CN117603268A - 一种兼有轴手性和膦中心手性的氮膦双齿配体及其制备方法 - Google Patents

一种兼有轴手性和膦中心手性的氮膦双齿配体及其制备方法 Download PDF

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CN117603268A
CN117603268A CN202311321807.0A CN202311321807A CN117603268A CN 117603268 A CN117603268 A CN 117603268A CN 202311321807 A CN202311321807 A CN 202311321807A CN 117603268 A CN117603268 A CN 117603268A
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phosphine
chloroform
nmr
chirality
benzoxazole
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李乾坤
俞杰
庞良智
汪纯
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Anhui Agricultural University AHAU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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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
    • C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5325—Aromatic phosphine oxides or thioxides (P-C aromatic linkage)
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    • C07—ORGANIC CHEMISTRY
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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
    • C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
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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
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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    • C07B2200/07—Optical isomers

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Abstract

本发明公开了一种兼有轴手性和膦中心手性的氮膦双齿配体及其制备方法，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、苯并噁唑/苯并噻唑和溶剂混合反应；在惰性气体保护下反应结束后，加入硫，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的氮膦双齿配体；本方法采用季鏻盐、苯并噁唑/苯并噻唑为原料，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同时具备轴手性和膦中心手性的氮膦双齿配体。

Description

一种兼有轴手性和膦中心手性的氮膦双齿配体及其制备方法
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的氮膦双齿配体及其制备方法。
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。
设计合成骨架新颖的轴手性氮膦配体是不对称催化领域的重要研究方向之一。1991年，首个轴手性氮膦配体QUINAP被合成出来，研究人员相继开发出Quinazalinap、PyPhos和StackPhos等配体。目前，合成该类配体的方法局限于两种，通过两个芳基单元偶联合成消旋骨架，利用当量手性Pd化合物和配体发生螯合，进行动力学拆分，再脱除Pd螯合单元，释放氮膦配体；通过不对称过渡金属催化偶联反应，由于生成的配体本身具有良好的配位能力，在反应中会使过渡金属催化剂中毒，因而成功案例罕见。
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的氮膦双齿配体及其制备方法，采用季鏻盐、苯并噁唑/苯并噻唑为原料，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轴手性和P-中心手性的氮膦双齿配体，实现了碳膦键的不对称反应。
为了实现上述目的，本发明提供了一种兼有轴手性和膦中心的氮膦双齿配体，所述兼有轴手性和膦中心的氮膦双齿配体的结构式为：
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；
R3为含取代基团的苯并噁唑或苯并噻唑。
优选地，R1和R2分别为甲基、乙基、异丙基、异丁基、叔丁基、环戊基、环己基、环庚基、叔丁基亚甲基、3-戊基、环氧己基或3-甲氧基丙基；
优选地，R3的结构式为：
本发明还提供了一种兼有轴手性和膦中心的氮膦双齿配体的制备方法，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、苯并噁唑/苯并噻唑和溶剂混合反应；
(2)加入硫，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的氮膦双齿配体；其中，反应路线式如下：
优选地，在步骤(1)中，混合反应的条件包括温度为40-50℃；和/或
时间为30-42h；
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，季鏻盐与苯并噁唑/苯并噻唑中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、异丁基、叔丁基、环戊基、环己基、环庚基、叔丁基亚甲基、3-戊基、环氧己基或3-甲氧基丙基。
优选地，苯并噁唑或苯并噻唑为包含取代基的苯并噁唑或苯并噻唑。
优选地，催化剂为烯丙基氯化钯二聚体、醋酸钯、三氟乙酸钯、氯化钯或Pd2(dba)3中的一种。
优选地，碱为碱为碳酸盐、磷酸盐、三乙胺或1,8-二氮杂双环[5.4.0]十一碳-7-烯；
优选地，碱为碳酸铯或磷酸钾；
优选地，添加剂为氯化亚铜、溴化亚铜或碘化亚铜中的一种。
优选地，溶剂为叔丁基甲基醚、2-甲基四氢呋喃、THF或DME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：苯并噁唑或苯并噻唑：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，实现了季鏻盐和苯并噁唑或苯并噻唑的偶联反应，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氮膦双齿配体的产率为45-98％，最高>99％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；
图19是本发明中实施例19的反应路线图；
图20是本发明中实施例20的反应路线图；
图21是本发明中实施例21的反应路线图；
图22是本发明中实施例22的反应路线图；
图23是本发明中实施例23的反应路线图；
图24是本发明中实施例24的反应路线图；
图25是本发明中实施例25的反应路线图；
图26是本发明中实施例26的反应路线图；
图27是本发明中实施例27的反应路线图；
图28是本发明中实施例28的反应路线图；
图29是本发明中实施例29的反应路线图；
图30是本发明中实施例30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醋酸钯、手性配体、溴化亚铜、季鏻盐、叔丁基甲基醚以及苯并噁唑或苯并噻唑，最后在45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，获得手性氮膦双齿配体。反应路线图如图1所示。
产物表征数据如下：White solid,Rf＝0.53(petroleum ether/ethyl acetate＝5:1),79％yield,95％ee,M.p.124℃.1H NMR(600MHz,Chloroform-d)δ8.63(d,J＝8.7Hz,1H),8.52(dd,J＝11.5,9.4Hz,1H),8.16(d,J＝8.7Hz,1H),8.11(d,J＝8.7Hz,1H),7.96(d,J＝8.0Hz,2H),7.56(d,J＝7.1Hz,2H),7.50(t,J＝7.0Hz,1H),7.38(t,J＝7.5Hz,1H),7.28-7.15(m,4H),7.12(t,J＝7.6Hz,1H),6.85(d,J＝8.0Hz,1H),0.85(d,J＝16.5Hz,9H),0.72(d,J＝12.7Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.6,150.4,141.3,139.5(d,J＝4.9Hz),137.0(d,J＝4.3Hz),135.1,134.1,133.92,133.89(d,J＝10.1Hz),130.7(d,J＝12.4Hz),129.7,129.0(d,J＝68.2Hz),128.42,128.39,128.2,127.9,127.8,127.58,127.55(d,J＝9.7Hz),127.3,127.1,126.0,125.3,124.9,124.7,120.1,110.2,36.1(d,J＝49.8Hz),24.8,15.0(d,J＝52.1Hz).31P NMR(243MHz,Chloroform-d)δ61.11.Theenantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.51min,t(major)＝8.33min.[α]D 25＝+76.0(c＝0.658,CH2Cl2).HRMS(ESI)calcd for:C32H29NOPS+[M+H]+506.1712；found:506.1712.
实施例2
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图2所示。
产物表征数据如下：Yellow solid,Rf＝0.39(petroleum ether/ethyl acetate＝5:1),79％yield,93％ee,M.p.106-107℃.1H NMR(600MHz,Chloroform-d)δ8.62(d,J＝8.6Hz,1H),8.52(dd,J＝11.3,9.2Hz,1H),8.14(d,J＝8.7Hz,1H),8.11(d,J＝8.8Hz,1H),7.97(t,J＝8.4Hz,2H),7.56(t,J＝7.4Hz,1H),7.52(t,J＝7.3Hz,1H),7.43(d,J＝8.0Hz,1H),7.39(t,J＝7.6Hz,1H),7.24-7.18(m,2H),7.17(d,J＝8.2Hz,1H),7.01(d,J＝7.9Hz,1H),6.61(s,1H),2.32(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.7Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.2,150.8,139.6(d,J＝4.6Hz),139.2,136.7(d,J＝2.7Hz),136.0,135.2,134.1,134.00(d,J＝2.7Hz),133.97(d,J＝6.2Hz),130.8(d,J＝12.6Hz),129.7,129.1(d,J＝67.9Hz),128.42,128.36,128.2,127.91,127.86,127.6,127.53,127.46,127.1,126.1,126.0,125.1,119.5,110.3,36.1(d,J＝49.8Hz),24.9,21.8,15.1(d,J＝51.9Hz).31P NMR(243MHz,Chloroform-d)δ61.20.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.61min,t(major)＝7.98min.[α]D 25＝+71.8(c＝0.265,CH2Cl2).HRMS(ESI)calcd for:C33H31NOPS+[M+H]+520.1858；found:520.1861.
实施例3
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图3所示。
产物表征数据如下：White solid,Rf＝0.54(petroleum ether/ethyl acetate＝5:1),67％yield,91％ee,M.p.120-121℃.1H NMR(600MHz,Chloroform-d)δ8.62(d,J＝8.7Hz,1H),8.52(dd,J＝11.7,9.2Hz,1H),8.15(d,J＝8.7Hz,1H),8.09(d,J＝8.7Hz,1H),8.00-7.86(m,2H),7.56(t,J＝7.1Hz,1H),7.48(t,J＝7.1Hz,1H),7.40(t,J＝7.3Hz,1H),7.30(d,J＝8.4Hz,1H),7.21-7.09(m,2H),7.02(t,J＝7.7Hz,1H),6.96(d,J＝7.1Hz,1H),6.80(d,J＝7.9Hz,1H),2.30(s,3H),0.87(d,J＝16.5Hz,9H),0.72(d,J＝12.8Hz,3H).13CNMR(151MHz,Chloroform-d)δ161.3,150.1,140.9,139.8(d,J＝4.7Hz),137.1(d,J＝3.7Hz),135.3,134.12(d,J＝2.1Hz),134.09,134.0(d,J＝10.6Hz),130.9(d,J＝12.5Hz),130.8,129.6,128.9(d,J＝67.8Hz),128.34,128.30,128.2,127.8,127.7,127.4(d,J＝12.2Hz),127.3,127.0,125.8,125.1,125.03,124.97,107.5,36.2(d,J＝49.8Hz),25.0(d,J＝2.1Hz),16.0,15.2(d,J＝52.2Hz).31P NMR(243MHz,Chloroform-d)δ61.09.Theenantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.62min,t(major)＝5.06min.[α]D 25＝+80.5(c＝0.605,CH2Cl2).HRMS(ESI)calcd for:C33H31NOPS+[M+H]+520.1858；found:520.1865.
实施例4
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图4所示。
产物表征数据如下：White solid,Rf＝0.53(petroleum ether/ethyl acetate＝5:1),78％yield,91％ee,M.p.126-127℃.1H NMR(600MHz,Chloroform-d)δ8.61(d,J＝8.7Hz,1H),8.52(dd,J＝11.9,9.0Hz,1H),8.15(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.96(d,J＝8.1Hz,2H),7.56(t,J＝7.4Hz,1H),7.50(t,J＝7.2Hz,1H),7.38(t,J＝7.6Hz,1H),7.33(s,1H),7.25-7.12(m,3H),6.93(d,J＝8.2Hz,1H),6.73(d,J＝8.3Hz,1H),2.35(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.7,148.7,141.5,139.5(d,J＝4.6Hz),136.8(d,J＝3.1Hz),135.2,134.5,134.1,134.0,133.9(d,J＝7.4Hz),130.8(d,J＝12.3Hz),129.7,129.0(d,J＝68.8Hz),128.39,128.37,128.2,127.9,127.8,127.6,127.5,127.4,127.1,126.5,126.0,125.0,120.0,109.6,36.1(d,J＝49.9Hz),24.9,21.5,15.0(d,J＝51.6Hz).31P NMR(243MHz,Chloroform-d)δ61.18.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.46min,t(major)＝10.71min.[α]D 25＝+76.7(c＝0.482,CH2Cl2).HRMS(ESI)calcd for:C33H31NOPS+[M+H]+520.1858；found:520.1863.
实施例5
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图5所示。
产物表征数据如下：Yellow solid,Rf＝0.38(petroleum ether/ethyl acetate＝5:1),85％yield,95％ee,M.p.128℃.1H NMR(600MHz,Chloroform-d)δ8.60(d,J＝8.7Hz,1H),8.52(dd,J＝11.9,9.0Hz,1H),8.15(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.96(d,J＝8.1Hz,2H),7.55(t,J＝7.3Hz,1H),7.51(t,J＝7.0Hz,1H),7.38(t,J＝7.4Hz,1H),7.20(t,J＝7.9Hz,2H),7.17(d,J＝8.4Hz,1H),7.02(s,1H),6.78-6.66(m,2H),3.76(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ163.3,157.5,145.2,142.2,139.5(d,J＝4.7Hz),136.8(d,J＝3.5Hz),135.2,134.1,134.0(d,J＝1.7Hz),133.9(d,J＝6.3Hz),130.8(d,J＝12.4Hz),129.7,129.0(d,J＝67.3Hz),128.40,128.38,128.2,127.9,127.8,127.6,127.5(d,J＝12.2Hz),127.4,127.1,125.9,125.0,114.3,110.4,102.7,55.9,36.1(d,J＝49.8Hz),24.9(d,J＝2.1Hz),15.1(d,J＝52.1Hz).31P NMR(243MHz,Chloroform-d)δ61.15.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.85min,t(major)＝11.06min.[α]D 25＝+95.9(c＝0.658,CH2Cl2).HRMS(ESI)calcd for:C33H31NO2PS+[M+H]+536.1808；found:536.1816.
实施例6
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图6所示。
产物表征数据如下：Yellow solid,Rf＝0.38(petroleum ether/ethyl acetate＝5:1),85％yield,95％ee,M.p.128℃.1H NMR(600MHz,Chloroform-d)δ8.60(d,J＝8.7Hz,1H),8.52(dd,J＝11.9,9.0Hz,1H),8.15(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.96(d,J＝8.1Hz,2H),7.55(t,J＝7.3Hz,1H),7.51(t,J＝7.0Hz,1H),7.38(t,J＝7.4Hz,1H),7.20(t,J＝7.9Hz,2H),7.17(d,J＝8.4Hz,1H),7.02(s,1H),6.78-6.66(m,2H),3.76(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ163.3,157.5,145.2,142.2,139.5(d,J＝4.7Hz),136.8(d,J＝3.5Hz),135.2,134.1,134.0(d,J＝1.7Hz),133.9(d,J＝6.3Hz),130.8(d,J＝12.4Hz),129.7,129.0(d,J＝67.3Hz),128.40,128.38,128.2,127.9,127.8,127.6,127.5(d,J＝12.2Hz),127.4,127.1,125.9,125.0,114.3,110.4,102.7,55.9,36.1(d,J＝49.8Hz),24.9(d,J＝2.1Hz),15.1(d,J＝52.1Hz).31P NMR(243MHz,Chloroform-d)δ61.15.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.85min,t(major)＝11.06min.[α]D 25＝+95.9(c＝0.658,CH2Cl2).HRMS(ESI)calcd for:C33H31NO2PS+[M+H]+536.1808；found:536.1816.
实施例7
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图7所示。
产物表征数据如下：Yellow solid,Rf＝0.39(petroleum ether/ethyl acetate＝5:1),70％yield,97％ee,M.p.119℃.1H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.8,9.0Hz,1H),8.16(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.97(t,J＝7.0Hz,2H),7.66(s,1H),7.58(t,J＝7.4Hz,1H),7.51(t,J＝7.3Hz,1H),7.39(t,J＝7.6Hz,1H),7.28-7.17(m,3H),7.14(d,J＝8.5Hz,1H),6.79(d,J＝8.6Hz,1H),0.86(d,J＝16.5Hz,9H),0.72(d,J＝12.7Hz,3H).13C NMR(151MHz,Chloroform-d)δ163.7,149.4,143.0,139.3(d,J＝4.9Hz),137.5(d,J＝3.0Hz),135.1,134.3,133.9,133.8(d,J＝10.3Hz),130.7(d,J＝12.2Hz),129.8,129.0(d,J＝68.3Hz),128.7,128.5,128.3,128.2,127.94,127.89,127.7,127.6,127.2,127.1,125.8,124.4,123.1,117.4,111.4,36.2(d,J＝49.8Hz),24.9,15.2(d,J＝51.8Hz).31P NMR(243MHz,Chloroform-d)δ60.94.Theenantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.88min,t(major)＝10.51min.[α]D 25＝+76.7(c＝0.569,CH2Cl2).HRMS(ESI)calcd for:C32H28NOPS79Br+[M+H]+584.0807；found:584.0808.
实施例8
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图8所示。
产物表征数据如下：White solid,Rf＝0.56(petroleum ether/ethyl acetate＝5:1),72％yield,96％ee,M.p.125-126℃.1H NMR(600MHz,Chloroform-d)δ8.58(d,J＝8.7Hz,1H),8.50(dd,J＝11.9,9.0Hz,1H),8.16(d,J＝8.7Hz,1H),8.11(d,J＝8.8Hz,1H),8.03-7.88(m,2H),7.57(t,J＝7.0Hz,1H),7.54-7.47(m,2H),7.39(t,J＝7.2Hz,1H),7.25-7.17(m,2H),7.14(d,J＝8.4Hz,1H),7.10(dd,J＝8.6,1.9Hz,1H),6.83(d,J＝8.6Hz,1H),0.86(d,J＝16.5Hz,9H),0.72(d,J＝12.7Hz,3H).13C NMR(151MHz,Chloroform-d)δ163.9,148.9,142.5,139.3(d,J＝5.0Hz),137.5(d,J＝2.0Hz),135.1,134.3,133.9,133.8(d,J＝10.8Hz),130.7(d,J＝12.4Hz),130.1,129.8,129.0(d,J＝66.2Hz),128.6,128.5,128.2,127.92,127.88,127.7,127.6,127.2,127.1,125.8,125.6,124.4,120.0,110.9,36.1(d,J＝49.9Hz),24.9,15.1(d,J＝52.3Hz).31P NMR(243MHz,Chloroform-d)δ60.96.Theenantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.66min,t(major)＝9.70min.[α]D 25＝+41.7(c＝0.895,CH2Cl2).HRMS(ESI)calcd for:C32H28NOPS35Cl+[M+H]+540.1312；found:540.1321.
实施例9
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图9所示。
产物表征数据如下：White solid,Rf＝0.37(petroleum ether/ethyl acetate＝5:1),84％yield,94％ee,M.p.128-129℃.1H NMR(600MHz,Chloroform-d)δ8.63(d,J＝8.7Hz,1H),8.51(dd,J＝11.7,9.1Hz,1H),8.18(d,J＝8.7Hz,1H),8.14(d,J＝8.7Hz,1H),7.99(t,J＝8.8Hz,2H),7.94(d,J＝8.3Hz,1H),7.64-7.46(m,4H),7.40(t,J＝7.4Hz,1H),7.25-7.18(m,2H),7.15(d,J＝8.5Hz,1H),3.88(s,3H),0.85(d,J＝16.5Hz,9H),0.74(d,J＝12.7Hz,3H).13CNMR(151MHz,Chloroform-d)δ166.5,165.3,150.1,145.2,139.2(d,J＝4.6Hz),137.8(d,J＝3.3Hz),135.1,134.4,133.9(d,J＝2.0Hz),133.8(d,J＝10.3Hz),130.7(d,J＝12.3Hz),129.9,129.1(d,J＝67.4Hz),128.8,128.5,128.2,128.1,127.9,127.83(d,J＝12.1Hz),127.77,127.3,127.2,126.4,126.0,124.4,119.7,111.9,52.4,36.1(d,J＝49.8Hz),24.9,15.2(d,J＝52.4Hz).31P NMR(243MHz,Chloroform-d)δ60.83.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.88min,t(major)＝8.33min.[α]D 25＝+78.4(c＝0.725,CH2Cl2).HRMS(ESI)calcd for:C34H31NO3PS+[M+H]+564.1757；found:564.1760.
实施例10
按照实施例1的方法进行，不同的是，苯并噁唑选择不同。反应路线图如图10所示。
产物表征数据如下：White solid,Rf＝0.37(petroleum ether/ethyl acetate＝5:1),84％yield,94％ee,M.p.128-129℃.1H NMR(600MHz,Chloroform-d)δ8.63(d,J＝8.7Hz,1H),8.51(dd,J＝11.7,9.1Hz,1H),8.18(d,J＝8.7Hz,1H),8.14(d,J＝8.7Hz,1H),7.99(t,J＝8.8Hz,2H),7.94(d,J＝8.3Hz,1H),7.64-7.46(m,4H),7.40(t,J＝7.4Hz,1H),7.25-7.18(m,2H),7.15(d,J＝8.5Hz,1H),3.88(s,3H),0.85(d,J＝16.5Hz,9H),0.74(d,J＝12.7Hz,3H).13CNMR(151MHz,Chloroform-d)δ166.5,165.3,150.1,145.2,139.2(d,J＝4.6Hz),137.8(d,J＝3.3Hz),135.1,134.4,133.9(d,J＝2.0Hz),133.8(d,J＝10.3Hz),130.7(d,J＝12.3Hz),129.9,129.1(d,J＝67.4Hz),128.8,128.5,128.2,128.1,127.9,127.83(d,J＝12.1Hz),127.77,127.3,127.2,126.4,126.0,124.4,119.7,111.9,52.4,36.1(d,J＝49.8Hz),24.9,15.2(d,J＝52.4Hz).31P NMR(243MHz,Chloroform-d)δ60.83.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.88min,t(major)＝8.33min.[α]D 25＝+78.4(c＝0.725,CH2Cl2).HRMS(ESI)calcd for:C34H31NO3PS+[M+H]+564.1757；found:564.1760.
实施例11
按照实施例1的方法进行，不同的是，苯并噻唑选择不同。反应路线图如图11所示。
产物表征数据如下：White solid,Rf＝0.54(petroleum ether/ethyl acetate＝5:1),57％yield,94％ee,M.p.128℃.1H NMR(600MHz,Chloroform-d)δ8.61(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.1Hz,1H),8.24-8.09(m,2H),8.02(d,J＝8.1Hz,1H),7.97(d,J＝7.9Hz,2H),7.59(t,J＝7.3Hz,1H),7.57-7.49(m,2H),7.43-7.33(m,2H),7.29(t,J＝7.5Hz,1H),7.23(t,J＝7.5Hz,1H),7.20(d,J＝8.5Hz,1H),7.17(d,J＝8.4Hz,1H),0.82(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ166.3,152.2,137.9(d,J＝4.4Hz),136.2,135.9(d,J＝2.1Hz),134.9,134.4(d,J＝10.0Hz),134.1,133.7,131.8,131.7(d,J＝12.4Hz),131.2(d,J＝66.4Hz),129.7,128.5,128.41,128.36,128.23,128.2,128.0,127.71,127.66,127.3,127.1,126.3,125.3,123.2,121.3,36.4(d,J＝49.5Hz),25.0,15.0(d,J＝52.6Hz).31P NMR(243MHz,Chloroform-d)δ61.49.Theenantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.78min,t(major)＝13.90min.[α]D 25＝+69.5(c＝0.380,CH2Cl2).HRMS(ESI)calcd for:C32H29NPS2 +[M+H]+522.1474；found:522.1477.
实施例12
按照实施例1的方法进行，不同的是，苯并噻唑选择不同。反应路线图如图12所示。
产物表征数据如下：White solid,Rf＝0.61(petroleum ether/ethyl acetate＝5:1),50％yield,96％ee,M.p.140℃.1H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.0Hz,1H),8.15(d,J＝8.0Hz,2H),8.10(s,1H),8.02(d,J＝8.2Hz,1H),7.97(d,J＝8.1Hz,1H),7.63-7.49(m,2H),7.43-7.36(m,2H),7.34(d,J＝8.5Hz,1H),7.29(t,J＝7.6Hz,1H),7.17(d,J＝8.5Hz,2H),0.84(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ168.0,153.4,137.7(d,J＝4.9Hz),136.2(d,J＝2.7Hz),135.0,134.8,134.3(d,J＝10.0Hz),134.1,133.9,131.8,131.7,131.4,131.3(d,J＝66.6Hz),129.8,128.54(d,J＝12.1Hz),128.46,128.42,128.35,128.3,128.2,127.8,127.7,127.2,127.0,126.0,122.4,119.9,36.5(d,J＝49.4Hz),25.0,15.1(d,J＝52.6Hz).31P NMR(243MHz,Chloroform-d)δ61.37.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝7.16min,t(major)＝13.87min.[α]D 25＝+88.9(c＝0.312,CH2Cl2).HRMS(ESI)calcd for:C32H28NPS2 79Br+[M+H]+600.0579；found:600.0591.
实施例13
按照实施例1的方法进行，不同的是，苯并噻唑选择不同。反应路线图如图13所示。
产物表征数据如下：White solid,Rf＝0.61(petroleum ether/ethyl acetate＝5:1),50％yield,96％ee,M.p.140℃.1H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.0Hz,1H),8.15(d,J＝8.0Hz,2H),8.10(s,1H),8.02(d,J＝8.2Hz,1H),7.97(d,J＝8.1Hz,1H),7.63-7.49(m,2H),7.43-7.36(m,2H),7.34(d,J＝8.5Hz,1H),7.29(t,J＝7.6Hz,1H),7.17(d,J＝8.5Hz,2H),0.84(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ168.0,153.4,137.7(d,J＝4.9Hz),136.2(d,J＝2.7Hz),135.0,134.8,134.3(d,J＝10.0Hz),134.1,133.9,131.8,131.7,131.4,131.3(d,J＝66.6Hz),129.8,128.54(d,J＝12.1Hz),128.46,128.42,128.35,128.3,128.2,127.8,127.7,127.2,127.0,126.0,122.4,119.9,36.5(d,J＝49.4Hz),25.0,15.1(d,J＝52.6Hz).31P NMR(243MHz,Chloroform-d)δ61.37.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝7.16min,t(major)＝13.87min.[α]D 25＝+88.9(c＝0.312,CH2Cl2).HRMS(ESI)calcd for:C32H28NPS2 79Br+[M+H]+600.0579；found:600.0591.
实施例14
按照实施例1的方法进行，不同的是，苯并噻唑选择不同。反应路线图如图14所示。
产物表征数据如下：White solid,Rf＝0.61(petroleum ether/ethyl acetate＝5:1),50％yield,96％ee,M.p.140℃.1H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.0Hz,1H),8.15(d,J＝8.0Hz,2H),8.10(s,1H),8.02(d,J＝8.2Hz,1H),7.97(d,J＝8.1Hz,1H),7.63-7.49(m,2H),7.43-7.36(m,2H),7.34(d,J＝8.5Hz,1H),7.29(t,J＝7.6Hz,1H),7.17(d,J＝8.5Hz,2H),0.84(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ168.0,153.4,137.7(d,J＝4.9Hz),136.2(d,J＝2.7Hz),135.0,134.8,134.3(d,J＝10.0Hz),134.1,133.9,131.8,131.7,131.4,131.3(d,J＝66.6Hz),129.8,128.54(d,J＝12.1Hz),128.46,128.42,128.35,128.3,128.2,127.8,127.7,127.2,127.0,126.0,122.4,119.9,36.5(d,J＝49.4Hz),25.0,15.1(d,J＝52.6Hz).31P NMR(243MHz,Chloroform-d)δ61.37.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝7.16min,t(major)＝13.87min.[α]D 25＝+88.9(c＝0.312,CH2Cl2).HRMS(ESI)calcd for:C32H28NPS2 79Br+[M+H]+600.0579；found:600.0591.
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：White solid,Rf＝0.65(petroleum ether/ethyl acetate＝5:1),74％yield,98％ee,M.p.91-92℃.1H NMR(600MHz,Chloroform-d)δ8.70(dd,J＝13.8,8.9Hz,1H),8.60(d,J＝8.7Hz,1H),8.23-8.12(m,2H),7.97(d,J＝7.5Hz,2H),7.61-7.53(m,2H),7.51(t,J＝7.3Hz,1H),7.34(t,J＝7.5Hz,1H),7.25-7.17(m,3H),7.17-7.10(m,2H),6.92(d,J＝8.0Hz,1H),1.95-1.82(m,1H),1.46-1.32(m,2H),0.89(d,J＝13.2Hz,3H),0.65(d,J＝6.5Hz,3H),0.40(d,J＝6.5Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,138.9(d,J＝6.4Hz),136.8(d,J＝3.6Hz),134.6,134.3(d,J＝2.0Hz),134.2,133.6(d,J＝10.7Hz),130.2,129.9,129.3(d,J＝13.5Hz),128.5,128.4,128.2,128.07,128.01,127.9,127.8,127.2,127.0,126.0,125.4,125.2,124.7,120.2,110.4,43.4(d,J＝51.7Hz),24.1(d,J＝11.0Hz),24.0(d,J＝3.6Hz),23.9(d,J＝7.8Hz),21.7(d,J＝54.9Hz).31P NMR(243MHz,Chloroform-d)δ43.40.The enantiomeric excesswas determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.80min,t(major)＝7.09min.[α]D 25＝+29.7(c＝0.684,CH2Cl2).HRMS(ESI)calcd for:C32H29NOPS+[M+H]+506.1712；found:506.1709.
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：Yellow solid,Rf＝0.45(petroleum ether/ethyl acetate＝5:1),65％yield,97％ee,M.p.107℃.1H NMR(600MHz,Chloroform-d)δ8.72(dd,J＝13.0,8.9Hz,1H),8.65(d,J＝8.7Hz,1H),8.18(d,J＝8.7Hz,1H),8.15(d,J＝8.7Hz,1H),7.98(t,J＝8.2Hz,2H),7.62-7.54(m,2H),7.51(t,J＝7.3Hz,1H),7.34(t,J＝7.5Hz,1H),7.24-7.17(m,3H),7.17-7.10(m,2H),6.87(d,J＝8.1Hz,1H),1.53-1.37(m,1H),1.33-1.15(m,5H),1.10-0.99(m,2H),0.92-0.82(m,1H),0.82-0.75(m,1H),0.72(d,J＝13.0Hz,3H),-0.35(q,J＝10.3Hz,1H).13C NMR(151MHz,Chloroform-d)δ162.5,150.6,141.4,139.6(d,J＝6.0Hz),136.9(d,J＝3.4Hz),134.8,134.4(d,J＝2.3Hz),134.2,133.7(d,J＝10.4Hz),130.8(d,J＝12.8Hz),129.9,128.4,128.2,128.1,128.0,127.8,127.7(d,J＝12.5Hz),127.5,127.1,126.0,125.5,124.9,124.8,120.2,110.3,40.7(d,J＝52.2Hz),25.9(d,J＝14.2Hz),25.3,25.2(d,J＝1.4Hz),24.8(d,J＝14.3Hz),24.7(d,J＝1.6Hz),17.9(d,J＝54.4Hz).31P NMR(243MHz,Chloroform-d)δ51.73.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.38min,t(major)＝8.04min.[α]D 25＝+43.9(c＝0.645,CH2Cl2).HRMS(ESI)calcd for:C34H31NOPS+[M+H]+532.1858；found:532.1869.
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：Yellow oil,Rf＝0.39(petroleum ether/ethyl acetate＝5:1),69％yield,97％ee.1H NMR(600MHz,Chloroform-d)δ8.69(dd,J＝13.5,8.9Hz,1H),8.61(d,J＝8.7Hz,1H),8.19(d,J＝8.9Hz,1H),8.16(d,J＝9.0Hz,1H),7.98(t,J＝9.3Hz,2H),7.58(t,J＝7.3Hz,1H),7.54(d,J＝7.8Hz,1H),7.50(t,J＝7.3Hz,1H),7.36(t,J＝7.4Hz,1H),7.24(d,J＝8.7Hz,1H),7.22-7.16(m,2H),7.14(t,J＝7.6Hz,1H),7.11(d,J＝8.6Hz,1H),6.93(d,J＝8.0Hz,1H),1.58(dq,J＝15.0,7.4Hz,2H),0.89(d,J＝13.2Hz,3H),0.68(dt,J＝20.1,7.4Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.5,150.5,141.4,139.4(d,J＝6.5Hz),136.8(d,J＝3.5Hz),134.5,134.4(d,J＝29.7Hz),133.5(d,J＝10.3Hz),129.9,129.8(d,J＝13.2Hz),128.5,128.4(d,J＝73.4Hz),128.254,128.250(d,J＝12.2Hz),128.12,128.05,128.0,127.9,127.2,126.9,126.0,125.5,125.1,124.7,120.2,110.3,28.7(d,J＝54.5Hz),20.1(d,J＝55.8Hz),6.4(d,J＝4.5Hz).31P NMR(243MHz,Chloroform-d)δ46.76.The enantiomeric excess was determined by DaicelChiralpak AD-H,n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝6.40min,t(major)＝13.96min.[α]D 25＝+44.4(c＝0.342,CH2Cl2).HRMS(ESI)calcd for:C30H25NOPS+[M+H]+478.1389；found:478.1396.
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：Yellow solid,Rf＝0.60(petroleum ether/ethyl acetate＝5:1),70％yield,94％ee,M.p.118℃.1H NMR(600MHz,Chloroform-d)δ8.79(dd,J＝13.3,8.9Hz,1H),8.60(d,J＝8.7Hz,1H),8.18(d,J＝8.7Hz,1H),8.15(d,J＝8.7Hz,1H),7.98(t,J＝7.4Hz,2H),7.59-7.53(m,2H),7.51(t,J＝7.0Hz,1H),7.33(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.17-7.10(m,2H),6.91(d,J＝8.0Hz,1H),1.63-1.46(m,3H),1.46-1.38(m,1H),1.37-1.29(m,1H),1.30-1.22(m,1H),1.21-1.11(m,1H),0.73(d,J＝13.1Hz,3H),0.69-0.59(m,1H),0.52-0.32(m,1H).13C NMR(151MHz,Chloroform-d)δ162.6,150.5,141.3,139.0(d,J＝6.3Hz),137.0(d,J＝3.1Hz),134.8,134.4(d,J＝2.2Hz),134.2,133.6(d,J＝10.6Hz),130.4(d,J＝13.0Hz),129.9,128.8(d,J＝72.5Hz),128.4,128.2,128.1,128.0(d,J＝12.4Hz),127.9,127.8,127.1,126.0,125.5,124.81,124.76,120.1,110.3,41.7(d,J＝55.1Hz),27.0,26.3,25.5(d,J＝11.7Hz),25.2(d,J＝12.3Hz),19.4(d,J＝55.5Hz).31P NMR(243MHz,Chloroform-d)δ51.43.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.84min,t(major)＝7.34min.[α]D 25＝+70.8(c＝0.694,CH2Cl2).HRMS(ESI)calcd for:C33H29NOPS+[M+H]+518.1702；found:518.1702.
实施例19
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19所示。
产物表征数据如下：White solid,Rf＝0.63(petroleum ether/ethyl acetate＝5:1),82％yield,98％ee,M.p.110-111℃.1H NMR(600MHz,Chloroform-d)δ8.61(d,J＝8.7Hz,1H),8.58(dd,J＝12.6,9.0Hz,1H),8.17(d,J＝8.8Hz,1H),8.15(d,J＝8.7Hz,1H),8.02-7.93(m,2H),7.61-7.54(m,2H),7.51(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.28-7.07(m,5H),6.87(d,J＝8.0Hz,1H),1.63-1.54(m,1H),1.47-1.19(m,6H),1.19-1.06(m,3H),1.05-0.92(m,2H),0.74(d,J＝12.7Hz,3H),0.59-0.46(m,1H).13C NMR(151MHz,Chloroform-d)δ162.5,150.6,141.4,139.4(d,J＝5.9Hz),136.9(d,J＝4.2Hz),134.6,134.22,134.18(d,J＝2.1Hz),133.8(d,J＝10.4Hz),129.9,129.8(d,J＝12.5Hz),128.8(d,J＝71.8Hz),128.5,128.2,128.1,128.03,128.01,127.8,127.10,127.05,125.9,125.4,125.0,124.7,120.2,110.3,42.5(d,J＝49.7Hz),27.9,27.5,27.3(d,J＝15.7Hz),27.2,26.8,26.7(d,J＝16.7Hz),17.4(d,J＝53.6Hz).31PNMR(243MHz,Chloroform-d)δ54.04.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.91min,t(major)＝8.41min.[α]D 25＝+62.9(c＝0.735,CH2Cl2).HRMS(ESI)calcd for:C35H33NOPS+[M+H]+546.2015；found:546.2020.
实施例20
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20所示。
产物表征数据如下：White solid,Rf＝0.68(petroleum ether/ethyl acetate＝5:1),77％yield,99％ee,M.p.96-97℃.1H NMR(600MHz,Chloroform-d)δ8.81(dd,J＝14.0,8.9Hz,1H),8.63(d,J＝8.7Hz,1H),8.24-8.12(m,2H),7.98(d,J＝8.1Hz,2H),7.60-7.52(m,2H),7.51(t,J＝7.3Hz,1H),7.33(t,J＝7.5Hz,1H),7.24-7.16(m,3H),7.16-7.10(m,2H),6.93(d,J＝8.0Hz,1H),1.50-1.44(m,2H),0.93(d,J＝13.3Hz,3H),0.73(s,9H).13CNMR(151MHz,Chloroform-d)δ162.4,150.5,141.5,138.3(d,J＝6.2Hz),137.1(d,J＝3.6Hz),134.8,134.3(d,J＝2.1Hz),134.2,133.5(d,J＝10.6Hz),131.4(d,J＝73.3Hz),129.9,129.6(d,J＝13.8Hz),128.5(d,J＝12.7Hz),128.4,128.2,128.1,128.0,127.7,127.1,126.0,125.4,125.2,124.7,120.2,110.4,47.1(d,J＝49.8Hz),32.5(d,J＝4.4Hz),30.9(d,J＝7.2Hz),23.2(d,J＝54.3Hz).31P NMR(243MHz,Chloroform-d)δ41.40.Theenantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.54min,t(major)＝6.53min.[α]D 25＝+51.4(c＝0.564,CH2Cl2).HRMS(ESI)calcd for:C33H31NOPS+[M+H]+520.1858；found:520.1863.
实施例21
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21所示。
产物表征数据如下：White solid,Rf＝0.64(petroleum ether/ethyl acetate＝5:1),91％yield,97％ee,M.p.94-95℃.1H NMR(600MHz,Chloroform-d)δ8.73-8.54(m,2H),8.17(d,J＝8.8Hz,1H),8.15(d,J＝8.9Hz,1H),7.98(t,J＝8.1Hz,2H),7.61-7.48(m,3H),7.35(t,J＝7.5Hz,1H),7.24-7.20(m,2H),7.17(t,J＝8.0Hz,2H),7.13(t,J＝7.6Hz,1H),6.89(d,J＝8.0Hz,1H),1.46-1.04(m,5H),0.77(d,J＝12.8Hz,3H),0.60(t,J＝7.4Hz,3H),0.27(t,J＝7.1Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.4(d,J＝6.0Hz),136.9(d,J＝2.9Hz),134.6,134.2,133.8(d,J＝10.4Hz),130.0(d,J＝12.6Hz),129.8,128.9(d,J＝70.1Hz),128.4,128.14,128.09,128.02,127.99,127.8,127.1,125.9,125.4,125.0,124.7,120.2,110.3,44.1(d,J＝50.6Hz),20.8,20.6,18.4(d,J＝53.3Hz),13.6(d,J＝9.8Hz),11.5(d,J＝13.4Hz).31P NMR(243MHz,Chloroform-d)δ53.68.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.40min,t(major)＝7.08min.[α]D 25＝+22.8(c＝0.763,CH2Cl2).HRMS(ESI)calcd for:C33H31NOPS+[M+H]+520.1858；found:520.1863.
实施例22
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22所示。
产物表征数据如下：White solid,Rf＝0.28(petroleum ether/ethyl acetate＝5:1),51％yield,97％ee,M.p.129℃.1H NMR(600MHz,Chloroform-d)δ8.70(dd,J＝12.7,9.3Hz,1H),8.65(d,J＝8.7Hz,1H),8.20(d,J＝8.6Hz,1H),8.16(d,J＝8.6Hz,1H),8.00(t,J＝9.0Hz,2H),7.59(t,J＝7.3Hz,1H),7.55(d,J＝7.1Hz,2H),7.36(t,J＝7.5Hz,1H),7.29-7.12(m,5H),6.89(d,J＝7.9Hz,1H),3.75-3.56(m,1H),3.35-3.19(m,1H),2.84(t,J＝11.5Hz,1H),1.76-1.54(m,3H),1.40-1.30(m,1H),1.05(d,J＝12.1Hz,1H),0.78-0.66(m,4H).13C NMR(151MHz,Chloroform-d)δ162.5,150.5,141.5,139.8(d,J＝6.4Hz),136.9(d,J＝3.6Hz),134.9,134.5(d,J＝2.1Hz),134.3,133.9(d,J＝10.7Hz),130.7(d,J＝12.9Hz),130.1,128.6,128.32,128.27,128.2,128.1,127.939,127.936(d,J＝12.5Hz),127.3,127.2,126.7,126.0,125.8,125.1,124.8,120.4,110.3,67.1(d,J＝13.9Hz),66.6(d,J＝14.2Hz),38.3(d,J＝54.4Hz),25.0(d,J＝2.9Hz),24.6(d,J＝2.5Hz),17.6(d,J＝55.1Hz).31P NMR(243MHz,Chloroform-d)δ52.0.The enantiomeric excess wasdetermined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.40min,t(major)＝8.95min.[α]D 25＝+55.1(c＝0.266,CH2Cl2).HRMS(ESI)calcd for:C33H29NO2PS+[M+H]+534.1651；found:534.1656.
实施例23
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23所示。
产物表征数据如下：White solid,Rf＝0.57(petroleum ether/ethyl acetate＝5:1),82％yield,96％ee,M.p.93-94℃.1H NMR(600MHz,Chloroform-d)δ8.77(dd,J＝13.2,8.9Hz,1H),8.62(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.8Hz,1H),8.03-7.95(m,2H),7.60-7.53(m,2H),7.51(t,J＝7.4Hz,1H),7.34(t,J＝7.6Hz,1H),7.23-7.17(m,3H),7.16-7.10(m,2H),6.89(d,J＝7.9Hz,1H),1.73-1.60(m,1H),0.81(dd,J＝18.8,6.8Hz,3H),0.76(d,J＝13.0Hz,3H),0.48(dd,J＝18.7,6.8Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.5,150.5,141.3,139.7(d,J＝6.2Hz),136.8(d,J＝3.3Hz),134.7,134.4(d,J＝2.2Hz),134.2,133.6(d,J＝10.1Hz),130.7(d,J＝12.5Hz),129.9,128.4,128.2,128.1,128.03,127.96,127.9,127.8,127.1,127.0,126.0,125.4,125.0,124.7,120.2,110.3,30.9(d,J＝52.9Hz),18.2(d,J＝54.2Hz),15.8,15.4.31PNMR(243MHz,Chloroform-d)δ55.31.The enantiomeric excess was determined by DaicelChiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.88min,t(major)＝7.42min.[α]D 25＝+26.4(c＝0.707,CH2Cl2).HRMS(ESI)calcd for:C31H27NOPS+[M+H]+492.1545；found:492.1558.
实施例24
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24所示。
产物表征数据如下：Yellow oil,Rf＝0.13(petroleum ether/ethyl acetate＝5:1),45％yield,97％ee.1H NMR(600MHz,Chloroform-d)δ8.68(dd,J＝13.6,8.8Hz,1H),8.61(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.9Hz,1H),7.98(t,J＝9.2Hz,2H),7.58(t,J＝7.4Hz,1H),7.54(d,J＝7.7Hz,1H),7.50(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.15(t,J＝7.6Hz,1H),7.10(d,J＝8.5Hz,1H),6.97(d,J＝8.1Hz,1H),2.95(s,3H),2.75-2.64(m,2H),1.79-1.57(m,3H),1.57-1.44(m,1H),0.89(d,J＝13.3Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.3(d,J＝6.5Hz),136.8(d,J＝4.1Hz),134.6,134.5,134.3,133.4(d,J＝11.2Hz),129.9,129.7(d,J＝13.4Hz),128.9,128.5,128.3(d,J＝12.6Hz),128.3,128.1,128.1,127.93,127.88,127.2,126.9,126.0,125.4,125.1,124.7,120.2,110.4,71.9(d,J＝18.0Hz),58.2,32.4(d,J＝54.6Hz),22.7,20.5(d,J＝56.1Hz).31P NMR(243MHz,Chloroform-d)δ44.53.Theenantiomeric excess was determined by Daicel Chiralpak IC,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝14.86min,t(minor)＝17.17min.[α]D 25＝+28.8(c＝0.316,CH2Cl2).HRMS(ESI)calcd for:C32H29NO2PS+[M+H]+522.1651；found:522.1651.
实施例25
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25所示。
产物表征数据如下：Yellow oil,Rf＝0.13(petroleum ether/ethyl acetate＝5:1),45％yield,97％ee.1H NMR(600MHz,Chloroform-d)δ8.68(dd,J＝13.6,8.8Hz,1H),8.61(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.9Hz,1H),7.98(t,J＝9.2Hz,2H),7.58(t,J＝7.4Hz,1H),7.54(d,J＝7.7Hz,1H),7.50(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.15(t,J＝7.6Hz,1H),7.10(d,J＝8.5Hz,1H),6.97(d,J＝8.1Hz,1H),2.95(s,3H),2.75-2.64(m,2H),1.79-1.57(m,3H),1.57-1.44(m,1H),0.89(d,J＝13.3Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.3(d,J＝6.5Hz),136.8(d,J＝4.1Hz),134.6,134.5,134.3,133.4(d,J＝11.2Hz),129.9,129.7(d,J＝13.4Hz),128.9,128.5,128.3(d,J＝12.6Hz),128.3,128.1,128.1,127.93,127.88,127.2,126.9,126.0,125.4,125.1,124.7,120.2,110.4,71.9(d,J＝18.0Hz),58.2,32.4(d,J＝54.6Hz),22.7,20.5(d,J＝56.1Hz).31P NMR(243MHz,Chloroform-d)δ44.53.Theenantiomeric excess was determined by Daicel Chiralpak IC,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝14.86min,t(minor)＝17.17min.[α]D 25＝+28.8(c＝0.316,CH2Cl2).HRMS(ESI)calcd for:C32H29NO2PS+[M+H]+522.1651；found:522.1651.
实施例26
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26所示。
产物表征数据如下：Yellow oil,Rf＝0.13(petroleum ether/ethyl acetate＝5:1),45％yield,97％ee.1H NMR(600MHz,Chloroform-d)δ8.68(dd,J＝13.6,8.8Hz,1H),8.61(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.9Hz,1H),7.98(t,J＝9.2Hz,2H),7.58(t,J＝7.4Hz,1H),7.54(d,J＝7.7Hz,1H),7.50(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.15(t,J＝7.6Hz,1H),7.10(d,J＝8.5Hz,1H),6.97(d,J＝8.1Hz,1H),2.95(s,3H),2.75-2.64(m,2H),1.79-1.57(m,3H),1.57-1.44(m,1H),0.89(d,J＝13.3Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.3(d,J＝6.5Hz),136.8(d,J＝4.1Hz),134.6,134.5,134.3,133.4(d,J＝11.2Hz),129.9,129.7(d,J＝13.4Hz),128.9,128.5,128.3(d,J＝12.6Hz),128.3,128.1,128.1,127.93,127.88,127.2,126.9,126.0,125.4,125.1,124.7,120.2,110.4,71.9(d,J＝18.0Hz),58.2,32.4(d,J＝54.6Hz),22.7,20.5(d,J＝56.1Hz).31P NMR(243MHz,Chloroform-d)δ44.53.Theenantiomeric excess was determined by Daicel Chiralpak IC,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝14.86min,t(minor)＝17.17min.[α]D 25＝+28.8(c＝0.316,CH2Cl2).HRMS(ESI)calcd for:C32H29NO2PS+[M+H]+522.1651；found:522.1651.
实施例27
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27所示。
产物表征数据如下：Yellow solid,Rf＝0.31(petroleum ether/ethyl acetate＝5:1),77％yield,87％ee,M.p.109-110℃.1H NMR(600MHz,Chloroform-d)δ8.60(dd,J＝13.6,8.9Hz,1H),8.55(d,J＝8.7Hz,1H),8.15-8.07(m,2H),7.92-7.81(m,2H),7.55(d,J＝7.7Hz,1H),7.41(d,J＝8.2Hz,1H),7.33(d,J＝8.2Hz,1H),7.20(t,J＝7.4Hz,1H),7.14(t,J＝7.5Hz,1H),7.01(s,1H),6.94(d,J＝8.0Hz,1H),6.85(s,1H),2.95(s,3H),2.72-2.62(m,2H),2.27(s,3H),2.15(s,3H),1.74-1.56(m,2H),1.54-1.41(m,1H),1.24-1.15(m,1H),0.86(d,J＝13.3Hz,3H).13C NMR(151MHz,Chloroform-d)δ162.7,150.5,141.5,138.7(d,J＝6.3Hz),138.0,136.9,136.3(d,J＝4.1Hz),134.8,133.7(d,J＝10.7Hz),132.9(d,J＝2.2Hz),132.7,130.8,130.2,129.6,128.8(d,J＝13.2Hz),128.07,128.05,128.0,127.9,126.8,125.7,125.3,125.1,125.0,124.6,120.1,110.4,72.0(d,J＝18.2Hz),58.2,32.4(d,J＝54.7Hz),22.7,22.11,22.09,20.5(d,J＝56.0Hz).31P NMR(243MHz,Chloroform-d)δ44.63.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.91min,t(major)＝6.40min.[α]D 25＝+79.7(c＝0.409,CH2Cl2).HRMS(ESI)calcd for:C34H33NO2PS+[M+H]+550.1964；found:550.1974.
实施例28
按照实施例1的方法进行，不同的是，季鏻盐和苯并噁唑的选择不同。反应路线图如图28所示。
产物表征数据如下：White solid,Rf＝0.49(petroleum ether/ethyl acetate＝5:1),46％yield,85％ee,M.p.111℃.1H NMR(600MHz,Chloroform-d)δ8.55(d,J＝8.7Hz,1H),8.46(dd,J＝12.0,9.0Hz,1H),8.04(d,J＝8.7Hz,1H),8.00(d,J＝8.7Hz,1H),7.72(s,2H),7.21(d,J＝8.3Hz,1H),7.08(d,J＝8.6Hz,1H),7.07-6.99(m,3H),6.78-6.69(m,2H),3.77(s,3H),2.49(s,3H),2.46(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H).13CNMR(151MHz,Chloroform-d)δ163.6,157.5,145.2,142.3,139.5(d,J＝4.9Hz),138.7,137.8,136.9(d,J＝3.8Hz),134.4,134.3(d,J＝1.9Hz),133.5,132.2(d,J＝10.6Hz),130.9(d,J＝12.5Hz),130.7,129.4,129.0,127.5,127.3,127.2,127.0,126.9,126.0,124.1,114.1,110.4,102.7,56.0,36.1(d,J＝49.9Hz),24.9,21.8,21.7,15.0(d,J＝51.9Hz).31P NMR(243MHz,Chloroform-d)δ60.99.The enantiomeric excess wasdetermined by Daicel Chiralpak IG,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝9.21min,t(minor)＝13.49min.[α]D 25＝+82.7(c＝0.222,CH2Cl2).HRMS(ESI)calcd for:C35H35NO2PS+[M+H]+564.2121；found:564.2122.
实施例29
按照实施例1的方法进行，不同的是，季鏻盐和苯并噁唑的选择不同。反应路线图如图29所示。
产物表征数据如下：White solid,Rf＝0.73(petroleum ether/ethyl acetate＝5:1),98％yield,88％ee,M.p.137-138℃.1H NMR(600MHz,Chloroform-d)δ8.55(d,J＝8.7Hz,1H),8.46(dd,J＝11.9,9.1Hz,1H),8.21(s,1H),8.08(d,J＝8.7Hz,1H),8.03(d,J＝8.8Hz,1H),7.88(d,J＝8.5Hz,1H),7.69(s,2H),7.21(d,J＝8.7Hz,1H),7.15(d,J＝8.7Hz,1H),7.06(d,J＝8.7Hz,1H),7.01(d,J＝8.6Hz,1H),6.92(d,J＝8.5Hz,1H),3.89(s,3H),2.85(d,J＝7.4Hz,2H),2.81(d,J＝7.3Hz,2H),2.71-2.53(m,2H),2.13-1.96(m,4H),1.90-1.79(m,4H),1.79-1.67(m,4H),0.83(d,J＝16.5Hz,9H),0.70(d,J＝12.7Hz,3H).13CNMR(151MHz,Chloroform-d)δ166.6,164.2,153.3,142.3,141.6,141.2,139.2(d,J＝4.9Hz),137.7(d,J＝3.0Hz),134.6,134.2(d,J＝1.6Hz),133.6,132.4(d,J＝10.3Hz),130.8(d,J＝12.5Hz),130.1,129.3,128.8,127.6,127.17(d,J＝23.4Hz),127.16,127.1,126.6,126.5,125.8,123.4,122.1,109.9,52.4,43.1,43.0,36.9,36.8,36.1(d,J＝50.0Hz),28.5,28.39,28.36,24.9,18.49,18.45,15.1(d,J＝51.6Hz).31P NMR(243MHz,Chloroform-d)δ60.85.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.05min,t(major)＝6.58min.[α]D 25＝+103.6(c＝0.635,CH2Cl2).HRMS(ESI)calcd for:C44H46NO3PSNa+[M+Na]+722.2828；found:722.2834.
实施例30
按照实施例1的方法进行，不同的是，季鏻盐和苯并噁唑的选择不同。反应路线图如图30所示。
产物表征数据如下：Colorless oil,Rf＝0.32(petroleum ether/ethyl acetate＝5:1),65％yield,95％ee.1H NMR(600MHz,Chloroform-d)δ8.42(dd,J＝15.9,7.7Hz,1H),8.27(d,J＝7.5Hz,1H),8.25(s,1H),8.01(d,J＝8.5Hz,1H),7.57-7.47(m,3H),7.46(d,J＝7.1Hz,1H),7.31(d,J＝8.5Hz,1H),3.93(s,3H),2.05(s,3H),1.96(s,3H),1.63-1.54(m,1H),1.45(t,J＝14.1Hz,1H),1.30(d,J＝13.2Hz,3H),0.76(s,9H).13C NMR(151MHz,Chloroform-d)δ166.7,163.7,153.3,141.9,139.8(d,J＝6.8Hz),139.6(d,J＝1.9Hz),139.5,137.4(d,J＝9.1Hz),134.0,133.0(d,J＝2.5Hz),132.8(d,J＝13.2Hz),129.0,128.4,128.0(d,J＝13.2Hz),127.3,127.2,126.3,122.4,110.3,52.4,48.0(d,J＝49.8Hz),32.6(d,J＝4.6Hz),31.1,31.0,22.8(d,J＝54.2Hz),20.7(d,J＝50.5Hz).31P NMR(243MHz,Chloroform-d)δ40.44.The enantiomeric excess was determined by DaicelChiralpak IE,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝8.91min,t(minor)＝10.22min.[α]D 25＝-52.0(c＝0.179,CH2Cl2).HRMS(ESI)calcd for:C29H33NO3PS+[M+H]+506.1913；found:506.1915.
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)

1.一种兼有轴手性和膦中心的氮膦双齿配体，其特征在于，所述兼有轴手性和膦中心的氮膦双齿配体的结构式为：
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；
R3为含取代基团的苯并噁唑或苯并噻唑。
2.根据权利要求1所述的兼有轴手性和膦中心的氮膦双齿配体，其中，R1和R2分别为甲基、乙基、异丙基、异丁基、叔丁基、环戊基、环己基、环庚基、叔丁基亚甲基、3-戊基、环氧己基或3-甲氧基丙基；
优选地，R3的结构式为：
3.一种如权利要求1或2所述的兼有轴手性和膦中心的氮膦双齿配体的制备方法，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、苯并噁唑或苯并噻唑和溶剂混合反应；
(2)加入硫，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的氮膦双齿配体；
4.根据权利要求3所述的制备方法，其中，在步骤(1)中，混合反应的条件包括温度为40-50℃；和/或
时间为30-42h；
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，季鏻盐与苯并噁唑/苯并噻唑中R为H、烷基、芳基或带有官能团的烷基；
优选地，R1和R2分别为甲基、乙基、异丙基、异丁基、叔丁基、环戊基、环己基、环庚基、叔丁基亚甲基、3-戊基、环氧己基或3-甲氧基丙基。
6.根据权利要求3所述的制备方法，其中，苯并噁唑或苯并噻唑为包含取代基的苯并噁唑或苯并噻唑。
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、醋酸钯、三氟乙酸钯、氯化钯或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、磷酸盐、三乙胺或1,8-二氮杂双环[5.4.0]十一碳-7-烯；
优选地，碱为碳酸铯；
优选地，添加剂为氯化亚铜、溴化亚铜或碘化亚铜中的一种。
优选地，溶剂为叔丁基甲基醚、2-甲基四氢呋喃、THF或DME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：苯并噁唑或苯并噻唑：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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