一种具有膦手性和轴手性化合物的合成方法

文档序号：1916053 发布日期：2021-12-03 浏览：11次 >En<

阅读说明：本技术 一种具有膦手性和轴手性化合物的合成方法 (Synthesis method of compound with phosphine chirality and axial chirality ) 是由段伟良张朝威于 2021-08-23 设计创作，主要内容包括：本案涉及一种具有膦手性和轴手性化合物的合成方法,在有机溶剂体系中,以二芳基膦氧类化合物和二芳基炔为基本原料,在铱催化剂、氧化剂和手性酰胺配体的作用下合成,反应液经后处理得到膦手性和轴手性的类化合物。本发明反应中使用的二芳基膦氧简单易合成,底物的普适性较好,反应操作简便效率高。配体的合成也比较方便,在反应中配体与金属结合,在底物的膦氧导向下对苯环上的C-H键进行选择性活化,实现了分子间碳氢键活化芳基化反应,以中等以上收率和较高的对映选择性合成具有膦手性和轴手性的化合物。所得的产物可以作为医药中间体或者手性配体；产物进一步还原后得到的三价膦也可以充当手性膦配体。(The scheme relates to a synthesis method of a compound with phosphine chirality and axial chirality, which comprises the steps of taking a diaryl phosphine oxide compound and diaryl alkyne as basic raw materials in an organic solvent system, synthesizing under the action of an iridium catalyst, an oxidant and a chiral amide ligand, and carrying out post-treatment on reaction liquid to obtain the compound with phosphine chirality and axial chirality. The diaryl phosphine oxide used in the reaction is simple and easy to synthesize, the substrate universality is good, and the reaction operation is simple and convenient and has high efficiency. The synthesis of the ligand is also convenient, the ligand is combined with metal in the reaction, and the C-H bond on the benzene ring is selectively activated under the guidance of phosphine oxide of a substrate, so that the intermolecular carbon-hydrogen bond activation arylation reaction is realized, and the compound with phosphine chirality and axial chirality is synthesized with yield more than medium and high enantioselectivity. The obtained product can be used as a medical intermediate or a chiral ligand; the trivalent phosphine obtained after further reduction of the product can also serve as a chiral phosphine ligand.)

一种具有膦手性和轴手性化合物的合成方法

技术领域

本发明涉及手性膦化合物合成技术领域，具体涉及一种具有膦手性和轴手性化合物的合成方法。

背景技术

膦化合物被广泛应用于催化、医药、材料化学等多个领域，尤其是手性膦化合物作为一种性能优良的配体，在作为有机催化剂或与过渡金属共同催化的不对称催化过程中表现出了极好的对映选择性。自从Knowles及其同事在20世纪70年代成功制备了膦手性配体DIPAMP以来，各种各样合成手性膦化合物的方法被开发出来。从最初通过手性拆分或不同的手性辅助基团等方法获得纯的对映异构手性膦化合物，到最近几年通过不对称催化或动力学拆分的方式得到手性膦化合物或手性膦配体。各种例子相继报道，但总体来看，立体选择性更高、底物使用性更广的催化体系并不是很多。

buchwald膦配体过渡金属催化的偶联反应中体现很好的效果，制备具有膦手性和轴手性的buchwald膦配体可以为不对称催化提供机会，但这方面的研究仍鲜有报道。

发明内容

针对现有技术中的不足之处，本发明提供一种自制的手性酰胺类化合物作为配体，与铱催化剂、氧化剂共同作用实现二芳基膦氧化合物不对称碳氢键活化芳基化制得具有膦手性和轴手性的化合物，其具有反应步骤短、原子经济效益好等特点。

为实现上述目的，本发明提供如下技术方案：

一种具有膦手性和轴手性化合物的合成方式，在有机溶剂中，使用式1)所示二芳基膦氧与式2)所示二芳基乙炔在催化剂、氧化剂、配体L的作用下生成具有膦手性和轴手性的式3)所示目标化合物；

其中，R¹所在苯环任选自3-甲基苯基、4-甲基苯基、3-甲氧基苯基、4-甲氧基苯基、4-异丙基苯基、4-叔丁基苯基、3-叔丁基苯基、3-苯基苯基、4-苯基苯基、4-氯苯基、4-氟苯基、4-N,N-二甲基胺基苯基、4-三甲基硅基苯基、2-萘基、3，4-二甲基苯基和3-甲基-4-甲氧基苯基中的一种；

R²所在苯环任选自4-甲基苯基、4-甲氧基苯基、4-氯苯基、4-溴苯基和3,5-二甲基苯基中的一种；

R³任选自叔丁基、环己基、1-金刚烷基和2，4-二甲基戊醇基；

所述配体L是手性酰胺类化合物，其结构通式为R₁选自-H、-CH₃、-CH₂CH(CH₃)₂、-OCH₃、-OCH₂CH₃、-OCH(CH₃)₂、-OCH(CH₃)₃、-OCH(CH₂CH₃)₂、中的一种；表示含芳环的取代基。

进一步优选地，所述配体L的结构式为

进一步优选地，所述有机溶剂为四氢呋喃；所述催化剂为五甲基环戊二烯基铱三乙腈二六氟锑酸；所述氧化剂为碳酸银。

进一步优选地，所述二芳基膦氧、二芳基乙炔、催化剂、氧化剂和配体L的摩尔比是1:3:0.15:1.1:0.3。

进一步优选地，所述合成方法的具体条件是在氮气下将有机溶剂、二芳基膦氧、二芳基乙炔、催化剂、氧化剂和配体L全部添加到密封管中，在90℃下反应12h；通过薄层层析或柱层析提纯法，所用展开剂为乙酸乙酯-石油醚的混合溶剂。

本发明的有益效果是：本发明由二芳基膦氧化合物出发，在铱催化剂和氧化剂以及手性酰胺化合物作为配体的存在下，实现了分子间碳氢键活化芳基化反应，以中等以上收率和较高的对映选择性合成具有膦手性和轴手性的化合物。反应中使用的二芳基膦氧简单易合成，底物的普适性较好，反应操作简便效率高。配体的合成也比较方便，在反应中配体与金属结合，在底物的膦氧导向下对苯环上的C-H键进行选择性活化，进而得到具有手性的化合物。所得的产物可以作为医药中间体或者手性配体；产物进一步还原后得到的三价膦也可以充当手性膦配体。

具体实施方式

下面将结合实施例对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。

此外，下面所描述的本发明不同实施方式中所涉及的技术特征只要彼此之间未构成冲突就可以相互结合。

本发明一种手性酰胺类化合物的合成方法，其合成路线如下所示：

上述反应方程式中涉及到的原料，如无特别说明均为本领域常规选择，部分原料通过自制所得。

一、配体L通过如下合成方法制得。

取100mL圆底烧瓶，将手性酸(10mmol)溶于30mL无水二氯甲烷，加入两滴N,N-二甲基甲酰胺，滴加草酰氯(15mmol)，在40℃下反应3h，然后将挥发物抽干得到酰氯粗品。取100mL圆底烧瓶，将环己基羟胺(10mmol)与三乙胺(15mmol)溶于无水二氯甲烷(20mL)。将上一步制得的酰氯溶于10mL二氯甲烷，再滴加进胺溶液。室温反应3小时。拉干反应溶液，通过薄层色谱法或柱层析法分离得到产物。白色固体，80％收率。

¹H NMR(400MHz,CDCl₃)δ10.07(s,1H),4.71(s,1H),3.79(s,1H),2.80(s,2H),2.00–1.89(m,2H),1.81–1.72(m,2H),1.70–1.18(m,14H),1.10(s,9H).¹³C NMR(101MHz,CDCl₃)δ180.1,178.9,165.9,83.2,64.9,48.5,48.3,42.2,39.5,39.4,35.7,30.5,28.2,25.5,24.7,24.7,23.7,23.6.HRMS(ESI,m/z)calcd for C₂₁H₃₂N₂NaO₄[M+Na]⁺:399.2254,found 397.2261.

二、制备二芳基膦氧化合物，其可通过如下合成方法制得。

制备步骤为：在氮气条件下，在100mL的Schlenk瓶中将芳基溴(11mmol)溶于无水四氢呋喃(15mL)。在-78℃下，将叔丁基锂(22mmol,1.3M的戊烷溶液)滴加到芳基溴溶液中，搅拌反应混合物30min，得到白色悬浮液。然后在-78℃下，将二氯化膦(5mmol)的THF(5.0mL)溶液缓慢加入到芳基锂的溶液中。完全加入后，放置在室温下搅拌反应1h。在0℃将H₂O₂(2.0mL)缓慢滴加入反应液中，搅拌1h，分离有机层，用水、盐水和Na₂SO₃进行洗涤。有机层在MgSO₄上干燥，减压过滤后浓缩。用闪速柱层析法在硅胶上进行纯化。

其中，R¹所在苯环任选自3-甲基苯基、4-甲基苯基、3-甲氧基苯基、4-甲氧基苯基、4-异丙基苯基、4-叔丁基苯基、3-叔丁基苯基、3-苯基苯基、4-苯基苯基、4-氯苯基、4-氟苯基、4-N,N-二甲基胺基苯基、4-三甲基硅基苯基、2-萘基、3，4-二甲基苯基和3-甲基-4-甲氧基苯基中的一种。

R²所在苯环任选自4-甲基苯基、4-甲氧基苯基、4-氯苯基、4-溴苯基和3，5二甲基苯基中的一种。

R³任选自叔丁基、环己基、1-金刚烷基和2，4-二甲基戊醇基中的一种。

当R³为2，4-二甲基戊醇基时，其制备方法如下：

将二苯基次膦酸(5mmol)，TBTU(5mmol)，Et₃N(5.0mmol),2,4-二甲基戊烷-3-醇(10mmol)溶解在DCE中(10mL)，在氮气下室温搅拌12h。通过柱层析法纯化得到产物。以下是本发明中制得的具体结构式的二芳基膦氧化合物，即底物1。

三、所用二芳基炔即底物2均可由试剂公司购买，本发明所用底物2的结构式如下：

以底物1a与底物2a合成过程为例，机理解释如下：

首先，催化剂上的配位乙腈掉落形成两个六氟锑酸根配位的铱络合物，在配体L的作用下形成中间体A，然后金属与底物膦氧的氧进行配位，金属铱在膦氧导向及配体的作用下对底物1a进行C-H键活化得到C。其中配体的氮原子与金属结合，在氧的作用下使之结合的更牢，与氧相连的环己基提供位阻与催化剂的五甲基环戊二烯形成优势构象，进而控制手性。底物2a的炔基插入C-Ir键，形成中间体D。中间体D的Ir-O键断开形成中间体E，金属Ir继续对二芳基炔的一个苯环进行活化形成中间体F，底物2的炔基插入C-Ir键形成中间体G或G^/，接着还原消除生成产物3a和Cp*Ir(I)。通过氧化剂碳酸银将Ir的价态升高，然后与配体L结合生成中间体A，完成催化循环。

实施例1：

从1a出发，与2a反应制得白色固体3a，56％产率，>20:1dr,92％ee。使用DaicelIE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇＝97:3,流速1.0mL/min,30℃,t_r(次)＝20.3min,t_r(主)＝18.3min).[α]_D ²⁵＝-113°(c0.100,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.70–7.60(m,2H),7.53–7.24(m,11H),7.18–7.11(m,2H),7.04–6.96(m,1H),6.93(d,J＝7.6Hz,1H),6.84–6.68(m,5H),6.64–6.52(m,2H),6.45(d,J＝7.6Hz,1H),5.91(t,J＝7.6Hz,1H),1.11(d,J＝14.8Hz,9H).¹³C NMR(101MHz,CDCl₃)δ148.5(d,J＝5.4Hz),140.5,139.7(d,J＝13.3Hz),138.5(d,J＝15.6Hz),137.8,137.4(d,J＝3.3Hz),136.8(d,J＝3.2Hz),135.62(d,J＝10.9Hz),136.6(d,J＝2.2Hz),135.6(d,J＝11.0Hz),133.2,133.1,132.7(d,J＝12.2Hz),132.1,132.0,131.8,131.6,131.2,130.9,130.6,130.28(d,J＝89.9Hz),128.2(d,J＝11.4Hz),128.0(d,J＝90.4Hz),127.3(d,J＝11.5Hz),127.1(d,J＝9.9Hz),126.3(d,J＝9.5Hz),126.2,126.1(d,J＝12.2Hz),126.0(d,J＝14.8Hz),125.3(d,J＝17.9Hz),125.0,36.0(d,J＝71.1Hz),26.0.HRMS(ESI,m/z)calcdfor C₄₄H₃₅Cl₂NaOP[M+Na]⁺:703.1695,found 703.1687.³¹P NMR(162MHz,CDCl₃)δ39.0.

实施例1-2：同实施例1，区别在于将反应中的配体L替换为(制备方法同上)，收率50％，13:1dr，55％ee。相较于实施例同样可以合成具有轴手性和膦手性的化合物，但ee值较低，即该结构的配体在该催化反应中的效率较低。

实施例2：

从1b出发，与2a反应制得白色固体3b，50％产率，>20:1dr,88％ee。使用DaicelAD-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:AD-H,254nm,正己烷/异丙醇99:1,流速1.0mL/min,30℃,t_r(minor)＝10.3min,t_r(major)＝8.5min).[α]_D ²⁵＝-66°(c0.11,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.79–7.71(m,1H),7.66–7.60(m,1H),7.52–7.39(m,4H),7.39–7.30(m,2H),7.30–7.07(m,5H),7.06–6.96(m,3H),6.93(d,J＝7.6Hz,1H),6.82–6.69(m,4H),6.66–6.61(m,1H),6.52(dd,J＝11.0,5.6Hz,2H),5.93(t,J＝7.5Hz,1H),1.11(d,J＝14.8Hz,9H).¹³C NMR(101MHz,CDCl₃)δ164.3(dd,J＝253.3Hz,2.8Hz),163.2(dd,J＝255.7Hz,3.3Hz),149.8(dd,J＝8.0Hz,6.5Hz),140.5,139.8,139.6,138.5,138.3,137.5,136.8,134.2,134.1,134.0,133.7(dd,J＝12.7Hz,8.5Hz),132.0,131.6(d,J＝1.4Hz),131.6,131.3,131.0,130.5,127.9(dd,J＝91.7Hz,3.5Hz),127.2(dd,J＝12.4Hz,8.3Hz),126.3,126.17(d,J＝7.3Hz),125.9(d,J＝10.9Hz),125.7(d,J＝92.2Hz),125.2(d,J＝20.9Hz),125.0(d,J＝3.4Hz),122.7(dd,J＝20.1Hz,11.2Hz),115.1(dd,J＝21.0Hz,11.9Hz),113.4(dd,J＝21.0Hz,12.5Hz),36.0(d,J＝71.5Hz),26.0.HRMS(ESI,m/z)calcdfor C₄₄H₃₅F₂NaOP[M+Na]⁺:671.2286,found 671.2287.³¹P NMR(162MHz,CDCl₃)δ38.8.

实施例3：

从1c出发，与2a反应制得白色固体3c，41％产率，14:1dr,88％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇80:20,流速1.0mL/min,30℃,t_r(次)＝12.5min,t_r(主)＝14.0min).[α]_D ²⁵＝-125°(c 0.090,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.67–7.56(m,3H),7.45–7.34(m,3H),7.34–7.27(m,2H),7.22–7.09(m,4H),6.91(d,J＝8.4Hz,1H),6.83–6.49(m,12H),6.01(t,J＝7.6Hz,1H),2.94(d,J＝26.8Hz,12H),1.12(d,J＝14.0Hz,9H).¹³C NMR(101MHz,CDCl₃)δ151.4(d,J＝2.3Hz),150.4(d,J＝2.3Hz),146.9(d,J＝5.8Hz),141.1,140.7,140.1,139.8(d,J＝2.5Hz),138.4,137.2(d,J＝15.4Hz),133.2(d,J＝9.2Hz),132.77(d,J＝12.5Hz),132.75,132.3,131.9(d,J＝7.0Hz),131.5,131.3,131.2,130.4,128.3,127.2,127.0,126.6,126.1(d,J＝10.0Hz),125.9(d,J＝8.5Hz),125.3,124.9,124.7,124.4(d,J＝1.9Hz),118.9(d,J＝100.2Hz),118.4(d,J＝10.0Hz),116.5(d,J＝99.6Hz),110.9(d,J＝11.5Hz),109.0(d,J＝12.2Hz),40.0,39.9,36.1(d,J＝72.3Hz),26.3.HRMS(ESI,m/z)calcd for C₄₈H₄₇N₂NaOP[M+Na]⁺:721.3318,found 721.3319.³¹P NMR(162MHz,CDCl₃)δ39.9.

实施例4：

从1d出发，与2a反应制得白色固体3d，72％产率，>20:1dr,91％ee。使用DaicelIE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇95:5,流速1.0mL/min,30℃,t_r(次)＝20.2min,t_r(主)＝18.5min).[α]_D ²⁵＝-163°(c 0.140,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.68(dd,J＝10.4,8.0Hz,1H),7.65–7.60(m,1H),7.52–7.40(m,4H),7.35–7.29(m,2H),7.27–7.08(m,8H),6.94(d,J＝7.5Hz,1H),6.82–6.65(m,6H),6.57(d,J＝7.6Hz,1H),6.53–6.47(m,1H),5.84(t,J＝7.6Hz,1H),2.36(d,J＝10.0Hz,6H),1.13(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ146.3(d,J＝5.1Hz),140.9,140.7(d,J＝2.8Hz),140.4,140.1(d,J＝2.7Hz),139.9,138.6(d,J＝2.5Hz),138.5,137.5(d,J＝3.1Hz),136.2(d,J＝10.4Hz),132.6,132.13,132.0(d,J＝8.3Hz),131.9(d,J＝20.2Hz),131.7(d,J＝11.8Hz),131.5,131.4,131.1,130.5,129.2(d,J＝91.1Hz),128.5(d,J＝11.3Hz),127.8,127.2(d,J＝9.0Hz),126.88(d,J＝91.8Hz),126.86,126.4(d,J＝11.8Hz),126.2(d,J＝15.3Hz),126.0,125.4,124.9(d,J＝21.9Hz),124.6(d,J＝8.7Hz),35.9(d,J＝70.6Hz),26.2,21.4,21.2.HRMS(ESI,m/z)calcd for C₄₆H₄₁NaOP[M+Na]⁺:663.2787,found 663.2781.³¹P NMR(162MHz,CDCl₃)δ39.6.

实施例5：

从1e出发，与2a反应制得白色固体3e，72％产率，>20:1dr,90％ee。使用DaicelIE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇95:5,流速1.0mL/min,30℃,t_r(次)＝16.6min,t_r(主)＝18.0min).[α]_D ²⁵＝-95°(c 0.14,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.64–7.57(m,2H),7.51–7.04(m,14H),6.92(d,J＝7.2Hz,1H),6.83–6.63(m,6H),6.55(d,J＝8.0Hz,1H),6.53–6.48(m,1H),5.86(t,J＝7.6Hz,1H),2.43(s,3H),2.30(s,3H),1.13(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ143.3(d,J＝4.8Hz),140.9,140.3,140.0,138.5,138.3(d,J＝2.3Hz),137.7,137.5,137.3(d,J＝10.8Hz),135.4(d,J＝10.8Hz),134.9(d,J＝11.5Hz),132.7(d,J＝8.9Hz),132.6,132.3(d,J＝11.2Hz),132.20,132.1(d,J＝89.4Hz),131.8,131.5,131.4,131.3(d,J＝2.7Hz),131.09,131.0(d,J＝2.9Hz),130.6,129.7(d,J＝89.3Hz),128.8(d,J＝8.4Hz),127.7,127.5(d,J＝11.6Hz),127.2(d,J＝3.3Hz),126.8,126.2,126.0(d,J＝8.8Hz),125.9,125.5,125.0,124.9(d,J＝22.8Hz),124.5(d,J＝14.1Hz),35.9(d,J＝70.0Hz),26.3,21.51,21.46.HRMS(ESI,m/z)calcd for C₄₆H₄₁NaOP[M+Na]⁺:663.2787,found663.2787.³¹P NMR(162MHz,CDCl₃)δ39.8.

实施例6：

从1f出发，与2a反应制得白色固体3f，63％产率，14:1dr,92％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇＝80:20,流速1.0mL/min,30℃,t_r(次)＝10.5min,t_r(主)＝9.5min).[α]_D ²⁵＝-95°(c 0.12,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.74–7.67(m,1H),7.64–7.58(m,1H),7.54–7.49(m,1H),7.48–7.39(m,3H),7.36–7.30(m,2H),7.26–7.08(m,5H),6.95–6.88(m,3H),6.85–6.65(m,8H),6.59(d,J＝7.6Hz,1H),6.57–6.51(m,1H),3.79(d,J＝19.2Hz,6H),1.11(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ161.3(d,J＝2.7Hz),160.3(d,J＝2.7Hz),148.3(d,J＝6.0Hz),140.8,140.2,139.8,138.5,138.3(d,J＝2.1Hz),137.7,137.4,133.6(d,J＝9.4Hz),133.2(d,J＝12.3Hz),132.4,132.1,131.8(d,J＝3.7Hz),131.42,131.36,131.1,130.4,127.7,127.2(d,J＝12.8Hz),126.8,126.2(d,J＝17.4Hz),126.0,125.0(d,J＝28.8Hz),124.8(d,J＝6.6Hz),123.9(d,J＝95.2Hz),121.8(d,J＝95.4Hz),120.0(d,J＝11.3Hz),113.2(d,J＝11.9Hz),112.5(d,J＝2.3Hz),55.33,55.23,36.0(d,J＝71.8Hz),26.2.HRMS(ESI,m/z)calcd for C₄₆H₄₁NaO₃P[M+Na]⁺:695.2686,found 695.2677.³¹P NMR(162MHz,CDCl₃)δ39.3.

实施例7：

从1g出发，与2a反应制得白色固体3g，60％产率，13:1dr,91％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇＝80:20,流速1.0mL/min,30℃,t_r(次)＝7.9min,t_r(主)＝12.9min).[α]_D ²⁵＝-95°(c 0.14,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.66–7.57(m,1H),7.49–7.40(m,2H),7.36–7.28(m,4H),7.26–7.20(m,2H),7.18–6.89(m,8H),6.82–6.62(m,6H),6.54–6.46(m,2H),5.87(t,J＝7.6Hz,1H),3.85(s,3H),3.75(s,3H),1.15(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ159.0(d,J＝13.5Hz),156.7(d,J＝14.5Hz),140.9,140.3,139.9,138.5,138.3(d,J＝4.5Hz),138.0,137.6,136.5(d,J＝11.9Hz),133.2(d,J＝88.3Hz),133.0,131.9,131.8(d,J＝5.2Hz),131.5,131.4,131.1,130.6(d,J＝89.2Hz),130.5,128.9(d,J＝2.8Hz),127.6,127.2(d,J＝6.3Hz),126.9,126.2(d,J＝15.7Hz),126.0(d,J＝5.6Hz),125.6,125.1,124.8(d,J＝7.7Hz),124.6,124.2(d,J＝8.1Hz),117.7(d,J＝12.6Hz),116.93,116.89(d,J＝11.0Hz),115.2(d,J＝2.6Hz),55.32,55.30,36.0(d,J＝70.0Hz),26.2.HRMS(ESI,m/z)calcd for C₄₆H₄₁NaO₃P[M+Na]⁺:695.2686,found695.2690.³¹P NMR(162MHz,CDCl₃)δ39.4.

实施例8：

从1h出发，与2a反应制得白色固体3h，66％产率，15:1dr,92％ee。使用Daicel ID-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:ID-H,254nm,正己烷/异丙醇95:5,流速1.0mL/min,30℃,t_r(次)＝8.1min,t_r(主)＝6.4min).[α]_D ²⁵＝-213°(c 0.200,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.71(dd,J＝10.4,8.0Hz,1H),7.66–7.61(m,1H),7.55–7.41(m,4H),7.37–7.31(m,2H),7.28-7.06(m,8H),6.94(d,J＝7.2Hz,1H),6.83–6.58(m,6H),6.43(td,J＝7.4,1.6Hz,2H),5.74(t,J＝7.4Hz,1H),2.97–2.85(m,J＝6.8Hz,2H),1.30–1.19(m,12H),1.13(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ151.4(d,J＝2.7Hz),150.7(d,J＝2.6Hz),146.3(d,J＝5.1Hz),140.9,140.2,139.9,139.0(d,J＝2.6Hz),138.5,137.6,137.5,133.8(d,J＝10.5Hz),132.6,132.2,132.0(d,J＝6.0Hz),131.9(d,J＝7.8Hz),131.7(d,J＝11.7Hz),131.43,131.37,131.0,130.5,129.4(d,J＝91.1Hz),127.8,127.2(d,J＝6.9Hz),127.0(d,J＝92.0Hz),126.8,126.1(d,J＝20.2Hz),126.0(d,J＝2.1Hz),125.9,125.2(d,J＝21.9Hz),124.8,124.6(d,J＝23.8Hz),123.8(d,J＝12.0Hz),36.3,35.6,33.9(d,J＝21.0Hz),26.1,23.90,23.87,23.7,23.1.HRMS(ESI,m/z)calcd for C₅₀H₄₉NaOP[M+Na]⁺:719.3413,found719.3399.³¹P NMR(162MHz,CDCl₃)δ39.1.

实施例9：

从1i出发，与2a反应制得白色固体3i，75％产率，18:1dr,95％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:ID-H,254nm,正己烷/异丙醇97:3,流速1.0mL/min,30℃,t_r(次)＝12.7min,t_r(主)＝14.8min).[α]_D ²⁵＝-145°(c 0.230,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.83(dd,J＝11.6,2.0Hz,1H),7.67–7.59(m,2H),7.53–7.41(m,4H),7.38-7.21(m,6H),7.19–7.04(m,3H),6.93(d,J＝7.6Hz,1H),6.80–6.68(m,3H),6.68–6.55(m,3H),6.46–6.34(m,2H),5.65(t,J＝7.6Hz,1H),1.39(s,9H),1.27(s,9H),1.12(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ150.3(d,J＝10.2Hz),148.1(d,J＝10.7Hz),143.4(d,J＝5.0Hz),140.9,140.0,139.9,138.6(d,J＝2.6Hz),138.4,137.7,137.4,135.2(d,J＝10.9Hz),131.92,131.90,131.8,131.51(d,J＝88.7Hz),131.46,131.4,131.0,130.3,129.4(d,J＝90.1Hz),129.2(d,J＝7.9Hz),128.8(d,J＝8.5Hz),128.3(d,J＝11.9Hz),127.6,127.5(d,J＝11.4Hz),127.4(d,J＝2.7Hz),127.2(d,J＝4.5Hz),127.0(d,J＝2.7Hz),126.8,126.2,126.0(d,J＝7.3Hz),125.7,125.3,125.0,124.7(d,J＝9.0Hz),124.4,35.74(d,J＝69.5Hz),34.8,34.6,31.32,31.26,26.1.HRMS(ESI,m/z)calcd for C₅₂H₅₃NaOP[M+Na]⁺:747.3726,found 747.3724.³¹P NMR(162MHz,CDCl₃)δ39.3.

实施例10：

从1j出发，与2a反应制得白色固体3j，75％产率，18:1dr,92％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇95:5,流速1.0mL/min,30℃,t_r(次)＝9.5min,t_r(主)＝10.7min).[α]_D ²⁵＝-160°(c 0.160,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.76–7.70(m,1H),7.67–7.62(m,1H),7.54–7.45(m,4H),7.42–7.39(m,1H),7.33(dt,J＝9.6,4.4Hz,5H),7.27–7.22(m,1H),7.13(h,J＝6.8,6.4Hz,3H),6.94(d,J＝7.6Hz,1H),6.80–6.58(m,6H),6.43(s,2H),5.71(t,J＝7.2Hz,1H),1.31(d,J＝12.8Hz,18H),1.14(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ153.5(d,J＝2.7Hz),152.8(d,J＝2.7Hz),145.9(d,J＝4.9Hz),140.9,140.3,139.9,139.2(d,J＝2.4Hz),138.4,137.6,137.3,133.0(d,J＝10.4Hz),132.6,132.0,131.9,131.9,131.8,131.5(d,J＝11.4Hz),131.4,131.1,130.4,129.1(J＝91.1Hz),127.8,127.1(J＝5.7Hz),126.8,126.7(d,J＝89.0Hz),126.1(d,J＝19.2Hz),125.9(d,J＝14.6Hz),125.1(d,J＝2.0Hz),124.7,124.6(J＝3.2Hz),124.3,122.1(J＝11.6Hz),36.2,35.5,34.7(J＝5.7Hz),31.0(J＝21.1Hz),26.1.HRMS(ESI,m/z)calcd for C₅₂H₅₃NaOP[M+Na]⁺:747.3726,found747.3730.³¹P NMR(162MHz,CDCl₃)δ38.9.

实施例11：

从1k出发，与2a反应制得白色固体3k，66％产率，>20:1dr,92％ee。使用DaicelIE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇95:5,流速1.0mL/min,30℃,t_r(次)＝6.7min,t_r(主)＝7.3min).[α]_D ²⁵＝-129°(c 0.230,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.77(dd,J＝10.4,7.6Hz,1H),7.67–7.62(m,1H),7.56–7.44(m,8H),7.37–7.30(m,2H),7.28–7.21(m,1H),7.18–7.08(m,3H),6.93(d,J＝7.6Hz,1H),6.83–6.57(m,6H),6.45–6.35(m,2H),5.66(t,J＝7.6Hz,1H),1.15(d,J＝14.4Hz,9H),0.27(d,J＝7.2Hz,18H).¹³C NMR(101MHz,CDCl₃)δ145.0(d,J＝4.2Hz),143.5(d,J＝1.9Hz),143.0(d,J＝2.3Hz),140.8,140.7(d,J＝10.1Hz),140.2,139.9,138.9(d,J＝2.5Hz),138.5,137.7,137.5,132.67,132.65,132.6,132.8(d,J＝88.6Hz),131.9,131.8(d,J＝6.1Hz),131.39,131.36,131.1(d,J＝2.7Hz),131.0,130.6(d,J＝11.0Hz),130.5,130.04(d,J＝11.3Hz),130.0(d,J＝89.3Hz),127.8,127.2(d,J＝4.6Hz),126.8,126.2,126.0(d,J＝4.1Hz),125.8,125.3,125.1,124.8,124.7,124.5,35.9(d,J＝70.0Hz),26.1,-1.3,-1.4.HRMS(ESI,m/z)calcd for C₅₀H₅₃NaOPSi₂[M+Na]⁺:779.3265,found779.3251.³¹P NMR(162MHz,CDCl₃)δ39.0.

实施例12：

从1l出发，与2a反应制得白色固体3l，92％产率，17:1dr,90％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇85:15,流速1.0mL/min,30℃,t_r(次)＝12.5min,t_r(主)＝16.2min).[α]_D ²⁵＝-388°(c 0.330,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.96–7.88(m,1H),7.69(d,J＝2.4Hz,1H),7.66–7.52(m,10H),7.48–7.30(m,9H),7.25–7.04(m,5H),6.97(d,J＝7.6Hz,1H),6.81–6.57(m,7H),6.47(t,J＝7.6Hz,1H),5.87(t,J＝7.6Hz,1H),1.21(d,J＝14.8Hz,9H).¹³C NMR(101MHz,CDCl₃)δ146.8(d,J＝5.1Hz),143.2(d,J＝2.7Hz),142.3(d,J＝2.8Hz),140.8,140.2,140.1,139.8,139.4,138.5,138.4(d,J＝2.4Hz),137.8(d,J＝10.9Hz),134.1(d,J＝10.6Hz),132.4(d,J＝8.3Hz),132.39,132.3(d,J＝11.5Hz),132.1,131.8(d,J＝2.0Hz),131.5,131.2(d,J＝33.0Hz),130.9(d,J＝89.9Hz),130.5,128.9(d,J＝3.5Hz),128.6(d,J＝90.4Hz),128.1,127.9,127.6,127.2,127.1,126.9,126.4(d,J＝11.2Hz),126.2(d,J＝14.6Hz),126.0(d,J＝5.7Hz),125.6,124.92(d,J＝41.1Hz),124.9(d,J＝6.3Hz),124.1(d,J＝11.9Hz),36.0(d,J＝76.3Hz),26.2.HRMS(ESI,m/z)calcd for C₅₆H₄₅NaOP[M+Na]⁺:787.3100,found 787.3091.³¹P NMR(162MHz,CDCl₃)δ39.5.

实施例13：

从1m出发，与2a反应制得白色固体3m，63％产率，10:1dr,90％ee。使用Daicel IG-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IG-H,254nm,正己烷/异丙醇97:3,流速1.0mL/min,30℃,t_r(次)＝9.3min,t_r(主)＝12.5min).[α]_D ²⁵＝-23°(c 0.15,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ8.08(dd,J＝11.2,2.0Hz,1H),7.86(d,J＝10.8Hz,1H),7.74(d,J＝8.0Hz,1H),7.70–7.30(m,18H),7.28–7.22(m,1H),7.18–7.03(m,3H),6.95(d,J＝7.6Hz,1H),6.79–6.60(m,6H),6.55(d,J＝7.6Hz,1H),6.33(t,J＝7.6Hz,1H),5.77(t,J＝7.6Hz,1H),1.20(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ145.5(d,J＝4.8Hz),140.7,140.5(d,J＝10.7Hz),140.3,139.9(d,J＝16.7Hz),139.8,138.5,138.2(d,J＝11.4Hz),138.0(d,J＝2.3Hz),137.8(d,J＝3.9Hz),136.2(d,J＝10.6Hz),132.6(d,J＝88.2Hz),132.3,132.1,131.8(d,J＝2.3Hz),131.5,131.3,131.0,130.8(d,J＝8.0Hz),130.6(d,J＝8.4Hz),130.4,130.2(d,J＝11.7Hz),129.2(d,J＝2.7Hz),128.9(d,J＝27.7Hz),128.7(d,J＝2.7Hz),128.4(d,J＝11.4Hz),127.7(d,J＝31.9Hz),127.6,127.2,127.0,126.9(d,J＝17.3Hz),126.2(d,J＝16.6Hz),125.95(d,J＝15.5Hz),125.5,125.1,124.8,124.7,36.1(d,J＝69.5Hz),26.3.HRMS(ESI,m/z)calcd for C₅₆H₄₅NaOP[M+Na]⁺:787.3100,found 787.3089.³¹P NMR(162MHz,CDCl₃)δ39.6.

实施例14：

从1n出发，与2a反应制得白色固体3n，56％产率，13:1dr,86％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇85:15,流速1.0mL/min,30℃,t_r(次)＝17.0min,t_r(主)＝11.4min).[α]_D ²⁵＝-186°(c 0.160,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ8.47(d,J＝12.4Hz,1H),8.10(d,J＝12.0Hz,1H),7.99–7.91(m,2H),7.86–7.74(m,4H),7.68–7.43(m,8H),7.35–7.22(m,3H),7.20–7.06(m,3H),6.91(d,J＝7.6Hz,1H),6.76–6.63(m,5H),6.51(t,J＝7.2Hz,2H),6.16–6.2(m,1H),5.33(t,J＝7.6Hz,1H),1.23(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ141.3(d,J＝5.5Hz),140.8,140.1,139.9,138.5,138.2(d,J＝1.6Hz),138.1,137.8,134.4(d,J＝9.8Hz),134.0(d,J＝2.4Hz),133.9(d,J＝7.6Hz),133.4(d,J＝2.3Hz),133.2(d,J＝11.2Hz),133.1,132.3(d,J＝12.2Hz),132.0,131.93,131.88,131.5,131.4,131.1,130.7,130.4(d,J＝2.9Hz),129.5(d,J＝88.9Hz),129.0,128.4,128.3(d,J＝87.6Hz),128.2,127.8,127.7,127.5,127.3,127.2,127.19(d,J＝8.9Hz),126.9,126.7,126.4,126.2,126.1(d,J＝5.3Hz),125.6(d,J＝31.6Hz),124.781(d,J＝60.2Hz),124.779,36.3(d,J＝70.5Hz),26.4.HRMS(ESI,m/z)calcd for C₅₂H₄₁NaOP[M+Na]⁺:735.2787,found 735.2780.³¹P NMR(162MHz,CDCl₃)δ40.3.

实施例15：

从1o出发，与2a反应制得白色固体3o，57％产率，13:1dr,90％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇85:15,流速1.0mL/min,30℃,t_r(次)＝9.9min,t_r(主)＝7.1min).[α]_D ²⁵＝-204°(c 0.160,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.62–7.56(m,1H),7.52(d,J＝10.8Hz,1H),7.50–7.45(m,1H),7.40(d,J＝8.1Hz,1H),7.34–7.27(m,3H),7.24–7.02(m,7H),6.92(d,J＝7.5Hz,1H),6.81–6.61(m,6H),6.56(d,J＝7.7Hz,1H),6.52–6.47(m,1H),5.83(t,J＝7.6Hz,1H),2.33(s,3H),2.27(s,3H),2.25(s,3H),2.20(s,3H),1.13(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ143.5(d,J＝4.7Hz),141.0,140.4,140.0,139.3(d,J＝2.6Hz),138.9(d,J＝3.0Hz),138.5(d,J＝3.6Hz),137.5(d,J＝20.1Hz),136.5(d,J＝10.6Hz),135.9(d,J＝11.1Hz),133.7(d,J＝11.8Hz),133.2(d,J＝8.1Hz),132.9,132.8(d,J＝2.0Hz),132.1,131.9,131.43,131.38,131.1,130.6,129.44(d,J＝90.4Hz),129.40(d,J＝8.3Hz),128.9(d,J＝11.7Hz),127.9,127.2(d,J＝9.1Hz),127.0(d,J＝92.3Hz),126.7,126.2,126.0(d,J＝6.5Hz),125.9,125.4,125.0,124.7(d,J＝15.2Hz),124.4,35.9(d,J＝70.1Hz),26.3,19.84,19.83,19.7,19.6.HRMS(ESI,m/z)calcd for C₄₈H₄₅NaOP[M+Na]⁺:691.3100,found691.3098.³¹P NMR(162MHz,CDCl₃)δ39.7.

实施例16：

从1p出发，与2a反应制得白色固体3p，60％产率，12:1dr,91％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇90:10,流速1.0mL/min,30℃,t_r(次)＝11.8min,t_r(主)＝10.9min).[α]_D ²⁵＝-138°(c 0.100,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.64–7.59(m,1H),7.57–7.49(m,2H),7.39(d,J＝7.6Hz,1H),7.35–7.28(m,3H),7.26–7.09(m,5H),6.91(d,J＝7.6Hz,1H),6.80–6.65(m,8H),6.60–6.49(m,2H),5.92(t,J＝7.6Hz,1H),3.84(s,3H),3.74(s,3H),2.27(s,3H),2.15(s,3H),1.13(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ159.6(d,J＝2.8Hz),158.6(d,J＝2.8Hz),145.9(d,J＝5.6Hz),140.9,140.4,139.9,138.7(d,J＝2.7Hz),138.5,137.5(d,J＝6.5Hz),134.2(d,J＝9.2Hz),133.6(d,J＝12.5Hz),132.7,132.1,131.9(d,J＝3.2Hz),131.5,131.38,131.37,131.1,130.3,127.9,127.3,127.1,126.7,126.1(d,J＝22.0Hz),126.0,125.9(d,J＝11.5Hz),125.5,125.1,124.8(d,J＝9.8Hz),124.57,123.9(d,J＝2.0Hz),123.5(d,J＝105.1Hz),121.09(d,J＝95.0Hz),116.8(d,J＝11.6Hz),109.0(d,J＝12.3Hz),55.3(d,J＝12.3Hz),36.0(d,J＝71.2Hz),26.4,16.3.HRMS(ESI,m/z)calcd forC₄₈H₄₅NaO₃P[M+Na]⁺:723.2999,found 723.2984.³¹P NMR(162MHz,CDCl₃)δ39.6.

实施例17：

从1q出发，与2a反应制得白色固体3q，70％产率，18:1dr,96％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇90:10,流速1.0mL/min,30℃,t_r(次)＝10.9min,t_r(主)＝14.3min).[α]_D ²⁵＝-67°(c 0.19,CH₂Cl₂).

¹H NMR(400MHz,Benzene-d₆)δ7.60(d,J＝8.4Hz,1H),7.49–7.38(m,3H),7.33(t,J＝9.2Hz,1H),7.12–6.93(m,5H),6.92–6.60(m,12H),6.54–6.42(m,3H),6.34(t,J＝7.6Hz,1H),6.19(t,J＝7.2Hz,1H),5.74(t,J＝7.6Hz,1H),1.59–1.47(m,6H),1.40(s,3H),1.14–1.00(m,6H).¹³C NMR(101MHz,Benzene-d₆)δ147.1(d,J＝4.9Hz),141.1,140.7,140.1,138.8,138.6(d,J＝2.5Hz),138.3,138.1,135.4(d,J＝10.2Hz),132.9,132.6,132.28(d,J＝87.3Hz),132.26(d,J＝7.6Hz),132.2(d,J＝6.1Hz),131.9,131.6(d,J＝10.9Hz),131.1,130.9,130.6,130.2(d,J＝2.6Hz),129.9(d,J＝88.2Hz),129.6(d,J＝2.7Hz),128.1,127.8,127.7,127.5,126.7,126.3,126.1,126.0,125.7,125.19(d,J＝12.2Hz),125.15(d,J＝5.3Hz),124.9,124.6,38.9(d,J＝71.4Hz),36.1,35.8,27.7,27.6.HRMS(ESI,m/z)calcd for C₅₀H₄₃NaOP[M+Na]⁺:713.2944,found 713.2940.³¹P NMR(162MHz,Benzene-d₆)δ33.4.

实施例18：

从1r出发，与2a反应，用[Cp*IrCl₂]₂(8mol％)作催化剂，AgNTf₂(32mol％),在60℃制得白色固体3r，60％产率，>20:1dr,76％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇70:30,流速1.0mL/min,30℃,t_r(次)＝17.0min,t_r(主)＝26.9min).[α]_D ²⁵＝-160°(c 0.100,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.90(dd,J＝11.2,7.6Hz,1H),7.49–7.03(m,15H),7.00–6.56(m,10H),6.44(s,1H),1.95–1.85(m,1H),1.67–1.24(m,7H),1.15–0.94(m,3H).¹³C NMR(101MHz,CDCl₃)δ143.4(d,J＝7.2Hz),140.7,139.6(d,J＝4.0Hz),138.5(d,J＝18.8Hz),137.4,137.3(d,J＝3.0Hz),135.0(d,J＝10.1Hz),133.3(d,J＝9.2Hz),132.7(d,J＝2.3Hz),132.2(d,J＝86.3Hz),131.7,131.3,131.26,131.25(d,J＝80.9Hz),131.1(d,J＝4.8Hz),131.0(d,J＝8.6Hz),130.8(d,J＝4.3Hz),130.4(d,J＝2.6Hz),130.0(d,J＝2.6Hz),127.5(d,J＝10.2Hz),127.3(d,J＝11.1Hz),127.2,126.6,126.52,126.50,126.48,126.45,126.2,125.4(d,J＝17.0Hz),125.2(d,J＝10.4Hz),37.4(d,J＝72.2Hz),26.2(d,J＝13.4Hz),25.6,24.8.HRMS(ESI,m/z)calcd for C₄₆H₃₉NaOP[M+Na]⁺:661.2631,found 661.2629.³¹P NMR(162MHz,CDCl₃)δ36.0.

实施例19：

从1s出发，与2b反应制得白色固体3s，69％产率，15:1dr,92％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇85:15,流速1.0mL/min,30℃,t_r(次)＝7.8min,t_r(主)＝10.1min).[α]_D ²⁵＝-145°(c 0.170,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.79–7.72(m,1H),7.52–7.22(m,11H),7.09(ddd,J＝20.8,8.4,2.0Hz,2H),6.97–6.85(m,2H),6.80(d,J＝7.8Hz,1H),6.58(d,J＝8.0Hz,2H),6.55–6.47(m,2H),6.47–6.40(m,1H),6.34(d,J＝7.6Hz,1H),5.57(d,J＝7.6Hz,1H),2.35(s,3H),2.29(s,3H),2.00(s,3H),1.84(s,3H),1.11(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ146.9(d,J＝4.9Hz),138.7,138.1,137.9(d,J＝2.6Hz),137.3(d,J＝13.2Hz),137.1(d,J＝7.1Hz),135.8(d,J＝10.3Hz),135.0,134.3,133.7,133.3,132.213(d,J＝89.2Hz),132.205,131.9,131.84,131.77(d,J＝9.4Hz),131.7,131.2,130.8(d,J＝17.1Hz),130.4,130.34(d,J＝2.7Hz),130.3,129.8(d,J＝2.7Hz),129.7(d,J＝90.0Hz),127.9(d,J＝11.7Hz),127.5(d,J＝11.0Hz),127.4,126.9,126.8,126.7,126.1,125.8,125.3(d,J＝11.7Hz),35.9(d,J＝70.2Hz),26.2,21.8,21.2,21.0,20.9.HRMS(ESI,m/z)calcd for C₄₈H₄₅NaOP[M+Na]⁺:691.3100,found 691.3091.³¹P NMR(162MHz,CDCl₃)δ39.5.

实施例20：

从1t出发，与2c反应制得白色固体3t，59％产率，18:1dr,90％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇85:15,流速1.0mL/min,30℃,t_r(次)＝7.0min,t_r(主)＝5.8min).[α]_D ²⁵＝-218°(c 0.150,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.80(t,J＝11.6Hz,1H),7.69(d,J＝1.6Hz,1H),7.58–7.27(m,13H),6.98(dd,J＝8.4,2.0Hz,1H),6.91(dd,J＝8.4,2.0Hz,1H),6.83–6.74(m,3H),6.47(ddd,J＝14.4,8.0,2.0Hz,2H),6.23(dd,J＝8.4,2.0Hz,1H),5.80(dd,J＝8.4,2.0Hz,1H),1.10(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ145.2(d,J＝4.5Hz),139.4(d,J＝2.4Hz),138.9,138.10,138.0,137.6,136.6,135.9,135.4(d,J＝9.8Hz),133.7,133.2(d,J＝6.3Hz),132.7,132.3,132.2(d,J＝11.1Hz),131.64,131.6(d,J＝89.0Hz),131.56,131.1,131.0(d,J＝2.5Hz),130.9,130.3(d,J＝2.7Hz),130.0(d,J＝9.4Hz),129.5(d,J＝89.3Hz),129.4(d,J＝6.3Hz),129.0,128.7(d,J＝8.9Hz),128.1(d,J＝10.0Hz),126.2(d,J＝11.3Hz),121.0,120.3,119.7(d,J＝37.2Hz),36.5(d,J＝70.5Hz),26.0.HRMS(ESI,m/z)calcd for C₄₄H₃₃Br₄NaOP[M+Na]⁺:946.8895,found 946.8888.³¹P NMR(162MHz,CDCl₃)δ40.0.

实施例21：

从1u出发，与2d反应制得白色固体3u，56％产率，14:1dr,90％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇85:15,流速1.0mL/min,30℃,t_r(次)＝6.5min,t_r(主)＝5.4min).[α]_D ²⁵＝-127°(c 0.130,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.83–7.76(m,1H),7.59–7.27(m,13H),7.15(dd,J＝8.4,2.4Hz,1H),6.89–6.80(m,3H),6.76(dd,J＝8.4,2.0Hz,1H),6.65(dd,J＝8.4,2.4Hz,1H),6.56(dd,J＝8.4,2.4Hz,1H),6.51(dd,J＝8.4,2.0Hz,1H),6.28(dd,J＝8.4,2.0Hz,1H),5.65(dd,J＝8.4,2.4Hz,1H),1.10(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ145.3(d,J＝4.5Hz),139.2(d,J＝2.5Hz),138.5,138.2,137.7,137.2,136.5,136.0,135.4(d,J＝9.8Hz),133.4,132.9(d,J＝5.7Hz),132.7,132.4,132.3,132.1(d,J＝11.1Hz),131.8(d,J＝8.2Hz),131.6(d,J＝9.2Hz),131.49(d,J＝89.2Hz),131.4(d,J＝16.3Hz),131.03,130.98(d,J＝2.7Hz),130.87,130.3(d,J＝2.7Hz),129.36(d,J＝88.3Hz),129.3,128.1(d,J＝2.7Hz),128.0,127.0(d,J＝11.5Hz),126.4,126.3,126.2,126.1,125.4,36.0(d,J＝70.2Hz),26.0.HRMS(ESI,m/z)calcd for C₄₄H₃₃Cl₄NaOP[M+Na]⁺:771.0915,found771.0903.³¹P NMR(162MHz,CDCl₃)δ40.0.

实施例22：

从1v出发，与2e反应制得白色固体3v，49％产率，13:1dr,92％ee。使用Daicel IE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇70:30,流速1.0mL/min,30℃,t_r(次)＝9.8min,t_r(主)＝10.6min).[α]_D ²⁵＝-83°(c 0.04,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.80–7.74(m,1H),7.56–7.28(m,10H),7.01–6.90(m,3H),6.82(dd,J＝8.4,2.8Hz,2H),6.71(dd,J＝8.4,2.8Hz,1H),6.56–6.50(m,2H),6.36(dt,J＝8.8,2.0Hz,2H),6.30(dd,J＝8.4,2.8Hz,1H),6.21(dd,J＝8.4,2.8Hz,1H),5.32(dd,J＝8.4,2.8Hz,1H),3.78(s,3H),3.69(s,3H),3.57(s,3H),3.42(s,3H),1.11(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ157.5,156.8,156.5,156.2,146.9(d,J＝4.7Hz),139.2,138.3(d,J＝2.3Hz),136.6,135.8,135.7(d,J＝10.0Hz),133.6(d,J＝43.2Hz),133.0(d,J＝3.7Hz),132.73,132.70(d,J＝18.4Hz),132.2(d,J＝88.9Hz),132.1(d,J＝25.6Hz),131.9,131.8(d,J＝11.5Hz),131.5,130.5(d,J＝2.6Hz),130.0(d,J＝2.6Hz),129.5(d,J＝89.7Hz),129.1,128.0,127.7(d,J＝10.8Hz),125.4(d,J＝11.6Hz),116.8,112.8(d,J＝33.7Hz),111.75(d,J＝8.7Hz),111.65,110.7,105.56,55.1,55.0,54.8,54.5,35.9(d,J＝70.0Hz),26.1.HRMS(ESI,m/z)calcd for C₄₈H₄₅NaO₅P[M+Na]⁺:755.2897,found755.2893.³¹P NMR(162MHz,CDCl₃)δ39.5.

实施例23：

从1w出发，与2f反应制得白色固体3w，75％产率，13:1dr,92％ee。使用Daicel OZ-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:OZ-H,254nm,正己烷/异丙醇98:2,流速1.0mL/min,30℃,t_r(次)＝4.5min,t_r(主)＝5.5min).[α]_D ²⁵＝105°(c 0.160,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.73(dd,J＝10.4,8.0Hz,1H),7.59–7.52(m,2H),7.50–7.27(m,6H),7.04(d,J＝20.0Hz,2H),6.94(s,1H),6.65(s,2H),6.54(s,1H),6.26(d,J＝17.6Hz,3H),6.13(d,J＝12.8Hz,2H),2.27(s,3H),2.14(s,3H),2.11(s,3H),1.97(s,3H),1.91(s,3H),1.88(s,3H),1.85(s,3H),1.15(s,3H),1.10(d,J＝14.4Hz,9H).¹³C NMR(101MHz,CDCl₃)δ147.5(d,J＝4.8Hz),143.0,140.7,140.4,140.0,137.8,137.5,137.0(d,J＝2.5Hz),135.9,135.8,135.6,135.4,135.3,135.2,134.24,134.19,134.14,133.7,133.0,132.5(d,J＝89.7Hz),132.0,131.9(d,J＝5.8Hz),131.5,130.7(d,J＝2.3Hz),130.2,130.0,129.8(d,J＝2.7Hz),129.6,129.5,129.4(d,J＝90.1Hz),129.1,128.9,128.5,127.8,127.7,126.8,126.4,125.9,125.5,125.2(d,J＝11.8Hz),36.2(d,J＝70.2Hz),25.4,21.3,21.1,21.0,20.80,20.75,20.2.HRMS(ESI,m/z)calcd for C₅₂H₅₃NaOP[M+Na]⁺:747.3726,found 747.3720.³¹P NMR(162MHz,CDCl₃)δ39.7.

实施例24：

从1s出发，与2a反应制得白色固体3s，50％产率，>20:1dr,81％ee。使用DaicelIE-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:IE-H,254nm,正己烷/异丙醇80:20,流速1.0mL/min,30℃,t_r(次)＝10.1min,t_r(主)＝8.9min).[α]_D ²⁵＝-28°(c 0.08,CH₂Cl₂).

¹H NMR(400MHz,CDCl3)δ8.06–7.98(m,1H),7.56–7.51(m,1H),7.47–7.09(m,20H),6.89–6.64(m,9H),6.39(t,J＝7.6Hz,1H),6.22(d,J＝7.6Hz,1H),4.07(dt,J＝9.9,5.2Hz,1H),1.89(dq,J＝13.4,6.7Hz,2H),0.85(d,J＝6.8Hz,3H),0.77(d,J＝6.7Hz,4H),0.68(d,J＝6.8Hz,3H),0.57(d,J＝6.9Hz,3H).¹³C NMR(101MHz,CDCl₃)δ143.20(d,J＝13.2Hz),140.67,139.76(d,J＝8.9Hz),138.57(d,J＝9.2Hz),138.09,136.84(d,J＝3.4Hz),134.19,133.97(d,J＝12.7Hz),133.39(d,J＝11.0Hz),133.21(d,J＝8.8Hz),132.46(d,J＝74.1Hz),131.71,131.61,131.54(d,J＝7.0Hz),131.39,131.26(d,J＝8.2Hz),131.03(d,J＝2.5Hz),130.95,130.62(d,J＝2.5Hz),127.77(d,J＝32.3Hz),127.44(d,J＝7.4Hz),127.28,126.56,126.50,126.42,126.25(d,J＝7.7Hz),125.94,125.36(d,J＝40.4Hz),125.03,86.65(d,J＝7.6Hz),30.72(d,J＝3.0Hz),30.15(d,J＝3.3Hz),29.68,19.84,19.06,17.57.HRMS(ESI,m/z)calcd for C₄₇H₄₃NaO₂P[M+Na]⁺:693.28923,found 693.2899.³¹P NMR(162MHz,CDCl₃)δ39.4.

上述产物进一步还原可得到具有轴手性和膦手性的三价膦化合物，以化合物3l为例，其还原方程式如下：

将重结晶的化合物3l(0.05mmol)加入到反应瓶中，在氮气氛围下，向反应瓶中加入0.25mL乙腈，对体系降温至0℃，加入三氟甲磺酸甲酯(25μl,0.2mmol)，并在0℃下搅拌4h。反应完成后旋转蒸发除去溶剂，再向反应管中加入无水THF(0.5mL)，将混合物冷却至-78℃，加入氢化铝锂溶液(0.13mL,0.3mmol,2.4M in THF)。在-78℃下搅拌反应4h，并用薄层色谱法监测反应过程。将混合物加热至0℃，搅拌30分钟。用iPrOH(0.2mL)淬灭反应，通过硅胶柱层析进行纯化。制得白色固体4l，60％产率，94％ee。使用Daicel OD-H手性柱色谱柱，采用高效液相色谱法测定其ee值。(HPLC:OD-H,254nm,正己烷/异丙醇49:1,流速0.5mL/min,30℃,t_r(次)＝12.3min,t_r(主)＝14.3min).[α]_D ²⁵＝63°(c 0.10,CH₂Cl₂).

¹H NMR(400MHz,CDCl₃)δ7.97(d,J＝8.0Hz,1H),7.60–7.49(m,6H),7.45–7.26(m,10H),7.25–7.20(m,2H),7.20–7.14(m,2H),7.12–7.02(m,4H),7.00–6.94(m,2H),6.94–6.76(m,7H),6.68(d,J＝8.4Hz,1H),6.47(ddd,J＝8.4,6.8,1.2Hz,1H),1.12(d,J＝12.8Hz,9H).¹³C NMR(101MHz,CDCl₃)δ147.0,146.7,141.0,140.8,140.6,140.4,139.8(d,J＝11.8Hz),138.6,138.4,137.71(d,J＝3.7Hz),137.67(d,J＝0.7Hz),136.2(d,J＝21.8Hz),135.77,135.56,135.4(d,J＝17.4Hz),132.8(d,J＝1.6Hz),131.9(d,J＝2.7Hz),131.8,131.6,131.6(d,J＝5.6Hz),131.5,131.3,131.28(d,J＝5.6Hz),131.27,128.7(d,J＝2.5Hz),127.5,127.4(d,J＝9.0Hz),127.2(d,J＝4.9Hz),127.0(d,J＝6.0Hz),126.4(d,J＝2.6Hz),126.26,126.2,126.1,126.0(d,J＝4.8Hz),125.4,125.1(d,J＝7.2Hz),124.9,124.4,30.6(d,J＝16.8Hz),29.1(d,J＝16.0Hz).HRMS(ESI,m/z)calcd for C₅₆H₄₅NaP[M+Na]⁺:771.3151,found 771.3166.³¹P NMR(162MHz,CDCl₃)δ3.7.

对比例1：

当使用酸作为配体时，所得产物收率仅40％，10:1dr，5％ee，与酰胺配体的结果相差较大。

尽管本发明的实施方案已公开如上，但其并不仅仅限于说明书和实施方式中所列运用，它完全可以被适用于各种适合本发明的领域，对于熟悉本领域的人员而言，可容易地实现另外的修改，因此在不背离权利要求及等同范围所限定的一般概念下，本发明并不限于特定的细节和这里示出与描述的示例。

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