CN112521333A - 一种手性2,3-二取代四氢喹啉衍生物的合成方法 - Google Patents

一种手性2,3-二取代四氢喹啉衍生物的合成方法 Download PDF

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CN112521333A
CN112521333A CN201910875074.2A CN201910875074A CN112521333A CN 112521333 A CN112521333 A CN 112521333A CN 201910875074 A CN201910875074 A CN 201910875074A CN 112521333 A CN112521333 A CN 112521333A
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胡向平
胡信虎
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Abstract

本发明公开了一种手性2,3‑二取代四氢喹啉衍生物的合成方法：以手性苯基骨架膦‑亚磷酰胺配体与金属铱前驱体反应原位制备配合物为催化剂，催化不对称氢化2,3‑二取代喹啉制备手性2,3‑二取代四氢喹啉衍生物。为合成四氢喹啉化合物提供了一条可行途径。与其它合成手性四氢喹啉方法相比，本方法用于氢化的手性苯基骨架膦‑亚磷酰胺配体合成简单、价格低廉、适宜公斤级生产，而且铱/手性二苯基骨架膦‑亚磷酰胺体系催化活性高、对映选择性高，产物的对映体过量值(ee值)最高达96％以上，氢化反应操作简单、条件温和、原子经济性高，具有很好的工业实用性。

Description

一种手性2,3-二取代四氢喹啉衍生物的合成方法
技术领域
本发明属于有机合成领域，具体涉及一种手性2,3-二取代四氢喹啉衍生物的合成方法，适用于非天然碱类的生产。
背景技术
手性四氢喹啉及衍生物是化学品、制药、生物合成中重要的中间体，在生物碱研究中起着至关重要的作用。最简洁、方便的合成手性四氢喹啉的方法是直接喹啉衍生物的不对称氢化。它是在手性催化剂及其他助剂的帮助下，使喹啉衍生物直接氢化生成手性四氢喹啉衍生物类化合物。近些年，关于有机小分子催化喹啉衍生物的不对称转移氢化已有很大的进展，而关于金属催化不对称氢化喹啉衍生物的报道很少。
2009年，周永贵团队(D.–W.Wang,X.-B.Wang,D.–S.Wang,S.–M.Lu,Y.–G.Zhou,Y.–X.Li.J.Org.Chem.2009,74,2780-2787；)利用(S)-MeO-BiPhep配体与环辛二烯氯化铱二聚体成功催化不对称氢化喹啉衍生物合成手性四氢喹啉衍生物，取得了最高96％的对映选择性。但是该法对2,3-二取代喹啉衍生物的对映选择性不理想。
2011年，范青华团队(T.L.Wang,L.–G.Zhou,Z.W.Li,F.Chen,Z.Y.Ding,Y.M..He,Q.–H.Fan,J.F.Xiang,Z.–X.Yu,Albert S.C.Chan.J.Am.Chem.Soc.2011,133,9878-9891)利用手性阳离子钌催化不对称氢化喹啉衍生物合成手性四氢喹啉衍生物，取得了最高99％的对映选择性。但是该法对2,3-二取代喹啉衍生物的非对映选择性和对映选择性都不理想。
2015年，杜海峰团队(Z.H.Zhang,Q.H,F.Du.Org.Lett.2015,17,6266-6269)报道了的二取代喹啉不对称氢化，在手性二烯和HB(C6F5)2催化下可以得到手二取代四氢喹啉产物，非对映选择性大于99/1，对映选择性最高达到97％。然而2,3-二取代的喹啉底物对映选择性适中。
因此，发展高活性、高立体选择性、底物适用广不对称还原2,3-二取代喹啉衍生物的催化剂，具有十分重要的意义。
发明内容
本发明的目的是提供一种手性2,3-二取代四氢喹啉衍生物的合成方法。
为实现上述目的，本发明的技术方案如下：
一种手性2,3-二取代四氢喹啉衍生物的合成方法，该方法采用手性催化剂Ir-L，2,3-二取代喹啉直接不对称氢化制备手性2,3-二取代四氢喹啉衍生物；
所述手性催化剂Ir-L由铱-环辛二烯络合物和手性苯基骨架膦-亚磷酰胺配体在溶剂中原位配位生成。
一种手性2,3-二取代四氢喹啉衍生物的合成方法，该方法具体为：
在氮气保护下，将铱-环辛二烯络合物与手性苯基骨架膦-亚磷酰胺配体溶于溶剂，室温下搅拌10分钟，加入溶于溶剂的底物2,3-二取代喹啉，将其置于高压反应釜中，氢气置换3次，然后通入氢气至20-100bar，-20-100℃下反应1-24小时，慢慢释放氢气，除去溶剂后用硅胶柱(洗脱液：乙酸乙酯/石油醚＝1/10)分离得到产物手性2,3-二取代四氢喹啉。
所述溶剂为四氢呋喃、二氧六环、二氯甲烷、1,2-二氯乙烷或甲苯；优选四氢呋喃、二氧六环。
为实现上述目的，本发明的技术方案如下：
Figure BDA0002204047630000011
本发明所涉及的2,3-二取代喹啉和制得的手性2,3-二取代四氢喹啉具有以下结构：
Figure BDA0002204047630000021
式中：
R1为C1～C10烷基如CH3、CH3CH2等，C3～C12环烷基如环戊基、环己基等，或含有N、S、O、P中一种或二种以上官能团的C1～C10烷基如甲氧甲基、乙氧甲基等，或含有N、S、O、P中一种或二种以上官能团的C3～C10环烷基如2-四氢呋喃基、4-四氢呋喃基等；或芳基等C6-C30内的含或不含N、S、O、P等官能团的芳香基团如苯基、4-甲氧基苯基等；
R2为C1～C10烷基，C3～C12环烷基，或含有N、S、O、P中一种或二种以上官能团的C1～C10烷基，或含有N、S、O、P中一种或二种以上官能团的C3～C10环烷基；或芳基等C6-C30内的含或不含N、S、O、P等官能团的芳香基团；
R3为C1～C10烷基，C3～C12环烷基，或含有N、S、O、P中一种或二种以上官能团的C1～C10烷基，或含有N、S、O、P中一种或二种以上官能团的C3～C10环烷基；或芳基等C6-C30内的含或不含N、S、O、P等官能团的芳香基团。
本发明所涉及的手性苯基骨架膦-亚磷酰胺配体具有以下结构：
Figure BDA0002204047630000022
式中:R1、R2为H；烷基和环烷基等C1～C40内的含或不含N、S、O、P等官能团的脂肪基团；苄基等C7-C60在内的含或不含N、S、O、P等官能团的芳香基团与脂肪基的组合基团；芳基等C6-C60内的含或不含N、S、O、P等官能团的芳香基团。
Ar为C6-C60内的含或不含N、S、O、P等官能团的芳香基团。
X基团为：手性或非手性的含或不含N、S、O、P等官能团的脂肪基团；含或不含N、S、O、P等官能团的芳香基团；手性或非手性的含或不含N、S、O、P等官能团的联苯、联萘或四氢联萘类芳香基团。
所述铱-环辛二烯络合物为：[Ir(COD)Cl]2、Ir(COD)2BF4或Ir(COD)2BARF。
所述反应体系中所述铱浓度为0.001-0.01mol/l，所述配体与铱的摩尔比为1-5：1；优选铱浓度为0.002mol/l，配体与铱的摩尔比为1:1。
所述底物和催化剂的摩尔比为50-500：1；优选50-100:1。
本发明的有益效果是：与其它合成手性2,3-二取代四氢喹啉方法相比，本方法用于氢化的手性苯基骨架膦-亚磷酰胺配体合成简单、价格低廉、适宜公斤级生产，而且铱/手性苯基骨架膦-亚磷酰胺体系催化活性高、对映选择性高，产物的对映体过量值(ee值)最高达96％以上，氢化反应操作简单、条件温和、原子经济性高，具有很好的工业实用性。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例中所需要使用的附图作简单地介绍，应当理解，以下附图仅示出了本发明的某些实施例，因此不应被看作是对范围的限定，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他相关的附图。
图1：实施例1制备的(2S,3R)-3-甲基-2-苯基四氢喹啉的核磁共振氢谱；
图2：实施例1制备的(2S,3R)-3-甲基-2-苯基四氢喹啉的核磁共振碳谱；
图3：实施例11制备的2-(2-氟苯基)-3-甲基四氢喹啉的核磁共振氢谱；
图4：实施例11制备的2-(2-氟苯基)-3-甲基四氢喹啉的核磁共振碳谱；
图5：实施例12制备的2-(3-氟苯基)-3-甲基四氢喹啉的核磁共振氢谱；
图6：实施例12制备的2-(3-氟苯基)-3-甲基四氢喹啉的核磁共振碳谱；
图7：实施例13制备的2-(4-氟苯基)-3-甲基四氢喹啉的核磁共振氢谱；
图8：实施例13制备的2-(4-氟苯基)-3-甲基四氢喹啉的核磁共振碳谱；
图9：实施例14制备的2-(4-氯苯基)-3-甲基四氢喹啉的核磁共振氢谱；
图10：实施例14制备的2-(4-氯苯基)-3-甲基四氢喹啉的核磁共振碳谱；
图11：实施例15制备的2-(4-溴苯基)-3-甲基四氢喹啉的核磁共振氢谱；
图12：实施例15制备的2-(4-溴苯基)-3-甲基四氢喹啉的核磁共振碳谱；
图13：实施例16制备的2-(4-甲基苯基)-3-甲基四氢喹啉的核磁共振氢谱；
图14：实施例16制备的2-(4-甲基苯基)-3-甲基四氢喹啉的核磁共振碳谱；
图15：实施例17制备的2-(4-甲氧基苯基)-3-甲基四氢喹啉的核磁共振氢谱；
图16：实施例17制备的2-(4-甲氧基苯基)-3-甲基四氢喹啉的核磁共振碳谱；
图17：实施例18制备的2-(2-萘基)-3-甲基四氢喹啉的核磁共振氢谱；
图18：实施例18制备的2-(2-萘基)-3-甲基四氢喹啉的核磁共振碳谱；
图19：实施例19制备的2-(2-呋喃基)-3-甲基四氢喹啉的核磁共振氢谱；
图20：实施例19制备的2-(2-呋喃基)-3-甲基四氢喹啉的核磁共振碳谱；
图21：实施例20制备的2-(2-噻吩基)-3-甲基四氢喹啉的核磁共振氢谱；
图22：实施例20制备的2-(2-噻吩基)-3-甲基四氢喹啉的核磁共振碳谱；
图23：实施例21制备的2-苯基-3-乙基四氢喹啉的核磁共振氢谱；
图24：实施例21制备的2-苯基-3-乙基四氢喹啉的核磁共振碳谱；
图25：实施例22制备的2-苯基-3-丙基四氢喹啉的核磁共振氢谱；
图26：实施例22制备的2-苯基-3-丙基四氢喹啉的核磁共振碳谱；
图27：实施例23制备的3,5-二甲基-2-苯基四氢喹啉的核磁共振氢谱；
图28：实施例23制备的3,5-二甲基-2-苯基四氢喹啉的核磁共振碳谱；
图29：实施例24制备的3,7-二甲基-2-苯基四氢喹啉的核磁共振氢谱；
图30：实施例24制备的3,7-二甲基-2-苯基四氢喹啉的核磁共振碳谱；
图31：实施例25制备的3,8-二甲基-2-苯基四氢喹啉的核磁共振氢谱；
图32：实施例25制备的3,8-二甲基-2-苯基四氢喹啉的核磁共振碳谱。
图33：实施例26制备的3,6-二甲基-2-苯基四氢喹啉的核磁共振氢谱；
图34：实施例26制备的3,6-二甲基-2-苯基四氢喹啉的核磁共振碳谱。
图35：实施例27制备的6-甲氧基-3-甲基-2-苯基四氢喹啉的核磁共振氢谱；
图36：实施例27制备的6-甲氧基-3-甲基-2-苯基四氢喹啉的核磁共振碳谱。
图37：实施例28制备的6-氟-3-甲基-2-苯基四氢喹啉的核磁共振氢谱；
图38：实施例28制备的6-氟-3-甲基-2-苯基四氢喹啉的核磁共振碳谱。
图39：实施例29制备的6-氯-3-甲基-2-苯基四氢喹啉的核磁共振氢谱；
图40：实施例29制备的6-氯-3-甲基-2-苯基四氢喹啉的核磁共振碳谱。
图41：实施例30制备的7-氯-3-甲基-2-苯基四氢喹啉的核磁共振氢谱；
图42：实施例30制备的7-氯-3-甲基-2-苯基四氢喹啉的核磁共振碳谱。
图43：实施例31制备的6-溴-3-甲基-2-苯基四氢喹啉的核磁共振氢谱；
图44：实施例31制备的6-溴-3-甲基-2-苯基四氢喹啉的核磁共振碳谱。
图45：实施例32制备的6-溴-3-甲基-2-(4-溴苯基)四氢喹啉的核磁共振氢谱；
图46：实施例32制备的6-溴-3-甲基-2-(4-溴苯基)四氢喹啉的核磁共振碳谱。
图47：实施例33制备的2,3-环己基四氢喹啉的核磁共振氢谱；
图48：实施例33制备的2,3-环己基四氢喹啉的核磁共振碳谱。
具体实施方式
下面的实施例将对本发明予以进一步的说明，但并不因此而限制本发明。核磁共振是通过Bruker核磁共振仪测定，高效液相色谱(HPLC)是通过Agilent 1100系列高效液相色谱测定。
实施例1
Figure BDA0002204047630000041
氮气保护下，将[Ir(COD)Cl]2(0.002mmol,0.5mol％)，手性苯基骨架膦-亚磷酰胺配体L1(0.0048mmol,1.1mol％)溶于二氧六环(1.0mL)，室温下搅拌10分钟，加入底物2-苯基-3-甲基喹啉(0.4mmol)的二氧六环(1.0mL)溶液，将其置于高压反应釜中，氢气置换3次，然后通入氢气至10个大气压，25℃下反应24小时。慢慢释放氢气，除去溶剂后用硅胶柱分离得到产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000042
Yellow solid was obtained in 96％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,20/1).M.p.:34-36℃.94％eewas determined by chiral HPLC(Chiralcel OJ-H,n-hexane/i-PrOH＝70/30,0.8ml/min,254nm,40℃):tR(major)＝14.7min,tR(minor)＝29.0min.[α]25 D＝17.8(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.30–7.14(m,5H),6.93(dd,J＝14.5,7.4Hz,2H),6.57(t,J＝7.4Hz,1H),6.46(d,J＝7.9Hz,1H),4.42(d,J＝3.5Hz,1H),4.02(bs,1H),2.88(dd,J＝16.1,4.9Hz,1H),2.42(dd,J＝16.1,6.7Hz,1H),2.22(dt,J＝10.9,5.8Hz,1H),0.74(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ143.12(s),141.89(s),128.67(s),127.08(s),126.10(d,J＝5.9Hz),125.84(s),118.98(s),116.04(s),112.63(s),58.32(s),32.34(s),30.85(s),14.11(s).
经检测，产物为：(2S,3R)-3-甲基-2-苯基四氢喹啉，图1和图2分别为(2S,3R)-3-甲基-2-苯基四氢喹啉的核磁共振氢谱图、碳谱图。
实施例2
将实施例1中的反应条件H2压力改为50个大气压，其余同实施例1，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率97％，对映选择性为93％ee。
实施例3
将实施例1中的反应条件配体改为L2，其余同实施例1，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率96％，对映选择性为58％ee。
配体L2结构式如下：
Figure BDA0002204047630000051
实施例4
将实施例1中的反应条件配体改为L3，其余同实施例1，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率95％，对映选择性为78％ee。
配体L3结构式如下：
Figure BDA0002204047630000052
实施例5
将实施例1中的反应条件配体改为L4，其余同实施例1，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率95％，对映选择性为79％ee。
配体L4结构式如下：
Figure BDA0002204047630000053
实施例6
将实施例1中的反应条件配体改为L5，其余同实施例1，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率95％，对映选择性为63％ee。
配体L5结构式如下：
Figure BDA0002204047630000061
实施例7
将实施例3中的反应条件溶剂改为二氯乙烷，其余同实施例3，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率94％，对映选择性为52％ee。
实施例8
将实施例3中的反应条件溶剂改为四氢呋喃，其余同实施例3，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率94％，对映选择性为35％ee。
实施例9
将实施例3中的反应条件溶剂改为苯，其余同实施例3，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率80％，对映选择性为52％ee。
实施例10
将实施例1中的底物与催化剂比例改为S/C＝500，即：[Ir(COD)Cl]2(0.000125mmol,0.025mol％)，手性膦-亚膦酰胺配体(0.00025mmol,0.11mol％)，反应得产物，经检测，产物为(2S,3R)-3-甲基-2-苯基四氢喹啉，收率92％，对映选择性为92％ee。
实施例11
将实施例1中的底物改为2-(2-氟苯基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000062
Yellow liquid was obtained in 95％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,10/1).89％ee wasdetermined by chiral HPLC(Chiralcel OJ-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(minor)＝35.9min,tR(major)＝53.6min.[α]25 D＝38.2(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.39(td,J＝7.6,1.7Hz,1H),7.22(tdd,J＝7.2,5.3,1.8Hz,1H),7.08(td,J＝7.5,1.0Hz,1H),7.05–6.97(m,3H),6.66(td,J＝7.4,1.1Hz,1H),6.55(dd,J＝7.9,0.8Hz,1H),4.90(d,J＝3.7Hz,1H),4.01(bs,1H),2.93(dd,J＝16.1,4.7Hz,1H),2.49(dd,J＝16.1,7.3Hz,1H),2.43–2.32(m,1H),0.84(dd,J＝6.9,1.7Hz,3H).13C NMR(101MHz,CDCl3)δ161.27(s),158.83(s),144.07(s),130.16(d,J＝12.8Hz),129.73(s),128.65–128.33(m),126.94(s),124.00(d,J＝3.5Hz),120.10(s),117.20(s),115.08(s),114.86(s),113.72(s),51.75(d,J＝2.8Hz),32.95(s),30.59(s),15.12(s).HRMS calcd forC16H17FN[M+H]+:242.1340,found:242.1338.
经检测，产物为：2-(2-氟苯基)-3-甲基四氢喹啉，2-(2-氟苯基)-3-甲基四氢喹啉的核磁共振氢谱如图3所示；2-(2-氟苯基)-3-甲基四氢喹啉的核磁共振碳谱如图4所示。
实施例12
将实施例1中的底物改为2-(3-氟苯基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000071
Yellow liquid was obtained in 96％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,10/1).93％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝16.4min,tR(minor)＝21.3min.[α]25 D＝17.8(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.34–7.22(m,1H),7.09–6.88(m,5H),6.65(t,J＝7.4Hz,1H),6.54(d,J＝7.9Hz,1H),4.48(d,J＝3.5Hz,1H),3.99(bs,1H),2.96(dd,J＝16.2,4.9Hz,1H),2.48(dd,J＝16.2,6.6Hz,1H),2.35–2.20(m,1H),0.81(dd,J＝6.9,1.4Hz,3H).13C NMR(101MHz,CDCl3)δ164.05(s),161.61(s),145.78(d,J＝6.4Hz),143.80(s),129.89–129.47(m),127.01(s),122.81(d,J＝2.7Hz),119.95(s),117.45(s),114.04(dd,J＝21.9,12.1Hz),59.04(s),33.36(s),31.93(s),15.12(s).HRMS calcd for C16H17FN[M+H]+:242.1340,found:242.1342.
经检测，产物为：2-(3-氟苯基)-3-甲基四氢喹啉，2-(3-氟苯基)-3-甲基四氢喹啉的核磁共振氢谱如图5所示；2-(3-氟苯基)-3-甲基四氢喹啉的核磁共振碳谱如图6所示。
实施例13
将实施例1中的底物改为2-(4-氟苯基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000072
Yellow liquid was obtained in 96％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,10/1).95％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝15.1min,tR(minor)＝19.7min.[α]25 D＝11.7(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.27–7.17(m,2H),7.06–6.91(m,4H),6.65(dd,J＝10.7,4.0Hz,1H),6.53(d,J＝7.9Hz,1H),4.46(d,J＝3.5Hz,1H),4.05(bs,1H),2.93(dd,J＝16.2,4.9Hz,1H),2.46(dd,J＝16.2,6.9Hz,1H),2.32–2.16(m,1H),0.79(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ163.25(s),160.81(s),143.98(s),138.67(d,J＝3.1Hz),129.78(s),128.70(d,J＝7.9Hz),127.02(s),120.00(s),117.32(s),115.06(s),114.85(s),113.80(s),58.80(s),33.23(s),31.94(s),15.24(s).HRMS calcd for C16H17FN[M+H]+:242.1340,found:242.1345.
经检测，产物为：2-(4-氟苯基)-3-甲基四氢喹啉，2-(4-氟苯基)-3-甲基四氢喹啉的核磁共振氢谱如图7所示；2-(4-氟苯基)-3-甲基四氢喹啉的核磁共振碳谱如图8所示。
实施例14
将实施例1中的底物改为2-(4-氯苯基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000073
Yellow solid was obtained in 97％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,10/1).M.p.:50-52℃.94％eewas determined by chiral HPLC(Chiralcel OJ-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(minor)＝44.7min,tR(major)＝48.5min.[α]25 D＝22.0(c1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.29–7.23(m,2H),7.19(dd,J＝6.1,4.2Hz,2H),7.05–6.92(m,2H),6.65(td,J＝7.4,1.1Hz,1H),6.52(dd,J＝7.9,0.7Hz,1H),4.44(d,J＝3.6Hz,1H),4.02(bs,1H),2.92(dd,J＝16.2,4.9Hz,1H),2.44(dd,J＝16.2,6.9Hz,1H),2.30–2.18(m,1H),0.78(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ143.89(s),141.51(s),132.84(s),129.79(s),128.61(s),128.31(s),127.99(s),127.12(d,J＝12.6Hz),119.98(s),117.39(s),113.84(s),58.87(s),33.21(s),31.88(s),15.27(s).HRMS calcd forC16H17ClN[M+H]+:258.1044,found:258.1045.
经检测，产物为：2-(4-氯苯基)-3-甲基四氢喹啉，2-(4-氯苯基)-3-甲基四氢喹啉的核磁共振氢谱如图9所示；2-(4-氯苯基)-3-甲基四氢喹啉的核磁共振碳谱如图10所示。
实施例15
将实施例1中的底物改为2-(4-溴苯基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000081
Yellow solid was obtained in 97％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,10/1).M.p.:60-62℃.92％eewas determined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝18.6min,tR(minor)＝25.8min.[α]25 D＝20.5(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.42(d,J＝8.3Hz,2H),7.15(d,J＝8.1Hz,2H),7.00(dd,J＝16.9,7.8Hz,2H),6.65(td,J＝7.4,0.9Hz,1H),6.53(d,J＝7.9Hz,1H),4.44(d,J＝3.6Hz,1H),4.04(bs,1H),2.93(dd,J＝16.2,4.8Hz,1H),2.45(dd,J＝16.2,6.8Hz,1H),2.34–2.17(m,1H),0.79(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ143.84(s),142.01(s),131.24(s),129.78(s),128.97(s),127.04(s),120.93(s),119.96(s),117.39(s),113.82(s),58.91(s),33.18(s),31.81(s),15.25(s).HRMS calcd for C16H17BrN[M+H]+:302.0539,found:302.0534.
经检测，产物为：2-(4-溴苯基)-3-甲基四氢喹啉，2-(4-溴苯基)-3-甲基四氢喹啉的核磁共振氢谱如图11所示；2-(4-溴苯基)-3-甲基四氢喹啉的核磁共振碳谱如图12所示。
实施例16
将实施例1中的底物改为2-(4-甲基苯基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000082
Yellow solid was obtained in 96％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,10/1).M.p.:54-56℃.94％eewas determined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝13.1min,tR(minor)＝16.3min.[α]25 D＝21.8(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.16(d,J＝8.0Hz,2H),7.11(d,J＝7.8Hz,2H),6.99(dd,J＝14.4,7.2Hz,2H),6.63(t,J＝7.3Hz,1H),6.51(d,J＝7.9Hz,1H),4.44(d,J＝3.2Hz,1H),4.03(bs,1H),2.93(dd,J＝16.1,4.7Hz,1H),2.48(dd,J＝16.1,6.7Hz,1H),2.32(s,3H),2.26(tdd,J＝8.8,6.0,3.1Hz,1H),0.90–0.73(m,3H).13C NMR(101MHz,CDCl3)δ144.30(s),139.99(s),136.75(s),129.78(s),128.88(s),127.16(s),126.94(s),120.12(s),117.09(s),113.74(s),59.21(s),33.47(s),31.98(s),21.15(s),15.25(s).HRMS calcd forC17H20N[M+H]+:238.1590,found:238.1592.
经检测，产物为：2-(4-甲基苯基)-3-甲基四氢喹啉，2-(4-甲基苯基)-3-甲基四氢喹啉的核磁共振氢谱如图13所示；2-(4-甲基苯基)-3-甲基四氢喹啉的核磁共振碳谱如图14所示。
实施例17
将实施例1中的底物改为2-(4-甲氧基苯基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000091
White solid was obtained in 99％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,10/1).M.p.:108-110℃.92％ee was determined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝15.6min,tR(minor)＝18.8min.[α]25 D＝18.3(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.24–7.15(m,2H),7.00(dd,J＝14.3,7.3Hz,2H),6.84(d,J＝8.2Hz,2H),6.64(t,J＝7.4Hz,1H),6.53(d,J＝7.9Hz,1H),4.44(d,J＝3.5Hz,1H),4.07(bs,1H),3.78(s,3H),2.93(dd,J＝16.1,4.9Hz,1H),2.47(dd,J＝16.1,6.8Hz,1H),2.25(ddd,J＝11.0,7.0,4.2Hz,1H),0.81(dd,J＝6.8,0.4Hz,3H).13C NMR(101MHz,CDCl3)δ158.75(s),144.24(s),135.06(s),129.73(s),128.25(s),126.91(s),120.11(s),117.06(s),113.61(d,J＝20.0Hz),58.85(s),55.30(s),33.34(s),32.01(s),15.28(s).HRMScalcd for C17H20NO[M+H]+:254.1539,found:254.1540.
经检测，产物为：2-(4-甲氧基苯基)-3-甲基四氢喹啉，2-(4-甲氧基苯基)-3-甲基四氢喹啉的核磁共振氢谱如图15所示；2-(4-甲氧基苯基)-3-甲基四氢喹啉的核磁共振碳谱如图16所示。
实施例18
将实施例1中的底物改为2-(2-萘基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000092
Yellow liquid was obtained in 95％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,10/1).93％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.8ml/min,254nm,40℃):tR(major)＝14.0min,tR(minor)＝21.3min.[α]25 D＝-17.3(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.77(ddd,J＝20.4,10.9,5.5Hz,4H),7.50–7.32(m,3H),7.08–6.94(m,2H),6.67(td,J＝7.4,1.1Hz,1H),6.57(dd,J＝7.9,0.8Hz,1H),4.62(d,J＝3.5Hz,1H),4.14(bs,1H),3.00(dd,J＝16.1,5.0Hz,1H),2.53(dd,J＝16.1,6.2Hz,1H),2.35(tdd,J＝6.4,5.1,3.7Hz,1H),0.81(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ144.23(s),140.57(s),133.28(s),132.83(s),129.89(s),128.09–127.60(m),127.01(s),126.16(s),125.78(d,J＝9.1Hz),125.50(s),120.15(s),117.32(s),113.90(s),59.49(s),33.75(s),32.11(s),15.05(s).HRMS calcd for C20H20N[M+H]+:274.1590,found:274.1596.
经检测，产物为：2-(2-萘基)-3-甲基四氢喹啉，2-(2-萘基)-3-甲基四氢喹啉的核磁共振氢谱如图17所示；2-(2-萘基)-3-甲基四氢喹啉的核磁共振碳谱如图18所示。
实施例19
将实施例1中的底物改为2-(2-呋喃基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000093
Colorless liquid was obtained in 94％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).89％ee wasdetermined by chiral HPLC(Chiralcel OJ-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝35.6min,tR(minor)＝49.2min.[α]25 D＝95.1(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.33(d,J＝0.8Hz,1H),6.99(dd,J＝13.5,7.3Hz,2H),6.65(t,J＝7.4Hz,1H),6.52(d,J＝7.9Hz,1H),6.35–6.23(m,1H),6.12(d,J＝3.2Hz,1H),4.50(d,J＝3.6Hz,1H),4.04(bs,1H),2.87(dd,J＝16.1,4.9Hz,1H),2.53(dd,J＝16.1,8.0Hz,1H),2.45–2.28(m,1H),0.92(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ156.18(s),143.24(s),141.41(s),129.62(s),126.85(s),120.49(s),117.57(s),114.12(s),110.16(s),106.16(s),54.01(s),32.86(s),30.51(s),16.08(s).HRMS calcd for C14H16NO[M+H]+:214.1226,found:214.1224.
经检测，产物为：2-(2-呋喃基)-3-甲基四氢喹啉，2-(2-呋喃基)-3-甲基四氢喹啉的核磁共振氢谱如图19所示；2-(2-呋喃基)-3-甲基四氢喹啉的核磁共振碳谱如图20所示。
实施例20
将实施例1中的底物改为2-(2-噻吩基)-3-甲基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000101
Colorless liquid was obtained in 95％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,10/1).95％ee wasdetermined by chiral HPLC(Chiralcel OJ-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝51.1min,tR(minor)＝65.4min.[α]25 D＝105.7(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.17(d,J＝5.0Hz,1H),7.06–6.89(m,4H),6.73–6.60(m,1H),6.52(d,J＝7.9Hz,1H),4.73(d,J＝3.4Hz,1H),4.17(bs,1H),2.93(dd,J＝16.3,5.0Hz,1H),2.57(dd,J＝16.3,7.6Hz,1H),2.41–2.23(m,1H),0.92(dd,J＝6.9,1.4Hz,3H).13C NMR(101MHz,CDCl3)δ146.12(s),143.27(s),129.69(s),126.96(s),126.55(s),124.33(s),123.93(s),120.37(s),117.79(s),114.31(s),55.89(s),32.87(s),32.18(s),16.03(s).HRMS calcdfor C14H16NS[M+H]+:230.0998,found:230.1001.
经检测，产物为：2-(2-噻吩基)-3-甲基四氢喹啉，2-(2-噻吩基)-3-甲基四氢喹啉的核磁共振氢谱如图21所示；2-(2-噻吩基)-3-甲基四氢喹啉的核磁共振碳谱如图22所示。
实施例21
将实施例1中的底物改为2-苯基-3-乙基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000102
Colorless liquid was obtained in 96％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).91％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝15.5min,tR(minor)＝21.8min.[α]25 D＝59.2(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.34–7.19(m,5H),7.07–6.92(m,2H),6.64(td,J＝7.4,1.1Hz,1H),6.52(d,J＝7.9Hz,1H),4.52(d,J＝3.8Hz,1H),4.19(bs,1H),2.86(dd,J＝16.3,4.7Hz,1H),2.53(dd,J＝16.3,8.6Hz,1H),2.05(dq,J＝13.0,4.4Hz,1H),1.28(dtd,J＝12.1,7.3,5.0Hz,1H),1.02(ddt,J＝13.8,8.8,7.1Hz,1H),0.89(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)δ144.40(s),143.20(s),129.71(s),128.16(s),127.41–126.96(m),120.25(s),116.99(s),113.62(s),58.91(s),38.90(s),29.56(s),22.57(s),12.10(s).HRMS calcdfor C17H20N[M+H]+:238.1590,found:238.1586.
经检测，产物为：2-苯基-3-乙基四氢喹啉，2-苯基-3-乙基四氢喹啉的核磁共振氢谱如图23所示；2-苯基-3-乙基四氢喹啉的核磁共振碳谱如图24所示。
实施例22
将实施例1中的底物改为2-苯基-3-丙基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000111
Colorless liquid was obtained in 97％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).90％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝13.5min,tR(minor)＝19.4min.[α]25 D＝66.9(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.32–7.19(m,5H),7.06–6.93(m,2H),6.64(td,J＝7.4,1.1Hz,1H),6.56–6.46(m,1H),4.50(d,J＝3.8Hz,1H),4.18(bs,1H),2.84(dd,J＝16.2,4.7Hz,1H),2.53(dd,J＝16.2,8.6Hz,1H),2.22–2.09(m,1H),1.48–1.31(m,1H),1.31–1.14(m,2H),1.08–0.93(m,1H),0.81(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ144.39(s),143.19(s),129.71(s),128.17(s),127.42–126.97(m),120.34(s),117.00(s),113.64(s),59.00(s),36.71(s),31.97(s),30.04(s),20.57(s),14.25(s).HRMS calcd for C18H22N[M+H]+:252.1747,found:252.1749.
经检测，产物为：2-苯基-3-丙基四氢喹啉，2-苯基-3-丙基四氢喹啉的核磁共振氢谱如图25所示；2-苯基-3-丙基四氢喹啉的核磁共振碳谱如图26所示。
实施例23
将实施例1中的底物改为3,5-二甲基-2-苯基喹啉.，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000112
Colorless liquid was obtained in 68％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).95％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝13.0min,tR(minor)＝14.9min.[α]25 D＝33.5(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.35–7.20(m,5H),6.93(t,J＝7.7Hz,1H),6.55(d,J＝7.4Hz,1H),6.43(d,J＝8.0Hz,1H),4.45(d,J＝3.2Hz,1H),4.10(bs,1H),2.91–2.72(m,1H),2.41–2.27(m,2H),2.18(d,J＝10.9Hz,3H),0.83(d,J＝6.7Hz,3H).13C NMR(101MHz,CDCl3)δ144.26(s),143.06(s),137.32(s),128.16(s),127.16(d,J＝12.5Hz),126.42(s),118.90(d,J＝15.9Hz),111.95(s),59.01(s),32.12(s),30.69(s),19.57(s),15.73(s).HRMS calcd forC17H20N[M+H]+:238.1590,found:238.1591.
经检测，产物为：3,5-二甲基-2-苯基四氢喹啉，3,5-二甲基-2-苯基四氢喹啉的核磁共振氢谱如图27所示；3,5-二甲基-2-苯基四氢喹啉的核磁共振碳谱如图28所示。
实施例24
将实施例1中的底物改为3,7-二甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000113
Yellow liquid was obtained in 95％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).93％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(minor)＝11.8min,tR(major)＝12.9min.[α]25 D＝0(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.35–7.20(m,5H),6.87(d,J＝7.6Hz,1H),6.48(dd,J＝7.5,0.9Hz,1H),6.37(s,1H),4.46(d,J＝3.6Hz,1H),4.03(bs,1H),2.91(dd,J＝16.0,4.9Hz,1H),2.44(dd,J＝16.0,6.7Hz,1H),2.32–2.25(m,1H),2.24(s,3H),0.80(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ144.04(s),143.09(s),136.59(s),129.65(s),128.18(s),127.20(d,J＝10.6Hz),118.19(s),117.20(s),114.35(s),59.46(s),33.09(s),32.15(s),21.29(s),15.23(s).HRMS calcd for C17H20N[M+H]+:238.1590,found:238.1594.
经检测，产物为：3,7-二甲基-2-苯基四氢喹啉，3,7-二甲基-2-苯基四氢喹啉的核磁共振氢谱如图29所示；3,7-二甲基-2-苯基四氢喹啉的核磁共振碳谱如图30所示。
实施例25
将实施例1中的底物改为3,8-二甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000121
White solid was obtained in 95％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,20/1).M.p.:44-46℃.96％eewas determined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝11.9min,tR(minor)＝15.1min.[α]25 D＝-22.9(c 2.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.29–7.13(m,5H),6.85(d,J＝7.3Hz,1H),6.81(d,J＝7.4Hz,1H),6.52(t,J＝7.4Hz,1H),4.50(d,J＝3.6Hz,1H),3.88(bs,1H),2.91(dd,J＝16.1,4.9Hz,1H),2.44(dd,J＝16.2,6.5Hz,1H),2.22(tdd,J＝6.8,4.9,3.8Hz,1H),2.05(s,3H),0.73(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ143.29(s),142.15(s),128.13(d,J＝18.0Hz),127.63(s),127.20(d,J＝1.8Hz),120.70(s),119.46(s),116.58(s),59.62(s),33.71(s),31.82(s),17.31(s),15.11(s).HRMS calcd for C17H20N[M+H]+:238.1590,found:238.1586.
经检测，产物为：3,8-二甲基-2-苯基四氢喹啉，3,8-二甲基-2-苯基四氢喹啉的核磁共振氢谱如图31所示；3,8-二甲基-2-苯基四氢喹啉的核磁共振碳谱如图32所示。
实施例26
将实施例1中的底物改为3,6-二甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000122
Colorless liquid was obtained in 95％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).93％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝10.3min,tR(minor)＝13.6min.[α]25 D＝19.2(c 2.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.34–7.19(m,5H),6.82(d,J＝10.3Hz,2H),6.46(d,J＝7.7Hz,1H),4.45(s,1H),3.91(s,1H),2.93(d,J＝16.2Hz,1H),2.45(dd,J＝16.0,5.7Hz,1H),2.32–2.24(m,1H),2.24–2.17(m,3H),0.85–0.68(m,3H).13C NMR(101MHz,CDCl3)δ143.17(s),141.86(s),130.31(s),128.16(s),127.52(s),127.17(d,J＝10.9Hz),126.33(s),120.12(s),113.92(s),59.54(s),33.56(s),32.17(s),20.55(s),15.10(s).HRMS calcd forC17H20N[M+H]+:238.1590,found:238.1588.
经检测，产物为：3,6-二甲基-2-苯基四氢喹啉，3,6-二甲基-2-苯基四氢喹啉的核磁共振氢谱如图33所示；3,6-二甲基-2-苯基四氢喹啉的核磁共振碳谱如图34所示。
实施例27
将实施例1中的底物改为6-甲氧基-3-甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000131
Yellow liquid was obtained in 94％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).88％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝13.3min,tR(minor)＝23.0min.[α]25 D＝4.2(c 4.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.34–7.27(m,4H),7.27–7.21(m,1H),6.64(dd,J＝8.6,2.9Hz,1H),6.60(d,J＝2.8Hz,1H),6.50(d,J＝8.6Hz,1H),4.45(d,J＝3.3Hz,1H),3.82(bs,1H),3.73(s,3H),3.00(dd,J＝16.3,5.1Hz,1H),2.47(dd,J＝16.3,6.0Hz,1H),2.28(dtd,J＝9.4,6.0,3.5Hz,1H),0.81(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ151.88(s),143.16(s),138.30(s),128.16(s),127.13(d,J＝5.9Hz),121.30(s),114.98(d,J＝19.4Hz),113.05(s),59.61(s),55.81(s),34.03(s),32.21(s),14.83(s).HRMS calcd for C17H20NO[M+H]+:254.1539,found:254.1539.
经检测，产物为：6-甲氧基-3-甲基-2-苯基四氢喹啉，6-甲氧基-3-甲基-2-苯基四氢喹啉的核磁共振氢谱如图35；6-甲氧基-3-甲基-2-苯基四氢喹啉的核磁共振碳谱如图36所示。
实施例28
将实施例1中的底物改为6-氟-3-甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000132
Colorless liquid was obtained in 95％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).96％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝12.7min,tR(minor)＝18.4min.[α]25 D＝-5.9(c 2.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.37–7.23(m,5H),6.74(dd,J＝13.1,5.2Hz,2H),6.50–6.41(m,1H),4.47(d,J＝2.7Hz,1H),3.91(bs,1H),2.97(dd,J＝16.4,4.6Hz,1H),2.47(dd,J＝16.4,6.0Hz,1H),2.28(ddd,J＝6.3,3.2,1.6Hz,1H),0.85–0.66(m,3H).13C NMR(101MHz,CDCl3)δ156.75(s),154.41(s),142.79(s),140.36(s),128.22(s),127.18(d,J＝12.2Hz),121.33(d,J＝6.7Hz),115.96(s),115.75(s),114.37(d,J＝7.5Hz),113.57(s),113.34(s),59.45(s),33.71(s),31.82(s),14.86(s).HRMS calcd for C16H17FN[M+H]+:242.1340,found:242.1346.
经检测，产物为：6-氟-3-甲基-2-苯基四氢喹啉，6-氟-3-甲基-2-苯基四氢喹啉的核磁共振氢谱如图37所示；6-氟-3-甲基-2-苯基四氢喹啉的核磁共振碳谱如图38所示。
实施例29
将实施例1中的底物改为6-氯-3-甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000133
Yellow solid was obtained in 97％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,10/1).M.p.:52-54℃.96％eewas determined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝13.7min,tR(minor)＝22.8min.[α]25 D＝48.6(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.43–7.17(m,5H),7.05–6.88(m,2H),6.53–6.37(m,1H),4.47(d,J＝3.5Hz,1H),4.08(bs,1H),2.90(dd,J＝16.3,4.9Hz,1H),2.45(dd,J＝16.3,6.8Hz,1H),2.34–2.15(m,1H),0.79(dd,J＝6.9,1.6Hz,3H).13C NMR(101MHz,CDCl3)δ142.77(s),142.51(s),129.29(s),128.24(s),127.23(d,J＝17.6Hz),126.77(s),121.62(s),121.40(s),114.71(s),59.35(s),33.24(s),31.59(s),15.12(s).HRMS calcd forC16H17ClN[M+H]+:258.1044,found:258.1047.
经检测，产物为：6-氯-3-甲基-2-苯基四氢喹啉，6-氯-3-甲基-2-苯基四氢喹啉的核磁共振氢谱如图39所示；6-氯-3-甲基-2-苯基四氢喹啉的核磁共振碳谱如图40所示。
实施例30
将实施例1中的底物改为7-氯-3-甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000141
Colorless liquid was obtained in 97％yield after purification withcolumn chromatography on silica gel(hexanes/ethyl acetate,20/1).93％ee wasdetermined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝12.5min,tR(minor)＝14.3min.[α]25 D＝-10.7(c 1.0,CH2Cl2).1HNMR(400MHz,CDCl3)δ7.37–7.17(m,5H),6.87(d,J＝8.0Hz,1H),6.59(d,J＝8.0Hz,1H),6.50(d,J＝2.0Hz,1H),4.46(d,J＝3.7Hz,1H),4.15(bs,1H),2.85(dd,J＝16.1,4.8Hz,1H),2.43(dd,J＝16.1,7.1Hz,1H),2.26(ddd,J＝10.9,7.2,4.0Hz,1H),0.84–0.68(m,3H).13C NMR(101MHz,CDCl3)δ145.16(s),142.37(s),132.20(s),130.68(s),128.24(s),127.27(d,J＝15.7Hz),118.42(s),116.86(s),113.09(s),59.21(s),32.72(s),31.64(s),15.32(s).HRMS calcd for C16H17ClN[M+H]+:258.1044,found:258.1050.
经检测，产物为：7-氯-3-甲基-2-苯基四氢喹啉，7-氯-3-甲基-2-苯基四氢喹啉的核磁共振氢谱如图41所示；7-氯-3-甲基-2-苯基四氢喹啉的核磁共振碳谱如图42所示。
实施例31
将实施例1中的底物改为6-溴-3-甲基-2-苯基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000142
Yellow solid was obtained in 98％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,10/1).M.p.:54-56℃.96％eewas determined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.6ml/min,254nm,40℃):tR(major)＝14.1min,tR(minor)＝24.2min.[α]25 D＝52.9(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.36–7.18(m,5H),7.08(d,J＝7.2Hz,2H),6.41(d,J＝8.9Hz,1H),4.46(d,J＝3.6Hz,1H),3.99(bs,1H),2.89(dd,J＝16.3,4.9Hz,1H),2.45(dd,J＝16.3,6.9Hz,1H),2.31–2.16(m,1H),0.79(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ143.21(s),142.43(s),132.12(s),129.61(s),128.24(s),127.23(d,J＝18.7Hz),122.17(s),115.15(s),108.45(s),59.30(s),33.14(s),31.52(s),15.16(s).HRMS calcd forC16H17BrN[M+H]+:302.0539,found:302.0546.
经检测，产物为：6-溴-3-甲基-2-苯基四氢喹啉，6-溴-3-甲基-2-苯基四氢喹啉的核磁共振氢谱如图43所示；6-溴-3-甲基-2-苯基四氢喹啉的核磁共振碳谱如图44所示。
实施例32
将实施例1中的底物改为6-溴-3-甲基-2-(4-溴苯基)喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000151
White solid was obtained in 97％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,20/1).M.p.:86-88℃.92％eewas determined by chiral HPLC(Chiralcel OD-H,n-hexane/i-PrOH＝90/10,0.8ml/min,254nm,40℃):tR(major)＝9.4min,tR(minor)＝22.2min.[α]25 D＝49.2(c 2.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.49–7.36(m,2H),7.18–7.02(m,4H),6.49–6.37(m,1H),4.44(s,1H),4.11(bs,1H),2.90(dd,J＝16.3,4.8Hz,1H),2.43(dd,J＝16.3,7.0Hz,1H),2.33–2.16(m,1H),0.78(d,J＝6.9Hz,3H).13C NMR(101MHz,CDCl3)δ142.84(s),141.44(s),132.12(s),131.30(s),129.70(s),128.83(s),122.01(s),121.09(s),115.22(s),108.72(s),58.78(s),32.91(s),31.40(s),15.11(s).HRMS calcd for C16H16Br2N[M+H]+:379.9644,found:379.9652.
经检测，产物为：6-溴-3-甲基-2-(4-溴苯基)四氢喹啉，6-溴-3-甲基-2-(4-溴苯基)四氢喹啉的核磁共振氢谱如图45所示；6-溴-3-甲基-2-(4-溴苯基)四氢喹啉的核磁共振碳谱如图46所示。
实施例33
将实施例1中的底物改为2,3-环己基喹啉，其余同实施例1，反应得产物。
对产物进行检测分析，NMR和HPLC数据如下所示：
Figure BDA0002204047630000152
White solid was obtained in 97％yield after purification with columnchromatography on silica gel(hexanes/ethyl acetate,20/1).M.p.:62-64℃.83％eewas determined by chiral HPLC(Chiralcel AS-H,n-hexane/i-PrOH＝99.5/0.5,0.6ml/min,254nm,40℃):tR(minor)＝8.8min,tR(major)＝9.2min.[α]25 D＝26.6(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ6.93(dd,J＝13.1,6.9Hz,2H),6.56(t,J＝7.3Hz,1H),6.43(d,J＝7.9Hz,1H),3.49(d,J＝2.9Hz,2H),2.89(dd,J＝16.3,5.5Hz,1H),2.51(dd,J＝16.2,3.5Hz,1H),1.95(dt,J＝8.8,4.2Hz,1H),1.64(ddd,J＝23.5,11.8,6.1Hz,4H),1.51–1.19(m,4H).13C NMR(101MHz,CDCl3)δ143.95(s),129.75(s),126.62(s),119.32(s),116.44(s),113.29(s),50.06(s),33.00(s),32.59(s),31.81(s),27.31(s),24.80(s),20.77(s).HRMS calcd for C13H18N[M+H]+:188.1434,found:188.1432.
经检测，产物为：2,3-环己基四氢喹啉，2,3-环己基四氢喹啉的核磁共振氢谱如图47所示；2,3-环己基四氢喹啉的核磁共振碳谱如图48所示。

Claims (7)

1.一种手性2,3-二取代四氢喹啉衍生物的合成方法，其特征在于：该方法采用手性催化剂铱-L、2,3-二取代喹啉不对称氢化制备手性2,3-二取代四氢喹啉衍生物；所述手性催化剂铱-L由铱-环辛二烯络合物和手性苯基骨架膦-亚磷酰胺配体在溶剂中原位配位生成。
2.根据权利要求1所述的一种手性2,3-二取代四氢喹啉衍生物的合成方法，其特征在于：
该方法具体为：在氮气保护下，将铱-环辛二烯络合物与手性苯基骨架膦-亚磷酰胺配体溶于溶剂，室温下搅拌10分钟，加入溶于溶剂的底物2,3-二取代四氢喹啉，将其置于高压反应釜中，氢气置换3次，然后通入氢气至20-100bar，-20-50℃下反应1-24小时，慢慢释放氢气，除去溶剂后用硅胶柱(洗脱液：乙酸乙酯/石油醚＝1/10)分离得到产物手性2,3-二取代四氢喹啉衍生物；
所述溶剂为四氢呋喃、二氧六环、二氯甲烷、1,2-二氯乙烷或甲苯。
3.根据权利要求1或2所述的一种手性2,3-二取代四氢喹啉衍生物的合成方法，其特征在于：所述的底物2,3-二取代喹啉和制得的手性2,3-二取代四氢喹啉衍生物分别具有以下结构：
Figure FDA0002204047620000011
式中：
R1为C1～C10烷基，C3～C12环烷基，或含有N、S、O、P中一种或二种以上官能团的C1～C10烷基，或含有N、S、O、P中一种或二种以上官能团的C3～C10环烷基；或芳基等C6-C30内的含或不含N、S、O、P等官能团的芳香基团；
R2为C1～C10烷基，C3～C12环烷基，或含有N、S、O、P中一种或二种以上官能团的C1～C10烷基，或含有N、S、O、P中一种或二种以上官能团的C3～C10环烷基；或芳基等C6-C30内的含或不含N、S、O、P等官能团的芳香基团；
R3为C1～C10烷基，C3～C12环烷基，或含有N、S、O、P中一种或二种以上官能团的C1～C10烷基，或含有N、S、O、P中一种或二种以上官能团的C3～C10环烷基；或芳基等C6-C30内的含或不含N、S、O、P等官能团的芳香基团。
4.根据权利要求1或2所述的一种手性2,3-二取代四氢喹啉衍生物的合成方法，其特征在于：所述手性苯基骨架膦-亚磷酰胺配体L其结构通式如下：
Figure FDA0002204047620000021
式中:R1、R2为H；烷基和环烷基等C1～C40内的含或不含N、S、O、P等官能团的脂肪基团；苄基等C7-C60在内的含或不含N、S、O、P等官能团的芳香基团与脂肪基的组合基团；芳基等C6-C60内的含或不含N、S、O、P等官能团的芳香基团；
Ar为C6-C60内的含或不含N、S、O、P等官能团的芳香基团；
X基团为：手性或非手性的含或不含N、S、O、P等官能团的脂肪基团；含或不含N、S、O、P等官能团的芳香基团；手性或非手性的含或不含N、S、O、P等官能团的联苯、联萘或四氢联萘类芳香基团。
5.根据权利要求1或2所述的一种手性2,3-二取代四氢喹啉衍生物的合成方法，其特征在于：所述铱-环辛二烯络合物为：[Ir(COD)Cl]2、Ir(COD)2BF4或Ir(COD)2BARF。
6.根据权利要求1或2所述的一种手性2,3-二取代四氢喹啉衍生物的合成方法，其特征在于：所述反应体系中所述铱浓度为0.001-0.01mol/l，所述手性苯基骨架膦-亚磷酰胺配体与铱的摩尔比为1-5：1。
7.根据权利要求1或2所述的一种手性2,3-二取代四氢喹啉衍生物的合成方法，其特征在于：所述2,3-二取代喹啉底物和手性催化剂铱-L的摩尔比为50-500：1。
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