CN110746448B - 手性1,2-乙二胺骨架的硼氮配体及其制备方法与应用 - Google Patents
手性1,2-乙二胺骨架的硼氮配体及其制备方法与应用 Download PDFInfo
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- CN110746448B CN110746448B CN201810820557.8A CN201810820557A CN110746448B CN 110746448 B CN110746448 B CN 110746448B CN 201810820557 A CN201810820557 A CN 201810820557A CN 110746448 B CN110746448 B CN 110746448B
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- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
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- B01J31/182—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine comprising aliphatic or saturated rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- C07F7/083—Syntheses without formation of a Si-C bond
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Abstract
本发明公开了一种手性1,2‑乙二胺骨架的硼氮配体及其制备方法与应用。所述硼氮配体的结构式如式(I)所示：
其中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基；R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自氢、卤素、取代或未取代的C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基。本发明的制备方法简单，可以制成消旋或手性的硼氮配体，该配体可用作不对称催化反应的催化剂，具有经济实用性和工业应用前景。
Description
技术领域
本发明涉及一种手性1,2-乙二胺骨架的硼氮配体及其制备方法与应用，属于有机化学技术领域。
背景技术
不对称催化合成是当前有机合成化学研究领域中的热点(Ohkuma,T.；Kitamura,M.；Noyori, R.1999,Catalytic asymmetric synthesis.2nd Ed.)。而设计和开发优良的手性配体及催化剂体系是不对称催化合成的关键。由于手性1,2-乙二胺结构是一类常用的手性源，所形成的过渡金属配合物在不对称催化反应中立体选择性和化学选择性高等优点，这类配体的研究已引起有机化学工作者的广泛关注。近年来，硼基配体由于其强的给电子能力逐渐引起了人们的重视，如基于1,2-苯二胺的三齿PBP配体能够与金属铱、铑和钴形成相应的络合物，它们在惰性键活化和小分子活化等反应中表现出良好的催化性能(J.Am.Chem.Soc.2013,135,7142；J.Am.Chem. Soc.2013,135,15310.)。另一类硼基配体为双齿硼氮配体，成功地应用于铱催化的碳氢键硼化反应中(J.Am.Chem.Soc.2015,137,8058；J.Am.Chem.Soc.2017,139,91)。然而目前，手性的硼基配体还未见报道。本领域尚需研制一种新型的手性配体，经过简单的反应即可得到消旋体或具有光学活性(光学纯)的配体，并能够用于催化反应中。
发明内容
本发明的主要目的在于提供一种手性1,2-乙二胺骨架的硼氮配体及其制备方法，以克服现有技术的不足。
本发明的另一目的在于提供前述手性1,2-乙二胺骨架的硼氮配体的应用。
为实现前述发明目的，本发明采用的技术方案包括：
本发明实施例提供了一种手性1,2-乙二胺骨架的硼氮配体，它的结构式如式(I)所示：
其中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基；
R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自氢、卤素、取代或未取代的 C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基。
本发明实施例还提供了前述手性1,2-乙二胺骨架的硼氮配体的制备方法，其包括：
使包含式(II)所示的化合物、硼硅试剂、质子酸催化剂和有机溶剂的均匀混合反应体系于反应，获得具有如式(I)所示结构的手性1,2-乙二胺骨架的硼氮配体；
其中，在式(I)和式(II)中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基；
R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自氢、卤素、取代或未取代的 C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基。
本发明实施例还提供了前述手性1,2-乙二胺骨架的硼氮配体作为催化剂或在用于合成催化剂领域中的应用。
本发明实施例还提供了一种用于不对称催化反应的催化剂，它由前述手性1,2-乙二胺骨架的硼氮配体和过渡金属络合反应形成。
进一步地，所述催化剂用于二芳基甲胺的不对称碳氢键活化硼化反应中。
本发明实施例还提供了一类手性二芳基甲胺类化合物的制备方法，其包括：
在前述催化剂作用下，使式(Ⅲ)所示的化合物反应获得式(Ⅳ)所示的化合物；
其中，在式(Ⅲ)和式(Ⅳ)中，R13、R14分别至少独立地选自氢、取代或未取代的C1～C10的烷基或C3～C30的环烷基；C1～C10的烷基或芳基；
R15、R16、R17、R18分别至少独立地选自氢、卤素、酯基、酰胺基、酰基、氨基、取代或未取代的C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
R19至少独立地选自取代或未取代的C1～C10的烷基或C3～C30的环烷基。
与现有技术相比，本发明的有益效果在于：
1)本发明提供了一种新型的具有光学活性的手性1,2-乙二胺骨架的硼氮配体，能够用于过渡金属催化的不对称催化反应的催化剂；
2)本发明提供了一种简单可行的制备消旋或具有光学活性的手性1,2-乙二胺骨架的硼氮配体的方法，可方便地由消旋或光学纯的1,2-乙二胺经过简单的反应制备，避免了通过拆分的方法获得手性配体，具有经济实用性和工业应用前景。
附图说明
图1是本发明实施例9得到的8n化合物的X射线晶体衍射图。
具体实施方式
如前所述，鉴于现有技术的不足，本案发明人经过广泛而深入的研究，得以提出本发明的技术方案，即采用简单的反应即制得了手性1,2-乙二胺骨架的硼氮配体，省却了拆分的步骤，且该配体可用作不对称催化反应的催化剂，具有经济实用性和工业应用前景。
下面将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。
首先需说明的是，本发明说明书中述及的术语的释义均是本领域技术人员所知悉的。例如，其中一些术语的定义如下：
术语“烷基”表示饱和的线性或支链烃部分，如-CH3或-CH(CH3)2。
术语“烷氧基”表示指烷基与氧原子连结后的生成基团，如-OCH3，-OCH2CH3。
术语“环烷基”表示饱和的环状烃基部分，例如环己基。
术语“芳基”表示包含一个或多个芳环的烃基部分，包括但不限于苯基、亚苯基、萘基、亚萘基、芘基、蒽基、菲基等。
除非另外说明，本发明所述的烷基、烷氧基、环烷基和芳基同时包括取代的和未取代的部分。烷基、烷氧基、环烷基、和芳基上可能的取代基包括，但不限于：C1-C6的烷基、C1-C6的卤代烷基、C2-C6的烯基、C2-C6的炔基、C3-C10的环烷基、C3-C10的环烯基、C1-C6的烷氧基、芳基、羟基、卤素、氨基等。
本发明实施例的一个方面提供的一种手性1,2-乙二胺骨架的硼氮配体，它的结构式如式 (I)所示：
其中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基；
R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自氢、卤素、取代或未取代的 C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基。
其中所述取代是被以下取代基取代：卤素、C1-6烷基、C1-6卤代烷基、或C1-6烷氧基。
在一些实施例中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基等，但不限于此，其中，所述取代采用的取代基的个数为一个以上，优选为1～3，也就是说，所述取代是被取代基单取代、二取代或三取代。
进一步地，所述取代基至少独立地选自卤素、C1～C6的烷基、C1～C6的卤代烷基或C1～C6的烷氧基等，但不限于此。
在一些实施例中，R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自苯基、取代的苯基、C3～C6的环烷基、C2～C6的烷基或C1～C4的烷氧基等，但不限于此，其中，所述取代采用的取代基的个数为一个以上，优选为1～3，也就是说，所述取代是被取代基单取代、二取代或三取代。
进一步地，所述取代基至少独立地选自卤素、C1～C6的烷基、C1～C6的卤代烷基或C1～C6的烷氧基等，但不限于此。
在一些实施例中，Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基等，但不限于此，其中，所述取代采用的取代基的个数为一个以上，优选为1～3，也就是说，所述取代是被取代基单取代、二取代或三取代。
进一步地，所述取代基至少独立地选自卤素、C1～C6的烷基、C1～C6的卤代烷基或C1～C6的烷氧基等，但不限于此。
在另一优选例中，所述芳基选自苯基、亚苯基、萘基、亚萘基、芘基、蒽基、菲基等中的任意一种或两种以上的组合，但不限于此。
在另一优选例中，Ar1与Ar2为结构相同的基团。
在一些实施例中，所述配体包括下式(Ia)～(Id)中任一者所示的结构：
各式中，R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、Ar1、Ar2的定义如前所述。
其中具体地讲，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～ C10的烷基或芳基；
R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自氢、卤素、取代或未取代的 C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基。
在另一优选例中，所述配体包含式(Ia)所示的化合物和式(Ib)所示的化合物。
在另一优选例中，所述配体选自：下式(Ia)～(Id)中任一者所示的结构或者下式(Ia)～(Id)中任一者所示结构的对映体、消旋体或非对映异构体。其中，消旋体是指式(Ia)～(Id)所示化合物中的任一个化合物与其对映体组成的消旋体。
在另一更为具体的优选例中，所述配体包括下式(6a)～(6j)中任一者所示的结构或者下式(6a)～(6j)中任一者所示结构的对映体、消旋体或非对映异构体；
本发明实施例的另一个方面还提供了前述手性1,2-乙二胺骨架的硼氮配体的制备方法，其包括：
使包含式(II)所示的化合物、硼硅试剂、质子酸催化剂和有机溶剂的均匀混合反应体系于反应，获得具有如式(I)所示结构的手性1,2-乙二胺骨架的硼氮配体；
各式中，R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、Ar1和Ar2的定义如前文所述。
其中具体地讲，在式(I)和式(II)中，R1、R2、R3分别至少独立地选自取代或未取代的 C3～C10的环烷基、C1～C10的烷基或芳基；
R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自氢、卤素、取代或未取代的 C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基。
在一些实施例中，所述Ar1与所述Ar2的结构相同。
在一些实施例中，所述硼硅试剂的化学式为R1R2R3Si-B(NiPr2)2，其中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基。
进一步地，在有机溶剂中，在质子酸催化剂的作用下，式(II)所示的化合物与R1R2R3Si- B(NiPr2)2反应，直接得到式(I)所示的化合物。其中，所述反应的反应式为：
在另一优选例中，所述硅硼试剂与式(II)所示的化合物的摩尔比为1:1～3:1，优选为 1.5:1～2:1。
在另一优选例中，所述质子酸催化剂与式(II)所示的化合物的摩尔比为0.001:1～1:1，优选为0.05:1～0.5:1。
进一步地，所述质子酸催化剂包括H2SO4、H3PO4、HCl、HBr、CH3CO2H、PhCO2H、CF3CO2H、CF3SO3H、p-CH3-C6H5SO3H、MeSO3H和tBuCO2H等中的任意一种或两种以上的组合，优选为HCl，但不限于此。
进一步地，所述有机溶剂包括苯、甲苯、二甲苯、二氯甲烷、氯仿、四氯化碳、1,2-二氯乙烷、***、1,4-二氧六环、四氢呋喃、甲醇、乙醇、N,N-二甲基甲酰胺和二甲基亚砜等中的任意一种或两种以上的组合，但不限于此。
在另一优选例中，所述反应的温度为0～180℃，优选为80～180℃，所述反应的时间为1～ 48h，优选为12～36h。
本发明实施例的另一个方面还提供了前述的手性1,2-乙二胺骨架的硼氮配体作为催化剂或在用于合成催化剂领域中的应用。
进一步地，所述催化剂为前述手性1,2-乙二胺骨架的硼氮配体和过渡金属形成的络合物。
进一步地，所述催化剂为不对称催化反应的催化剂。
进一步地，本发明的配体化合物可作为不对称催化反应的催化剂。在1,2-乙二胺骨架的包含芳基取代基，通过芳基取代基的改变可对手性环境进行有效的调节，从而调节配体在不同的不对称催化反应中的手性控制能力。
在一优选例中，本发明的配体与过渡金属络合后可作为催化剂，用于二芳基甲胺的不对称碳氢键活化硼化反应中，用于制备一类具有广泛用途的手性的二芳基甲胺类化合物。
本发明实施例的另一个方面还提供了一种用于不对称催化反应的催化剂，它由前述手性 1,2-乙二胺骨架的硼氮配体和过渡金属络合反应形成。
进一步地，所述催化剂用于二芳基甲胺的不对称碳氢键活化硼化反应中。
相应的，本发明实施例的另一个方面还提供了一类手性二芳基甲胺类化合物的制备方法，其包括：
在前述催化剂作用下，使式(Ⅲ)所示的化合物反应获得式(Ⅳ)所示的化合物；
其中，在式(Ⅲ)和式(Ⅳ)中，R13、R14分别至少独立地选自氢、取代或未取代的C1～C10的烷基或C3～C30的环烷基；C1～C10的烷基或芳基；
R15、R16、R17、R18分别至少独立地选自氢、卤素、酯基、酰胺基、酰基、氨基、取代或未取代的C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
R19至少独立地选自取代或未取代的C1～C10的烷基或C3～C30的环烷基。
优选的，所述催化剂与式(Ⅲ)所示的化合物的摩尔比为0.001：1～0.02：1。
优选的，所述反应的温度为40～100℃，时间2～72h。
具体地，所述手性二芳基甲胺类化合物的制备方法的反应式如下：
藉由上述技术方案，本发明提供的新型的具有光学活性的手性1,2-乙二胺骨架的硼氮配体，能够用于过渡金属催化的不对称催化反应的催化剂；并且，本发明提供了一种简单可行的制备消旋或具有光学活性的手性1,2-乙二胺骨架的硼氮配体的方法，可方便地由消旋或光学纯的1,2-乙二胺经过简单的反应制备，避免了通过拆分的方法获得手性配体，具有经济实用性和工业应用前景。
为了进一步理解本发明，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，该领域技术人员在本发明核心指导思想下做出的非本质改进和调整，仍然属于本发明的保护范围。下列实施例中未注明具体条件的实验方法，通常按照常规条件或按照制造厂商所建议的条件。
下面所用的实施例中所采用的实验材料，如无特殊说明，均可由常规的生化试剂商店购买得到。
实施例1
本实施例中，式3a化合物的制备方法操作步骤如下，反应路线如下所示。
在手套箱中，向50mL单口瓶中加入2-苯基溴苯2a(2.33g，10.0mmol)，(S,S)-1,2-苯基- 1,2-乙二胺1a(4.24g，20.0mmol，2.0equiv)，Pd2(dba)3(230mg，0.25mmol)，消旋BINAP (310mg，0.5mmol)，叔丁醇钠(1.34g，14.0mmol，1.4equiv)，甲苯15mL，110℃回流18h；冷却到室温后加入20mL乙酸乙酯稀释，用20mL水洗，分离有机相，水相用乙酸乙酯萃取三次(3x 20mL)，合并有机相，用无水硫酸钠干燥，过滤；母液浓缩后经柱层析分离(石油醚/乙酸乙酯＝10：1)，得2.19g淡黄色固体式3a化合物，产率为60％。
经检测，本实施例所获式3a化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.48 (dd,J＝14.1,6.8Hz,1H),7.39(t,J＝8.8Hz,1H),7.28(d,J＝4.0Hz,2H),7.19(dd,J＝12.5,5.2Hz, 2H),7.14(d,J＝7.2Hz,1H),7.01(d,J＝7.2Hz,1H),6.92(t,J＝7.6Hz,1H),6.59(t,J＝7.2Hz,1H), 6.20(d,J＝8.0Hz,1H),5.33(s,1H),4.45(s,1H),4.24(d,J＝3.2Hz,1H)；13C NMR(100MHz, CDCl3)δ144.0,142.5,141.2,139.5,129.8,129.5,129.5,128.7,128.5,128.3,128.1,127.6,127.2, 127.2,127.1,126.8,126.6,116.2,111.3,63.5,60.7；HRMS(ESI)calcd for C26H24N2([M+H]+) 365.2012,found 365.2015.
实施例2
参考实施例1的制备方法，分别制备了式3b-3j化合物，其结构分别如下式所示：
经检测，本实施例所获式3b化合物为2.25g淡黄色固体，产率为60％，
(c 0.96,CHCl3)。式3b化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.42–7.16(m, 14H),7.01(d,J＝7.2Hz,1H),6.94(t,J＝7.6Hz,1H),6.60(t,J＝7.2Hz,1H),6.20(d,J＝8.4Hz, 1H),5.34(d,J＝5.2Hz,1H),4.47(brs,1H),4.29(brs,1H),2.47(s,3H)；13C NMR(101MHz,CDCl3) δ144.07,142.54,141.26,136.66,136.48,129.91,129.38,128.52,128.10,127.63,127.21,127.15, 126.84,126.69,116.24,111.21,63.55,60.82,21.29；HRMS(ESI)calcd for C27H27N2([M+H]+) 379.2169,found 379.2171.
经检测，本实施例所获式3c化合物为2.45g淡黄色固体，产率为61％，
(c 0.72,CHCl3)。式3c化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.25–7.19(m,10H), 7.01(s,3H),6.90(d,J＝7.2Hz,1H),6.41(d,J＝7.2Hz,1H),6.06(s,1H),5.37(brs,1H),4.49(brs, 1H),4.24(brs,1H),2.40(s,6H),2.08(s,3H)；13C NMR(100MHz,CDCl3)δ143.8,142.6,141.3, 139.4,138.0,137.8,129.7,128.6,128.4,128.0,127.3,127.1,127.0,126.8,126.7,125.3,117.0,111.9, 63.4,60.8,21.5,21.4；HRMS(ESI)calcd for C29H31N2([M+H]+)407.2482,found 407.2481.
经检测，本实施例所获式3d化合物为2.02g淡黄色固体，产率为45％，
(c 0.65,CHCl3)。式3d化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.27–7.02(m, 10H),6.93(d,J＝7.2Hz,1H),6.92(t,J＝7.2Hz,1H),6.60–6.53(m,4H),6.22(d,J＝8.0Hz,1H), 4.45(brs,1H),4.24(brs,1H),3.81(s,6H)；13C NMR(101MHz,CDCl3)δ160.9,143.9,142.4,141.4, 141.2,129.4,128.4,128.3,128.1,127.5,127.1,126.8,126.7,116.1,111.2,107.4,99.4,63.4,60.8, 55.3.HRMS(ESI)calcd forC28H28N2NaO2([M+Na]+)447.2043,found 447.2045.
经检测，本实施例所获式3e化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.26 (s,1H),7.25(s,2H),7.21–7.09(m,10H),7.04(dd,J＝7.2,1.2Hz,1H),6.93–6.88(m,1H),6.58(t, J＝7.2Hz,1H),6.22(d,J＝8.0Hz,1H),5.48(d,J＝4.8Hz,1H),4.45(s,1H),4.21(d,J＝3.6Hz, 1H),2.72(q,J＝7.6Hz,4H),1.31(t,J＝7.6Hz,6H)；13C NMR(100MHz,CDCl3)δ144.8,144.3, 143.0,141.7,139.8,130.1,128.7,128.4,128.3,128.3,127.4,127.1,126.9,126.7,126.6,116.4,111.4, 63.7,61.2,29.2,16.0；HRMS(ESI)calcd forC30H32N2Na([M+Na]+)443.2458,found 443.2466.
经检测，本实施例所获式3f化合物为2.84g淡黄色固体，产率为64％，
(c 0.8,CHCl3)。式3f化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.30–7.06(m,14H), 6.94(t,J＝7.6Hz,1H),6.61(t,J＝7.6Hz,1H),6.24(d,J＝8.0Hz,1H),5.49(s,1H),4.44(d,J＝1.6 Hz,1H),4.23(d,J＝3.2Hz,1H),3.05–2.95(m,2H),1.35(d,J＝6.4Hz,6H),1.34(d,J＝6.8Hz, 6H)；13C NMR(100MHz,CDCl3)δ149.2,144.1,142.7,141.5,139.3,129.7,128.5,128.4,128.1, 128.0,127.2,127.1,126.9,126.7,124.9,123.7,116.2,111.1,63.4,60.9,34.3,24.3,24.1；HRMS(ESI) calcd for C32H37N2Na([M+H]+)449.2951,found 449.2950.
经检测，本实施例所获式3g化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.50 (s,1H),7.33–7.22(m,7H),7.09–7.03(m,6H),6.95(t,J＝7.6Hz,1H),6.62(t,J＝7.2Hz,1H),6.24 (d,J＝8.0Hz,1H),5.49(s,1H),4.41(s,1H),4.21(d,J＝3.2Hz,1H),1.42(s,18H)；13C NMR(100 MHz,CDCl3)δ151.0,144.2,142.6,141.6,138.6,129.7,128.8,128.5,128.1,128.0,127.1,127.1, 126.9,126.6,123.7,121.0,116.1,111.0,63.3,61.0,35.0,31.6；HRMS(ESI)calcd for C34H41N2 ([M+H]+)477.3264,found 477.3262.
经检测，本实施例所获式3h化合物为2.51g淡黄色固体，产率为50％，
(c 0.87,CHCl3)。式3h化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.97(s,2H),7.95(s, 1H),7.44–6.93(m,10H),6.65(t,J＝7.2Hz,1H),6.26(d,J＝8.0Hz,1H),5.46(d,J＝4.4Hz,1H), 4.47(brs,1H),4.27(brs,1H)；13C NMR(101MHz,CDCl3)δ143.9,142.6,142.0,141.1,132.0(q,JCF＝33Hz),130.1,129.8,128.7,128.3,127.5,127.4,126.7,126.3,124.4,123.4(q,JCF＝270Hz),121.0 (q,JCF＝3.7Hz)116.8,112.1,63.3,60.8.HRMS(ESI)calcd for C28H22F6N2([M+H]+)501.1760, found 501.1762.
经检测，本实施例所获式3i化合物为3.95g淡黄色固体，产率为75％，
(c 0.94,CHCl3)。式3i化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.88(s,1H),7.75(d, J＝7.6Hz,4H),7.66(s,2H),7.50(t,J＝7.2Hz,4H),7.40(t,J＝7.2Hz,2H),7.35–7.27(m,4H), 7.26–7.19(m,1H),7.15(d,J＝7.2Hz,1H),7.11–6.90(m,6H),6.65(t,J＝7.2Hz,1H),6.26(d,J＝ 8.4Hz,1H),5.59(brs,1H),4.49(brs,1H),4.27(brs,1H)；13C NMR(100MHz,CDCl3)δ157.6,147.8, 144.0,142.2,140.8,140.3,139.6,138.9,137.2,130.1,128.8,128.6,128.3,128.2,128.1,127.5,127.4, 127.3,127.1,127.2,125.0,117.3,113.4,111.9,107.41,63.4,61.0；HRMS(ESI)calcd for C38H33N2 ([M+H]+)517.2638,found 517.2634.
经检测，本实施例所获式3j化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.25– 7.19(m,10H),7.01(s,3H),6.90(d,J＝7.2Hz,1H),6.41(d,J＝7.2Hz,1H),6.06(s,1H),5.37(s, 1H),4.49(s,1H),4.24(s,1H),2.40(s,6H),2.08(s,3H)；13C NMR(100MHz,CDCl3)δ143.8,142.6, 141.3,139.4,138.0,137.8,129.7,128.6,128.4,128.0,127.3,127.1,127.0,126.8,126.7,125.3,117.0, 111.9,63.4,60.8,21.5,21.4；HRMS(ESI)calcdfor C29H31N2([M+H]+)407.2482,found 407.2481.
实施例3
本实施例中，式5a化合物的制备方法操作步骤如下，反应路线如下所示。
在手套箱中，向50毫升单口烧瓶中加入实施例1中制备好的化合物3a(1.82g，5.0mmol)，2-溴吡啶4a(0.87g，5.5mmol)，Pd2dba3(114mg，0.125mmol)，Xantphos(0.145 mg，0.25mmol)，叔丁醇钠(670mg，7.0mmol，1.4equiv)，甲苯7.5mL。110℃回流18h。冷却至室温后过滤，加入20mL乙酸乙酯稀释，用20mL水洗，分离有机相，水相用乙酸乙酯萃取三次(3x20mL)，合并有机相，用无水硫酸钠干燥，过滤；母液浓缩后经柱层析分离(石油醚/乙酸乙酯＝20:1)，得1.66g淡黄色固体式5a化合物，产率为75％。
经检测，本实施例所获式5a化合物
(c 1.58,CHCl3)。式5a化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.89(d,J＝4.0Hz,1H),7.41–7.26(m,5H),7.23–7.06(m, 9H),7.04–6.88(m,4H),6.66(t,J＝7.2Hz,1H),6.44(d,J＝6.4Hz,1H),6.39(d,J＝8.0Hz,1H), 6.04(d,J＝8.4Hz,1H),5.05(d,J＝6.4Hz,1H),4.95(t,J＝6.4Hz,1H),4.89(d,J＝4.8Hz,1H), 4.71(t,J＝5.6Hz,1H)；13C NMR(100MHz,CDCl3)δ157.5,148.0,143.7,139.4,139.1,138.9,137.2, 129.9,129.3,128.8,128.3,127.4,127.3,127.1,117.2,113.3,111.7,107.2,63.1,61.0；HRMS(ESI) calcd for C31H28N3([M+H]+)442.2278,found442.2282.
实施例4
参考实施例3的制备方法，分别制备了式5b-5j化合物，其结构分别如下式所示：
经检测，本实施例所获式5b化合物为1.85g淡黄色固体，产率为76％，
(c 0.87,CHCl3)。式5b化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.92(brs,1H),7.22 –6.93(m,17H),6.67(t,J＝7.2Hz,1H),6.46(t,J＝5.2Hz,1H),6.37(d,J＝8.0Hz,1H),6.08(d,J＝ 8.4Hz,1H),5.05(d,J＝5.2Hz,1H),4.94(t,J＝5.6Hz,1H),4.88(d,J＝3.6Hz,1H),4.71(d,J＝4.4 Hz,1H),2.40(s,3H)；13C NMR(100MHz,CDCl3)δ157.6,148.0,143.9,139.6,139.0,137.2,136.7, 136.1,129.9,129.5,129.2,128.3,128.2,127.4,127.2,117.2,113.3,111.7,107.3,63.2,61.0,21.2； HRMS(ESI)calcd forC32H29N3Na([M+Na]+)478.2259,found 478.2263.
经检测，本实施例所获式5c化合物为1.32g淡黄色固体，产率为56％，
(c 0.81,CHCl3)。式5c化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.96(d,J＝4.8Hz, 1H),7.27–6.90(m,16H),6.67(t,J＝7.6Hz,1H),6.53–6.47(m,1H),6.39(d,J＝8.4Hz,1H),6.10 (d,J＝8.4Hz,1H),5.12(d,J＝6.4Hz,1H),4.90(t,J＝6.4Hz,1H),4.85(d,J＝4.8Hz,1H),4.71(t, J＝6.0Hz,1H),2.31(s,6H)；13C NMR(100MHz,CDCl3)δ157.7,148.1,143.7,139.5,139.0,138.3, 137.3,129.8,128.9,128.6,128.3,128.2,127.6,127.5,127.4,127.3,127.1,117.2,113.5,111.6,107.2, 63.1,61.1,21.3；HRMS(ESI)calcd for C33H32N3([M+H]+)470.2596,found 470.2594.
经检测，本实施例所获式5d化合物为1.26g淡黄色固体，产率为50％，
(c 0.62,CHCl3)。式5d化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.95(d,J＝3.6Hz, 1H),7.25–7.00(m,11H),6.92(d,J＝6.8Hz,2H),6.67(t,J＝7.2Hz,1H),6.52–6.46(m,4H),6.40 (d,J＝8.0Hz,1H),6.12(d,J＝8.4Hz,1H),5.05(d,J＝6.8Hz,1H),4.97–4.93(m,2H),4.73(t,J＝ 5.6Hz,1H),3.82(s,6H)；13C NMR(100MHz,CDCl3)δ161.0,157.6,148.0,143.7,141.1,139.4, 138.8,137.3,129.6,128.5,128.3,127.6,127.5,127.3,117.0,113.5,111.7,107.3,107.1,99.8,82.8, 60.9,55.3；HRMS(ESI)calcdfor C33H32N3O2([M+H]+)502.2495,found 502.2486.
经检测，本实施例所获式5e化合物为1.42g淡黄色固体，产率为57％，
(c 1.54,CHCl3)。式5e化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.94(d,J＝5.2Hz, 1H),7.26–7.00(m,14H),6.91(d,J＝7.2Hz,2H),6.69(t,J＝7.2Hz,1H),6.52–6.47(m,1H),6.43 (d,J＝8.0Hz,1H),6.09(d,J＝8.8Hz,1H),5.22(d,J＝6.0Hz,1H),4.88(t,J＝6.0Hz,2H),4.71(t, J＝6.0Hz,1H),2.63(q,J＝7.6Hz,4H),1.23(t,J＝7.6Hz,6H)；13C NMR(100MHz,CDCl3)δ 157.6,147.8,144.7,143.7,139.4,139.0,138.9,137.4,129.9,128.8,128.3,128.2,127.5,127.4,127.3, 127.2,126.5,126.2,117.2,113.4,111.6,107.2,63.0,61.0,28.8,15.6；HRMS(ESI)calcd for C35H36N3 ([M+H]+)498.2729,found 498.2724.
经检测，本实施例所获式5f化合物为1.92g淡黄色固体，产率为70％，
(c 0.56,CHCl3)。式5f化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.91(d,J＝4.4Hz, 1H),7.21–7.00(m,14H),6.89(d,J＝7.2Hz,2H),6.69(t,J＝7.2Hz,1H),6.47(d,J＝7.2Hz,2H), 6.06(d,J＝8.4Hz,1H),5.13(d,J＝6.0Hz,1H),4.93(d,J＝5.2Hz,1H),4.88(t,J＝6.0Hz,1H), 4.71(t,J＝5.6Hz,1H),2.96–2.84(m,2H),1.25(d,J＝6.8Hz,12H)；13C NMR(100MHz,CDCl3)δ 157.6,149.3,148.0,143.7,139.4,139.0,138.9,137.2,129.9,129.0,128.3,128.2,128.1,127.5,127.5, 127.3,127.2,124.8,123.8,117.2,113.4,111.5,107.2,62.9,61.0,34.1,24.2,24.0；HRMS(ESI)calcd for C37H39N3Na([M+Na]+)548.3042,found 548.3048.
经检测，本实施例所获式5g化合物为2.14g淡黄色固体，产率为77％，
(c 0.80,CHCl3)。式5g化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.89(d,J＝4.8Hz, 1H),7.43(s,1H),7.26(s,2H),7.21(m,4H),7.11–7.00(m,7H),6.87(d,J＝7.6Hz,2H),6.71(t,J＝ 7.2Hz,1H),6.48(dd,J＝13.2,7.2Hz,2H),6.06(d,J＝8.4Hz,1H),5.09(d,J＝6.0Hz,1H),4.93(d, J＝5.6Hz,1H),4.89(t,J＝5.6Hz,1H),4.71(t,J＝5.6Hz,1H),1.34(s,18H)；13C NMR(100MHz, CDCl3)δ157.5,151.1,148.0,143.8,139.4,138.9,138.2,137.1,130.0,129.5,128.3,128.2,128.1, 127.5,127.5,127.3,127.1,123.6,121.1,117.2,113.4,111.5,107.3,62.8,60.9,34.9,31.5；HRMS(ESI) calcd forC39H44N3([M+H]+)554.3535,found 554.3519.
经检测，本实施例所获式5h化合物为2.10g淡黄色固体，产率为70％，
(c 1.20,CHCl3)。式5h化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.86(s,3H),7.68(d, J＝4.4Hz,1H),7.29–7.03(m,11H),6.97–6.92(m,3H),6.71(t,J＝7.2Hz,1H),6.56(d,J＝8.4Hz, 1H),6.45(t,J＝6.0Hz,1H),6.15(d,J＝8.4Hz,1H),5.10(m,2H),4.82(d,J＝6.8Hz,1H),4.73(t,J ＝6.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.5,147.5,143.9,141.9,139.6,139.0,137.2,132(q, JCF＝33.0Hz),130.1,129.8,128.4,128.3,127.7,127.6,127.2,125.0,123.3(q,JCF＝271.1Hz),121.0 (q,JCF＝4.1Hz),,117.5,113.6,112.2,108.0,63.7,60.7；HRMS(ESI)calcd for C33H25F6N3Na ([M+Na]+)600.1850,found 600.1850.
经检测，本实施例所获式5i化合物为1.63g淡黄色固体，产率为55％，
(c 1.27,CHCl3)。式5i化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.81(s,2H),7.66(d, J＝7.2Hz,4H),7.58(s,2H),7.46(t,J＝7.2Hz,4H),7.38(t,J＝7.2Hz,2H),7.23–6.87(m,13H), 6.72(t,J＝7.2Hz,1H),6.49(d,J＝8.0Hz,1H),6.38(t,J＝5.6Hz,1H),6.00(d,J＝8.4Hz,1H), 5.15–5.05(m,2H),4.97(t,J＝5.2Hz,1H),4.76(s,1H)；13C NMR(100MHz,CDCl3)δ157.7,148.0, 144.1,142.4,141.0,140.4,139.7,139.1,137.3,130.2,129.0,128.8,128.5,128.4,128.3,127.6,127.5, 127.4,127.3,127.2,125.2,117.5,113.5,112.1,107.6,63.5,61.1；HRMS(ESI)calcd for C43H36N3 ([M+H]+)594.2909,found 594.2905.
经检测，本实施例所获式5j化合物为1.64g淡黄色固体，产率为65％，
(c 0.83,CHCl3)。式5j化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.97(s,1H),7.28– 7.06(m,9H),6.89–6.98(m,6H),6.47–6.53(m,2H),6.24(s,1H),6.10(d,J＝8.0Hz,1H),5.14(d, J＝5.6Hz,1H),4.90(t,J＝6.4Hz,1H),4.79(d,J＝4.0Hz,1H),4.71(t,J＝6.0Hz,1H),2.29(s,6H), 2.15(s,3H)；13C NMR(100MHz,CDCl3)δ157.7,148.1,143.6,139.5,139.1,139.0,138.2,137.9, 137.3,129.7,128.7,128.3,128.2,127.6,127.5,127.4,127.3,127.2,125.9,118.0,113.4,112.4,107.2, 63.0,60.9,21.6,21.3；HRMS(ESI)calcd for C34H33N3Na([M+H]+)506.2572,found 506.2576.
实施例5-1
本实施例中，式(S,S)-6a化合物的制备方法操作步骤如下，反应路线如下所示。
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(520mg，1.50mmol，1.5equiv)，甲苯1.0mL，并加入5μL盐酸的1,4二氧六环溶液(4M)，在160℃下反应24h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物。
经检测，本实施例所获式6a化合物为360mg白色固体，产率为61％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ8.07(d,J＝4.4Hz,1H),7.71(d,J＝6.8Hz,2H),7.30–7.12(m,13H),7.05–6.96(m,9H),6.89(d,J＝7.2Hz,1H),6.63(t,J＝6.0Hz,1H),6.03(d,J＝8.4Hz,1H), 4.79(s,1H),3.98(s,1H),0.32(s,3H),0.22(s,3H).；13C NMR(100MHz,CDCl3)δ156.5,147.3, 142.8,142.4,142.2,140.7,139.7,138.0,137.1,134.3,131.5,130.5,128.7,128.5,128.2,128.1,127.9, 127.6,127.3,127.1,127.0,126.8,126.6,125.9,125.3,115.6,109.0,75.2,70.4,-0.6,-1.0；HRMS(ESI) calcd for C39H37BN3Si([M+H]+)586.2850,found 586.2860.
实施例5-2
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(1040mg，3.0mmol，3.0equiv)，甲苯1.0mL，并加入5μL盐酸的1,4二氧六环溶液(4M)，在160℃下反应24h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率48％。
实施例5-3
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(347mg，1.0mmol，1.0equiv)，甲苯1.0mL，并加入5μL盐酸的 1,4二氧六环溶液(4M)，在160℃下反应24h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率30％。
实施例5-4
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(520mg，1.50mmol，1.5equiv)，甲苯1.0mL，并加入2.5μL盐酸的1,4二氧六环溶液(4M)，在160℃下反应24h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率20％。
实施例5-5
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(520mg，1.50mmol，2.0equiv)，甲苯1.0mL，并加入10μL盐酸的1,4二氧六环溶液(4M)，在80℃下反应24h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率38％。
实施例5-6
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(520mg，1.50mmol，1.5equiv)，甲苯1.0mL，并加入5μL盐酸的1,4二氧六环溶液(4M)，在0℃下反应48h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率3％。
实施例5-7
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(520mg，1.50mmol，1.5equiv)，甲苯1.0mL，并加入5μL盐酸的1,4二氧六环溶液(4M)，在180℃下反应1h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率55％。
实施例5-8
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(520mg，1.50mmol，1.5equiv)，甲苯1.0mL，并加入5μL盐酸的1,4二氧六环溶液(4M)，在160℃下反应12h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率32％。
实施例5-9
在手套箱中，向25mL史莱克管中加入实施例3中制备好的式5a化合物(442mg，1.0mmol)，PhMe2Si-B(NiPr2)2(520mg，1.50mmol，1.5equiv)，甲苯1.0mL，并加入5μL盐酸的1,4二氧六环溶液(4M)，在160℃下反应36h后，冷却到室温，除去溶剂，残余物用正己烷重结晶得到配体式6a化合物，收率60％。
实施例6
参考实施例5的制备方法，分别制备了式6b-6j化合物，其结构分别如下式所示：
经检测，本实施例所获式6b化合物为420mg白色固体，产率为70％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ8.07(d,J＝3.2Hz,1H),7.71(d,J＝6.4Hz,2H),7.30–6.85(m,20H),6.77(d,J＝7.6Hz,2H),6.68–6.60(m,1H),6.03(d,J＝8.2Hz,1H),4.78(s,1H),3.99(s,1H), 2.20(s,3H),0.32(s,3H),0.22(s,3H)；13C NMR(100MHz,CDCl3)δ156.6,147.7,147.3,142.8, 142.4,142.3,140.8,138.0,137.1,136.8,136.1,134.3,131.4,130.4,129.6,129.2,128.7,128.5,128.4, 127.9,127.7,127.5,127.1,126.8,126.7,125.9,125.4,115.5,109.0,75.3,70.3,21.1,-0.6,-1.1；HRMS (ESI)calcd for C40H39BN3Si([M+H]+)600.3001,found 600.3003.
经检测，本实施例所获式6c化合物为450mg黄色固体，产率为73％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.98(d,J＝4.0Hz,1H),7.68(d,J＝7.2Hz,2H),7.30–6.82(m,20H),6.69(s,1H),6.61–6.54(m,1H),5.99(d,J＝8.4Hz,1H),4.80(d,J＝3.2Hz,1H),4.15(d,J＝ 3.6Hz,1H),2.20(s,6H),0.29(s,3H),0.22(s,3H)；13C NMR(100MHz,CDCl3)δ156.5,147.1, 142.9,142.8,142.5,140.8,140.0,139.5,137.2,136.9,134.0,131.6,130.4,128.6,128.5,128.4,127.5, 127.4,127.1,126.8,126.3,125.8,125.1,115.4,108.8,76.3,70.5,21.4,-0.5,-0.7；HRMS(ESI)calcd for C41H41BN3Si([M+H]+)614.3163,found614.6164.
经检测，本实施例所获式6d化合物为426mg黄色固体，产率为66％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ8.02(d,J＝3.2Hz,1H),7.71(dd,J＝7.6,1.6Hz,2H),7.33–7.12 (m,10H),7.10–6.93(m,7H),6.89(d,J＝7.6Hz,1H),6.61(dd,J＝6.8,5.2Hz,1H),6.36(d,J＝2.4 Hz,2H),6.12(t,J＝2.0Hz,1H),6.04(d,J＝8.0Hz,1H),4.79(d,J＝2.8Hz,1H),4.20(d,J＝2.8Hz, 1H),3.71(s,6H),0.33(s,3H),0.17(s,3H)；13C NMR(100MHz,CDCl3)δ160.1,156.6,147.2,142.8, 142.6,142.4,142.0,140.7,138.8,137.1,134.2,131.6,130.3,128.6,128.5,128.3,127.7,127.6,127.5, 127.4,127.3,127.1,126.9,126.8,125.8,125.0,115.6,109.0,107.1,106.8,98.7,76.0,70.7,55.1,-0.5, -0.8.；HRMS(ESI)calcd for C41H41BN3O2Si([M+H]+)646.3061,found 646.3056.
经检测，本实施例所获式6e化合物为482mg黄色固体，产率为75％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ.97(d,J＝5.2Hz,1H),7.68(d,J＝7.2Hz,2H),7.25–6.99(m,15H),6.93–6.82(m,5H),6.74(s,1H),6.60–6.55(m,1H),5.99(d,J＝8.0Hz,1H),4.78(d,J＝3.2 Hz,1H),4.16(d,J＝3.2Hz,1H),2.59–2.43(m,4H),1.17(t,J＝7.6Hz,6H),0.31(s,3H),0.22(s, 3H)；13C NMR(100MHz,CDCl3)δ156.4,147.0,144.7,143.5,142.8,142.7,142.4,140.8,140.1, 139.7,136.9,134.6,134.2,134.0,131.5,130.4,128.4,128.2,128.0,127.7,127.5,127.4,127.3,127.0, 126.7,126.2,126.0,125.7,125.4,125.0,115.3,108.9,76.2,70.6,28.7,15.5,-0.6,-0.7.HRMS(ESI) calcd for C43H44BN3Si([M+H]+)642.3470,found 642.3480.
经检测，本实施例所获式6f化合物为435mg黄色固体，产率为65％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.94(d,J＝4.4Hz,1H),7.67(dd,J＝7.6,1.2Hz,2H),7.29–6.97 (m,16H),6.94–6.87(m,3H),6.82(d,J＝6.8Hz,2H),6.56(dd,J＝7.2,5.2Hz,1H),6.00(d,J＝8.4 Hz,1H),4.77(d,J＝4.2Hz,1H),4.23(d,J＝4.2Hz,1H),2.87–2.72(m,2H),1.21(d,J＝6.8Hz, 6H),1.18(d,J＝6.8Hz,6H),0.32(s,3H),0.17(s,3H)；13C NMR(100MHz,CDCl3)δ156.5,147.9, 147.0,143.0,142.8,142.3,140.9,140.3,136.9,134.0,131.8,130.6,128.6,128.4,128.2,128.1,127.6, 127.5,127.3,127.2,127.0,126.8,125.7,125.2,124.3,123.3,115.4,109.1,76.6,71.2,33.9,24.3,23.9, -0.3,-0.4.；HRMS(ESI)calcd for C45H49BN3Si([M+H]+)670.3789,found 670.3797.
经检测，本实施例所获式6g化合物为489mg黄色固体，产率为70％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.92(d,J＝4.1Hz,1H),7.66(d,J＝6.2Hz,2H),7.26–6.96(m,18H),6.92(d,J＝7.6Hz,1H),6.81(d,J＝6.4Hz,2H),6.60–6.51(m,1H),6.02(d,J＝8.4Hz,1H), 4.77(d,J＝4.2Hz,1H),4.35(d,J＝4.2Hz,1H),1.27(s,18H),0.31(s,3H),0.15(s,3H)；13C NMR (100MHz,CDCl3)δ156.6,149.9,147.0,143.0,142.9,142.2,141.0,140.9,140.0,136.9,134.1,131.9, 130.8,128.7,128.4,127.5,127.4,127.4,127.1,127.0,126.9,125.6,125.4,123.1,120.7,115.5,109.3, 76.6,71.5,31.5,-0.2,-0.5；HRMS(ESI)calcd for C47H53BN3Si([M+H]+)698.4102,found 698.4107.
经检测，本实施例所获式6h化合物为362mg黄色固体，产率为50％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ8.05(d,J＝4.4Hz,1H),7.59(d,J＝6.8Hz,2H),7.52(d,J＝8.0 Hz,3H),7.25–7.01(m,15H),6.91(dd,J＝19.6,14.8Hz,4H),6.65(dd,J＝7.2,5.2Hz,1H),5.99(d, J＝8.0Hz,1H),4.77(s,1H),3.85(s,1H),0.42(s,3H),0.25(s,3H)；13C NMR(100MHz,CDCl3)δ 156.3,147.3,142.2,142.1,141.7,140.9,137.2,136.7,134.0,132.0,130.5(q,JCF＝30.0Hz),130.0, 129.8,128.8,128.4,127.9,127.6,127.5,127.1,127.0,126.7,126.3,124.5,123.2(q,JCF＝270.7Hz), 120.6,115.9,109.1,77.6,70.3,-1.0,-1.1；HRMS(ESI)calcd for C41H35BF6N3Si([M+H]+)722.2597, found 722.2596.
经检测，本实施例所获式6i化合物为458mg黄色固体，产率为70％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.99(d,J＝2.4Hz,1H),7.70–7.58(m,7H),7.53–7.46(m 6H),7.43 –7.36(m,3H),7.23–7.08(m,9H),7.05(d,J＝6.8Hz,3H),6.96(s,2H),6.80(s,3H),6.62–6.54(m, 1H),5.95(d,J＝7.1Hz,1H),4.80(s,1H),4.27(s,1H),0.35(s,3H),0.28(s,3H)；13C NMR(100MHz, CDCl3)δ156.5,147.1,142.6,142.5,142.3,142.2,141.3,141.0,140.6,139.0,137.0,134.1,131.8, 130.6,128.8,128.6,128.5,127.6,127.4,127.4,127.2,127.1,126.8,126.2,126.0,124.8,124.4,115.6, 109.1,76.7,70.8,-0.4,-0.7；HRMS(ESI)calcd for C51H45BN3Si([M+H]+)738.3476,found 738.3475.
经检测，本实施例所获式6j化合物为434mg黄色固体，产率为69％，其核磁共振数据为：1H NMR(400MHz,CDCl3)δ8.03(d,J＝2.8Hz,1H),7.69(d,J＝6.4Hz,2H),7.26–7.09(m,9H), 7.03(d,J＝6.0Hz,2H),6.97–6.76(m,7H),6.67(s,2H),6.58(s,1H),5.99(d,J＝8.4Hz,1H),4.77 (s,1H),4.16(s,1H),2.18(s,6H),2.10(s,3H),0.32(s,3H),0.25(s,3H)；13C NMR(100MHz,CDCl3) δ156.6,147.7,147.3,142.8,142.4,142.3,140.8,138.0,137.1,136.8,136.1,134.3,131.4,130.4,129.6, 129.2,128.7,128.5,128.4,127.9,127.7,127.5,127.1,126.8,126.7,125.9,125.4,115.5,109.0,75.3, 70.3,21.1,20.7,-0.6,-1.1；HRMS(ESI)calcd for C42H43BN3O2Si([M+H]+)628.3319,found 628.3320.
实施例7
在本实施例中，以不同的硼氮配体(S,S)-6与各类金属前体现场制备催化剂，应用于不对称的C-H键硼化反应中，制备手性化合物8a。
反应步骤如下：向25mL干燥的史莱克管中，加入配体6a-6j(0.01mmol)，金属前体(0.005mmol)，7a(21.2mg，0.10mmol)，B2pin2(25.4mg，0.10mmol)，加入溶剂1.0mL。在加热条件下反应后冷却至室温，旋蒸除去溶剂，残留物用硅胶进行柱层析分离(石油醚/乙酸乙酯＝10:1)，得到硼化产物8a。不同的反应条件对底物7a的不对称硼化制备(S)-8a的结果如表1所示。
表1不对称硼化结果
*括号中为分离收率，其余为核磁收率。
实施例8-1
本实施例中，式(S)-8a化合物的制备方法操作步骤如下，反应路线如下所示。
在手套箱中，向25毫升干燥的史莱克管中，加入配体6c(6.2mg，0.01mmol)， [IrCl(COD)]2(3.3mg，0.005mmol)，化合物7a(21.2mg,0.10mmol)，B2pin2(25.4mg,0.10 mmol)，加入THF 1.0mL。在70℃下反应12小时后冷却至室温，旋蒸除去溶剂，残留物用硅胶进行柱层析分离(石油醚/乙酸乙酯＝10:1)，得到硼化产物8a。
经检测，本实施例所获式8a化合物为29.7mg白色油状液体，产率为88％，94％ee(对映体过量百分数)，
(c 0.94,CHCl3)。式8a化合物的核磁共振数据为：1HNMR(400 MHz,CDCl3)δ7.61(d,J＝7.2Hz,1H),7.46–7.40(m,3H),7.34–7.23(m,3H),7.14(t,J＝7.2Hz, 1H),6.77(d,J＝7.6Hz,1H),5.23(s,1H),2.34(s,6H),1.36(s,6H),1.32(s,6H)；13C NMR(100MHz, CDCl3)δ141.7,132.5,132.3,130.5,129.2,128.3,127.5,127.0,124.0,80.2,75.0,41.1,27.4,26.3； HRMS(ESI)calcd for C21H29BNO2([M+H]+)338.2286,found 338.2299.
实施例8-2
本实施例与实施例8-1基本一致，不同之处在于：催化剂与式7a化合物的摩尔比为0.001：1，反应的温度为40℃，时间72h。
实施例8-3
本实施例与实施例8-1基本一致，不同之处在于：催化剂与式7a化合物的摩尔比为0.02： 1，反应的温度为100℃，时间2h。
实施例9
参考实施例8的制备方法，分别制备了式8b-8z化合物，其结构分别如下式所示：
经检测，本实施例所获式8b化合物为20.9mg黄色油状液体，产率为60％，86％ee，
(c 0.76,CHCl3)。式8b化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.62(d,J＝7.2Hz,1H),7.47–7.40(m,5H),7.24(t,J＝7.2Hz,1H),7.13(t,J＝7.2Hz,1H),6.83(d, J＝7.6Hz,1H),5.15(s,1H),3.75–3.58(m,4H),1.99–1.90(m,2H),1.40(s,6H),1.38(s,6H)；13C NMR(100MHz,CDCl3)δ142.0,135.0,131.8,130.9,129.0,128.5,127.4,127.3,124.0,80.2,74.4, 48.9,27.1,26.5,15.3；HRMS(ESI)calcd for C22H29BNO2([M+H]+)350.2286,found 350.2299.
经检测，本实施例所获式8c化合物为25.6mg黄色油状液体，产率为70％，88％ee，
(c 0.85,CHCl3)。式8c化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.45(s,1H),7.27(d,J＝7.6Hz,2H),7.22(d,J＝7.6Hz,2H),6.99(d,J＝7.6Hz,1H),6.71(d,J＝ 7.6Hz,1H),5.20(s,1H),2.44(s,3H),2.39(s,3H),2.35(s,6H),1.40(s,6H),1.36(s,6H)；13C NMR (100MHz,CDCl3)δ139.0,139.0,136.6,132.1,131.1,129.5,128.9,127.6,123.8,80.0,74.5,40.9, 27.4,26.3,21.3,21.1；HRMS(ESI)calcd for C23H33BNO2([M+H]+)366.2599,found 366.2605.
经检测，本实施例所获式8d化合物为30.2mg黄色油状液体，产率为76％，85％ee，
(c 0.94,CHCl3)。式8d化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.21(d,J＝7.6Hz,2H),7.14(s,1H),6.95(d,J＝8.4Hz,2H),6.69(s,2H),5.15(s,1H),3.85(s,3H), 3.82(s,3H),2.30(s,6H),1.35(s,6H),1.31(s,6H).13C NMR(100MHz,CDCl3)δ160.3,159.3,134.1, 133.4,125.0,124.5,114.9,113.7,113.2,80.1,74.5,55.3,55.2,40.7,27.4,26.4；HRMS(ESI)calcd for C23H33BNO2([M+H]+)398.2497,found 398.2500.
经检测，本实施例所获式8e化合物为30.6mg黄色油状液体，产率为82％，90％ee，
(c 0.93,CHCl3)。式8e化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.33–7.27(m,3H),7.18(t,J＝8.4Hz,2H),6.86(td,J＝8.4,2.0Hz,1H),6.78–6.71(m,1H),5.21(s, 1H),2.36(s,6H),1.38(s,6H),1.34(s,6H)；13C NMR(101MHz,CDCl3)δ163.3(d,JCF＝248Hz), 163.0(d,JCF＝245Hz),136.7,133.8(d,JCF＝8Hz),128.1(d,JCF＝3Hz),125.4(d,JCF＝8Hz), 116.8(d,JCF＝19Hz),115.6(d,JCF＝21Hz),114.0(d,JCF＝23Hz),80.4,73.8,41.1,27.3,26.4； HRMS(ESI)calcd for C21H27BF2NO2([M+H]+)374.2097,found374.2102.
经检测，本实施例所获式8f化合物为38.6mg黄色油状液体，产率为95％，88％ee，
(c 1.30,CHCl3)。式8f化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.55(s,1H),7.43(d,J＝8.4Hz,2H),7.21(d,J＝8.4Hz,2H),7.13(d,J＝9.6Hz,1H),6.69(d,J＝ 8.4Hz,1H),5.13(s,1H),2.32(s,6H),1.35(s,6H),1.30(s,6H)；13C NMR(100MHz,CDCl3)δ139.6, 135.7,133.9,133.3,130.7,130.6,128.8,127.3,125.3,80.5,73.8,41.2,27.4,26.4；HRMS(ESI)calcd for C21H27BCl2NO2([M+H]+)406.1506,found 406.1513.
经检测，本实施例所获式8g化合物为32.7mg黄色油状液体，产率为66％，82％ee，
(c 0.83,CHCl3)。式8g化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.70(s,1H),7.58(d,J＝8.0Hz,2H),7.29(s,1H),7.15(d,J＝8.0Hz,2H),6.63(d,J＝8.0Hz,1H), 5.09(s,1H),2.32(s,6H),1.34(s,6H),1.30(s,6H)；13C NMR(100MHz,CDCl3)δ140.1,133.6,133.5, 131.8,131.2,130.2,125.7,123.9,122.6,80.5,74.0,41.3,27.3,26.4；HRMS(ESI)calcd for C15H15BBr2NO2([M+H]+)496.0476,found 496.0479.
经检测，本实施例所获式8h化合物为30.7mg黄色油状液体，产率为65％，95％ee，
(c 0.93,CHCl3)。式8h化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.86(s,1H),7.72(d,J＝8.0Hz,2H),7.44(d,J＝8.0Hz,3H),6.87(d,J＝8.0Hz,1H),5.26(s,1H), 2.37(s,6H),1.37(s,6H),1.32(s,6H)；13C NMR(100MHz,CDCl3)δ145.1,136.5,132.3,131.7(q, JCF＝33Hz),130.0(q,JCF＝31Hz),127.8(q,JCF＝4Hz),125.6(q,JCF＝4Hz),124.6(q,JCF＝271 Hz),124.5(q,JCF＝4Hz),124.2,123.8(q,JCF＝271Hz),80.8,74.2,41.7,27.2,26.4；HRMS(ESI) calcd for C23H27BF6NO2([M+H]+)474.2034,found474.2033.
经检测，本实施例所获式8i化合物为43.3mg黄色油状液体，产率为86％，82％ee，
(c 0.85,CHCl3)。式8i化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.43(s, 1H),7.32(q,J＝8.8Hz,4H),7.00(d,J＝8.4Hz,1H),6.78(d,J＝8.4Hz,1H),5.20(s,1H),2.35(s, 6H),1.35(s,6H),1.31(s,6H)；13C NMR(100MHz,CDCl3)δ150.1,149.3,139.6,133.5,130.8,125.2, 122.9,120.8,120.6(q,JCF＝255Hz),120.4(q,JCF＝257Hz),119.9,80.6,73.7,41.3,27.3,26.3； HRMS(ESI)calcd for C23H27BF6NO4([M+H]+)506.1932,found 506.1937.
经检测，本实施例所获式8j化合物为38.6mg黄色油状液体，产率为79％，90％ee，
(c 1.30,CHCl3)。式8j化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.82(s, 1H),7.70–7.60(m,6H),7.50–7.37(m,8H),7.31(t,J＝7.4Hz,1H),6.91(d,J＝7.7Hz,1H),5.31(s, 1H),2.42(s,6H),1.38(s,6H),1.34(s,6H)；13C NMR(100MHz,CDCl3)δ142.3,142.1,141.0,140.5, 140.3,132.7,131.5,129.5,128.9,128.5,127.7,127.3,127.1,127.0,126.7,126.4,124.4,80.3,74.6, 41.2,27.4,26.4；HRMS(ESI)calcd forC33H37BNO2([M+H]+)490.2912,found 490.2915.
经检测，本实施例所获式8k化合物为25.6mg黄色油状液体，产率为70％，81％ee，
(c 0.76,CHCl3)。式8k化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.49(d,J＝7.2Hz,1H),7.31(t,J＝7.6Hz,1H),7.25(d,J＝8.0Hz,1H),7.12–7.05(m,3H),6.60(s, 1H),5.15(s,1H),2.39(s,3H),2.32(s,6H),2.23(s,3H),1.34(s,6H),1.30(s,6H)；13C NMR(100 MHz,CDCl3)δ142.2,137.9,136.5,132.9,132.7,130.4,129.8,129.3,128.3,128.1,124.6,80.0,74.9, 41.2,27.3,26.3,21.5,21.4；HRMS(ESI)calcd forC23H33BNO2([M+H]+)366.2599,found 366.2597.
经检测，本实施例所获式8l and 8l’(4:1)化合物为28.7mg黄色油状液体，产率为77％，94％ ee and 88％ee，
(c 1.03,CHCl3)；1H NMR(400MHz,CDCl3)δ7.57(t,J＝7.2Hz,1H), 7.43(t,J＝7.6Hz,1H),7.19–6.95(m,4H),6.54(d,J＝10.0Hz,1H),5.15(s,1H),2.34(s,6H),1.35 (s,6H),1.31(s,6H)(minor isomer)；1H NMR(400MHz,CDCl3)δ7.41(t,J＝7.6Hz),7.19–6.95(m, 4H),6.90(t,J＝8.4Hz,1H),6.57(d,J＝7.2Hz,1H),5.13(s,1H),2.36(s,6H),1.37(s,6H),1.35(s, 6H)(major isomer)；13C NMR(100MHz,CDCl3)δ165.0(d,JCF＝242.7Hz),162.9(d,JCF＝242.1 Hz),162.6(d,JCF＝246.1Hz),162.5(d,JCF＝245.7Hz),144.3(d,JCF＝11.4Hz),143.9(d,JCF＝7.3 Hz),135.4(d,JCF＝6.1Hz),134.8(d,JCF＝6.8Hz),132.6(d,JCF＝7.9Hz),130.0(d,JCF＝7.8Hz), 129.9(d,JCF＝8.0Hz),129.4(d,JCF＝7.9Hz),127.9,127.5,120.1(d,JCF＝2.6Hz),118.8(d,JCF＝21.5Hz),118.6(d,JCF＝21.8Hz),116.5(d,JCF＝21.1Hz),116.4(d,JCF＝21.0Hz),114.9(d,JCF＝ 25.5Hz),114.8(d,JCF＝19.6Hz),111.2(d,JCF＝22.0Hz),80.8,80.6,73.9,73.8,41.7,41.2,27.5, 27.2,26.4,26.3(mixture)；HRMS(ESI)calcd for C21H27BF2NO2([M+H]+)374.2097,found 374.2104.
经检测，本实施例所获式8m化合物为30.0mg黄色油状液体，产率为74％，93％ee，
(c 1.02,CHCl3)。式8m化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.0Hz,1H),7.45(d,J＝8.0Hz,1H),7.39(t,J＝8.0Hz,1H),7.30(s,1H),7.25(d,J＝7.6 Hz,1H),7.18(d,J＝7.2Hz,1H),6.79(s,1H),5.10(s,1H),2.33(s,6H),1.34(s,6H),1.30(s,6H)；13C NMR(101MHz,CDCl3)δ143.6,134.7,134.6,133.3,132.3,131.8,129.9,129.8,129.6,128.0,124.1, 80.6,74.0,41.6,27.2,26.3；HRMS(ESI)calcd forC21H27BCl2NO2([M+H]+)406.1506,found 406.1513.
经检测，本实施例所获式8n化合物为31.2mg黄色油状液体，产率为65％，93％ee，
(c 1.08,CHCl3)。式8n化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.60(d,J＝8.0Hz,1H),7.50–7.45(m,2H),7.40(d,J＝7.2Hz,1H),7.33(t,J＝7.6Hz,1H),7.22(d, J＝7.6Hz,1H),6.93(s,1H),5.09(s,1H),2.33(s,6H),1.34(s,6H),1.30(s,6H)；13C NMR(100MHz, CDCl3)δ143.9,135.0,134.7,132.7,132.6,130.8,130.3,130.1,126.9,122.7,121.5,80.6,73.9,41.6, 27.2,26.3；HRMS(ESI)calcd for C21H27BBr2NO2([M+H]+)496.0476,found 496.0480.
经检测，本实施例所获式8o化合物为42.6mg黄色油状液体，产率为90％，96％ee，
(c 1.23,CHCl3)。式8o化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.75(d,J＝7.6Hz,2H),7.64–7.53(m,3H),7.48(d,J＝7.6Hz,1H),7.01(s,1H),5.24(s,1H),2.36 (s,6H),1.36(s,6H),1.31(s,6H)；13C NMR(100MHz,CDCl3)δ142.0,134.8,133.6,131.4,131.3(q, JCF＝32Hz),129.9(q,JCF＝32Hz),129.2,128.7(q,JCF＝3Hz),126.5(q,JCF＝3Hz),124.7(q,JCF＝ 3Hz),124.4(q,JCF＝270Hz),123.7(q,JCF＝270Hz),120.5(q,JCF＝3Hz),80.8,74.3,41.6,27.2, 26.4；HRMS(ESI)calcd for C23H26BF6NO2([M+Na]+)496.1853,found 496.1855.
经检测，本实施例所获式8p化合物为39.1mg黄色油状液体，产率为80％，92％ee，
(c 1.10,CHCl3)。式8p化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.69(t,J＝7.6Hz,2H),7.59(d,J＝6.4Hz,3H),7.54–7.42(m,6H),7.39–7.29(m,4H),7.25(t,J＝ 7.2Hz,1H),7.09(s,1H),5.31(s,1H),2.41(s,6H),1.38(s,6H),1.34(s,6H)；13CNMR(101MHz, CDCl3)δ142.6,141.7,141.4,140.4,140.2,133.5,131.1,131.0,130.7,128.9,128.8,128.5,128.0, 127.6,127.2,127.1,126.8,126.7,122.8,80.3,75.4,41.6,27.3,26.4；HRMS(ESI)calcd for C33H37BNO2([M+H]+)490.2912,found 490.2921.
经检测，本实施例所获式8q化合物为32.0mg黄色油状液体，产率为70％，87％ee，
(c 0.72,CHCl3)。式8q化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.10(s,1H),6.91(s,2H),6.82(s,1H),6.38(s,1H),5.07(s,1H),3.93(s,6H),3.81(s,3H),3.70(s, 3H),2.34(s,6H),1.34(s,6H),1.31(s,6H)；13C NMR(100MHz,CDCl3)δ149.7,148.7,148.6,134.4, 126.0,124.7,114.5,112.8,110.5,107.8,80.1,75.2,56.0,55.9,55.8,41.8,27.2,26.4；HRMS(ESI) calcd for C25H37BNO6([M+H]+)458.2708,found458.2708.
经检测，本实施例所获式8r化合物为25.9mg黄色油状液体，产率为61％，82％ee，
(c 0.87,CHCl3)。式8r化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ6.86(d,J＝8.0Hz,1H),6.80(dd,J＝8.0,1.2Hz,1H),6.74(s,1H),6.60(d,J＝8.0Hz,1H),6.28(d,J ＝8.0Hz,1H),6.01(d,J＝3.2Hz,2H),5.98(s,2H),5.05(s,1H),2.32(s,6H),1.33(s,12H)；13C NMR (100MHz,CDCl3)δ148.6,148.4,147.6,146.6,136.3,126.5,125.9,117.5,111.8,108.0,106.9,101.4, 100.4,80.4,74.7,40.8,27.3,26.0；HRMS(ESI)calcdfor C23H29BNO6([M+H]+)426.2082,found 426.2088.
经检测，本实施例所获式8s化合物为39.4mg黄色油状液体，产率为83％，88％ee，
(c 1.30,CHCl3)。式8s化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.64(s,1H),7.53(d,J＝8.4Hz,1H),7.41(d,J＝2.0Hz,1H),7.12(dd,J＝8.4,2.0Hz,1H),6.89(s, 1H),5.02(s,1H),2.33(s,6H),1.34(s,6H),1.30(s,6H)；13C NMR(100MHz,CDCl3)δ141.5,134.1, 133.4,133.1,133.0,132.9,132.2,131.4,130.7,130.6,126.0,80.9,73.1,41.8,27.1,26.4；HRMS(ESI) calcd for C21H25BCl4NO2([M+H]+)476.0698,found476.0706.
经检测，本实施例所获式8t化合物为35.4mg黄色油状液体，产率为76％，86％ee，
(c 0.99,CHCl3)。式8t化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.56(s, 1H),7.40(d,J＝8.1Hz,1H),6.97(s,1H),6.87(d,J＝8.1Hz,1H),6.44(s,1H),4.98(s,1H),3.85(s, 3H),3.73(s,3H),2.34(s,6H),1.33(s,6H),1.30(s,6H)；13C NMR(100MHz,CDCl3)δ155.0,154.7, 142.4,134.4,132.8,130.0,124.1,123.5,122.3,115.0,108.4,80.7,75.2,56.2,56.1,42.7,26.9,26.5； HRMS(ESI)calcd for C23H31BCl2NO4([M+H]+)466.1718,found 466.1729.
经检测，本实施例所获式8u化合物为39.7mg黄色油状液体，产率为71％，79％ee，
(c 1.29,CHCl3)。式8u化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.72(s,1H),7.57(d,J＝8.0Hz,1H),6.94(s,1H),6.81(d,J＝8.0Hz,1H),6.42(s,1H),4.95(s,1H), 3.84(s,3H),3.73(s,3H),2.34(s,6H),1.32(s,6H),1.30(s,6H)；13C NMR(101MHz,CDCl3)δ155.9, 155.5,143.3,136.0,135.3,133.0,124.5,114.8,112.7,111.8,108.4,80.7,75.2,56.3,56.2,42.8,26.8, 26.5；HRMS(ESI)calcd for C23H31BBr2NO4([M+H]+)556.0687,found 556.0688.
经检测，本实施例所获式8v化合物为31.4mg黄色油状液体，产率为60％，89％ee，
(c 0.72,CHCl3)。式8v化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.47(d,J＝1.6Hz,1H),7.45(s,1H),7.29(d,J＝8.0Hz,1H),7.11(dd,J＝8.0,1.2Hz,1H),6.96(s, 1H),5.05(s,1H),2.45(s,3H),2.39(s,3H),2.31(s,6H),1.34(s,6H),1.30(s,6H)；13C NMR(100 MHz,CDCl3)δ141.4,139.2,136.8,135.5,133.3,132.2,130.8,130.4,127.7,125.0,123.9,80.5,73.3, 41.4,27.2,26.3,22.8,22.7；HRMS(ESI)calcd forC23H31BBr2NO2([M+H]+)524.0789,found 524.0788.
经检测，本实施例所获式8w化合物为30.9mg黄色油状液体，产率为77％，85％ee，
(c 0.76,CHCl3)。式8w化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)1HNMR(400MHz,CDCl3)δ7.20(d,J＝9.2Hz,1H),7.10(d,J＝7.2Hz,1H),7.07(d,J＝6.8Hz,2H), 6.56(d,J＝6.8Hz,1H),5.07(s,1H),2.31(s,9H),2.16(s,3H),1.33(s,6H),1.29(s,6H)；13C NMR (100MHz,CDCl3)δ161.8(d,JCF＝246Hz),161.6(d,JCF＝243Hz),136.8(d,JCF＝2Hz),135.1(d, JCF＝5Hz),131.0(d,JCF＝8Hz),128.2(d,JCF＝4Hz),126.9(d,JCF＝4Hz),125.1(d,JCF＝18Hz), 123.4(d,JCF＝19Hz),116.4(d,JCF＝21Hz),115.0(d,JCF＝23Hz),80.2,74.0,41.2,27.3,26.4,14.7； HRMS(ESI)calcd for C23H31BF2NO2([M+H]+)402.2410,found 402.2415.
经检测，本实施例所获式8x and 8x’化合物为37.2mg黄色油状液体，产率为86％，89％ee and 82％ee，
(c 1.40,CHCl3)；1H NMR(400MHz,CDCl3)δ7.18(d,J＝9.2Hz,1H), 7.09–6.95(m,3H),6.54(d,J＝12.0Hz,1H),5.06(s,1H),3.94(s,3H),3.92(s,3H),2.32(s,6H), 1.35(s,6H),1.31(s,6H)(minor isomer)；1H NMR(400MHz,CDCl3)δ7.09–6.95(m,3H),6.77(t,J ＝8.0Hz,1H),6.50(d,J＝8.0Hz,1H),5.05(s,1H),3.94(s,3H),3.85(s,3H),2.32(s,6H),1.35(s, 6H),1.34(s,6H)(major isomer)；13C NMR(100MHz,CDCl3)δ153.80(d,JCF＝243.6Hz),152.3(d, JCF＝243.2Hz),151.9(d,JCF＝247.1Hz),151.9(d,JCF＝247.1Hz),148.5(d,JCF＝10.7Hz),147.3 (d,JCF＝14.0Hz),147.2(d,JCF＝21.7Hz),135.1(d,JCF＝10.5Hz),133.9(d,JCF＝6.4Hz),128.3, 128.0,125.1,124.8(d,JCF＝5.5Hz),120.0(d,JCF＝3.1Hz),119.2(d,JCF＝9.9Hz),119.1(d,JCF＝ 16.0Hz),115.0,112.9(d,JCF＝6.4Hz),112.0(d,JCF＝19.5Hz),80.8,80.3,73.6,73.2,56.5,56.2, 41.3,40.8,27.6,26.3(mixture)；HRMS(ESI)calcd for C23H31BF2NO4([M+H]+)434.2309,found434.2312.
经检测，本实施例所获式8y化合物为39.8mg黄色油状液体，产率为90％，85％ee，
(c 1.43,CHCl3)。式8y化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ7.22(d,J＝8.0Hz,1H),7.11(s,1H),6.95(t,J＝9.6Hz,2H),6.58(s,1H),4.96(s,1H),2.36(s,6H), 1.35(s,6H),1.33(s,6H)；13C NMR(100MHz,CDCl3)δ164.9(d,JCF＝236Hz),162.4(d,JCF＝240 Hz),145.3(d,JCF＝13Hz),136.1(d,J＝8Hz),135.6(d,J＝10Hz),134.3(d,JCF＝10Hz),127.7(d, JCF＝3Hz),120.4(d,JCF＝3Hz),117.6(d,JCF＝25Hz),117.0(d,JCF＝22Hz),116.0(d,JCF＝29.3 Hz),81.2,73.4,41.8,27.4,26.4；HRMS(ESI)calcd forC21H25BCl2F2NO2([M+H]+)442.1318,found 442.1320.
经检测，本实施例所获式8z化合物为38.9mg黄色油状液体，产率为89％，91％ee，
(c 1.01,CHCl3)。式8z化合物的核磁共振数据为：1H NMR(400MHz,CDCl3)δ8.10(s,1H),7.95–7.85(m,5H),7.64–7.53(m,3H),7.46–7.38(m,2H),7.34(t,J＝7.2Hz,1H), 7.25(s,1H),5.59(s,1H),2.43(s,6H),1.43(s,6H),1.38(s,6H)；13C NMR(100MHz,CDCl3)δ140.5, 133.8,133.6,133.3,133.0,132.6,130.2,129.7,128.9,128.2,128.1,127.9,127.7,127.7,127.0,126.6, 125.2,125.0,122.8,80.4,74.8,41.0,27.4,26.4；HRMS(ESI)calcd for C29H33BNO2([M+H]+) 438.2599,found 438.2609.
综上所述，本发明的制备方法简单，可以制成消旋或手性的硼氮配体，该配体可用作不对称催化反应的催化剂，具有经济实用性和工业应用前景。
此外，本案发明人还参照实施例1-9的方式，以本说明书中列出的其它原料和条件等进行了试验，亦可达成相应的效果，可以制成消旋或手性的硼氮配体，该配体可用作不对称催化反应的催化剂，应用前景广泛。
应当理解，上述实施例仅为说明本发明的技术构思及特点，其目的在于让熟悉此项技术的人士能够了解本发明的内容并据以实施，并不能以此限制本发明的保护范围。凡根据本发明精神实质所作的等效变化或修饰，都应涵盖在本发明的保护范围之内。
Claims (21)
1.一种手性1，2-乙二胺骨架的硼氮配体，其特征在于，所述手性1，2-乙二胺骨架的硼氮配体选自下式(6a)～(6j)中任一者所示的结构：
2.如权利要求1所述手性1，2-乙二胺骨架的硼氮配体的制备方法，其特征在于包括：
使包含式(II)所示的化合物、硼硅试剂、质子酸催化剂和有机溶剂的均匀混合反应体系于反应，获得具有如式(I)所示结构的手性1，2-乙二胺骨架的硼氮配体；
其中，在式(I)和式(II)中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基；
R4、R5、R6、R7、R8、R9、R10、R11、R12分别至少独立地选自氢、卤素、取代或未取代的C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
Ar1和Ar2分别至少独立地选自取代或未取代的C6～C30的芳基。
3.根据权利要求2所述的制备方法，其特征在于：Ar1和Ar2的结构相同。
4.根据权利要求2所述的制备方法，其特征在于：所述硼硅试剂的化学式为R1R2R3Si-B(NiPr2)2，其中，R1、R2、R3分别至少独立地选自取代或未取代的C3～C10的环烷基、C1～C10的烷基或芳基。
5.根据权利要求2或4所述的制备方法，其特征在于：所述硅硼试剂与式(II)所示的化合物的摩尔比为1∶1～3∶1。
6.根据权利要求5所述的制备方法，其特征在于：所述硅硼试剂与式(II)所示的化合物的摩尔比为1.5∶1～2∶1。
7.根据权利要求2所述的制备方法，其特征在于：所述质子酸催化剂与式(II)所示的化合物的摩尔比为0.001∶1～1∶1。
8.根据权利要求7所述的制备方法，其特征在于：所述质子酸催化剂与式(II)所示的化合物的摩尔比为0.05∶1～0.5∶1。
9.根据权利要求2所述的制备方法，其特征在于：所述质子酸催化剂选自H2SO4、H3PO4、HCl、HBr、CH3CO2H、PhCO2H、CF3CO2H、CF3SO3H、p-CH3-C6H5SO3H、MeSO3H和tBuCO2H中的任意一种或两种以上的组合。
10.根据权利要求9所述的制备方法，其特征在于：所述质子酸催化剂为HCl。
11.根据权利要求2所述的制备方法，其特征在于：所述有机溶剂选自苯、甲苯、二甲苯、二氯甲烷、氯仿、四氯化碳、1，2-二氯乙烷、***、1，4-二氧六环、四氢呋喃、甲醇、乙醇、N，N-二甲基甲酰胺和二甲基亚砜中的任意一种或两种以上的组合。
12.根据权利要求2所述的制备方法，其特征在于：所述反应的温度为0～180℃，所述反应的时间为1～48h。
13.根据权利要求12所述的制备方法，其特征在于：所述反应的温度为80～180℃，所述反应的时间为12～36h。
14.权利要求1所述手性1，2-乙二胺骨架的硼氮配体作为催化剂或在用于合成催化剂领域中的应用。
15.根据权利要求14所述的应用，其特征在于：所述催化剂为不对称催化反应的催化剂。
16.根据权利要求14所述的应用，其特征在于：所述催化剂为权利要求1所述手性1，2-乙二胺骨架的硼氮配体和过渡金属形成的络合物，所述过渡金属为铱。
17.一种用于不对称催化反应的催化剂，其特征在于，它由权利要求1所述手性1，2-乙二胺骨架的硼氮配体和过渡金属络合反应形成，所述过渡金属为铱。
18.根据权利要求17所述的催化剂，其特征在于：所述催化剂用于二芳基甲胺的不对称碳氢键活化硼化反应中。
19.一类手性二芳基甲胺类化合物的制备方法，其特征在于包括：
在权利要求17或18所述的催化剂作用下，使式(III)所示的化合物反应获得式(Ⅳ)所示的化合物；
其中，在式(III)和式(Ⅳ)中，R13、R14分别至少独立地选自氢、取代或未取代的C1～C10的烷基或C3～C30的环烷基；C1～C10的烷基或芳基；
R15、R16、R17、R18分别至少独立地选自氢、卤素、酯基、酰胺基、酰基、氨基、取代或未取代的C1～C10的烷基、C1～C4的烷氧基、C3～C30的环烷基或芳基；
R19至少独立地选自取代或未取代的C1～C10的烷基或C3～C30的环烷基。
20.根据权利要求19所述的制备方法，其特征在于：所述催化剂与式(III)所示的化合物的摩尔比为0.001∶1～0.02∶1。
21.根据权利要求19所述的制备方法，其特征在于：所述反应的温度为40～100℃，时间2～72h。
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