CN108929345B - 手性二茂铁双膦配体及其制备方法和应用 - Google Patents

手性二茂铁双膦配体及其制备方法和应用 Download PDF

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CN108929345B
CN108929345B CN201810786786.2A CN201810786786A CN108929345B CN 108929345 B CN108929345 B CN 108929345B CN 201810786786 A CN201810786786 A CN 201810786786A CN 108929345 B CN108929345 B CN 108929345B
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聂慧芳
张生勇
王巧峰
姚琳
魏朝
李穆琼
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Fourth Military Medical University FMMU
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Abstract

本发明公开了一类手性二茂铁双膦配体，该配体是以手性二茂铁胺为原料，邻位锂化后与膦氯化物反应得到单膦中间体，该中间体与不同仲膦反应，得到具有不同手性中心的二茂铁双膦配体。本发明的双膦配体结构新颖，对空气稳定，合成简便，与金属形成的络合物催化剂，底物普适性强，在对潜手性烯烃、潜手性酮和潜手性亚胺等的不对称氢化反应中都表现出很高的催化活性和立体选择性。

Description

手性二茂铁双膦配体及其制备方法和应用
技术领域
本发明涉及一类手性二茂铁双膦配体及其制备方法和应用。
背景技术
合成光学活性化合物的方法主要有：外消旋体拆分、手性源合成、不对称诱导、手性放大以及催化不对称合成等，而在催化不对称合成中的不对称催化氢化由于其原子经济性和后处理简单等优点成为最理想的合成手性化合物的方法。不对称催化氢化反应的关键是高活性和高立体选择性的金属络合物催化剂，而配体则是其核心和关键。因此，设计合成结构新颖的配体一直是不对称催化氢化反应研究的热点，也是不对称合成研究中最活跃的领域。
二茂铁骨架是一类非常优秀的配体骨架，由于其具有高度热稳定性、化学稳定性和特殊的电子效应，它在催化剂领域得到了广泛应用，更难得的是许多优秀的催化剂已经应用于工业生产当中，如Josiphos、Taniaphos和ChenPhos等。虽然人们已经报道了数以万计的手性配体，其中许多也表现出很高的立体选择性，然而由于催化活性或者制备繁琐等原因真正应用于工业生产的例子并不多。近年来报道的一些二茂铁骨架手性配体催化剂不仅表现出高立体选择性，更取得超高的催化活性，展现出巨大的应用潜力，发展新型二茂铁骨架手性配体催化剂具有重大现实意义。
发明内容
本发明的目的在于提供一类手性二茂铁双膦配体及其制备方法和在不对称氢化反应中的应用。
本发明实现过程如下：
结构式（I）或（II）所示的手性二茂铁双膦配体，
Figure DEST_PATH_IMAGE001
R1为C1～C6的烷基，环烷基，或 C6～C20的芳基或烷基取代的芳基；
R2为C1～C6的烷基，苯基，苄基，C7～C20的芳基或烷基取代的芳基；
Figure DEST_PATH_IMAGE002
为：
Figure DEST_PATH_IMAGE003
或
Figure DEST_PATH_IMAGE004
。
上述手性二茂铁双膦配体具体结构为：
Figure DEST_PATH_IMAGE005
。
上述手性二茂铁双膦配体的制备方法：
Figure DEST_PATH_IMAGE006
将仲膦R2 2PH在惰性气氛下加至结构式（A）或（B）所示的二茂铁单膦中间体的醋酸溶液中，在50～120℃充分反应，蒸干溶剂得到粗产物，经柱层析或重结晶得手性二茂铁双膦配体，二茂铁单膦中间体与仲膦R2 2PH的摩尔比为 1：1～1.5；
二茂铁单膦中间体的结构式为：
Figure DEST_PATH_IMAGE007
式中：R1为C1～C6的烷基，环烷基，或 C6～C20的芳基或烷基取代的芳基；
Figure 582808DEST_PATH_IMAGE002
为：
Figure 87739DEST_PATH_IMAGE003
或
Figure 838526DEST_PATH_IMAGE004
仲膦R2 2PH中，R2为C1～C6的烷基，苯基，苄基，C7～C20的芳基或烷基取代的芳基。
上述式3或式5所示的单膦中间体的制备方法如下，
Figure DEST_PATH_IMAGE008
（1）仲丁基锂加至二茂铁胺（C）的乙醚溶液中，二茂铁胺（C）与仲丁基锂的摩尔比为1：1～1.2，室温搅拌下反应1～6 h；
（2）继续加入氯化膦（D）的乙醚溶液，二茂铁胺（C）与氯化膦（D）的摩尔比为1：1～2，回流反应4～12h，淬灭，萃取后干燥，柱层析或重结晶得式3和式5的单膦中间体。
上述式4或式6所示的单膦中间体的制备方法如下，
Figure DEST_PATH_IMAGE009
（1）将仲丁基锂加至二茂铁胺（C）的乙醚溶液中，二茂铁胺（C）与仲丁基锂的摩尔比为1：1～1.2，室温搅拌下反应1～6 h，加入三甲基氯硅烷的乙醚溶液，三甲基氯硅烷与二茂铁胺（C）的摩尔比为1～1.5：1，回流反应2～6h，淬灭，萃取后干燥，柱层析得油状产物（E）；
Figure DEST_PATH_IMAGE010
（2）将仲丁基锂加至步骤（1）得到的油状产物（E）的乙醚溶液中，油状产物（E）与仲丁基锂的摩尔比为1：1～1.2，室温搅拌下反应1～6 h，加入氯化膦（D）的乙醚溶液，油状产物（E）与氯化膦的摩尔比为1：1～2，回流反应4～12h，淬灭，萃取后干燥，柱层析或重结晶得TMS保护的单膦中间体（F）；
（3）将步骤（2）得到的单膦中间体（F）和四丁基氟化铵的四氢呋喃溶液混合，单膦中间体（F）和四丁基氟化铵的摩尔比为1：15～20，回流反应3～6h，淬灭，萃取后干燥，柱层析或重结晶得式4或式6所示的单膦中间体。
上述氯化膦（D）的制备方法如下：
Figure DEST_PATH_IMAGE011
将正丁基锂和TMEDA加至二甲基联萘的乙醚溶液中，二甲基联萘与正丁基锂和TMEDA的摩尔比为1：（2.5～3）：（2.6～3.2），室温搅拌反应得黑褐色悬浊液，在氮气气氛下抽滤、洗涤得到锂盐（G），冰浴下将三氯化磷加入锂盐（G）的正己烷溶液中，按摩尔比三氯化磷：锂盐（G） = 1.05：1，室温充分反应，在氮气氛围下过滤除去氯化锂，干燥甲苯洗涤滤饼，蒸干溶剂得到粗品，用干燥的二氯甲烷和正己烷重结晶得氯化膦（D）。
含有上述手性双膦配体的过渡金属络合物催化剂，所述金属是Ru、Rh、Ir、Pd或Pt。得到的过渡金属络合物催化剂在不对称氢化反应中的应用，所述不对称氢化反应包括：苯或取代苯甲酰基乙酸酯类的催化不对称氢化反应、苯或取代苯甲酰基甲酸酯类的催化不对称氢化反应、N-烷基和N-芳基亚胺的催化不对称氢化、N-酰基腙、磺酰亚胺和膦酰亚胺的催化不对称氢化反应、芳香和非芳香氮杂环的催化不对称氢化反应。
本发明提供的手性二茂铁双膦配体具有合成简洁、对氧气和湿气稳定等特点；合成过程中无需高温、高压等剧烈的操作条件；合成用的手性胺原料方便易得。手性配体与钌(Ru)、铑(Rh)、铱(Ir)、钯(Pd)或铂(Pt)等的金属络合物催化剂在C=C、C=O、C=N键的不对称氢化反应中表现出优秀的反应活性和立体选择性。反应在1～100 atm，-20～200℃的温度进行，溶剂可用质子性的醇类溶剂，也可以用二氯甲烷、1,2-二氯乙烷、氯仿、四氢呋喃、甲苯和乙酸乙酯等非质子性溶剂。
具体实施方式
本发明的技术特征已在发明内容部分作了较充分的说明，下面的实施例是用来对本发明作进一步的描述，但不是对本发明的限定。
A、配体的合成
实施例1
在0℃下，向2.5 M正丁基锂(76 mL，190 mmol)正己烷溶液中滴加(S)-8(21 g，74.5 mmol)的乙醚溶液，滴加完毕后，再缓慢加入干燥过得TMEDA (28.6 mL，192 mmol)，加毕，将反应液升至室温反应24 h。静置，用注射器抽出上层清液得到大量深紫色固体，用干燥的乙醚洗涤两次，用同样方法抽出上层清液，再用油泵除去剩余溶剂，得到双锂化盐13.1g，不需纯化可直接用于下步反应。在手套箱中称取上步所得锂盐(2.94 g，10 mmol)加入单口瓶中，在氮气氛围下注入60 mL干燥的正己烷，再缓慢注入三氯化磷(0.87 mL，10mmol)，室温搅拌12 h。抽滤除去不溶物，蒸干溶剂得棕色固体粗品，用干燥的二氯甲烷和正己烷重结晶得1.38 g氯化膦(S)-5。
Figure DEST_PATH_IMAGE013
在0℃下，向(R)-二茂铁胺4(2.57 g，10 mmol)的乙醚溶液缓慢滴加1.3 M叔丁基锂(8.5 mL，11.05 mmol)戊烷溶液，滴加完毕后升至室温反应1.5h；再次将反应液置于0℃以下，用注射器缓慢加入溶于乙醚的氯化膦(S)-5 (3.46g，10mmol)，缓慢升至室温反应6h。向反应液中加入饱和碳酸氢钠溶液淬灭反应，溶液分层后有机相依次用蒸馏水和饱和食盐水洗涤，然后用无水硫酸钠干燥，过滤，旋干，柱层析(乙酸乙酯:石油醚:三乙胺= 1:5:0.5%)分离纯化得橘黄色泡状产物(R,S,S)-2 3.57 g，产率63%。1H NMR (400 Hz, CDCl3) δ 7.98 (d, J = 8.3 Hz, 1H), 7.90 (dd, J = 12.2, 8.3 Hz, 3H), 7.72 (d, J = 8.3Hz, 1H), 7.55-7.49 (m, 1H), 7.41-7.32 (m, 2H), 7.27-7.13 (m, 3H), 7.09 (d, J= 8.5 Hz, 1H), 4.35-4.27 (m, 1H), 4.22 (d, J = 2.0 Hz, 1H), 4.18 (s, 5H),4.17-4.13 (m, 1H), 4.14-4.10 (m, 1H), 3.16 (d, J = 14.5 Hz, 1H), 3.10-2.88(m, 2H), 2.69-2.54 (m, 1H), 2.13 (s, 6H), 1.22 (d, J = 6.8 Hz, 3H); 13C NMR(101 Hz, CDCl3) δ 135.96, 134.98, 133.75, 132.74, 132.53, 132.45, 132.29,132.14, 128.83, 128.37, 128.27, 128.00, 127.88, 127.10, 126.94, 126.72,125.89, 125.71, 124.87, 124.62, 97.93, 77.95, 69.66, 69.43, 68.28, 67.99 ,56.92, 39.11, 35.36, 30.30, 8.03; 31P NMR (162 Hz,CDCl3) δ -6.09; HRMS (ESI)calcd for C36H35FeNP[M+H]+: 568.1857, Found:568.1844.
实施例2
Figure DEST_PATH_IMAGE015
以(R)-8为原料按实施实例1相同步骤得氯化膦(R)-5。以氯化膦(R)-5为原料按实施实例1相同步骤得橘黄色泡状产物(R,S,R)-2 3.74 g，产率66%(乙酸乙酯:石油醚:三乙胺= 1:5:0.5%)。1H NMR (400Hz, CDCl3) δ 7.97-7.81 (m, 3H), 7.69 (t, J = 8.4 Hz,2H), 7.45-7.37 (m, 2H), 7.33-7.28 (m, 1H), 7.28-7.12 (m,3H), 6.74 (d, J = 8.3Hz, 1H), 4.39-4.22 (m, 1H), 4.11 (dd, J = 6.9, 2.7 Hz, 1H), 4.07-4.04 (m,1H), 4.02 (s, 5H), 3.43-3.30 (m, 1H), 2.98- 2.79 (m, 1H), 2.80-2.66 (m, 2H),2.54 (t, J = 13.0 Hz, 1H), 2.14 (s, 6H), 1.25 (d, J = 6.8 Hz, 3H); 13C NMR(101 Hz, CDCl3)δ 135.48, 135.17, 133.83, 132.70, 132.33, 132.23, 132.07,131.83, 128.93, 128.20, 128.13, 127.57, 126.95, 126.72, 126.54, 125.79,125.63, 124.84, 124.46, 96.83, 73.63, 70.30, 69.47, 69.26, 67.48, 56.79,39.17, 32.80, 29.50, 7.89; 31P NMR (162 Hz, CDCl3) δ -6.58;HRMS (ESI)calcd forC36H35FeNP[M+H]+: 568.1857, Found:568.1839。
实施例3
Figure DEST_PATH_IMAGE017
向单膦中间体(R,S,R)-2 (284 mg，0.5 mmol)的冰醋酸溶液加入双(3,5-二甲基苯基)膦3a(133 mg，0.55mmol)，反应温度升至82～107℃，核磁监测至反应结束。冷却至室温，二氯甲烷稀释反应液，依次用水、饱和碳酸氢钠溶液和饱和食盐水洗涤，干燥，旋干，柱层析(乙酸乙酯:石油醚= 1:30)得橘黄色双膦配体(R,S,R)-Ia275 mg，产率72%。1H NMR(400 Hz, CDCl3) δ 8.03 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.85(dd, J = 16.0, 8.2 Hz, 2H), 7.77 (d, J = 8.3 Hz, 1H), 7.54-7.40 (m, 2H), 7.37(t, J = 7.5 Hz, 1H), 7.24-7.14 (m, 3H), 7.11 (d, J = 8.5 Hz, 1H), 6.96 (d, J= 7.1 Hz, 3H), 6.89-6.75 (m, 3H), 4.27 (s, 5H), 4.14 (s, 1H), 4.11 (s, 1H),3.81 (t, J = 5.7 Hz, 1H), 3.75 (s, 1H), 3.25 (d, J = 14.4 Hz, 1H), 3.05 (td,J = 14.3, 13.3, 5.0 Hz, 2H), 2.51 (dd, J = 11.7, 4.4 Hz, 1H), 2.26 (s, 6H),2.21 (s, 6H), 1.37 (t, J = 7.2 Hz, 3H); 13C NMR (101 Hz, CDCl3) δ 137.78,137.61, 136.99, 135.95, 134.74, 134.05, 133.82, 133.03, 132.83 , 132.60,132.53, 132.39, 132.25, 130.73, 129.63, 129.48, 129.27, 128.78, 128.27,128.05, 127.90, 127.25, 127.08, 126.71, 125.92, 125.68, 124.99, 124.66,99.00, 69.66, 69.25, 68.48, 68.32, 53.48, 36.00, 31.16, 30.21, 21.38, 16.24;31P NMR (162 Hz, CDCl3) δ 11.69 (d, J = 23.5 Hz), -10.34 (d, J = 23.5 Hz);HRMS (ESI)calcd for C50H47FeP2[M+H]+:765.2502, Found:765.2505.
实施例4
Figure DEST_PATH_IMAGE019
向单膦中间体(R,S,S)-2 (284 mg，0.5 mmol)的冰醋酸溶液加入双(3,5-二甲基苯基)膦3a (133 mg，0.55mmol)，反应温度升至82～107℃，核磁监测至反应结束。冷却至室温，二氯甲烷稀释反应液，依次用水、饱和碳酸氢钠溶液和饱和食盐水洗涤，干燥，旋干，柱层析(乙酸乙酯:石油醚= 1:30)得橘黄色双膦配体(R,S,S)-IIa 267 mg，产率70%。1H NMR(400 Hz, CDCl3) δ 7.92 (t, J = 7.9 Hz, 3H), 7.78 (d, J = 8.3 Hz, 1H), 7.70(d, J = 8.3 Hz, 1H), 7.51-7.39 (m, 2H), 7.33-7.27 (m, 1H), 7.24-7.17 (m, 3H),7.07-6.91 (m, 5H), 6.91-6.84 (m, 2H), 4.07 (s, 6H), 3.89 (s, 1H), 3.82 (dd, J= 7.0, 4.2 Hz, 1H), 3.27 (dd, J = 2.6, 1.3 Hz, 1H), 3.06-2.69 (m, 2H), 2.64-2.42 (m, 2H), 2.31 (s, 6H), 2.24 (s, 6H), 1.49-1.35 (m, 3H); 13C NMR (101 Hz,CDCl3) δ 137.55, 137.28, 137.06, 135.03, 134.54, 134.35, 133.70, 132.85,132.73, 132.65, 132.46, 132.13, 131.84, 130.72, 130.05, 129.89, 129.54,129.27, 128.24, 128.16, 127.44, 126.86, 126.80, 126.63, 125.78, 125.63,124.90, 124.59, 98.28, 71.90, 69.64, 69.39, 68.97, 67.97, 32.74, 30.72,29.44, 21.36, 17.20; 31P NMR (162 Hz, CDCl3) δ 10.12 (d, J = 17.5 Hz), -10.96(d, J = 17.2 Hz); HRMS (ESI)calcd for C50H47FeP2 [M+H]+: 765.2502, Found:765.2492。
实施例5
Figure DEST_PATH_IMAGE021
向单膦中间体(R,S,S)-2 (284 mg，0.5 mmol)的冰醋酸溶液加入二苯基膦3b(102 mg，0.55mmol)，反应温度升至82～107℃，核磁监测至反应结束。冷却至室温，二氯甲烷稀释反应液，依次用水、饱和碳酸氢钠溶液和饱和食盐水洗涤，干燥，旋干，柱层析(乙酸乙酯:石油醚= 1:20)得橘黄色双膦配体(R,S,S)-IIb 283 mg，产率80%。1H NMR (400 Hz,CDCl3) δ 8.03 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.87 (d, J = 8.2Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.50-7.38 (m,2H), 7.37-7.28 (m, 6H), 7.27-7.15 (m, 8H), 7.10 (d, J = 8.5 Hz, 1H), 4.28 (s,5H), 4.11 (s, 2H), 3.88 (dd, J = 7.2, 4.2 Hz, 1H), 3.80 (d, J = 2.3 Hz, 1H),3.25 (d, J = 14.4 Hz, 1H), 3.04 (t, J = 14.3 Hz, 1H), 2.89 (t, J = 12.5 Hz,1H), 2.51 (dd, J = 11.8, 4.4 Hz, 1H), 1.39 (t, J = 7.5 Hz, 3H); 13C NMR (101Hz, CDCl3) δ 137.94, 137.75, 135.82, 135.29, 135.09, 134.63, 134.43, 134.24,133.77, 132.58, 132.48, 132.32, 132.22, 132.16, 132.00, 131.85, 129.07,128.68, 128.25, 128.00, 127.85, 127.77, 127.53, 127.12, 127.03, 126.66,125.89, 125.64, 124.96, 124.62, 98.69, 69.80, 69.74, 69.25, 68.71, 68.06,35.86, 31.21, 30.33, 16.39; 31P NMR (162 Hz, CDCl3) δ 10.98 (d, J = 23.5 Hz),-10.82 (d, J = 23.5 Hz); HRMS (ESI)calcd for C46H39FeP2 [M+H]+: 709.1876,Found:709.1874。
实施例6
Figure DEST_PATH_IMAGE023
向单膦中间体(R,S,S)-2 (284 mg，0.5 mmol)的冰醋酸溶液加入二叔丁基膦3c(81 mg，0.55mmol)，反应温度升至82～107℃，核磁监测至反应结束。冷却至室温，二氯甲烷稀释反应液，依次用水、饱和碳酸氢钠溶液和饱和食盐水洗涤，干燥，旋干，柱层析(乙酸乙酯:石油醚= 1:20)得橘黄色双膦配体(R,S,S)-IIc 217 mg，产率65%。1H NMR (400 Hz,CDCl3) δ 8.00 (d, J = 8.3 Hz, 1H), 7.91 (dd, J = 17.8, 8.2 Hz, 3H), 7.77 (d,J = 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.44-7.37 (m, 2H), 7.23-7.14 (m,3H), 7.11 (d, J = 8.5 Hz, 1H), 4.23 (s, 7H), 4.11 (s, 1H), 3.88 (t, J = 11.0Hz, 1H), 3.52 (d, J = 7.7 Hz, 1H), 3.26 (d, J = 14.4 Hz, 1H), 3.04 (t, J =15.0 Hz, 1H), 2.60 (dd, J = 11.5, 4.8 Hz, 1H), 1.80 (dd, J = 7.4, 3.5 Hz,3H), 1.42 (d, J = 10.4 Hz, 9H), 1.00 (d, J = 10.6 Hz, 9H); 13C NMR (101 Hz,CDCl3) δ 136.48, 135.45, 133.77, 132.56, 132.51, 132.44, 132.29, 132.18,128.92, 128.37, 128.25, 128.02, 127.84, 127.06, 127.00, 126.77, 125.89,125.67, 124.88, 124.58, 102.47, 70.14, 69.43, 68.73, 67.89, 36.61, 34.26,33.82, 31.70, 30.69, 16.59; 31P NMR (162 Hz, CDCl3) δ 52.92 (d, J = 44.2 Hz),-10.07 (d, J = 44.4 Hz); HRMS (ESI)calcd for C42H47FeP2 [M+H]+:669.2502, Found:669.2493。
实施例7
Figure DEST_PATH_IMAGE025
向单膦中间体(R,S,S)-2 (284 mg，0.5 mmol)的冰醋酸溶液加入二环己基膦3d(109 mg，0.55mmol)，反应温度升至82～107℃，核磁监测至反应结束。冷却至室温，二氯甲烷稀释反应液，依次用水、饱和碳酸氢钠溶液和饱和食盐水洗涤，干燥，旋干，柱层析(乙酸乙酯:石油醚= 1:20)得橘黄色双膦配体(R,S,S)-IId 245 mg，产率68%。1H NMR (400 Hz,CDCl3) δ 8.00 (d, J = 8.3 Hz, 1H), 7.95-7.84 (m, 3H), 7.75 (d, J = 8.3 Hz,1H), 7.59 (d, J = 8.3 Hz, 1H), 7.46-7.37 (m, 2H), 7.23-7.14 (m, 3H), 7.10 (d,J = 8.5 Hz, 1H), 4.24 (s, 5H), 4.18 (d, J = 2.5 Hz, 2H), 4.14 (d, J = 3.0 Hz,1H), 3.68 (t, J = 11.6 Hz, 1H), 3.30 (d, J = 7.6 Hz, 1H), 3.24 (d, J = 14.4Hz, 1H), 3.04 (t, J = 14.5 Hz, 1H), 2.59 (dd, J = 11.6, 4.7 Hz, 1H), 2.04-1.61 (m, 9H), 1.66-1.25 (m, 8H), 1.23-0.80 (m, 8H); 13C NMR (101 Hz, CDCl3) δ 136.29, 135.07, 133.78, 132.51, 132.40, 132.24, 132.18, 128.83, 128.35,128.23, 127.99, 127.84, 127.06, 126.99, 126.72, 125.87, 125.64, 124.89,124.57, 101.04, 69.88, 69.30, 68.16, 67.80, 53.46, 36.49, 33.30, 33.09,32.74, 32.54, 31.95, 31.77, 31.37, 31.28, 31.15, 30.23, 30.1, 30.03 , 29.94,27.69, 27.63, 27.50, 27.22, 27.14, 27.00, 26.89, 26.70, 26.46, 15.10; 31P NMR(162 Hz, CDCl3) δ 17.22 (d, J = 35.5 Hz), -10.25 (d, J = 35.2 Hz); HRMS (ESI)calcd for C46H51FeP2 [M+H]+: 721.2815, Found:721.2808.
B、催化不对称氢化反应
Figure DEST_PATH_IMAGE027
实施例8
在氮气保护下，[Ir(COD)Cl]2（1.68 mg, 0.0025 mmol）和二茂铁配体(R,S,S)-IId (3.96 mg，0.0055 mmol)和5 mL甲苯置于Schlenk反应管中，搅拌反应30 min，将催化剂溶液转移至反应釜中，依次加入5g 亚胺底物9、0.6 mg TBAI和11 mg 三氟乙酸，氮气置换三次后再用氢气置换三次，在50 ℃和70 atm H2下反应8 h，用短硅胶柱过滤，将过滤所得滤液浓缩后得产物(R)-1，GC测反应转化率97%，对映体过量83%ee。
实施例9
在氮气保护下，[Ir(COD)Cl]2（1.68 mg, 0.0025 mmol）和二茂铁配体(S,R,R)-VIId (3.96 mg，0.0055 mmol)和5 mL甲苯置于Schlenk反应管中，搅拌反应30 min，将催化剂溶液转移至反应釜中，依次加入5g 亚胺底物9、0.6 mg TBAI和11 mg 三氟乙酸，氮气置换三次后再用氢气置换三次，在50 ℃和70 atm H2下反应8 h，用短硅胶柱过滤，将过滤所得滤液浓缩后得产物(S)-1，GC测反应转化率98%，对映体过量85%ee。

Claims (8)

1.结构式（I）或（II）所示的手性二茂铁双膦配体，
Figure 269654DEST_PATH_IMAGE001
R1为C1～C6的烷基，环烷基，或 C6～C20的芳基或烷基取代的芳基；
R2为C1～C6的烷基，苯基，苄基，C7～C20的芳基或烷基取代的芳基；
Figure 11346DEST_PATH_IMAGE002
为：
Figure 5846DEST_PATH_IMAGE003
或
Figure 740453DEST_PATH_IMAGE004
。
2.根据权利要求1所述的手性二茂铁双膦配体，其特征在于手性二茂铁双膦配体为：
Figure 441693DEST_PATH_IMAGE005
。
3.权利要求1所述手性二茂铁双膦配体的制备方法，其特征在于：
Figure 744498DEST_PATH_IMAGE006
将仲膦R2 2PH在惰性气氛下加至结构式（A）或（B）所示的二茂铁单膦中间体的醋酸溶液中，在50～120℃充分反应，蒸干溶剂得到粗产物，经柱层析或重结晶得手性二茂铁双膦配体，二茂铁单膦中间体与仲膦R2 2PH的摩尔比为 1：1～1.5；
二茂铁单膦中间体的结构式为：
Figure 787147DEST_PATH_IMAGE007
式中：R1为C1～C6的烷基，环烷基，或 C6～C20的芳基或烷基取代的芳基；
Figure 935232DEST_PATH_IMAGE002
为：
Figure 943508DEST_PATH_IMAGE003
或
Figure 417215DEST_PATH_IMAGE004
仲膦R2 2PH中，R2为C1～C6的烷基，苯基，苄基，C7～C20的芳基或烷基取代的芳基。
4.根据权利要求3所述的制备方法，其特征在于：式3或式5所示的单膦中间体的制备方法如下，
Figure 746827DEST_PATH_IMAGE008
（1）仲丁基锂加至二茂铁胺（C）的乙醚溶液中，二茂铁胺（C）与仲丁基锂的摩尔比为1：1～1.2，室温搅拌下反应1～6 h；
（2）继续加入氯化膦（D）的乙醚溶液，二茂铁胺（C）与氯化膦（D）的摩尔比为1：1～2，回流反应4～12h，淬灭，萃取后干燥，柱层析或重结晶得式3和式5的单膦中间体。
5.根据权利要求3所述的制备方法，其特征在于：式4或式6所示的单膦中间体的制备方法如下，
Figure 308389DEST_PATH_IMAGE009
（1）将仲丁基锂加至二茂铁胺（C）的乙醚溶液中，二茂铁胺（C）与仲丁基锂的摩尔比为1：1～1.2，室温搅拌下反应1～6 h，加入三甲基氯硅烷的乙醚溶液，三甲基氯硅烷与二茂铁胺（C）的摩尔比为1～1.5：1，回流反应2～6h，淬灭，萃取后干燥，柱层析得油状产物（E）；
Figure 312118DEST_PATH_IMAGE010
（2）将仲丁基锂加至步骤（1）得到的油状产物（E）的乙醚溶液中，油状产物（E）与仲丁基锂的摩尔比为1：1～1.2，室温搅拌下反应1～6 h，加入氯化膦（D）的乙醚溶液，油状产物（E）与氯化膦的摩尔比为1：1～2，回流反应4～12h，淬灭，萃取后干燥，柱层析或重结晶得TMS保护的单膦中间体（F）；
（3）将步骤（2）得到的单膦中间体（F）和四丁基氟化铵的四氢呋喃溶液混合，单膦中间体（F）和四丁基氟化铵的摩尔比为1：15～20，回流反应3～6h，淬灭，萃取后干燥，柱层析或重结晶得式4或式6所示的单膦中间体。
6.根据权利要求3或4所述的制备方法，其特征在于氯化膦（D）的制备方法如下：
Figure 878097DEST_PATH_IMAGE011
将正丁基锂和TMEDA加至二甲基联萘的乙醚溶液中，二甲基联萘与正丁基锂和TMEDA的摩尔比为1：（2.5～3）：（2.6～3.2），室温搅拌反应得黑褐色悬浊液，在氮气气氛下抽滤、洗涤得到锂盐（G），冰浴下将三氯化磷加入锂盐（G）的正己烷溶液中，按摩尔比三氯化磷：锂盐（G） = 1.05：1，室温充分反应，在氮气氛围下过滤除去氯化锂，干燥甲苯洗涤滤饼，蒸干溶剂得到粗品，用干燥的二氯甲烷和正己烷重结晶得氯化膦（D）。
7.含有权利要求1所述手性双膦配体的过渡金属络合物催化剂，所述催化剂为所述手性双膦配体与[Ir(COD)Cl]2原位生成的铱配合物。
8.权利要求7所述过渡金属络合物催化剂在N-芳基亚胺不对称氢化反应中的应用。
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