CN111018911B - 一种手性1,2-二(杂)芳基乙二胺化合物及其制备方法 - Google Patents

一种手性1,2-二(杂)芳基乙二胺化合物及其制备方法 Download PDF

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CN111018911B
CN111018911B CN201911317692.1A CN201911317692A CN111018911B CN 111018911 B CN111018911 B CN 111018911B CN 201911317692 A CN201911317692 A CN 201911317692A CN 111018911 B CN111018911 B CN 111018911B
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郭其祥
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吴赵伟
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Abstract

本发明公开了一种手性1,2‑二(杂)芳基乙二胺化合物及其制备方法，将亚胺、催化剂与溶剂混合，然后加入胺甲基吡啶和有机碱，继续反应至胺甲基吡啶消失即可，其中亚胺和胺甲基吡啶的摩尔比为1.3:1，本发明提供的制备方法以胺甲基吡啶作为原料，通过手性醛催化胺甲基吡啶与醛亚胺的α‑不对称加成反应，从而构建了含有吡啶结构单元的手性1,2‑二(杂)芳基乙二胺化合物，该方法操作步骤简单，不浪费，采用本发明提供的方法所制备的1,2‑二(杂)芳基乙二胺化合物可作为合成手性的有机催化剂以及具有p53‑MDM2抑制活性的先导化合物DS‑5272和具有钾通道阻断作用的活性分子AZD‑2502等。

Description

一种手性1,2-二(杂)芳基乙二胺化合物及其制备方法
技术领域
本发明涉及具有光学活性的手性化合物技术领域，具体涉及一种手性1,2-二(杂)芳基乙二胺化合物及其制备方法。
背景技术
光学活性的1,2-二芳基乙二胺化合物被广泛的用于合成手性配体(图1a)、手性辅基(图1c)、手性有机催化剂(图1b)以及生物活性分子(图1d)。例如，手性的1,2-苯基乙二胺可以用于合成烯烃复分解反应的Grubbs催化剂、不对称氢化Noyori催化剂以及手性亚胺试剂等。
目前，光学活性的1,2-二芳基乙二胺化合物的合成主要有两个途径：一是通过底物诱导合成，但该方法需要使用化学计量的手性试剂，造成手性试剂的浪费；二是先合成手性的硝基化合物前体，再经过硝基的还原来获得相应的胺基化合物，该方法将增加额外的反应步骤，对于原子经济性和步骤经济性都是不利的。
发明内容
有鉴于此，本发明提供了一种含有吡啶结构单元的手性1,2-二(杂)芳基乙二胺化合物及其制备方法。
其技术方案如下：一种由下列通式表示的化合物：
Figure BDA0002326294240000011
其中，PG为PO(Ph)2、PO(2-MeC6H4)2、PO(3,5-Me2C6H3)2或PO(2,6-Me2C6H3)2；
Ar为Ph、2-FC6H4、2-MeC6H4、3-FC6H4、3-ClC6H4、3-MeC6H4、3-OMeC6H4、4-FC6H4、4-ClC6H4、4-BrC6H4、4-OCF3C6H4、4-MeC6H4、3,4-Cl2C6H3、3,4-Me2C6H3、2-Naphthyl、2-Furyl、2-Thienyl、3-Thienyl、或3-1-(phenylsulfonyl)-1H-indolyl；
R为MeO、Br、Me、Ph或H。
一种上述化合物的制备方法，其关键在于包括按以下步骤进行：将亚胺、催化剂与溶剂混合，然后加入胺甲基吡啶和有机碱，继续反应至胺甲基吡啶消失即可，其中亚胺和胺甲基吡啶的摩尔比为1.3:1；
其中亚胺的结构式为：
Figure BDA0002326294240000021
其中Ar为Ph、2-FC6H4、2-MeC6H4、3-FC6H4、3-ClC6H4、3-MeC6H4、3-OMeC6H4、4-FC6H4、4-ClC6H4、4-BrC6H4、4-OCF3C6H4、4-MeC6H4、3,4-Cl2C6H3、3,4-Me2C6H3、2-Naphthyl、2-Furyl、2-Thienyl、3-Thienyl、或3-1-(phenylsulfonyl)-1H-indolyl；
PG为PO(Ph)2、PO(2-MeC6H4)2、PO(3,5-Me2C6H3)2或PO(2,6-Me2C6H3)2；
胺甲基吡啶的结构式为：
Figure BDA0002326294240000022
其中R为MeO、Br、Me、Ph或H；
催化剂的结构式为：
Figure BDA0002326294240000023
其中R1为H、Me、nPr、TMS、SiPh3、4-PhC6H4、4-ClC6H4、3,5-(MeO)2C6H3、3,5-(CF3)2C6H3、1-Naphthyl、2-Naphthyl、9-Anthryl、9-Phenanthryl、I、Br、Cl、CF3或CN；
X为H、Br或NO2，R2为H、或Br；
R3为Me、Ph、4-TMSC6H4、2-Naphthyl、MeO、tBuCOO、2,6-F2C6H3COO、4-FC6H4COO或Ph2P(O)；
Y为Br或H，R4为Ph、H、2-Naphthyl、4-PhC6H4、4-TMSC6H4、4-tBuC6H4、3,5-(tBu)2C6H3或OH。
与现有技术相比，本发明的有益效果：本发明提供的制备方法以胺甲基吡啶作为原料，通过手性醛催化胺甲基吡啶与醛亚胺的α-不对称加成反应，从而构建了含有吡啶结构单元的手性1,2-二(杂)芳基乙二胺化合物，该方法操作步骤简单，不浪费，采用本发明提供的方法所制备的1,2-二(杂)芳基乙二胺化合物可作为合成手性的有机催化剂以及具有p53-MDM2抑制活性的先导化合物DS-5272和具有钾通道阻断作用的活性分子AZD-2502等。
附图说明
图1为含有手性1,2-二芳基乙二胺结构的配体、催化剂和生物活性分子示的结构式示意图。
具体实施方式
以下结合实施例和实验数据对本发明作进一步说明。
实施例1，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol式(R)-1的催化剂溶于0.5mL的PhCH3，将反应体系冷却至20℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的DBU(1,8-二氮杂二环十一碳-7-烯)，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约12h)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，反应过程如下式：
Figure BDA0002326294240000031
其中催化剂的R1如表1所示，当R1为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表1不同催化剂催化反应
Figure BDA0002326294240000032
注：[b]为分离收率；[c]通过手性HPLC测定。
实施例2，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol式(R)-2的催化剂溶于0.5mL的PhCH3，将反应体系冷却至20℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的DBU(1,8-二氮杂二环十一碳-7-烯)，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约12h)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，式(R)-2结构式如下；
Figure BDA0002326294240000041
其中催化剂的X和R2如表2所示，当R2为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表2不同催化剂催化反应
Figure BDA0002326294240000042
注：[b]为分离收率；[c]通过手性HPLC测定。
实施例3，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol式(S)-2的催化剂溶于0.5mL的PhCH3，将反应体系冷却至20℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约12h)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，式(S)-2结构如下：
Figure BDA0002326294240000043
其中催化剂的R3如表3所示，当R3为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表3不同催化剂催化反应
Figure BDA0002326294240000044
Figure BDA0002326294240000051
注：[b]为分离收率；[c]通过手性HPLC测定。
实施例4，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol式(S)-3的催化剂溶于0.5mL的PhCH3，将反应体系冷却至20℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，式(S)-3结构如下：
Figure BDA0002326294240000052
其中催化剂的Y和R4如表4所示，当R4为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表4不同催化剂催化反应
Figure BDA0002326294240000053
注：[b]为分离收率；[c]通过手性HPLC测定；[e]分别为anti-和syn-产物的对映选择性。
上述实施例1-4中的溶剂还可以是CH2Cl2、CHCl3、THF、CPME、EtOAc、CH3CN、iPrOH、PhCl、Et2O、CCl4、CH2ClCH2Cl、cyclohexane、MeOtBu、PhCl、PhOMe、PhCN、benzene、PhEt、PhnBu、o-xylene、m-xylene、p-xylene或Mesitylene中的任一种。
实施例5，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol实施例1中序号为15的催化剂溶于相应体积的CH2Cl2，将反应体系冷却至T℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.07mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失大约t小时，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，其中溶剂体积变化和反应温度变化如表5所示，所获得的目标产物的分离收率及通过手性HPLC测定结果见表5。
表5溶剂体积及反应温度变化
Figure BDA0002326294240000061
实施例6，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol实施例4中序号为6的催化剂溶于相应体积的o-xylene，将反应体系冷却至T℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失约t小时，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，其中溶剂体积变化和反应温度变化如表6所示，所获得的目标产物的分离收率及通过手性HPLC测定结果见表6。
表6溶剂体积及反应温度变化
Figure BDA0002326294240000062
Figure BDA0002326294240000071
实施例7，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1的亚胺、0.01mmol实施例1中序号为15的催化剂溶于0.5mL的CH2Cl2，将反应体系冷却至0℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.07mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约66h)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，反应过程如下式：
Figure BDA0002326294240000072
其中亚胺的PG如表7所示，当PG为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表7不同的亚胺反应
Figure BDA0002326294240000073
注：[b]为分离收率；[c]通过手性HPLC测定；[d]通过1HNMR测定。
实施例8，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1c的亚胺、0.01mmol实施例1中序号为15的催化剂溶于0.5mL的CH2Cl2，将反应体系冷却至0℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.07mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约t小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，反应过程如下式：
Figure BDA0002326294240000074
其中亚胺的Ar如表8所示，当Ar为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表8不同的亚胺反应
Figure BDA0002326294240000075
Figure BDA0002326294240000081
注：[b]为分离收率；[c]通过手性HPLC测定；[d]通过1HNMR测定。
实施例9，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1的亚胺、0.01mmol实施例4中序号为6的催化剂溶于0.5mL的o-xylene，将反应体系冷却至-10℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约t小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，反应过程如下式：
Figure BDA0002326294240000082
其中亚胺的PG如表10所示，当PG为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表10不同的亚胺反应
Figure BDA0002326294240000091
注：[b]为分离收率；[c]通过手性HPLC测定；[d]通过1HNMR测定。
实施例10，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1c的亚胺、0.01mmol实施例4中序号为6的催化剂溶于1mL的o-xylene，将反应体系冷却至-10℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约t小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，反应过程如下式：
Figure BDA0002326294240000092
其中亚胺的Ar如表10所示，当Ar为不同的基团时获得的产物的分离收率及通过手性HPLC测定结果如下：
表10不同的亚胺反应
Figure BDA0002326294240000093
Figure BDA0002326294240000101
注：[b]为分离收率；[c]通过手性HPLC测定；[d]通过1HNMR测定；[e]分别为anti-和syn-产物的对映选择性。
实施例11，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1a的亚胺、0.01mmol实施例1中序号为15的催化剂溶于0.5mL的CH2Cl2，将反应体系冷却至0℃，搅拌10min，然后一次性加入0.1mmol式4.2的胺甲基吡啶和0.07mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约t小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，反应过程如下式：
Figure BDA0002326294240000102
其中胺甲基吡啶为
Figure BDA0002326294240000103
Figure BDA0002326294240000104
将上述几种胺甲基吡啶按顺序以代码4.2b、4.2c、4.2d、4.2e、4.2f、4.2g表示,反应如表11所示。
表11不同的胺甲基吡啶反应
Figure BDA0002326294240000105
注：[b]为分离收率；[c]通过手性HPLC测定；[d]通过1HNMR测定。
实施例12，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol实施例4中序号为6的催化剂溶于1mL的o-xylene，将反应体系冷却至-10℃，搅拌10min，然后一次性加入0.1mmol式4.2的胺甲基吡啶和0.07mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约t小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物，反应过程如下式：
Figure BDA0002326294240000111
其中胺甲基吡啶分别用实施例11中的4.2b、4.2c、4.2d、4.2e、4.2f以及4.2g代替，反应结果如表12所示：
表12不同的胺甲基吡啶反应
Figure BDA0002326294240000112
注：[b]为分离收率；[c]通过手性HPLC测定；[d]通过1HNMR测定。
实施例13，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol实施例1中序号为15的催化剂溶于0.5mL的CH2Cl2，将反应体系冷却至20℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.03mmol的如表13所示的有机碱，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约t小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物。
表11反应中采用不同种类的有机碱
Figure BDA0002326294240000113
注：[b]为分离收率；[c]通过手性HPLC测定。
实施例14，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol实施例4中序号为6的催化剂溶于0.5mL的o-xylene，将反应体系冷却至20℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和如表14所示量的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约12小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物。
表14反应中添加不同量的有机碱
Figure BDA0002326294240000121
注：[b]为分离收率。[c]通过手性HPLC测定。[e]分别为anti-和syn-产物的对映选择性。
实施例15，一种手性1,2-二(杂)芳基乙二胺化合物的制备方法，按以下步骤进行：将0.13mmol式4.1b的亚胺、0.01mmol实施例1中序号为15的催化剂混合后，再加入如表15所示的添加剂混合，将其溶于0.5mL的CH2Cl2，将反应体系冷却至20℃，搅拌10min，然后一次性加入0.1mmol式4.2a的胺甲基吡啶和0.07mmol的DBU，继续反应，TLC检测反应进程，至胺甲基吡啶完全消失(约12小时)，反应混合物通过减压浓缩后，经柱层析分离即获得目标产物。
表15反应中添加不同种类的添加剂
Figure BDA0002326294240000122
注：[b]为分离收率；[c]通过手性HPLC测定。
上述实施例1-15所制备的1,2-二(杂)芳基乙二胺化合物的表征数据如下：
①N-((1R,2R)-2-amino-1-phenyl-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000123
2H),7.69(dd,J＝12.0,7.8Hz,2H),7.52–7.41(m,4H),7.37(t,J＝7.4Hz,1H),7.24(td,J＝7.5,2.7Hz,2H),7.14–7.08(m,4H),6.91–6.86(m,2H),6.85(d,J＝7.8Hz,1H),5.44–5.37(m,1H),4.58(td,J＝11.1,4.4Hz,1H),4.35(d,J＝3.8Hz,1H)；13C NMR(151MHz,CDCl3)δ160.56,148.71,140.61,140.59,136.31,133.76,132.92,132.59,132.53,132.42,131.75,131.69,131.58,128.51,128.43,128.21,128.13,127.88,126.97,126.89,123.29,122.39,61.37,60.73；HRMS(ESI):calcd.for C25H25N3OP(M+H)+:414.1730,found:414.1724.
②N-((1R,2R)-2-amino-1-(2-fluorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000131
J＝11.7,7.5Hz,2H),7.69(dd,J＝11.7,7.7Hz,2H),7.53–7.36(m,5H),7.30–7.24(m,2H),7.16–7.08(m,3H),6.97(t,J＝7.4Hz,1H),6.90(d,J＝7.8Hz,1H),6.82(t,J＝9.2Hz,1H),5.45(dd,J＝9.3,7.7Hz,1H),4.84(td,J＝11.2,4.4Hz,1H),4.39(d,J＝4.3Hz,1H)；13C NMR(151MHz,CDCl3)δ160.50,159.87,158.87,148.75,136.46,133.29,132.43,132.36,132.15,131.86,131.84,131.79,131.75,131.73,131.28,128.92,128.89,128.80,128.75,128.58,128.50,128.33,128.25,123.85,123.83,123.51,122.64,115.06,114.91,59.76,55.14；HRMS(ESI):calcd.for C25H24FN3OP(M+H)+:432.1636,found:432.1631.
③N-((1R,2R)-2-amino-2-(pyridin-2-yl)-1-(o-tolyl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000132
＝11.7,7.6Hz,2H),7.61(dd,J＝12.0,7.7Hz,2H),7.52–7.40(m,4H),7.36(t,J＝7.3Hz,1H),7.21(td,J＝7.6,3.0Hz,2H),7.15(dd,J＝6.9,5.4Hz,1H),7.05(t,J＝7.3Hz,1H),7.00(t,J＝7.3Hz,1H),6.93(d,J＝7.4Hz,1H),6.88(d,J＝7.6Hz,1H),6.79(d,J＝7.7Hz,1H),5.58(dd,J＝9.7,6.5Hz,1H),4.83–4.75(m,1H),4.34(d,J＝4.0Hz,1H),1.73(s,3H)；13C NMR(151MHz,CDCl3)δ159.03,148.80,138.55,138.51,136.49,134.93,133.21,132.63,132.57,132.36,131.88,131.86,131.79,131.73,131.68,131.67,130.82,130.01,128.58,128.50,128.24,128.16,127.01,126.81,125.66,124.15,122.87,59.23,59.22,56.03,18.71；HRMS(ESI):calcd.forC26H27N3OP(M+H)+:428.1886,found:428.1888.
④N-((1R,2R)-2-amino-1-(3-fluorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000133
8.10min；1H NMR(600MHz,CDCl3)δ8.43(d,J＝4.3Hz,1H),7.93–7.82(m,2H),7.75–7.66(m,2H),7.55–7.43(m,4H),7.39(t,J＝6.7Hz,1H),7.29–7.24(m,2H),7.15–7.11(m,1H),7.08(dd,J＝13.0,6.5Hz,1H),6.88(d,J＝7.3Hz,1H),6.83(t,J＝7.8Hz,1H),6.68(d,J＝7.1Hz,1H),6.61(d,J＝9.6Hz,1H),5.58–5.49(m,1H),4.65–4.56(m,1H),4.36(d,J＝3.6Hz,1H)；13C NMR(151MHz,CDCl3)δ163.33,161.70,159.84,148.83,143.34,143.30,143.26,136.56,133.43,132.56,132.50,132.10,131.92,131.91,131.80,131.78,131.73,131.67,131.23,129.44,129.39,128.64,128.56,128.34,128.26,123.33,122.67,122.65,114.01,113.91,113.87,113.77,60.97,60.96,60.06；HRMS(ESI):calcd.for C25H24FN3OP(M+H)+:432.1636,found:432.1633.
⑤N-((1R,2R)-2-amino-1-(3-chlorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000141
13.06min；1H NMR(600MHz,CDCl3)δ8.43(d,J＝3.6Hz,1H),7.84(dd,J＝11.5,7.8Hz,2H),7.69(dd,J＝11.9,7.6Hz,2H),7.55–7.49(m,2H),7.47–7.42(m,2H),7.40(t,J＝7.1Hz,1H),7.32–7.27(m,2H),7.18–7.10(m,2H),7.06(t,J＝7.6Hz,1H),6.90(d,J＝7.5Hz,1H),6.86–6.81(m,2H),5.54(dd,J＝9.4,6.2Hz,1H),4.64(td,J＝11.0,3.9Hz,1H),4.49(d,J＝3.6Hz,1H)；13C NMR(151MHz,CDCl3)δ158.72,148.86,142.18,136.69,133.88,133.13,132.58,132.51,132.28,132.03,132.01,131.94,131.93,131.69,131.63,130.82,129.30,128.68,128.60,128.43,128.34,127.38,127.06,125.29,123.57,122.92,60.59,59.67；HRMS(ESI):calcd.for C25H24ClN3OP(M+H)+:448.1340,found:448.1337.
⑥N-((1R,2R)-2-amino-2-(pyridin-2-yl)-1-(m-tolyl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000142
tR(minor)11.93min；1H NMR(600MHz,CDCl3)δ8.43(d,J＝4.6Hz,1H),7.81(dd,J＝11.9,7.4Hz,2H),7.69(dd,J＝12.0,7.6Hz,2H),7.49(q,J＝6.5Hz,2H),7.44–7.37(m,3H),7.29–7.24(m,2H),7.14(dd,J＝7.0,5.2Hz,1H),7.03(t,J＝7.5Hz,1H),6.96(d,J＝7.5Hz,1H),6.87(d,J＝7.7Hz,1H),6.72(d,J＝7.5Hz,1H),6.68(s,1H),5.35(dd,J＝10.3,6.3Hz,1H),4.65(td,J＝11.0,4.2Hz,1H),4.57(d,J＝4.1Hz,1H),2.19(s,3H)；13C NMR(151MHz,CDCl3)δ158.34,148.70,139.41,139.37,137.60,136.49,133.22,132.64,132.58,132.36,131.90,131.89,131.84,131.82,131.69,131.63,130.79,128.59,128.51,128.36,128.28,128.04,127.94,127.73,123.91,123.75,122.81,60.66,59.90,21.33；HRMS(ESI):calcd.forC26H27N3OP(M+H)+:428.1886,found:428.1880.
⑦N-((1R,2R)-2-amino-1-(3-methoxyphenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic
Figure BDA0002326294240000143
80/20,flow rate 1.0mL/min,T＝30℃),UV 210nm,tR(major)18.48min,tR(minor)12.73min；1H NMR(600MHz,CDCl3)δ8.43(d,J＝4.4Hz,1H),7.84(dd,J＝11.8,7.4Hz,2H),7.70(dd,J＝12.0,7.6Hz,2H),7.51–7.46(m,2H),7.45–7.40(m,2H),7.38(t,J＝7.1Hz,1H),7.27–7.22(m,2H),7.12(dd,J＝7.0,5.2Hz,1H),7.05(t,J＝7.9Hz,1H),6.89(d,J＝7.8Hz,1H),6.68(dd,J＝8.1,2.1Hz,1H),6.50(d,J＝7.5Hz,1H),6.43(s,1H),5.42(dd,J＝9.9,6.5Hz,1H),4.58(td,J＝11.2,4.4Hz,1H),4.38(d,J＝4.5Hz,1H),3.63(s,3H)；13C NMR(151MHz,CDCl3)δ160.21,159.25,148.71,142.07,142.03,136.41,133.62,132.77,132.60,132.54,132.25,131.77,131.76,131.73,131.67,131.63,131.37,128.93,128.53,128.45,128.26,128.18,123.37,122.48,119.36,112.76,112.55,77.24,61.20,61.18,60.55,55.12；HRMS(ESI):calcd.for C26H27N3O2P(M+H)+:444.1835,found:444.1839.
⑧N-((1R,2R)-2-amino-1-(4-fluorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000151
18.94min；1H NMR(600MHz,CDCl3)δ8.42(d,J＝4.3Hz,1H),7.85(dd,J＝11.7,7.7Hz,2H),7.68(dd,J＝11.9,7.7Hz,2H),7.53–7.47(m,2H),7.47–7.42(m,2H),7.38(t,J＝7.3Hz,1H),7.26–7.23(m,2H),7.12(dd,J＝6.8,5.4Hz,1H),6.88(d,J＝7.7Hz,1H),6.85–6.78(m,4H),5.45(dd,J＝9.3,6.7Hz,1H),4.60–4.53(m,1H),4.31(d,J＝4.4Hz,1H)；13C NMR(151MHz,CDCl3)δ162.64,161.01,160.43,148.81,136.48,136.44,136.41,136.40,136.38,133.56,132.71,132.55,132.49,132.37,131.85,131.83,131.75,131.72,131.69,131.49,128.60,128.52,128.47,128.30,128.21,123.24,122.53,114.81,114.67,61.28,61.26,59.97；HRMS(ESI):calcd.for C25H24FN3OP(M+H)+:432.1636,found:432.1641.
⑨N-((1R,2R)-2-amino-1-(4-chlorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000152
22.61min；1H NMR(600MHz,CDCl3)δ8.41(d,J＝4.5Hz,1H),7.83(dd,J＝11.9,7.3Hz,2H),7.67(dd,J＝12.0,7.4Hz,2H),7.52–7.47(m,2H),7.46–7.37(m,3H),7.29–7.24(m,2H),7.13(dd,J＝7.1,5.3Hz,1H),7.09(d,J＝8.3Hz,2H),6.90(d,J＝7.8Hz,1H),6.83(d,J＝8.3Hz,2H),5.56(dd,J＝10.0,6.3Hz,1H),4.61(td,J＝11.1,4.2Hz,1H),4.42(d,J＝4.2Hz,1H)；13C NMR(151MHz,CDCl3)δ159.43,148.81,138.82,138.79,136.60,133.27,132.90,132.51,132.45,131.91,131.90,131.81,131.79,131.70,131.63,131.11,128.61,128.53,128.36,128.28,128.09,123.41,122.69,60.84,60.82,59.73；HRMS(ESI):calcd.forC25H24ClN3OP(M+H)+:448.1340,found:448.1333.
⑩N-((1R,2R)-2-amino-1-(4-bromophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000153
210nm,tR(major)13.66min,tR(minor)24.89min；1H NMR(600MHz,CDCl3)δ8.42(d,J＝3.4Hz,1H),7.84(dd,J＝11.0,8.1Hz,2H),7.69(dd,J＝11.1,8.1Hz,2H),7.55–7.37(m,5H),7.28–7.22(m,4H),7.15–7.09(m,1H),6.90(d,J＝7.6Hz,1H),6.76(d,J＝8.1Hz,2H),5.56–5.47(m,1H),4.55(td,J＝11.1,3.8Hz,1H),4.35(d,J＝3.6Hz,1H)；13C NMR(151MHz,CDCl3)δ159.92,148.83,139.59,139.55,136.59,133.40,132.53,132.47,132.17,131.90,131.88,131.79,131.78,131.74,131.68,131.29,131.02,128.69,128.62,128.54,128.37,128.29,123.32,122.63,121.00,60.98,60.96,60.03；HRMS(ESI):calcd.for C25H24BrN3OP(M+H)+:492.0835,found:492.0831.
Figure BDA0002326294240000161
N-((1R,2R)-2-amino-2-(pyridin-2-yl)-1-(4-(trifluoromethoxy)phenyl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000162
tR(minor)19.38min；1H NMR(600MHz,CDCl3)δ8.41(d,J＝3.8Hz,1H),7.85(dd,J＝11.5,7.7Hz,2H),7.67(dd,J＝11.7,7.8Hz,2H),7.53–7.41(m,4H),7.38(t,J＝7.2Hz,1H),7.26–7.22(m,2H),7.15–7.10(m,1H),6.98–6.86(m,5H),5.57–5.46(m,1H),4.58(td,J＝11.0,4.4Hz,1H),4.32(d,J＝4.1Hz,1H)；13C NMR(151MHz,CDCl3)δ160.37,148.81,148.12,139.46,139.43,136.53,133.47,132.62,132.51,132.45,132.34,131.89,131.87,131.75,131.72,131.71,131.68,131.47,128.61,128.53,128.36,128.28,128.19,123.16,122.59,121.29,120.26,119.59,61.17,61.15,60.04；HRMS(ESI):calcd.for C26H24F3N3O2P(M+H)+:498.1553,found:498.1552.
Figure BDA0002326294240000163
N-((1R,2R)-2-amino-2-(pyridin-2-yl)-1-(p-tolyl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000164
tR(minor)9.98min；1H NMR(600MHz,CDCl3)δ8.42(d,J＝3.6Hz,1H),7.82(dd,J＝11.5,7.7Hz,2H),7.68(dd,J＝11.6,7.9Hz,2H),7.51–7.46(m,2H),7.44–7.36(m,3H),7.27–7.23(m,2H),7.16–7.09(m,1H),6.94(d,J＝7.6Hz,2H),6.88(d,J＝7.7Hz,1H),6.79(d,J＝7.7Hz,2H),5.36(dd,J＝9.7,6.2Hz,1H),4.59(td,J＝10.9,3.6Hz,1H),4.46(d,J＝3.7Hz,1H),2.26(s,3H)；13C NMR(151MHz,CDCl3)δ159.35,148.71,136.92,136.88,136.70,136.46,133.41,132.62,132.55,131.96,131.83,131.81,131.75,131.69,131.09,128.72,128.56,128.48,128.33,128.25,126.80,123.57,122.62,61.01,61.00,60.06,21.05；HRMS(ESI):calcd.for C26H27N3OP(M+H)+:428.1886,found:428.1880.
Figure BDA0002326294240000165
N-((1R,2R)-2-amino-1-(naphthalen-2-yl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000166
tR(minor)21.37min；1H NMR(600MHz,CDCl3)δ8.42(d,J＝3.9Hz,1H),7.87(dd,J＝11.6,7.6Hz,2H),7.77–7.72(m,1H),7.69(dd,J＝11.7,7.8Hz,2H),7.65–7.62(m,1H),7.60(d,J＝8.4Hz,1H),7.50(t,J＝7.1Hz,1H),7.46–7.38(m,5H),7.35–7.29(m,2H),7.21–7.14(m,2H),7.12–7.06(m,1H),6.99(d,J＝8.4Hz,1H),6.85(d,J＝7.7Hz,1H),5.54(dd,J＝9.2,6.4Hz,1H),4.74(td,J＝11.1,4.4Hz,1H),4.43(d,J＝4.3Hz,1H)；13C NMR(151MHz,CDCl3)δ160.63,148.76,138.13,138.09,136.41,133.72,132.98,132.87,132.58,132.52,132.31,131.78,131.71,131.62,131.60,131.43,128.56,128.47,128.24,128.16,127.90,127.59,127.53,125.97,125.89,125.68,124.99,123.26,122.44,61.44,61.43,60.97；HRMS(ESI):calcd.forC29H27N3OP(M+H)+:464.1886,found:428.1877.
Figure BDA0002326294240000171
N-((1R,2R)-2-amino-1-(3,4-dichlorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000172
tR(minor)21.37min；1H NMR(600MHz,CDCl3)δ8.42(d,J＝4.0Hz,1H),7.85(dd,J＝11.7,7.5Hz,2H),7.68(dd,J＝11.8,7.7Hz,2H),7.56–7.50(m,2H),7.48–7.38(m,3H),7.32–7.28(m,2H),7.18–7.13(m,2H),6.97–6.90(m,2H),6.70(d,J＝8.2Hz,1H),5.54(dd,J＝9.1,6.9Hz,1H),4.56–4.48(m,1H),4.31(d,J＝4.3Hz,1H)；13C NMR(151MHz,CDCl3)δ160.16,148.88,141.04,141.00,136.68,132.44,132.38,131.98,131.97,131.92,131.86,131.84,131.72,131.66,130.97,129.79,129.06,128.67,128.58,128.39,128.31,126.47,123.12,122.70,60.98,60.96,59.73；HRMS(ESI):calcd.for C25H23Cl2N3OP(M+H)+:482.0950,found:482.0942.
Figure BDA0002326294240000173
N-((1R,2R)-2-amino-1-(3,4-dimethylphenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000174
12.47min；1H NMR(600MHz,CDCl3)δ8.43(d,J＝4.4Hz,1H),7.84–7.77(m,2H),7.71–7.65(m,2H),7.51–7.46(m,2H),7.44–7.36(m,3H),7.27–7.24(m,2H),7.13(dd,J＝7.0,5.3Hz,1H),6.90(dd,J＝15.4,7.6Hz,2H),6.64–5.56(m,2H),5.22(dd,J＝10.2,6.4Hz,1H),4.52(td,J＝10.9,4.6Hz,1H),4.39(d,J＝4.6Hz,1H),2.17(s,3H),2.09(s,3H)；13C NMR(151MHz,CDCl3)δ160.18,148.64,137.44,137.41,136.34,135.94,135.23,133.59,132.74,132.59,132.53,132.29,131.76,131.70,131.60,131.59,131.41,129.22,128.49,128.41,128.33,128.25,128.16,124.30,123.42,122.45,61.34,61.31,60.37,19.66,19.33；HRMS(ESI):calcd.for C27H29N3OP(M+H)+:442.2043,found:442.2037.
Figure BDA0002326294240000175
N-((1S,2R)-2-amino-1-(furan-2-yl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000176
25:1)；HPLC:Daicel Chirapak IC-H column(hexane/isopropanol＝70/30,flow rate1.0mL/min,T＝30℃),UV 210nm,tR(major)22.22min,tR(minor)13.84min；1H NMR(600MHz,CDCl3)δ8.43(d,J＝4.4Hz,1H),7.80(td,J＝12.5,7.8Hz,4H),7.54(td,J＝7.7,1.3Hz,1H),7.51–7.47(m,1H),7.45–7.40(m,3H),7.35(td,J＝7.6,3.1Hz,2H),7.21(s,1H),7.12(dd,J＝6.9,5.3Hz,1H),7.06(d,J＝7.8Hz,1H),6.15(dd,J＝2.6,1.7Hz,1H),5.93(d,J＝3.0Hz,1H),5.00(dd,J＝9.8,8.1Hz,1H),4.65(td,J＝10.6,4.7Hz,1H),4.53(d,J＝4.6Hz,1H)；13C NMR(151MHz,CDCl3)δ160.15,153.56,148.81,141.64,136.52,133.28,132.53,132.46,132.29,131.89,131.88,131.84,131.82,131.79,131.73,131.41,128.58,128.50,128.44,128.36,122.71,122.50,110.14,107.53,59.71,55.04；HRMS(ESI):calcd.forC23H23N3O2P(M+H)+:404.1522,found:404.1515.
Figure BDA0002326294240000181
N-((1S,2R)-2-amino-2-(pyridin-2-yl)-1-(thiophen-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000182
10.31min；1H NMR(600MHz,CDCl3)δ8.42(d,J＝3.6Hz,1H),7.90(dd,J＝11.5,7.7Hz,2H),7.82(dd,J＝11.8,7.6Hz,2H),7.57–7.47(m,2H),7.47–7.38(m,3H),7.35–7.30(m,2H),7.14–7.10(m,1H),7.09–7.04(m,2H),6.80–6.75(m,1H),6.54(s,1H),5.57(dd,J＝9.5,6.5Hz,1H),4.89(td,J＝10.9,3.8Hz,1H),4.51(d,J＝3.8Hz,1H)；13C NMR(151MHz,CDCl3)δ159.89,148.75,144.70,144.65,136.59,133.40,132.63,132.57,131.93,131.91,131.83,131.81,131.74,131.06,128.62,128.53,128.40,128.32,126.58,124.66,124.15,123.30,122.58,61.07,61.06,56.86；HRMS(ESI):calcd.for C23H23N3OPS(M+H)+:420.1294,found:420.1296.
Figure BDA0002326294240000183
N-((1R,2R)-2-amino-2-(pyridin-2-yl)-1-(thiophen-3-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000184
16.36min；1H NMR(600MHz,CDCl3)δ8.43(d,J＝4.3Hz,1H),7.84(dd,J＝11.8,7.3Hz,2H),7.74(dd,J＝11.9,7.4Hz,2H),7.53–7.47(m,2H),7.45–7.39(m,3H),7.33–7.28(m,2H),7.12(dd,J＝6.9,5.2Hz,1H),7.09(dd,J＝4.8,3.0Hz,1H),6.99(d,J＝7.8Hz,1H),6.76(d,J＝1.9Hz,1H),6.59(d,J＝4.9Hz,1H),5.31(dd,J＝9.7,7.2Hz,1H),4.69(td,J＝10.7,4.3Hz,1H),4.39(d,J＝4.3Hz,1H)；13C NMR(151MHz,CDCl3)δ160.84,148.70,141.92,141.89,136.41,133.67,132.82,132.56,132.49,131.73,131.67,131.64,128.53,128.44,128.30,128.22,126.38,125.24,122.94,122.38,121.72,61.02,61.01,57.13；HRMS(ESI):calcd.forC23H23N3OPS(M+H)+:420.1294,found:420.1292.
Figure BDA0002326294240000185
N-((1R,2R)-2-amino-1-(1-(phenylsulfonyl)-1H-indol-3-yl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000186
25:1)；HPLC:Daicel Chirapak IC-H column(hexane/isopropanol＝70/30,flow rate1.0mL/min,T＝30℃),UV 210nm,tR(major)21.51min,tR(minor)14.13min；1H NMR(600MHz,CDCl3)δ8.31(d,J＝3.9Hz,1H),7.90–7.83(m,3H),7.74–7.68(m,4H),7.57–7.49(m,2H),7.47–7.38(m,4H),7.32(dd,J＝15.8,7.8Hz,2H),7.24(s,1H),7.22(t,J＝7.7Hz,1H),7.16–7.07(m,3H),7.04(t,J＝6.5Hz,2H),6.74(d,J＝7.7Hz,1H),5.52(dd,J＝8.9,7.1Hz,1H),4.81(td,J＝11.3,3.8Hz,1H),4.47(d,J＝3.9Hz,1H)；13C NMR(151MHz,CDCl3)δ160.47,148.79,138.29,136.43,134.99,133.68,133.52,132.67,132.43,132.36,132.25,131.92,131.90,131.70,131.67,131.61,131.38,129.21,129.09,128.65,128.56,128.30,128.22,126.68,124.66,124.43,123.51,123.47,123.21,122.96,122.47,119.65,113.58,59.44,53.98；HRMS(ESI):calcd.for C33H30N4O3PS(M+H)+:593.1771,found:593.1757.
Figure BDA0002326294240000191
N-((1R,2R)-2-amino-2-(4-methoxypyridin-2-yl)-1-phenylethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000192
＝11.6,7.5Hz,2H),7.69(dd,J＝11.7,7.6Hz,2H),7.50(t,J＝6.9Hz,1H),7.46–7.40(m,2H),7.37(t,J＝7.0Hz,1H),7.26–7.20(m,2H),7.18–7.11(m,3H),6.97–6.91(m,2H),6.64(dd,J＝5.6,2.2Hz,1H),6.34(s,1H),5.53–5.45(m,1H),4.57(td,J＝11.3,4.4Hz,1H),4.28(d,J＝4.4Hz,1H),3.66(s,3H)；13C NMR(151MHz,CDCl3)δ166.00,161.17,149.71,140.32,140.29,133.45,132.63,132.56,132.02,131.84,131.83,131.74,131.68,131.14,128.58,128.49,128.32,128.24,128.04,127.15,126.95,109.64,108.92,61.16,61.15,60.28,55.17；HRMS(ESI):calcd.for C26H27N3O2P(M+H)+:444.1835,found:444.1835.
Figure BDA0002326294240000193
N-((1R,2R)-2-amino-2-(5-bromopyridin-2-yl)-1-phenylethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000194
tR(minor)8.38min；1H NMR(600MHz,CDCl3)δ8.46(s,1H),7.90(dd,J＝11.9,7.8Hz,2H),7.83(dd,J＝11.6,7.6Hz,2H),7.67(dd,J＝11.7,7.8Hz,2H),7.58(dd,J＝8.2,1.7Hz,1H),7.50(dd,J＝16.2,7.8Hz,2H),7.38(t,J＝7.2Hz,1H),7.26–7.22(m,2H),7.19–7.14(m,3H),6.91(d,J＝3.4Hz,2H),6.79(d,J＝8.2Hz,1H),5.16(dd,J＝9.9,6.1Hz,1H),4.59(td,J＝11.1,4.2Hz,1H),4.40(d,J＝3.9Hz,1H)；13C NMR(151MHz,CDCl3)δ158.69,149.85,139.97,139.94,138.94,133.81,133.43,132.95,132.59,132.52,131.98,131.91,131.89,131.87,131.83,131.79,131.76,131.71,131.64,131.10,128.61,128.55,128.53,128.47,128.34,128.26,128.12,127.25,126.88,124.59,119.50,60.88,60.87,60.26；HRMS(ESI):calcd.forC25H24BrN3OP(M+H)+:492.0835,found:492.0821.
Figure BDA0002326294240000195
N-((1R,2R)-2-amino-2-(6-methylpyridin-2-yl)-1-phenylethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000201
tR(minor)7.54min；1H NMR(600MHz,CDCl3)δ7.84(dd,J＝11.6,7.7Hz,2H),7.69(dd,J＝11.9,7.7Hz,2H),7.50(t,J＝7.1Hz,1H),7.46–7.41(m,2H),7.39–7.32(m,2H),7.27–7.22(m,2H),7.15–7.12(m,3H),6.98(d,J＝7.6Hz,1H),6.95–6.91(m,2H),6.59(d,J＝7.5Hz,1H),5.81(dd,J＝8.6,7.3Hz,1H),4.64(td,J＝11.3,3.9Hz,1H),4.38(d,J＝3.7Hz,1H),2.38(s,3H)；13C NMR(151MHz,CDCl3)δ158.26,157.55,140.46,140.42,136.86,133.60,132.76,132.66,132.60,131.97,131.85,131.83,131.76,131.74,131.58,131.52,131.09,128.56,128.48,128.30,128.21,127.97,127.08,126.89,122.28,120.73,60.57,60.55,60.28,24.23；HRMS(ESI):calcd.for C26H27N3OP(M+H)+:428.1886,found:428.1882.
Figure BDA0002326294240000202
N-((1R,2R)-2-amino-1-phenyl-2-(quinolin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000203
tR(minor)7.61min；1H NMR(600MHz,CDCl3)δ7.95–7.89(m,2H),7.86–7.81(m,3H),7.75(d,J＝8.0Hz,1H),7.72–7.64(m,3H),7.52–7.49(m,1H),7.52–7.41(m,2H),7.37(t,J＝7.0Hz,1H),7.25–7.21(m,2H),7.13–7.08(m,3H),6.97–6.90(m,3H),5.70–5.61(m,1H),4.70(td,J＝11.1,4.2Hz,1H),4.54(d,J＝4.0Hz,1H)；13C NMR(151 MHz,CDCl3)δ160.97,147.16,140.58,140.55,136.37,133.76,132.91,132.64,132.58,132.30,131.93,131.92,131.85,131.80,131.78,131.68,131.66,131.63,131.56,131.41,129.60,129.01,128.58,128.55,128.49,128.47,128.26,128.17,128.00,127.64,127.41,127.06,126.89,126.44,121.54,61.81,61.79,60.58；HRMS(ESI):calcd.for C26H27N3OP(M+H)+:464.1886,found:428.1872.
Figure BDA0002326294240000204
N-((1R,2S)-2-amino-1-phenyl-2-(pyridin-3-yl)ethyl)-P,P-diphenylphosphinic amide
Figure BDA0002326294240000205
15.04min；1H NMR(600MHz,CD3OD)δ8.62(d,J＝4.1Hz,1H),8.54(s,1H),7.92(d,J＝7.9Hz,1H),7.56–7.47(m,5H),7.41–7.32(m,11H),4.76(d,J＝7.6Hz,1H),4.73–4.68(m,1H)；13CNMR(151MHz,CD3OD)δ149.61,149.13,138.16,138.14,136.58,132.29,132.28,132.18,132.17,131.93,131.86,131.37,131.28,131.21,131.11,130.86,130.52,130.25,128.95,128.57,128.38,128.33,128.30,128.25,127.25,124.19,58.06,57.60,57.56；HRMS(ESI):calcd.for C25H25N3OP(M+H)+:414.1730,found:414.1729.
Figure BDA0002326294240000206
N-((1R,2S)-2-amino-1-phenyl-2-(pyridin-4-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000207
53.22min；1H NMR(600MHz,CD3OD)δ8.51(d,J＝5.7Hz,2H),7.54–7.38(m,8H),7.36–7.31(m,7H),7.28–7.23(m,2H),4.48–4.43(m,2H)；13C NMR(151MHz,CD3OD)δ149.60,148.99,148.80,139.25,139.23,132.09,132.07,132.01,131.99,131.90,131.83,131.77,131.55,131.39,131.32,130.91,130.69,128.48,128.30,128.23,128.22,128.15,127.93,127.30,123.59,121.71,59.96,59.89,59.85；HRMS(ESI):calcd.for C25H25N3OP(M+H)+:414.1730,found:414.1727.
Figure BDA0002326294240000211
N-((1R,2R)-2-amino-1-phenyl-2-(pyridin-2-yl)ethyl)-P,P-di-o-tolylphosphinic amide:
Figure BDA0002326294240000212
＝13.5,7.6Hz,1H),7.63(dd,J＝13.4,7.7Hz,1H),7.47(t,J＝7.6Hz,1H),7.38(t,J＝7.4Hz,1H),7.29–7.17(m,3H),7.14–7.08(m,4H),7.08–7.04(m,1H),7.00(t,J＝7.1Hz,1H),6.93(d,J＝7.7Hz,1H),6.87(d,J＝6.6Hz,2H),5.33–5.25(m,1H),4.72(td,J＝10.6,4.4Hz,1H),4.39(d,J＝4.4Hz,1H),2.45(s,3H),2.21(s,3H)；13C NMR(151MHz,CDCl3)δ160.75,148.63,142.37,142.30,141.70,141.64,140.41,140.37,136.33,133.46,133.39,132.83,132.76,131.88,131.75,131.73,131.68,131.61,131.58,131.56,131.53,131.49,131.45,131.08,130.64,127.87,127.19,127.00,125.49,125.40,125.18,125.09,123.28,122.37,61.65,61.63,60.72,21.52,21.49,21.44,21.41；HRMS(ESI):calcd.for C27H29N3OP(M+H)+:442.2043,found:4422038
Figure BDA0002326294240000213
N-((1R,2R)-2-amino-1-phenyl-2-(pyridin-2-yl)ethyl)-P,P-bis(3,5-dimethylphenyl)phosphinicamide:
Figure BDA0002326294240000214
7.24(d,J＝12.3Hz,2H),7.17–7.09(m,5H),6.96(s,1H),6.91–6.86(m,3H),5.27(dd,J＝9.4,7.0Hz,1H),4.55(td,J＝11.9,4.4Hz,1H),4.35(d,J＝4.3Hz,1H),2.33(s,6H),2.10(s,6H)；13C NMR(151MHz,CDCl3)δ160.48,148.68,140.88,140.84,138.15,138.07,137.78,137.69,136.31,133.56,133.49,133.47,133.29,133.27,132.72,131.95,131.08,130.41,130.35,129.22,129.16,127.83,127.05,126.92,123.32,122.41,61.36,61.34,60.62,21.32,21.01；HRMS(ESI):calcd.for C29H33N3OP(M+H)+:470.2356,found:470.2345.
Figure BDA0002326294240000215
N-((1R,2R)-2-amino-1-phenyl-2-(pyridin-2-yl)ethyl)-P,P-bis(2,6-dimethylphenyl)phosphinicamide:
Figure BDA0002326294240000216
1H NMR(600MHz,CDCl3)δ8.48(d,J＝3.9Hz,1H),7.46(t,J＝6.9Hz,1H),7.18(t,J＝7.3Hz,1H),7.15–7.12(m,1H),7.10(t,J＝7.5Hz,1H),7.04(t,J＝7.2Hz,1H),7.02–6.95(m,4H),6.83(dd,J＝7.2,3.9Hz,2H),6.80(d,J＝7.6Hz,1H),6.61(d,J＝7.4Hz,2H),5.72(d,J＝5.7Hz,1H),4.50–4.41(m,1H),4.23(d,J＝4.1Hz,1H),2.40(s,6H),2.25(s,6H)；13C NMR(151MHz,CDCl3)δ160.86,148.69,142.02,141.95,141.10,141.03,140.53,140.49,136.33,133.75,132.94,132.65,131.84,130.44,130.42,130.06,129.98,129.87,129.79,127.50,127.21,126.76,123.49,122.49,62.79,61.42,61.40,23.04,23.02,22.89,22.86；HRMS(ESI):calcd.forC29H33N3OP(M+H)+:470.2356,found:470.2351.
Figure BDA0002326294240000221
N-((1S,2R)-2-amino-1-phenyl-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000222
18.06min；1H NMR(600MHz,CD3OD)δ8.46(d,J＝4.3Hz,1H),7.69(dd,J＝12.1,7.4Hz,2H),7.63(dd,J＝12.2,7.5Hz,2H),7.57–7.53(m,1H),7.52–7.43(m,4H),7.34(td,J＝7.7,3.2Hz,2H),7.18(dd,J＝6.9,5.2Hz,1H),7.15–7.11(m,3H),6.99–6.94(m,2H),6.91(d,J＝7.7Hz,1H),4.35–4.30(m,1H),4.26(d,J＝8.2Hz,1H)；13C NMR(151MHz,CD3OD)δ158.05,148.68,140.57,140.54,136.50,132.25,132.18,132.07,132.05,132.00,131.97,131.95,131.51,131.44,131.37,131.13,130.50,128.41,128.32,128.21,128.13,127.97,127.11,126.86,123.57,122.77,62.08,62.05,61.86；HRMS(ESI):calcd.for C25H25N3OP(M+H)+:414.1730,found:414.1728.
Figure BDA0002326294240000223
N-((1S,2R)-2-amino-1-(3-fluorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000224
14.47min；1H NMR(600MHz,CD3OD)δ8.47(d,J＝4.3Hz,1H),7.68(dd,J＝12.2,7.5Hz,2H),7.64(dd,J＝12.2,7.7Hz,2H),7.56(t,J＝7.5Hz,2H),7.51–7.44(m,3H),7.36(td,J＝7.6,3.1Hz,2H),7.21(dd,J＝7.0,5.3Hz,1H),7.12(dd,J＝13.9,7.8Hz,1H),6.99(d,J＝7.8Hz,1H),6.88–6.84(m,1H),6.78(d,J＝9.9Hz,1H),6.74(d,J＝7.6Hz,1H),4.38–4.33(m,1H),4.22(d,J＝8.0Hz,1H)；13C NMR(151MHz,CD3OD)δ163.46,161.84,158.30,148.75,143.62,136.66,132.15,132.12,132.10,132.08,132.02,132.00,131.52,131.46,130.96,130.54,129.69,129.63,128.45,128.36,128.23,128.14,123.42,122.86,122.79,122.77,113.81,113.75,113.66,113.60,62.01,61.98,61.46；HRMS(ESI):calcd.for C25H24FN3OP(M+H)+:432.1636,found:432.1631.
Figure BDA0002326294240000225
N-((1S,2R)-2-amino-2-(pyridin-2-yl)-1-(m-tolyl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000226
tR(minor)20.05min；1H NMR(600MHz,CDCl3)δ8.55(d,J＝4.1Hz,1H),7.64(dd,J＝11.9,7.5Hz,2H),7.56(t,J＝7.0Hz,1H),7.51(dd,J＝11.9,7.5Hz,2H),7.41(dd,J＝13.0,6.3Hz,2H),7.32–7.27(m,4H),7.20–7.16(m,1H),7.12–7.06(m,2H),6.98(t,J＝6.0Hz,2H),6.90(s,1H),4.93(t,J＝8.5Hz,1H),4.45–4.39(m,2H),2.24(s,3H)；13C NMR(151MHz,CDCl3)δ160.14,148.86,141.08,137.77,136.26,132.45,132.38,131.87,131.80,131.61,131.59,128.36,128.28,128.22,128.15,128.14,128.04,127.90,124.20,122.53,122.46,61.99,61.95,60.84,21.37；HRMS(ESI):calcd.for C26H27N3OP(M+H)+:428.1886,found:428.1886.
Figure BDA0002326294240000231
N-((1S,2R)-2-amino-1-(3-methoxyphenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000232
12.51min；1H NMR(600MHz,CD3OD)δ8.48(d,J＝4.2Hz,1H),7.71(dd,J＝12.1,7.6Hz,2H),7.64(dd,J＝12.2,7.6Hz,2H),7.59–7.46(m,5H),7.38–7.33(m,2H),7.22–7.18(m,1H),7.05(t,J＝7.9Hz,1H),6.93(d,J＝7.8Hz,1H),6.69(dd,J＝8.1,1.9Hz,1H),6.55(d,J＝7.4Hz,1H),6.50(s,1H),4.35–4.29(m,1H),3.63(s,3H)；13C NMR(151MHz,CD3OD)δ159.67,157.29,148.76,141.65,136.58,132.27,132.21,132.16,132.15,132.03,132.02,131.86,131.48,131.41,131.19,131.00,130.32,129.09,128.45,128.36,128.23,128.14,123.71,122.97,119.04,112.99,112.41,61.76,61.73,61.51,54.24；HRMS(ESI):calcd.forC26H27N3O2P(M+H)+:444.1835,found:444.1834.
Figure BDA0002326294240000233
N-((1S,2R)-2-amino-1-(4-fluorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000234
36.51min；1H NMR(600MHz,CD3OD)δ8.48(d,J＝4.4Hz,1H),7.71(dd,J＝12.2,7.8Hz,2H),7.63(dd,J＝12.2,7.8Hz,2H),7.59–7.53(m,2H),7.52–7.46(m,3H),7.36(td,J＝7.5,2.9Hz,2H),7.21(dd,J＝6.8,5.4Hz,1H),6.96(m,3H),6.99–6.93(t,J＝8.6Hz,2H),4.37(t,J＝9.3Hz,1H),4.31–4.26(m,1H)；13C NMR(151MHz,CD3OD)δ162.82,161.20,157.52,148.84,136.64,132.20,132.17,132.16,132.13,132.04,132.02,131.80,131.49,131.42,131.26,130.94,130.39,128.83,128.77,128.45,128.37,128.25,128.17,123.62,122.97,114.68,114.53,61.89,61.86,60.84；HRMS(ESI):calcd.for C25H24FN3OP(M+H)+:432.1636,found:432.1635.
Figure BDA0002326294240000235
N-((1S,2R)-2-amino-1-(4-chlorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000236
46.90min；1H NMR(400MHz,CD3OD)δ8.46(d,J＝4.5Hz,1H),7.73–7.60(m,4H),7.56(td,J＝7.6,1.4Hz,2H),7.50–7.43(m,3H),7.36(td,J＝7.7,3.3Hz,2H),7.20(dd,J＝7.0,5.0Hz,1H),7.12(d,J＝8.4Hz,2H),7.01–6.91(m,3H),4.37–4.30(m,1H),4.23(d,J＝8.1Hz,1H)；13C NMR(101MHz,CD3OD)δ158.15,148.79,139.56,136.71,132.81,132.18,132.15,132.12,132.09,132.03,132.00,131.56,131.46,130.70,130.27,128.53,128.48,128.36,128.29,128.16,127.98,123.53,122.90,61.98,61.93,61.23；HRMS(ESI):calcd.forC25H24ClN3OP(M+H)+:448.1340,found:448.1339.
Figure BDA0002326294240000241
N-((1S,2R)-2-amino-1-(4-bromophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000242
44.29min；1H NMR(600MHz,CD3OD)δ8.47(d,J＝4.2Hz,1H),7.70(dd,J＝12.2,7.5Hz,2H),7.64(dd,J＝12.1,7.7Hz,2H),7.56(t,J＝7.3Hz,2H),7.52–7.43(m,3H),7.36(td,J＝7.6,3.0Hz,2H),7.27(d,J＝8.3Hz,2H),7.21(dd,J＝6.9,5.3Hz,1H),6.99(d,J＝7.7Hz,1H),6.90(d,J＝8.2Hz,2H),4.34(t,J＝9.1Hz,1H),4.26(d,J＝8.1Hz,1H)；13C NMR(151MHz,CD3OD)δ158.02,148.82,139.96,139.94,136.70,132.16,132.14,132.12,132.09,132.01,131.99,131.81,131.54,131.47,131.40,131.06,131.00,130.95,130.53,128.90,128.46,128.38,128.27,128.18,123.54,122.93,120.87,61.84,61.80,61.18；HRMS(ESI):calcd.forC25H24BrN3OP(M+H)+:492.0835,found:492.0834.
Figure BDA0002326294240000243
N-((1S,2R)-2-amino-2-(pyridin-2-yl)-1-(4-(trifluoromethoxy)phenyl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000244
tR(minor)30.54min；1H NMR(400MHz,CD3OD)δ8.47(d,J＝4.5Hz,1H),7.73–7.60(m,4H),7.59–7.53(m,2H),7.50–7.44(m,3H),7.34(td,J＝7.7,3.2Hz,2H),7.23–7.19(m,1H),7.08–6.98(m,5H),4.41(t,J＝9.0Hz,1H),4.29(dd,J＝8.0,2.4Hz,1H)；13C NMR(101MHz,CD3OD)δ157.95,148.84,148.19,139.90,139.87,136.68,132.18,132.14,132.04,132.01,131.98,131.92,131.55,131.45,130.62,130.26,128.67,128.49,128.36,128.25,128.12,123.50,122.95,120.39,61.89,61.84,60.94；HRMS(ESI):calcd.for C26H24F3N3O2P(M+H)+:498.1553,found:498.1551.
Figure BDA0002326294240000245
N-((1S,2R)-2-amino-2-(pyridin-2-yl)-1-(p-tolyl)ethyl)-P,P-diphenylphosphinic amide:
白色固体(22.4mg,52％)；m.p.＝113-114℃；Rf＝0.22(CH2Cl2/MeOH＝25:1)；HPLC:Daicel Chirapak IA-H column(hexane/isopropanol＝70/30,flow rate 0.8mL/min,T＝30℃),UV 210nm,tR(major)14.18min,tR(minor)35.22min；1H NMR(400MHz,CD3OD)δ8.47(d,J＝4.5Hz,1H),7.74–7.68(m,2H),7.66–7.60(m,2H),7.58–7.48(m,5H),7.35(td,J＝7.5,3.2Hz,2H),7.19(dd,J＝7.4,5.1Hz,1H),6.97–6.80(m,5H),4.35–4.31(m,2H),2.23(s,
Figure BDA0002326294240000251
61.07 19.67；HRMS(ESI):calcd.for C26H27N3OP(M+H)+:428.1886,found:428.1885.
Figure BDA0002326294240000252
N-((1S,2R)-2-amino-1-(naphthalen-2-yl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000253
tR(minor)26.94min；1H NMR(400MHz,CD3OD)δ8.45(d,J＝4.7Hz,1H),7.75–7.59(m,7H),7.56–7.51(m,1H),7.46–7.38(m,6H),7.32(s,1H),7.28–7.19(m,3H),7.15–7.10(m,1H),6.92(d,J＝7.8Hz,1H),4.53–4.46(m,1H),4.37(d,J＝8.1Hz,1H)；13C NMR(101MHz,CD3OD)δ158.37,148.69,138.02,136.54,133.05,132.72,132.25,132.18,132.15,132.09,132.06,131.94,131.92,131.60,131.56,131.47,130.88,130.29,128.45,128.33,128.19,128.06,127.79,127.48,127.18,126.10,125.82,125.68,124.49,123.51,122.75,62.15,62.01,61.96；HRMS(ESI):calcd.for C29H27N3OP(M+H)+:464.1886,found:464.1885.
Figure BDA0002326294240000254
N-((1S,2R)-2-amino-1-(3,4-dichlorophenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000255
tR(minor)13.86min；1H NMR(600MHz,CD3OD)δ8.51(d,J＝4.4Hz,1H),7.76–7.70(m,2H),7.68–7.58(m,4H),7.54–7.48(m,3H),7.40(td,J＝7.5,3.0Hz,2H),7.29–7.24(m,2H),7.12(d,J＝1.5Hz,1H),7.06(d,J＝7.8Hz,1H),6.93(d,J＝8.3Hz,1H),4.40(t,J＝9.0Hz,1H),4.30(d,J＝7.8Hz,1H)；13C NMR(151MHz,CD3OD)δ157.66,148.94,141.33,136.80,132.21,132.19,132.05,132.04,131.99,131.72,131.59,131.49,131.43,131.31,130.88,130.73,130.45,129.95,129.24,128.47,128.39,128.24,128.15,126.80,123.49,123.08,61.59,61.55,60.52；HRMS(ESI):calcd.for C25H23Cl2N3OP(M+H)+:482.0950,found:482.0948.
Figure BDA0002326294240000256
N-((1S,2R)-2-amino-1-(3,4-dimethylphenyl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000257
31.38min；1H NMR(600MHz,CDCl3)δ8.51(d,J＝4.1Hz,1H),7.64(dd,J＝11.9,7.5Hz,2H),7.55(dd,J＝11.9,7.8Hz,2H),7.50(t,J＝7.6Hz,1H),7.43–7.39(m,2H),7.32–7.27(m,4H),7.17–7.13(m,1H),6.97(dd,J＝13.8,7.9Hz,2H),6.86(d,J＝7.6Hz,1H),6.83(s,1H),5.16(t,J＝9.1Hz,1H),4.56(d,J＝6.1Hz,1H),4.36(dd,J＝16.2,9.8Hz,1H),2.18(s,3H),2.13(s,3H)；13C NMR(151MHz,CDCl3)δ159.05,148.83,138.12,138.09,136.38,136.29,135.63,132.56,132.49,131.85,131.78,131.71,131.69,131,66,131.64,129.57,128.45,128.40,128.32,128.26,128.17,124.58,122.97,122.60,61.57,61.54,60.51,19.69,19.38；HRMS(ESI):calcd.for C27H29N3OP(M+H)+:442.2043,found:442.2042.
Figure BDA0002326294240000261
N-((1R,2R)-2-amino-1-(furan-2-yl)-2-(pyridin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000262
min；1H NMR(600MHz,CD3OD)δ8.46(d,J＝4.6Hz,1H),7.70(dd,J＝12.3,7.4Hz,2H),7.65–7.62(m,3H),7.55–7.51(m,2H),7.45–7.41(m,4H),7.33(d,J＝0.8Hz,1H),7.24(dd,J＝7.2,5.2Hz,1H),7.14(d,J＝7.8Hz,1H),6.15(dd,J＝2.9,2.0Hz,1H),5.87(d,J＝3.2Hz,1H),4.46–4.40(m,2H)；13C NMR(151MHz,CD3OD)δ158.27,152.90,152.88,148.67,147.26,141.82,136.70,132.06,132.03,132.01,131.99,131.97,131.43,131.36,128.38,128.29,128.28,128.19,122.84,109.77,107.51,59.93,59.90,55.35；
Figure BDA0002326294240000263
N-((1R,2R)-2-amino-2-(pyridin-2-yl)-1-(thiophen-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000264
16.50min；1H NMR(600MHz,CDCl3)δ8.54(d,J＝3.9Hz,1H),7.70(dd,J＝11.9,7.6Hz,2H),7.59–7.56(m,3H),7.42(dd,J＝14.7,7.3Hz,2H),7.34–7.29(m,4H),7.21–7.17(m,2H),7.12(d,J＝4.4Hz,1H),6.83–6.79(m,2H),5.10(t,J＝8.6Hz,1H),4.76(td,J＝9.6,5.1Hz,1H),4.49(d,J＝4.8Hz,1H)；13C NMR(151MHz,CDCl3)δ160.16,148.82,145.50,136.47,132.88,132.62,132.42,132.35,132.03,131.86,131.79,131.75,131.68,131.66,128.43,128.34,128.29,128.21,126.60,125.52,124.47,122.53,122.42,62.05,62.02,57.21；HRMS(ESI):calcd.for C23H23N3OPS(M+H)+:420.1294,found:420.1296.
Figure BDA0002326294240000265
N-((1S,2R)-2-amino-2-(pyridin-2-yl)-1-(thiophen-3-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000266
1H NMR(600MHz,CD3OD)δ8.50(d,J＝4.5Hz,1H),7.70(ddd,J＝15.8,6.9,4.8Hz,4H),7.61–7.51(m,3H),7.49–7.46(m,2H),7.42–7.39(m,2H),7.27–7.23(m,2H),7.04(d,J＝7.8Hz,1H),6.88(d,J＝1.8Hz,1H),6.85(d,J＝4.9Hz,1H),4.53(t,J＝9.1Hz,1H),4.35(dd,J＝7.8,3.8Hz,1H)；13C NMR(151MHz,CD3OD)δ157.71,148.71,141.34,136.60,132.19,132.12,132.08,132.01,131.99,131.93,131.87,131.43,131.37,128.40,128.31,128.26,128.18,125.85,125.68,123.44,122.91,122.15,61.57,61.54,57.35；HRMS(ESI):calcd.forC23H23N3OPS(M+H)+:420.1294,found:420.1293.
Figure BDA0002326294240000271
N-((1S,2R)-2-amino-2-(4-methoxypyridin-2-yl)-1-phenylethyl)-P,P-diphenylphosphinicamide:
Figure BDA0002326294240000272
J＝12.2,7.5Hz,2H),7.64(dd,J＝12.3,7.4Hz,2H),7.58–7.55(m,1H),7.51–7.45(m,4H),7.36–7.34(m,1H),7.18–7.16(m,3H),7.00–6.98(m,2H),6.76(dd,J＝5.7,2.3Hz,1H),6.45(d,J＝2.1Hz,1H),4.39–4.32(m,2H),3.65(s,3H)；13C NMR(151MHz,CD3OD)δ166.34,158.06,149.94,139.85,132.26,132.20,132.09,132.07,131.47,131.40,128.44,128.36,128.27,128.19,128.09,127.41,126.96,109.72,109.31,61.64,61.61,60.93,54.51；HRMS(ESI):calcd.for C26H27N3O2P(M+H)+:444.1835,found:444.1836.
Figure BDA0002326294240000273
N-((1S,2R)-2-amino-2-(5-bromopyridin-2-yl)-1-phenylethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000274
12.39min；1H NMR(600MHz,CDCl3)δ8.53(s,1H),7.62–7.55(m,5H),7.44–7.38(m,2H),7.34–7.30(m,2H),7.29–7.26(m,2H),7.21–7.16(m,3H),7.11(d,J＝6.9Hz,2H),6.87(d,J＝8.3Hz,1H),5.21–5.16(m,1H),4.44–4.38(m,2H)；13C NMR(151MHz,CDCl3)δ158.66,149.95,141.00,140.98,138.69,132.78,132.45,132.38,132.32,131.93,131.78,131.72,131.70,131.68,131.59,128.42,128.34,128.32,128.28,128.19,127.35,127.14,123.95,119.26,61.58,61.55,60.86；HRMS(ESI):calcd.for C25H24BrN3OP(M+H)+:492.0835,found:492.0840.
Figure BDA0002326294240000275
N-((1S,2R)-2-amino-2-(6-methylpyridin-2-yl)-1-phenylethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000276
tR(minor)6.71min；1H NMR(600MHz,CDCl3)δ7.62(td,J＝12.5,7.6Hz,4H),7.43(t,J＝6.9Hz,1H),7.39(t,J＝7.0Hz,1H),7.36–7.30(m,3H),7.26–7.24(m,1H),7.18–7.15(m,3H),7.11–7.06(m,2H),6.99(d,J＝7.6Hz,1H),6.65(d,J＝7.6Hz,1H),5.73(t,J＝9.0Hz,1H),4.60(d,J＝6.6Hz,1H),4.41(dd,J＝16.7,9.9Hz,1H),2.47(s,3H)；13C NMR(151MHz,CDCl3)δ157.66,140.75,140.72,136.56,132.55,132.49,131.83,131.78,131.76,131.69,131.67,128.43,128.34,128.25,128.22,128.17,127.43,127.35,122.23,119.95,61.11,61.08,60.67,24.32 HRMS(ESI):calcd.for C26H27N3OP(M+H)+:428.1886,found:428.1877.
Figure BDA0002326294240000277
N-((1S,2R)-2-amino-1-phenyl-2-(quinolin-2-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000278
flow rate 1.0mL/min,T＝30℃),UV 210nm,tR(major)10.00min,tR(minor)6.52min；1HNMR(600MHz,CDCl3)δ8.05(d,J＝8.4Hz,1H),7.96(d,J＝8.4Hz,1H),7.79(d,J＝8.0Hz,1H),7.73(t,J＝7.6Hz,1H),7.62(dd,J＝11.9,7.6Hz,2H),7.55(t,J＝7.4Hz,1H),7.41–7.31(m,4H),7.26–7.18(m,7H),7.13–7.07(m,3H),5.35(t,J＝9.1Hz,1H),4.71(d,J＝5.2Hz,1H),4.54(td,J＝9.5,5.5Hz,1H)；13C NMR(151MHz,CDCl3)δ159.93,147.25,141.24,136.24,132.39,132.33,131.76,131.69,131.65,131.63,131.55,131.54,129.66,129.15,128.33,128.24,128.23,128.16,128.14,127.63,127.49,127.36,127.31,126.52,120.53,61.93,61.89,60.67；HRMS(ESI):calcd.for C26H27N3OP(M+H)+:464.1886,found:428.1878.
Figure BDA0002326294240000281
N-((1S,2S)-2-amino-1-phenyl-2-(pyridin-3-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000282
NMR(600MHz,CDCl3)δ8.33(s,1H),8.24–8.22(m,1H),7.82(d,J＝7.4Hz,1H),7.76(dd,J＝12.0,7.8Hz,2H),7.42(dd,J＝12.0,7.8Hz,2H),7.37(dd,J＝12.4,6.5Hz,2H),7.31–7.27(m,2H),7.17–7.12(m,2H),7.10–7.03(m,3H),6.98–6.92(m,3H),5.06(d,J＝10.1Hz,1H),4.58(dd,J＝21.4,10.7Hz,1H)；13C NMR(151MHz,CDCl3)δ149.81,149.34,139.32,136.14,132.85,132.78,132.23,131.90,131.83,131.48,131.27,130.43,129.56,128.70,128.61,128.47,128.29,128.20,127.73,127.50,123.28,60.24,58.28；HRMS(ESI):calcd.forC25H25N3OP(M+H)+:414.1730,found:414.1728.
Figure BDA0002326294240000283
N-((1S,2S)-2-amino-1-phenyl-2-(pyridin-4-yl)ethyl)-P,P-diphenylphosphinic amide:
Figure BDA0002326294240000284
(600MHz,CDCl3)δ8.30(s,2H),7.74(dd,J＝12.3,7.4Hz,2H),7.62(dd,J＝12.3,7.5Hz,2H),7.53(t,J＝7.2Hz,1H),7.47–7.42(m,3H),7.29(td,J＝7.7,3.3Hz,2H),7.21–7.14(m,3H),6.90(d,J＝4.0Hz,2H),6.83(d,J＝7.2Hz,2H),4.81–4.74(m,1H),4.22(q,J＝10.8Hz,1H),3.74(t,J＝10.0Hz,1H),1.44(s,9H)；13C NMR(151MHz,CDCl3)δ149.37,132.83,132.76,132.37,132.36,132.15,132.13,131.31,131.25,130.37,128.68,128.59,128.58,128.46,128.37,127.96,127.21,122.59,79.80,61.05,59.91,28.45；
Figure BDA0002326294240000285
N-((1S,2R)-2-amino-1-phenyl-2-(pyridin-2-yl)ethyl)-P,P-di-o-tolylphosphinic amide:
Figure BDA0002326294240000286
＝24.8,13.4,7.6Hz,2H),7.43(t,J＝7.6Hz,1H),7.32–7.25(m,2H),7.15–7.01(m,10H),6.91(d,J＝7.6Hz,1H),5.29–5.21(m,1H),4.55(dd,J＝15.2,9.1Hz,1H),4.44(d,J＝5.7Hz,1H),2.23(s,3H),2.11(s,3H)；13C NMR(151MHz,CDCl3)δ160.19,148.71,141.99,141.92,141.76,141.69,141.41,141.39,136.11,133.30,133.24,132.83,132.76,131.89,131.58,131.56,131.52,131.47,131.45,131.44,131.42,131.34,131.05,130.73,128.03,127.37,127.08,125.35,125.27,125.13,125.04,122.58,122.27,61.97,61.94,61.33,21.39,21.37,21.34,21.31；HRMS(ESI):calcd.for C27H29N3OP(M+H)+:442.2043,found:442.2038.
Figure BDA0002326294240000291
N-((1S,2R)-2-amino-1-phenyl-2-(pyridin-2-yl)ethyl)-P,P-bis(3,5-dimethylphenyl)phosphinicamide:
Figure BDA0002326294240000292
(m,1H),7.27–7.23(m,2H),7.21–7.15(m,5H),7.12–7.08(m,3H),7.03(s,1H),6.98(s,1H),6.83(d,J＝7.7Hz,1H),5.33(t,J＝7.5Hz,1H),4.54(d,J＝6.7Hz,1H),4.38(dd,J＝17.1,9.9Hz,1H),2.25(s,6H),2.15(s,6H)；13C NMR(151MHz,CDCl3)δ159.19,148.84,141.19,141.16,138.05,137.96,137.80,137.71,136.11,133.56,133.54,133.34,133.32,132.48,132.04,131.64,131.17,130.33,130.26,129.30,129.24,128.14,127.40,127.22,123.00,122.50,61.74,61.72,61.02,21.27,21.08；HRMS(ESI):calcd.for C29H33N3OP(M+H)+:470.2356,found:470.2358.
最后需要说明的是，上述描述仅仅为本发明的优选实施例，本领域的普通技术人员在本发明的启示下，在不违背本发明宗旨及权利要求的前提下，可以做出多种类似的表示，这样的变换均落入本发明的保护范围之内。

Claims (7)

1.一种化合物的制备方法，其特征在于，所述化合物的通式如下：
Figure FDA0002742651970000011
按以下步骤制备：将亚胺、催化剂与溶剂混合，然后加入胺甲基吡啶和有机碱，继续反应至胺甲基吡啶消失即可，其中亚胺和胺甲基吡啶的摩尔比为1.3:1；
其中亚胺的结构式为：
Figure FDA0002742651970000012
胺甲基吡啶的结构式为：
Figure FDA0002742651970000013
Ar为Ph、2-FC6H4、2-MeC6H4、3-FC6H4、3-ClC6H4、3-MeC6H4、3-OMeC6H4、4-FC6H4、4-ClC6H4、4-BrC6H4、4-OCF3C6H4、4-MeC6H4、3,4-Cl2C6H3、3,4-Me2C6H3、2-萘基、2-呋喃基、2-噻吩基、3-噻吩基、或3-1-(苯磺酰基)-1H-吲哚基；
PG为PO(Ph)2、PO(2-MeC6H4)2、PO(3,5-Me2C6H3)2或PO(2,6-Me2C6H3)2；
R为MeO、Br、Me、Ph或H；
催化剂的结构式为：
Figure FDA0002742651970000014
其中R1为H、Me、nPr、TMS、SiPh3、4-PhC6H4、4-ClC6H4、3,5-(MeO)2C6H3、3,5-(CF3)2C6H3、1-萘基、2-萘基、9-蒽基、9-菲基、I、Br、Cl、CF3或CN；
X为H、Br或NO2，R2为H、或Br；
R3为Me、Ph、4-TMSC6H4、2-萘基、MeO、tBuCOO、2,6-F2C6H3COO、4-FC6H4COO或Ph2P(O)；
Y为Br或H，R4为Ph、H、2-萘基、4-PhC6H4、4-TMSC6H4、4-tBuC6H4、3,5-(tBu)2C6H3或OH。
2.根据权利要求1所述的化合物的制备方法，其特征在于：将所述亚胺、催化剂溶解在溶剂中后，将其冷却至-20℃-20℃。
3.根据权利要求1或2所述的化合物的制备方法，其特征在于：所述溶剂的熔点大于0℃。
4.根据权利要求3所述的化合物的制备方法，其特征在于：所述有机碱为脒类化合物或胍类化合物，所述有机碱与所述胺甲基吡啶的摩尔比为1-10:1。
5.根据权利要求1所述的化合物的制备方法，其特征在于：还可以加入添加剂，将所述亚胺、催化剂与添加剂混合后，再与溶剂混合，所述添加剂为PhCOOH、水杨酸、水或无水Na2SO4，所述添加剂与所述胺甲基吡啶的摩尔比为5-35:1。
6.根据权利要4所述的化合物的制备方法，其特征在于：所述有机碱为DBU、DBN、
Figure FDA0002742651970000021
或TMG。
7.根据权利要求2所述的化合物的制备方法，其特征在于：所述溶剂为PhCH3、CH2Cl2、CHCl3、THF、CPME、EtOAc、CH3CN、iPrOH、PhCl、Et2O、CCl4、CH2ClCH2Cl、环己烷、MeOtBu、PhCl、PhOMe、PhCN、苯、PhEt、PhnBu、o-二甲苯、m-二甲苯、p-二甲苯或均三甲基苯中的任一种。
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