线图；
图16是本发明中实施例16的反应路线图；
图17是本发明中实施例17的反应路线图；
图18是本发明中实施例18的反应路线图。
具体实施方式
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明，而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
在反应管中加入碳酸铯，然后将体系密封，抽真空，用热风枪烘烤除去碳酸铯中的水；待反应管冷却到室温后，依次向反应体系中加入烯丙基氯化钯二聚体、手性配体、氯化亚铜、季鏻盐、硼酸以及2-甲基四氢呋喃，最后在40度油浴锅内反应36小时；反应结束后，向反应瓶中加入硫，然后氮气保护下室温反应2小时；过滤，浓缩，柱层析，获得手性膦化合物。反应路线图如图1所示。
产物表征数据如下：Light yellow solid,Rf＝0.20(petroleum ether/ethylacetate/dichloromethane＝40:1:4),76％yield,95％ee.1H NMR(600MHz, Chloroform-d)δ8.25(dd,J＝11.7,8.9Hz,1H),8.05(d,J＝8.6Hz,1H),7.97(d, J＝8.4Hz,1H),7.93(d,J＝8.1Hz,1H),7.89(d,J＝8.1Hz,1H),7.72(d,J＝ 8.6Hz,1H),7.55(t,J＝7.2Hz,1H),7.43(t,J＝7.2Hz,1H),7.32(t,J＝7.2Hz, 1H),7.29-7.23(m,2H),7.06(d,J＝8.8Hz,2H),6.91(d,J＝8.6Hz,1H),6.59(d, J＝8.8Hz,2H),3.67(s,3H),0.91-0.76(m,12H).13C NMR(151MHz, Chloroform-d)δ158.94,139.98(d,J＝5.2Hz),137.65,135.33(d,J＝10.8Hz),134.80,133.62,133.15(d,J＝3.4Hz),132.13,130.97,130.42,130.34,129.90, 129.50,128.62,128.29,128.14,127.84,127.79,127.61,127.55,127.47,127.09, 126.35,113.86,55.34,36.04(d,J＝49.9Hz),25.43(d,J＝2.1Hz),15.22(d,J＝ 52.2Hz).31P NMR(243MHz,Chloroform-d)δ60.37.The enantiomeric excess was determined by DaicelChiralpak IA,n-hexane/isopropanol＝80/20,1 mL/min,λ＝254nm,t(minor)＝6.64min,t(major)＝8.08min.[α]D 25＝173.2(c ＝0.477,CH2Cl2).HRMS(ESI)calcd for:C32H32OPS+[M+H]+495.1906； found:495.1911.
实施例2
按照实施例1的方法进行，不同的是，利用硼烷二甲硫醚代替硫。反应路线图如图2所示。
产物表征数据如下：Orange solid,Rf＝0.33(petroleum ether/ethyl acetate＝20:1),68％yield,97％ee.1H NMR(600MHz,Chloroform-d)δ8.05(d,J＝ 8.6Hz,1H),7.99-7.91(m,3H),7.89(d,J＝8.1Hz,1H),7.72(d,J＝8.6Hz,1H), 7.54(t,J＝7.4Hz,1H),7.42(t,J＝7.4Hz,1H),7.33-7.28(m,1H),7.28-7.21(m, 2H),7.05(d,J＝8.7Hz,2H),6.86(d,J＝8.6Hz,1H),6.58(d,J＝8.7Hz,2H), 3.67(s,3H),0.80(d,J＝13.6Hz,9H),0.50(d,J＝10.2Hz,3H),0.70-0.07(m, 3H).13C NMR(151MHz,Chloroform-d)δ158.88,142.14,138.01,135.78(d,J ＝7.9Hz),134.86,133.75,133.46(d,J＝1.8Hz),133.20(d,J＝3.2Hz),132.20, 131.00,130.87(d,J＝14.5Hz),129.43,128.56,128.30,127.83,127.79,127.64, 127.42,127.28,127.27,127.18,126.43(d,J＝45.0Hz),126.24,113.81,55.35,30.65(d,J＝31.5Hz),26.63(d,J＝2.3Hz),5.95(d,J＝36.1Hz).31P NMR (243MHz,Chloroform-d)δ33.95(br,J＝50.4Hz).The enantiomeric excess was determined byDaicel Chiralpak IC,n-hexane/isopropanol＝95/5,1mL/min, λ＝254nm,t(minor)＝15.37min,t(major)＝16.58min.[α]D 25＝226.6(c＝ 0.203,CH2Cl2).HRMS(ESI)calcd for:C32H35BOP+[M+H]+477.2513；found: 477.2520.
实施例3
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 3所示。
产物表征数据如下：Yellow solid,Rf＝0.23(petroleum ether/ethyl acetate＝20:1),76％yield,96％ee.1H NMR(600MHz,Chloroform-d)δ8.21(dd,J＝ 11.4,9.1Hz,1H),8.08(d,J＝8.6Hz,1H),7.96(d,J＝8.8Hz,1H),7.91(t,J＝ 8.7Hz,2H),7.74(d,J＝8.6Hz,1H),7.54(t,J＝7.3Hz,1H),7.44(t,J＝7.3Hz, 1H),7.34-7.26(m,2H),7.24(d,J＝8.9Hz,1H),7.14(d,J＝7.3Hz,2H), 7.10-7.01(m,3H),6.95(d,J＝8.6Hz,1H),0.89(d,J＝12.9Hz,3H),0.82(d,J ＝16.4Hz,9H).13C NMR(151MHz,Chloroform-d)δ141.13,139.79(d,J＝5.2 Hz),137.98,135.35(d,J＝10.7Hz),134.64,133.57(d,J＝3.4Hz),133.53(d,J ＝2.2Hz),132.31,130.16(J＝12.3Hz),130.11(d,J＝68.4Hz),129.78,129.50, 128.62,128.25,128.23,128.09,127.79,127.78,127.55,127.47,127.21,127.13, 126.51,36.00(d,J＝49.9Hz),25.40(d,J＝2.0Hz),15.33(d,J＝52.1Hz).31P NMR(243MHz,Chloroform-d)δ60.13.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝6.20min,t(major)＝6.73min.[α]D 25＝125.1(c＝0.781, CH2Cl2).HRMS(ESI)calcd for:C31H30PS+[M+H]+465.1800；found: 465.1811.
实施例4
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 4所示。
产物表征数据如下：Orange solid,Rf＝0.23(petroleum ether/ethyl acetate/dichloromethane＝40:1:4),69％yield,93％ee,1H NMR(600MHz, Chloroform-d)δ8.23(dd,J＝11.5,9.0Hz,1H),8.07(d,J＝8.6Hz,1H),7.97(d, J＝8.6Hz,1H),7.93(d,J＝8.2Hz,1H),7.90(d,J＝8.1Hz,1H),7.71(d,J＝ 8.6Hz,1H),7.55(t,J＝7.3Hz,1H),7.44(t,J＝7.3Hz,1H),7.32(t,J＝7.5Hz, 1H),7.28(t,J＝7.6Hz,1H),7.23(d,J＝8.5Hz,1H),7.05(d,J＝8.3Hz,2H), 6.94(d,J＝8.4Hz,3H),2.35(s,3H),0.88(d,J＝13.2Hz,3H),0.85(d,J＝16.5 Hz,9H).13C NMR(151MHz,Chloroform-d)δ139.82(d,J＝5.2Hz),137.97,137.86,137.45,135.37,135.30,134.75,133.62(d,J＝2.2Hz),133.52(d,J＝3.4 Hz),132.35,130.32(d,J＝12.3Hz),130.19,130.14(d,J＝65.7Hz),129.63, 128.39,128.33,128.11,127.91,127.85,127.70,127.67,127.58,127.22,126.59, 126.42,36.14(d,J＝49.8Hz),25.46(d,J＝2.2Hz),15.83,15.35(d,J＝52.2 Hz).31P NMR(243MHz,Chloroform-d)δ60.12.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝7.25min,t(major)＝8.58min.[α]D 25＝158.8(c＝0.578, CH2Cl2).HRMS(ESI)calcd for:C32H32PS2 +[M+H]+511.1678；found: 511.1677.
实施例5
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 5所示。
产物表征数据如下：Yellow solid,Rf＝0.32(petroleum ether/ethyl acetate＝20:1),76％yield,93％ee.1H NMR(600MHz,Chloroform-d)δ8.23(dd,J＝ 11.7,8.9Hz,1H),8.08(d,J＝8.6Hz,1H),7.97(d,J＝8.8Hz,1H),7.93(d,J＝ 8.2Hz,1H),7.91(d,J＝8.2Hz,1H),7.74(d,J＝8.6Hz,1H),7.55(t,J＝7.4Hz, 1H),7.45(t,J＝7.4Hz,1H),7.32(t,J＝7.2Hz,1H),7.29(t,J＝7.2Hz,1H), 7.24(d,J＝8.6Hz,1H),7.10(s,4H),6.94(d,J＝8.6Hz,1H),6.55(dd,J＝17.6, 10.9Hz,1H),5.61(d,J＝17.6Hz,1H),5.16(d,J＝10.9Hz,1H),0.88(d,J＝ 12.9Hz,3H),0.83(d,J＝16.5Hz,9H).13C NMR(151MHz,Chloroform-d)δ 140.55,139.76(d,J＝5.2Hz),137.64,136.42,136.15,135.29(d,J＝10.7Hz), 134.68,133.56,133.54,132.32,130.24(d,J＝12.3Hz),130.16(d,J＝64.8Hz),129.94,129.53,128.41,128.25,128.07,127.83,127.80,127.60,127.58,127.50,127.19,126.54,126.08,114.18,36.04(d,J＝49.9Hz),25.38(d,J＝2.2Hz), 15.30(d,J＝52.1Hz).31P NMR(243MHz,Chloroform-d)δ60.19.The enantiomeric excess wasdetermined by Daicel Chiralpak IA, n-hexane/isopropanol＝95/5,1mL/min,λ＝254nm,t(minor)＝12.83min,t (major)＝18.14min,[α]D 25＝225.4(c＝0.114,CH2Cl2).HRMS(ESI)calcd for: C33H32PS+[M+H]+491.1957；found:491.1953.
实施例6
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 6所示。
产物表征数据如下：White solid,Rf＝0.24(petroleum ether/ethyl acetate/dichloromethane＝40:1:4),42％yield,95％ee.1H NMR(600MHz, Chloroform-d)δ8.23-8.14(m,1H),7.96(d,J＝8.6Hz,1H),7.94-7.83(m,3H), 7.67(d,J＝8.6Hz,1H),7.51(t,J＝7.4Hz,1H),7.43(t,J＝7.4Hz,1H), 7.33-7.21(m,2H),7.16(d,J＝8.6Hz,1H),7.10-7.01(m,1H),6.98(d,J＝8.5 Hz,1H),6.87(d,J＝4.8Hz,1H),6.77(d,J＝8.2Hz,1H),6.41(t,J＝7.4Hz, 1H),3.71(s,3H),1.12(d,J＝12.9Hz,3H),0.92(d,J＝16.3Hz,9H).13C NMR(151MHz,Chloroform-d)δ156.58,135.28,135.21,135.08,134.90,134.33, 133.69,132.26,130.74,130.41,130.10,130.01,129.65,128.83,128.60,128.10, 127.72,127.61,127.59,127.54,127.46,127.24,127.19,127.11,126.42,120.14, 110.96,54.88,35.78(d,J＝48.8Hz),25.58,15.61(d,J＝51.9Hz).31P NMR (243MHz,Chloroform-d)δ60.96.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝95/5,1mL/min,λ＝254nm,t (minor)＝16.68min,t(major)＝18.05min.[α]D 25＝125.5(c＝0.573,CH2Cl2). HRMS(ESI)calcd for:C32H32OPS+[M+H]+495.1906；found:495.1917.
实施例7
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 7所示。
产物表征数据如下：Orange solid,Rf＝0.16(petroleum ether/ethyl acetate＝20:1),81％yield,93％ee.1H NMR(600MHz,Chloroform-d)δ8.17-8.07(m, 2H),7.98(d,J＝8.2Hz,1H),7.93(d,J＝8.1Hz,1H),7.90(d,J＝8.8Hz,1H), 7.83-7.78(m,2H),7.71(d,J＝7.9Hz,1H),7.68-7.62(m,1H),7.60(d,J＝8.3 Hz,1H),7.46(t,J＝7.4Hz,1H),7.44-7.40(m,2H),7.37(d,J＝8.3Hz,1H), 7.36-7.29(m,2H),7.24(t,J＝7.6Hz,1H),7.10(t,J＝8.7Hz,2H),0.92(d,J＝12.8Hz,3H),0.73(d,J＝16.5Hz,9H).13C NMR(151MHz,Chloroform-d)δ 139.98(d,J＝5.1Hz),139.79,138.27,137.95,137.35,135.62(d,J＝10.7Hz), 135.24,134.77,133.72(d,J＝3.4Hz),133.53(d,J＝2.1Hz),132.32,130.30(d,J＝12.2Hz),130.00(d,J＝68.2Hz),129.57,128.72,128.69,128.36,128.30, 127.91,127.85,127.73,127.62,127.49(d,J＝11.8Hz),127.29,126.80,126.55, 124.42,122.78,122.61,122.47,121.16,36.04(d,J＝49.8Hz),25.39(d,J＝1.9 Hz),15.46(d,J＝52.1Hz).31P NMR(243MHz,Chloroform-d)δ60.00.The enantiomeric excess wasdetermined by Daicel Chiralpak IA, n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝7.80min,t (major)＝8.93min.[α]D 25＝75.6(c＝0.852,CH2Cl2).HRMS(ESI)calcd for: C37H32PS2 +[M+H]+571.1678；found:571.1680.
实施例8
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 8所示。
产物表征数据如下：Orange solid,Rf＝0.27(petroleum ether/ethyl acetate＝20:1),59％yield,92％ee.1H NMR(600MHz,Chloroform-d)δ8.18-8.10(m, 2H),7.99-7.92(m,3H),7.85(d,J＝8.6Hz,1H),7.65(d,J＝7.9Hz,1H), 7.63-7.57(m,2H),7.51(d,J＝8.6Hz,1H),7.48(t,J＝7.4Hz,1H),7.41-7.29 (m,6H),7.26(d,J＝9.2Hz,1H),7.04(d,J＝8.5Hz,1H),0.93(d,J＝12.8Hz, 3H),0.69(d,J＝16.5Hz,9H).13C NMR(151MHz,Chloroform-d)δ140.00(d, J＝5.3Hz),138.58,138.11,135.50(d,J＝10.8Hz),134.81,133.97(d,J＝3.5 Hz),133.67(d,J＝2.1Hz),133.15,132.43,132.19,130.26(d,J＝12.2Hz), 130.13(d,J＝68.3Hz),129.60,129.33,128.83,128.31,128.14,127.92,127.69, 127.65,127.58(d,J＝12.0Hz),127.38,127.34,126.65,126.24,126.20,36.11(d, J＝50.0Hz),25.40(d,J＝2.2Hz),15.48(d,J＝52.2Hz).31P NMR(243MHz,Chloroform-d)δ60.03.The enantiomeric excess was determined by DaicelChiralpak IA,n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝7.26min,t(major)＝8.87min.[α]D 25＝188.0(c＝0.599,CH2Cl2).HRMS(ESI) calcd for:C35H32PS+[M+H]+515.1957；found:515.1953.
实施例9
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 9所示。
产物表征数据如下：Orange solid,Rf＝0.15(petroleum ether/ethyl acetate＝20:1),82％yield,90％ee.1H NMR(600MHz,Chloroform-d)δ8.17-8.08(m, 2H),7.97(d,J＝8.8Hz,1H),7.94(d,J＝8.2Hz,2H),7.69(d,J＝8.6Hz,1H), 7.56(t,J＝7.3Hz,1H),7.48(t,J＝7.3Hz,1H),7.36-7.28(m,4H),7.28-7.19(m, 3H),7.02(d,J＝8.5Hz,1H),0.96(d,J＝12.7Hz,3H),0.84(d,J＝16.5Hz,9H). 13C NMR(151MHz,Chloroform-d)δ145.03,139.79(d,J＝5.4Hz),136.88, 135.28(d,J＝10.6Hz),134.50,134.13(d,J＝3.4Hz),133.58(d,J＝2.1Hz), 132.70,130.13,129.97(d,J＝12.1Hz),129.73,129.79(d,J＝65.6Hz),129.19 (q,J＝32.6Hz),128.41,128.05,128.02,127.97,127.85,127.79,127.71,127.67, 127.47,126.92,124.97(dd,J＝7.4,3.8Hz),124.11(q,J＝272.1Hz),36.28(d,J ＝50.1Hz),25.45(d,J＝2.1Hz),15.84(d,J＝52.2Hz).19F NMR(564MHz,cdcl3)δ-62.01～-63.65(m).31P NMR(243MHz,Chloroform-d)δ59.15.The enantiomericexcess was determined by Daicel Chiralpak IA, n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝5.81min,t (major)＝6.60min.[α]D25＝117.1(c＝0.591,CH2Cl2).HRMS(ESI)calcd for: C32H29F3PS+[M+H]+533.1674；found:533.1681.
实施例10
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 10所示。
产物表征数据如下：Orange solid,Rf＝0.23(petroleum ether/ethyl acetate＝10:1),64％yield,95％ee.1H NMR(600MHz,Chloroform-d)δ8.13(dd,J＝ 11.0,9.3Hz,1H),8.09(d,J＝8.6Hz,1H),7.95(d,J＝8.9Hz,1H),7.92(d,J＝ 8.0Hz,2H),7.71(d,J＝6.5Hz,3H),7.55(t,J＝7.4Hz,1H),7.47(t,J＝7.4Hz, 1H),7.35-7.27(m,2H),7.25-7.19(m,3H),7.03(d,J＝8.5Hz,1H),3.82(s,3H), 0.95(d,J＝12.7Hz,3H),0.84(d,J＝16.5Hz,9H).13C NMR(151MHz, Chloroform-d)δ166.73,145.98,139.82(d,J＝5.2Hz),137.26,135.21(d,J＝ 10.6Hz),134.53,134.02(d,J＝3.5Hz),133.53(d,J＝2.1Hz),132.61,130.03, 130.01(d,J＝12.0Hz),129.79,129.59,129.27,128.58,128.31,128.15,127.94,127.91,127.68,127.58,127.42,126.82,52.08,36.22(d,J＝50.0Hz),25.49(d,J ＝2.1Hz),15.73(d,J＝52.1Hz).31P NMR(243MHz,Chloroform-d)δ59.38. The enantiomericexcess was determined by Daicel Chiralpak IA, n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝7.25min,t (major)＝8.20min.[α]D 25＝157.8(c＝0.605,CH2Cl2).HRMS(ESI)calcd for: C33H32O2PS+[M+H]+523.1855；found:523.1858.
实施例11
按照实施例1的方法进行，不同的是，硼酸选择不同。反应路线图如图 11所示。
产物表征数据如下：Orange solid,Rf＝0.21(petroleum ether/ethyl acetate＝20:1),68％yield,91％ee.1H NMR(600MHz,Chloroform-d)δ8.61(dd,J＝ 11.6,9.3Hz,1H),8.10(d,J＝8.8Hz,1H),8.05(d,J＝8.8Hz,1H),8.00(d,J＝ 8.7Hz,1H),7.95(d,J＝8.2Hz,1H),7.87(d,J＝8.1Hz,1H),7.53(t,J＝7.4Hz, 1H),7.43(t,J＝7.4Hz,1H),7.30(t,J＝7.6Hz,1H),7.26(t,J＝7.6Hz,1H), 7.23-7.11(m,5H),7.08(d,J＝7.4Hz,2H),7.02(d,J＝8.5Hz,1H),6.69(d,J＝ 16.3Hz,1H),1.13(d,J＝16.4Hz,9H),0.75(d,J＝12.9Hz,3H).13C NMR (151MHz,Chloroform-d)δ138.85(d,J＝5.2Hz),136.99,135.39,134.51(d,J＝3.3Hz),134.30(d,J＝2.2Hz),133.70,132.84(d,J＝10.6Hz),132.67,130.94 (d,J＝67.3Hz),130.93(d,J＝12.7Hz),130.09,129.46,128.74,128.19,128.13, 128.03,128.02,128.00,127.73(d,J＝12.2Hz),127.60,127.43,127.34,126.75, 126.61,126.55,122.07,36.46(d,J＝49.9Hz),25.90(d,J＝2.1Hz),15.06(d,J ＝52.4Hz).31P NMR(243MHz,Chloroform-d)δ61.36.The enantiomeric excess was determined by DaicelChiralpak ID,n-hexane/isopropanol＝80/20,1 mL/min,λ＝254nm,t(minor)＝10.56min,t(major)＝11.88min.[α]D 25＝101.6 (c＝0.582,CH2Cl2).HRMS(ESI)calcd for:C33H32PS+[M+H]+491.1957； found:491.1961.
实施例12
按照实施例1的方法进行，不同的是，季鏻盐和手性亚磷酰胺配体的选择不同。反应路线图如图12所示。
产物表征数据如下：Orange solid,Rf＝0.20(petroleum ether/ethyl acetate＝20:1),54％yield,97％ee.1H NMR(600MHz,Chloroform-d)δ8.50(dd,J＝ 12.7,8.8Hz,1H),8.07(d,J＝8.7Hz,1H),8.01(d,J＝8.8Hz,1H),7.97(d,J＝ 8.2Hz,1H),7.90(d,J＝8.1Hz,1H),7.77(d,J＝8.6Hz,1H),7.57(t,J＝7.3Hz, 1H),7.44(t,J＝7.4Hz,1H),7.32(t,J＝7.5Hz,1H),7.28-7.20(m,2H),7.01(d, J＝8.7Hz,2H),6.91(d,J＝8.5Hz,1H),6.63(d,J＝8.7Hz,2H),3.68(s,3H), 1.62(s,1H),1.36-1.16(m,4H),1.12-0.95(m,4H),0.75(d,J＝13.2Hz,3H), 0.65-0.50(m,1H).13C NMR(151MHz,Chloroform-d)δ159.09,139.61(d,J＝ 6.4Hz),137.43,135.10(d,J＝10.6Hz),134.98,133.95(d,J＝2.2Hz),133.26 (d,J＝3.6Hz),133.18,132.12,131.01(d,J＝12.7Hz),130.71,129.73,128.93, 128.52,128.45,127.93,127.89,127.83,127.57,127.54,127.48(d,J＝12.5Hz), 127.17,126.33,114.12,55.24,39.36(d,J＝51.7Hz),25.95(d,J＝14.4Hz), 25.57,25.11(d,J＝14.2Hz),24.80(d,J＝13.5Hz),24.78(d,J＝13.9Hz), 17.16(d,J＝54.6Hz).31P NMR(243MHz,Chloroform-d)δ52.03.The enantiomeric excess was determined by DaicelChiralpak IA, n-hexane/isopropanol＝90/10,1mL/min,λ＝254nm,t(minor)＝11.04min,t (major)＝14.52min.[α]D 25＝232.2(c＝0.505,CH2Cl2).HRMS(ESI)calcd for:C34H34OPS+[M+H]+521.2062；
实施例13
按照实施例1的方法进行，不同的是，季鏻盐和手性亚磷酰胺配体的选择不同。反应路线图如图13所示。
产物表征数据如下：Brown solid,Rf＝0.25(petroleum ether/ethyl acetate＝20:1),60％yield,94％ee.1H NMR(600MHz,Chloroform-d)δ8.03(d,J＝ 8.5Hz,1H),7.92(d,J＝8.1Hz,2H),7.87(d,J＝8.4Hz,1H),7.62-7.52(m,3H), 7.44(d,J＝8.6Hz,1H),7.38(t,J＝7.4Hz,1H),7.34(t,J＝7.6Hz,1H),7.15(t, J＝7.5Hz,1H),7.06(d,J＝8.4Hz,1H),6.94(d,J＝8.6Hz,2H),6.49(d,J＝ 8.6Hz,2H),3.64(s,3H),2.19-2.09(m,1H),1.69-1.57(m,1H),0.95(d,J＝15.7 Hz,9H),0.45(dt,J＝18.4,7.5Hz,3H).13C NMR(151MHz,Chloroform-d)δ 158.22,145.93(d,J＝5.7Hz),139.91,136.26(d,J＝10.4Hz),134.77,133.97, 133.46,132.44,131.96,131.49,129.02,128.74(d,J＝10.6Hz),128.54,128.44,128.23,128.03,127.95,127.86,127.28,126.47(d,J＝10.8Hz),125.46,125.17, 112.87,55.27,37.55(d,J＝49.2Hz),26.45,22.27(d,J＝50.9Hz),6.12.31P NMR(243MHz,Chloroform-d)δ64.89.The enantiomeric excess was determined by DaicelChiralpak IC,n-hexane/isopropanol＝95/5,1mL/min,λ＝ 254nm,t(major)＝12.30min,t(minor)＝14.48min.[α]D 25＝71.8(c＝0.617, CH2Cl2).HRMS(ESI)calcd for:C33H34OPS+[M+H]+509.2062；found: 509.2063.
实施例14
按照实施例1的方法进行，不同的是，季鏻盐和手性亚磷酰胺配体的选择不同。反应路线图如图14所示。
产物表征数据如下：White solid,Rf＝0.23(petroleum ether/ethyl acetate＝20:1),51％yield,91％ee.1H NMR(600MHz,Chloroform-d)δ8.58(dd,J＝12.9,8.9Hz,1H),8.08(d,J＝8.6Hz,1H),8.01(d,J＝8.6Hz,1H),7.93(d,J＝ 8.1Hz,2H),7.73(d,J＝8.6Hz,1H),7.53(t,J＝7.3Hz,1H),7.44(t,J＝7.3Hz, 1H),7.32-7.26(m,1H),7.26-7.18(m,2H),6.99(d,J＝8.5Hz,2H),6.95(d,J＝ 8.6Hz,1H),6.56(d,J＝8.6Hz,2H),3.64(s,3H),1.51-1.37(m,1H),1.37-1.16 (m,2H),1.14-1.00(m,1H),0.69(dt,J＝19.5,7.4Hz,3H),0.59(dt,J＝19.3,7.4 Hz,3H).13C NMR(151MHz,Chloroform-d)δ158.84,140.12(d,J＝6.9Hz), 138.47,134.72,134.65,134.38,134.01(d,J＝2.2Hz),133.00,132.98,132.20, 130.76,130.68,130.59,129.55,128.76,128.35,128.04,127.90,127.82,127.40, 127.28,126.92,126.21,113.71,55.26,25.25(d,J＝52.8Hz),24.14(d,J＝53.4Hz),6.99(d,J＝4.6Hz),6.50(d,J＝4.6Hz).31P NMR(243MHz, Chloroform-d)δ57.63.Theenantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝90/10,1mL/min,λ＝254nm,t(minor)＝ 7.38min,t(major)＝9.81min.[α]D 25＝127.1(c＝0.278,CH2Cl2).HRMS(ESI) calcd for:C31H30OPS+[M+H]+481.1749；found:481.1745.
实施例15
按照实施例1的方法进行，不同的是，季鏻盐选择不同。反应路线图如图15所示。
产物表征数据如下：Orange solid,Rf＝0.16(petroleum ether/ethyl acetate＝20:1),70％yield,84％ee.1H NMR(600MHz,Chloroform-d)δ8.15(dd,J＝ 11.6,8.8Hz,1H),8.00(d,J＝8.3Hz,1H),7.92(d,J＝7.7Hz,1H),7.83(d,J＝ 8.1Hz,1H),7.79(d,J＝8.1Hz,1H),7.64(d,J＝8.5Hz,1H),7.38(d,J＝7.5 Hz,1H),7.26(d,J＝8.4Hz,1H),7.10-6.96(m,3H),6.71(s,1H),6.58(d,J＝ 8.7Hz,2H),3.67(s,3H),2.24(s,3H),2.23(s,3H),0.97-0.69(m,12H).13C NMR(151MHz,Chloroform-d)δ158.82,139.43(d,J＝5.3Hz),137.58,137.20 (d,J＝3.1Hz),135.54(d,J＝10.8Hz),135.04,133.89,132.71(d,J＝3.2Hz), 131.88(d,J＝2.0Hz),130.94,130.44,130.09(d,J＝69.1Hz),130.05,129.42,129.34,129.07,128.61,128.08,127.65,127.56,127.16(d,J＝12.1Hz),126.99, 126.30,113.74,55.30,36.03(d,J＝49.8Hz),25.51(d,J＝2.0Hz),22.16,22.08, 15.18(d,J＝52.2Hz).31P NMR(243MHz,Chloroform-d)δ60.26.The enantiomeric excess wasdetermined by Daicel Chiralpak IA, n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝5.17min,t (major)＝5.84min.[α]D 25＝116.0(c＝0.362,CH2Cl2).HRMS(ESI)calcd for: C34H36OPS+[M+H]+523.2219；found:523.2221.
实施例16
按照实施例1的方法进行，不同的是，季鏻盐选择不同。反应路线图如图16所示。
产物表征数据如下：Orange solid,Rf＝0.10(petroleum ether/ethyl acetate＝20:1),65％yield,93％ee.1H NMR(600MHz,Chloroform-d)δ8.21(t,J＝ 10.3Hz,1H),7.95(d,J＝8.5Hz,1H),7.87(d,J＝8.8Hz,1H),7.71-7.63(m, 3H),7.13(s,2H),7.10(d,J＝8.7Hz,1H),7.06(d,J＝7.1Hz,2H),6.79(d,J＝ 8.5Hz,1H),6.59(d,J＝7.1Hz,2H),3.67(s,3H),2.50(s,3H),2.44(s,3H), 0.90-0.79(m,12H).13C NMR(151MHz,Chloroform-d)δ158.86,139.91(d,J ＝5.3Hz),137.83,136.63,136.14,133.88(d,J＝2.3Hz),133.81,133.65(d,J＝10.9Hz),133.18(d,J＝3.4Hz),133.14,132.38,130.94,130.49(d,J＝12.4Hz), 129.92,129.87,129.01(d,J＝69.4Hz),128.83,128.61,128.03,127.35,126.924, 126.921(d,J＝12.0Hz),126.80,113.87,55.35,35.99(d,J＝50.0Hz),25.42(d,J＝2.2Hz),21.69,21.56,15.11(d,J＝52.1Hz).31P NMR(243MHz, Chloroform-d)δ60.30.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝ 6.71min,t(major)＝7.19min.[α]D 25＝163.4(c＝0.201,CH2Cl2).HRMS(ESI) calcd for:C34H36OPS+[M+H]+523.2219；found:523.2227.
实施例17
按照实施例1的方法进行，不同的是，季鏻盐选择不同。反应路线图如图17所示。
产物表征数据如下：Light yellow solid,Rf＝0.22(petroleum ether/ethylacetate＝20:1),77％yield,90％ee.1H NMR(600MHz,Chloroform-d)δ8.22 (dd,J＝11.7,9.0Hz,1H),7.96(d,J＝8.6Hz,1H),7.89(d,J＝8.7Hz,1H),7.67 (d,J＝8.6Hz,1H),7.63(s,1H),7.59(s,1H),7.12(dd,J＝19.7,8.8Hz,2H), 7.07(d,J＝8.8Hz,1H),7.04(d,J＝8.7Hz,2H),6.81(d,J＝8.7Hz,1H),6.58 (d,J＝8.7Hz,2H),3.66(s,3H),2.85(d,J＝7.5Hz,2H),2.80(d,J＝7.5Hz, 2H),2.74-2.57(m,2H),2.15-1.98(m,4H),1.92-1.81(m,4H),1.80-1.69(m,4H), 0.93-0.75(m,12H).13C NMR(151MHz,Chloroform-d)δ158.75,141.04, 139.80(d,J＝5.2Hz),139.38,136.59,133.78,133.71,133.28,133.06(d,J＝3.3Hz),132.20,130.85,130.40,130.31,129.13,129.11,128.91,128.46,127.95, 126.97,126.89,126.87,126.64,126.06,113.74,55.24,42.91,36.81,36.79,35.87 (d,J＝50.0Hz),28.51,28.50,28.41,28.39,25.33,25.32,18.44,14.99(d,J＝ 52.0Hz).31P NMR(243MHz,Chloroform-d)δ60.37.The enantiomeric excess was determined by DaicelChiralpak IA,n-Hexanes/isopropanol＝90/10,1 mL/min,λ＝254nm,t(minor)＝6.68min,t(major)＝7.97min.[α]D 25＝60.1(c ＝0.254,CH2Cl2).HRMS(ESI)calcd for:C42H48OPS+[M+H]+631.3158； found:631.3154.
实施例18
按照实施例1的方法进行，不同的是，季鏻盐选择不同。反应路线图如图18所示。
产物表征数据如下：Light yellow solid,Rf＝0.17(petroleum ether/ethylacetate＝20:1),60％yield,91％ee.1H NMR(600MHz,Chloroform-d)δ8.28 (dd,J＝11.1,9.4Hz,1H),8.16-8.06(m,3H),8.03(d,J＝8.6Hz,1H),7.74(d,J ＝8.6Hz,1H),7.67(d,J＝8.3Hz,2H),7.62(t,J＝8.2Hz,3H),7.56(d,J＝8.9 Hz,1H),7.50(d,J＝8.3Hz,2H),7.47(d,J＝8.3Hz,2H),7.35(d,J＝8.9Hz, 1H),7.11(d,J＝8.6Hz,2H),7.03(d,J＝8.9Hz,1H),6.61(d,J＝8.7Hz,2H), 3.68(s,3H),1.37(s,9H),1.36(s,9H),0.95(d,J＝12.8Hz,3H),0.86(d,J＝ 16.4Hz,9H).13C NMR(151MHz,Chloroform-d)δ158.91,151.10,150.59,140.10,139.82(d,J＝5.1Hz),138.74,137.59,137.47,137.12,134.34(d,J＝ 10.7Hz),133.98(d,J＝1.8Hz),133.85,133.60,133.00(d,J＝3.2Hz),132.47, 130.96,130.78(d,J＝12.4Hz),129.97,129.72,129.51,129.01,128.67,127.69 (d,J＝12.0Hz),127.56,127.20,127.09,127.04,126.00,125.86,125.54,125.22, 113.88,55.30,36.05(d,J＝49.8Hz),34.68,34.64,31.46,31.43,25.39,15.24(d, J＝52.0Hz).31P NMR(243MHz,Chloroform-d)δ60.36.The enantiomeric excess was determined by DaicelChiralpak IA,n-Hexanes/isopropanol＝90/10, 1mL/min,λ＝254nm,t(minor)＝8.69min,t(major)＝17.84min.[α]D 25＝ 102.8(c＝0.618,CH2Cl2).HRMS(ESI)calcd for:C52H56OPS+[M+H]+ 759.3784；found:759.3804.
以上结合附图详细描述了本发明的优选实施方式，但是，本发明并不限于上述实施方式中的具体细节，在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，这些简单变型均属于本发明的保护范围。
另外需要说明的是，在上述具体实施方式中所描述的各个具体技术特征，在不矛盾的情况下，可以通过任何合适的方式进行组合，为了避免不必要的重复，本发明对各种可能的组合方式不再另行说明。
此外，本发明的各种不同的实施方式之间也可以进行任意组合，只要其不违背本发明的思想，其同样应当视为本发明所公开的内容。
Claims (10)
1.一种含有轴手性和膦中心手性化合物，其特征在于，所述含有轴手性和膦中心手性化合物的结构式为：
其中，R为H、烷基、芳基、或带有官能团的烷基；
R1和R2分别为烷基；
X为S或BH3；
R3为含取代基团的芳基或烯基。
2.根据权利要求1所述的含有轴手性和膦中心手性化合物，其中，R1和R2为甲基、乙基、异丙基、叔丁基或环己基；
优选地，R3的结构式为：
3.一种含有轴手性和膦中心手性化合物的制备方法，其特征在于，所述制备方法包括：
(1)将碱、催化剂、手性亚磷酰胺配体、添加剂、季鏻盐、硼酸和溶剂混合反应；
(2)加入硫或硼烷二甲硫醚，在惰性气体保护下混合反应；
(3)过滤、浓缩、柱层析得到含有轴手性和膦中心手性化合物；其中，反应路线如下：
4.根据权利要求3所述的制备方法，其中，在步骤(1)中，混合反应的优选条件包括温度为38-42℃；和/或
时间为35-37h；
优选地，在步骤(2)中，混合反应的条件包括温度为24-26℃；和/或
时间为110-130min。
5.根据权利要求3所述的制备方法，其中，季鏻盐中R为H、烷基、芳基或带有官能团的烷基；
R1和R2分别为烷基；
优选地，R1和R2分别为甲基、乙基、异丙基、叔丁基或环己基。
6.根据权利要求3所述的制备方法，其中，硼酸为包含取代基的芳基硼酸或烯基硼酸。
7.根据权利要求3所述的制备方法，其中，催化剂为烯丙基氯化钯二聚体、肉桂基氯化钯二聚体、醋酸钯、三氟乙酸钯、氯化钯、Pd(dba)2或Pd2(dba)3中的一种。
8.根据权利要求3所述的制备方法，其中，碱为碳酸盐或磷酸盐；
优选地，碱为碳酸铯、碳酸钾或磷酸钾；
优选地，添加剂为氯化亚铜、溴化亚铜、碘化亚铜或氧化亚铜中的一种。
优选地，溶剂为2-甲基四氢呋喃、THF、DME、乙醚或叔丁醇甲醚中的一种。
9.根据权利要求3所述的制备方法，其中，手性亚磷酰胺配体的结构式为：
其中，R4为异丙基或环己基。
10.根据权利要求3所述的制备方法，其中，各原料按以下配比混合：
季鏻盐：硼酸：催化剂：手性亚磷酰胺配体：添加剂：碱：溶剂＝1毫摩尔:0.1～10毫摩尔:0.01～1毫摩尔:0.01～1毫摩尔:0.1～5毫摩尔:0.1～5毫摩尔:0-100毫升。
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