CN110003105B - 轴手性吡啶化合物、其制备方法及应用 - Google Patents
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Abstract
Description
技术领域
本发明属于有机合成领域,具体涉及一种轴手性吡啶化合物、其制备方法及应用。
背景技术
轴手性的联芳基化合物普遍存在于天然产物和具有生物活性的化合物中(Bringmann,G.;Gulder,T.;Gulder,T.A.M.;Breuning,M.Chem.Rev.2011,111,563–639.Brunel,J.M.;Chem.Rev.2005,105,857–897.),并且作为有机催化剂或手性配体在不对称催化中起着重要作用(Privileged Chiral Ligands and Catalysts;Zhou,Q.-L.Ed.;Wiley-VCH:Weinheim,Germany,2011)。由于该结构的重要性,利用催化对映选择性的方法构建联芳基骨架吸引了研究者的广泛兴趣并取得了很大的进展。
越来越多的轴手性吡啶类化合物及其衍生物作为手性配体和催化剂应用在不对称催化反应之中(Rokade,B.V.;Guiry,P.J.ACS Catal.2018,8,624-643.Francos,J.;Grande-Carmona,F.;Faustino,H.;Iglesias-Sigüenza,J.;Díez,E.;Alonso,I.;Fernández,R.;Lassaletta,J.M.;López,F.;J.L.J.Am.Chem.Soc.2012,134,14322-14325.Malkov,A.V.;Ramírez-López,P.;Biedermannová,L.;L.;Dufková,L.;Kotora,M.;Zhu,F.;P.J.Am.Chem.Soc.2008,130,5341-5348.),但目前为止合成该类化合物最常用的方法还是手性拆分以及动力学拆分。C-H键的直接不对称官能团反应是合成该类化合物非常简洁的方法(Kakiuchi,F.;Gendre,P.L.;Yamada,A.;Ohtaki,H.;Murai,S.Tetrahedron:Asymmetry 2000,11,2647.Zheng,J.;You,S.-L.Angew.Chem.Int.Ed.2014,53,13244-13247.Gao,D.-W.;Gu,Q.;You,S.-L.ACSCatal.2014,4,2741-2745.Zheng,J.;Cui,W.-J.;Zheng,C.;You,S.-L.J.Am.Chem.Soc.2016,138,5242-5245.),但这些反应大多存在底物普适性较差、对映选择性较低等缺陷。
2013年,Abel Ros等人利用Suzuki-Miyaura交叉偶联反应成功合成了轴手性的吡啶化合物(Ros,A.;Estepa,B.;Ramirez-López,P.;E.;Fernandez,R.;Lassaletta,J.M.,J.Am.Chem.Soc.2013,135,15730-15733.),其反应如下所示。然而,该反应的步骤较为繁琐,原料需要进行预处理,即事先要在原料的的苯环上引入三氟甲磺酰基(-OTf),且产物收率和对映选择性较低。
鉴于轴手性吡啶化合物及其衍生物广泛的用途,但又缺乏高效的合成方法,因此寻找合适的催化体系,发展高效的不对称C-H键的直接官能团化反应来合成该类化合物具有重要的意义。
发明内容
本发明所要解决的技术问题在于克服现有的轴手性吡啶化合物的制备方法较为单一,且存在操作复杂,收率和对映选择性较低的缺陷,而提供了一种轴手性吡啶化合物、其制备方法及应用。本发明的制备方法可一步合成轴手性吡啶化合物,无需对原料进行预处理,在简化操作的基础上,还能进一步使得产物具有相当或者更高的收率和对映选择性,且底物普适性较好。
本发明通过以下技术方案解决上述技术问题。
本发明提供了一种化合物1的制备方法,其包括以下步骤:在保护气体氛围下,有机溶剂中,在铑催化剂、膦配体和碱的存在下,将如式II所示化合物与如式III所示化合物进行如下所示的芳基化反应,即可;所述的化合物1为如式I和/或式I’所示化合物:
其中,X为卤素(所述的卤素可为氯、溴或碘,又可为溴);
Z为CH或N;
R2、R5和R6独立地为氢、卤素(所述的卤素可为氟、氯、溴或碘,又可为氟)、C1-10的烷基(所述的C1-10的烷基可为C1-4的烷基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、异丁基或叔丁基,又可为甲基)、或C1-10的烷氧基(所述的C1-10的烷氧基可为C1-4的烷氧基,例如甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、异丁氧基或叔丁氧基,又可为甲氧基);
R3和R4独立地为C1-10的烷基(所述的C1-10的烷基可为C1-4的烷基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、异丁基或叔丁基,又可为甲基)、或C1-10的烷氧基(所述的C1-10的烷氧基可为C1-4的烷氧基,例如甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、异丁氧基或叔丁氧基,又可为甲氧基);
R7为未取代或R7-1取代的C6-10的芳基(所述R7-1的个数可为一个或多个,又可为1、2、3或4个,当存在多个R7-1时,所述的R7-1可相同或不同)、未取代或R7-2取代的“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基(所述R7-2的个数可为一个或多个,又可为1、2或3个,当存在多个R7-2时,所述的R7-2可相同或不同)、或、未取代或R7-3取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基(所述R7-3的个数可为一个或多个,又可为1、2或3个,当存在多个R7-3时,所述的R7-3可相同或不同);
R7-1、R7-2和R7-3独立地为氢、氰基、卤素(所述的卤素可为氟、氯、溴或碘,又可为氟、氯或溴)、C1-6的卤代烷基(所述的C1-6的卤代烷基可为C1-3的卤代烷基,例如三氟甲基)、C1-10的烷基(所述的C1-10的烷基可为C1-4的烷基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、异丁基或叔丁基,又可为甲基或叔丁基)、C1-10的烷氧基(所述的C1-10的烷氧基可为C1-4的烷氧基,例如甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、异丁氧基或叔丁氧基,又可为甲氧基)、C6-10的芳基(所述的C6-10的芳基可为苯基或萘基)、或、NR7-1-1R7-1-2;
R7-1-1和R7-1-2独立地为氢或C1-6的烷基(所述的C1-6的烷基可为C1-4的烷基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、异丁基或叔丁基,又可为甲基);
或者,R2、R3与其间的碳原子一起形成C6-10的芳基(所述的C6-10的芳基可为苯基或萘基,例如)、“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基(所述的杂芳基可为“杂原子选自N、O和S,杂原子个数为1-3个”的5-6元的杂芳基,例如呋喃基、吡咯基、噻吩基、吡喃基、或吡啶基,又可为噻吩基,例如)、或、C3-7的环烯基(所述的C3-7的环烷基可为环丙烯基、环丁烯基、环戊烯基或环己烯基,又可为环己烯基,例如);
或者,R5、R6与其间的碳原子一起形成C6-10的芳基(所述的C6-10的芳基可为苯基或萘基,例如)、或、C3-7的环烯基(所述的C3-7的环烷基可为环丙烯基、环丁烯基、环戊烯基或环己烯基,又可为环戊烯基,例如);
或者,R4、R5、R6与其间的碳原子一起形成C10-20的芳基(所述的C10-20的芳基可为C10-15的芳基,又可为)、或、C9-10的芳基并环烯基(所述的C9-10的芳基并环烯基可为C9-10的苯并环烯基,又可为苯并环戊烯基,例如)。
本发明中,当R7为未取代或R7-1为取代的C6-10的芳基时,所述的C6-10的芳基可为苯基或萘基。
本发明中,当R7为未取代或R7-2为取代的“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基时,所述的杂芳基可为“杂原子选自N、O和S,杂原子个数为1-3个”的5-6元单环杂芳基(例如呋喃基、吡咯基、噻吩基、吡喃基、或吡啶基,又可为噻吩基或吡啶基,例如)、或、“杂原子选自N、O和S,杂原子个数为1-3个”的9-10元双环杂芳基(例如苯并呋喃基或苯并噻吩基,又例如 )。
本发明中,当R7为未取代或R7-3为取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基,所述的芳基并杂环烯基可为“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的苯并杂环烯基,例如苯并二氧戊环烯基或苯并二氧六环烯基,又例如
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):Z为CH。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):
X为卤素;
Z为CH;
R2、R5和R6独立地为氢、卤素、C1-10的烷基、或C1-10的烷氧基;
R3为C1-10的烷基、或C1-10的烷氧基;
R4为C1-10的烷氧基;
R7为未取代或R7-1为取代的C6-10的芳基、未取代或R7-2为取代的“杂原子为N,杂原子个数为1-3个的5-10元”的杂芳基、或、未取代或R7-3为取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基;
R7-1、R7-2和R7-3独立地为氢、卤素、C1-6的卤代烷基、C1-10的烷基、C1-10的烷氧基、C6-10的芳基、或、NR7-1-1R7-1-2;
R7-1-1和R7-1-2独立地为氢或C1-6的烷基;
或者,R2、R3与其间的碳原子一起形成C6-10的芳基、或、C3-7的环烯基;
或者,R4、R5与其间的碳原子一起形成C6-10的芳基;
或者,R5、R6与其间的碳原子一起形成C6-10的芳基、或、C3-7的环烯基;
或者,R4、R5、R6与其间的碳原子一起形成C10-20的芳基、或、C9-10的芳基并环烯基。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):Z为CH。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):
R2、R5和R6独立地为氢、卤素、C1-10的烷基、或C1-10的烷氧基。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):
R4为C1-10的烷氧基。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):
R7为未取代或R7-1为取代的C6-10的芳基、未取代或R7-2为取代的“杂原子为N,杂原子个数为1-3个的5-10元”的杂芳基、或、未取代或R7-3为取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):
R7-1、R7-2和R7-3独立地为氢、卤素、C1-6的卤代烷基、C1-10的烷基、C1-10的烷氧基、C6-10的芳基、或、NR7-1-1R7-1-2。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):
R2、R3与其间的碳原子一起形成C6-10的芳基、或、C3-7的环烯基。
本发明某一实施方案中,所述的如式I或式I’所示化合物的某些基团的定义如下(未定义的基团如前任一方案所述):所述化合物1为如式I或式I’所示化合物。
本发明中,所述的如式I或式I’所示化合物选自以下任一结构:
本发明中,所述的保护气体可为本领域常规的保护气体,例如氦气、氖气、氮气和氩气中的一种或多种,又例如氩气。
本发明中,所述的有机溶剂可为本领域常规的有机溶剂,较佳地为芳烃类溶剂{例如甲苯(toluene)、对二甲苯(p-xylene)和1,3,5-三甲基苯(Mesitylene)中的一种或多种,又例如对二甲苯}和/或醚类溶剂{例如甲基叔丁基醚(MTBE)}。
本发明中,所述的如式II所示化合物在所述的有机溶剂中的摩尔浓度可为本领域常规的摩尔浓度,较佳地为0.1-0.8mol/L,更佳地为0.4-0.6mol/L(例如0.5mol/L)。
本发明中,所述的如式III所示化合物与所述的如式II所示化合物的摩尔比可为本领域常规的摩尔比,较佳地为1:1-8:1,更佳地为2:1-4:1(例如3:1)。
本发明中,所述的铑催化剂可为本领域常规的铑催化剂,较佳地为[Rh(C2H4)2Cl]2、[Rh(CO)2Cl]和[Rh(cod)Cl]中的一种或多种,更佳地为[Rh(C2H4)2Cl]2。
本发明中,所述的铑催化剂与所述的如式II所示化合物的摩尔比可为本领域常规的摩尔比,较佳地为0.04:1-0.2:1,更佳地为0.05:1-0.07:1(例如0.05:1或0.055:1)。
本发明中,所述的膦配体可为本领域常规的单膦配体,又可为手性单膦配体或手性单膦配体的外消旋体,较佳地为酒石酸(taddol)衍生的亚磷酸酯配体,更佳地为进一步更佳地为其中,R8和R8’独立地为C6-C10的芳基(例如苯基),R9和R9’独立地为未取代或R9-1取代的C6-C10的芳基(所述R9-1的个数可为一个或多个,例如1、2或3个,当存在多个R9-1时,所述的R9-1可相同或不同。所述的C6-C10的芳基可为苯基),R9-1为C1-3卤代烷基(例如三氟甲基)、C1-4烷基或C1-4烷氧基(例如甲氧基)。
本发明中,所述的膦配体较佳地为以下任一结构:
本发明中,所述的膦配体与所述的如式II所示化合物的摩尔比可为本领域常规的摩尔比,较佳地为0.05:1-0.35:1(例如0.1:1、0.2:1或0.3:1),更佳地为0.05:1-0.2:1(例如0.1:1)。
本发明中,所述的碱可为本领域常规的碱,较佳地为叔丁醇钠、叔丁醇钾、碳酸钾和碳酸铯中的一种或多种,更佳地为叔丁醇钠。
本发明中,所述的碱与所述的如式II所示化合物的摩尔比可为本领域常规的摩尔比,较佳地为1:1-5:1,更佳地为2:1-4:1(例如3:1)。
本发明中,所述的芳基化反应的温度可为本领域常规的温度,较佳地为0-100℃,更佳地为40-80℃(例如40℃、50℃、60℃或80℃)。
本发明中,所述的芳基化反应的进程可采用本领域中的常规测试方法(如TLC、HPLC、GC或NMR)进行监控,一般以所述的如式II所示化合物不再反应时作为反应终点。所述芳基化反应的时间较佳地为0.5-12h(例如0.5h、1h、3h、5h或12h)。
本发明某一实施方案中(未定义的基团如前任一方案所述),在保护气体氛围下,在有机溶剂中,在铑催化剂、膦配体和碱的存在下,将如式II所示化合物与如式III所示化合物进行芳基化反应;所述的有机溶剂为芳烃类溶剂;所述的铑催化剂为[Rh(C2H4)2Cl]2、[Rh(CO)2Cl]和[Rh(cod)Cl]中的一种或多种;所述的膦配体为 所述的碱为叔丁醇钠、叔丁醇钾、碳酸钾和碳酸铯中的一种或多种。
本发明某一实施方案中(未定义的基团如前任一方案所述),在保护气体氛围下,在有机溶剂中,在铑催化剂、膦配体和碱的存在下,将如式II所示化合物与如式III所示化合物进行芳基化反应;所述的有机溶剂为芳烃类溶剂;所述的铑催化剂为[Rh(C2H4)2Cl]2、[Rh(CO)2Cl]和[Rh(cod)Cl]中的一种或多种;所述的膦配体为 所述的碱为叔丁醇钠、叔丁醇钾、碳酸钾和碳酸铯中的一种或多种;所述的如式II所示化合物在所述的有机溶剂中的摩尔浓度为0.4-0.6mol/L;所述的如式III所示化合物与所述的如式II所示化合物的摩尔比为2:1-4:1;所述的铑催化剂与所述的如式II所示化合物的摩尔比为0.05:1-0.07:1;所述的膦配体与所述的如式II所示化合物的摩尔比为0.05:1-0.35:1;所述的碱与所述的如式II所示化合物的摩尔比为2-4:1。
本发明某一实施方案中,所述的化合物1的制备方法包括以下步骤:将铑催化剂、膦配体和有机溶剂混合,加热至70-90℃反应0.5-3h,冷却至20-30℃,再加入如式II、如式III所示化合物和碱,在40-80℃进行所述的芳基化反应,即可。
所述的芳基化反应结束后,较佳地,其还可进一步包括后处理操作,所述的后处理操作和条件可为本领域该类反应常规的后处理的操作和条件,较佳地包括以下步骤:稀释反应液,浓缩,分离纯化。所述稀释的操作和条件可为本领域常规的操作和条件,所述稀释的溶剂较佳地为酯类溶剂(例如乙酸乙酯)。所述浓缩的操作和条件可为本领域常规的操作和条件,较佳地为减压浓缩。所述分离纯化的操作和条件可为本领域常规的操作和条件,较佳地为柱层析分离;所述的柱层析分离的展开剂体系可为本领域该类反应常规的展开剂体系,较佳地为酯类溶剂/醚类溶剂(例如乙酸乙酯/石油醚),更佳地为酯类溶剂/醚类溶剂=1/10。
本发明还提供了一种如式I或式I’所示化合物,其结构如下所示,
其中,R2-R7的定义如前任一方案所述;
所述的如式I或式I’所示化合物不为以下任一结构:
所述的如式I所示化合物可为以下任一结构:
本发明还提供了一种如式I或式I’所示化合物作为中间体在合成轴手性吡啶类化合物衍生的配体中的应用。
本发明还提供了一种如式IV所示化合物,
如无特别说明,本发明所用术语具有如下含义:
术语“多个”是指2个、3个、4个或5个。
术语“卤素”是指氟、氯、溴或碘。
术语“烷基”是指具有指定的碳原子数的直链或支链烷基。烷基的实例包括甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、仲丁基、正戊基、正己基、正庚基、正辛基及其类似烷基。
术语“烷氧基”是指基团-O-RX,其中,RX为如上文所定义的烷基。
术语“卤代烷基”是指被一个或多个卤素取代的烷基,例如三氟甲基,其中,“多个”、“卤素”和“烷基”均如上文所定义。
术语“环烷基”是指单价饱和的环状烷基,优选具有3-7个环碳原子、更优选3-6个碳原子的单价饱和的环状烷基,例如环丙基、环丁基、环戊基或环己基。
术语“杂环烷基”是指具有杂原子的饱和的单环基团,优选含有1个、2个或3个独立选自N、O和S的环杂原子的3-7元饱和的单环。杂环烷基的示例为:吡咯烷基、四氢呋喃基、四氢吡喃基、四氢噻吩基、四氢吡啶基、四氢吡咯基、氮杂环丁烷基、噻唑烷基、唑烷基、哌啶基、吗啉基、硫代吗啉基、哌嗪基、氮杂环庚烷基、二氮杂环庚烷基、氧氮杂环庚烷基、二氧戊环基、二氧六环基等。
术语“环烯基”是指含有双键的不饱和的非芳香基团,优选具有3-7个环碳原子、更优选3-6个碳原子的含有一个双键的非芳香基团,例如环丙烯基、环丁烯基、环戊烯基或环己烯基。
术语“杂环烯基”是指具有杂原子的含有双键的不饱和的非芳香基团,优选含有1个、2个或3个独立选自N、O和S的环杂原子的3-7元,更优选3-6元不饱和的非芳香基团。优选的杂环烷基为1,3-二氧戊环烯基、1,4-二氧六环烯基。
术语“芳基”是指具有指定的碳原子数的芳香基团,优选单环、双环或者三环的芳香基团,当为双环或者三环时,每个环均满足休克尔规则。单环的芳基例如C6芳基(苯基),双环的芳基例如C10芳基(萘基),三环的芳基例如C13芳基(非那烯基)。
术语“杂芳基”是指含有杂原子的芳香基团,优选含有1个、2个或3个独立选自氮、氧和硫的芳族5-6元单环或9-10元双环,例如呋喃基、吡啶基、哒嗪基、嘧啶基、吡嗪基、噻吩基、异唑基、噁唑基、二唑基、咪唑基、吡咯基、吡唑基、三唑基、四唑基、噻唑基、异噻唑基、噻二唑基、苯并咪唑基、吲哚基、吲唑基、苯并呋喃基、苯并噻唑基、苯并异噻唑基、苯并唑基、苯并异唑基、喹啉基、异喹啉基等。
在不违背本领域常识的基础上,上述各优选条件,可任意组合,即得本发明各较佳实例。
本发明所用试剂和原料均市售可得。
本发明的积极进步效果在于:本发明的制备方法可一步合成轴手性吡啶化合物,无需对原料进行预处理,在简化操作的基础上,还能进一步使得产物具有相当或者更高的收率和对映选择性,且底物普适性较好。
附图说明
图1为单晶X衍射测得的化合物IV的结构图。
具体实施方式
下面通过实施例的方式进一步说明本发明,但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法,按照常规方法和条件,或按照商品说明书选择。
实施例1:化合物I的合成
在氩气氛围下,向干燥的Schlenk反应瓶中加入L1(14.4mg,0.025mmol),[Rh(C2H4)2Cl]2(5.4mg,0.0138mmol)和无水p-xylene(0.5mL),加热至80℃反应一小时,冷却至室温,在氩气氛围下加入化合物II(0.25mmol)和相应的卤代芳烃III(0.75mmol,3.0equiv.)。在手套箱中加入叔丁醇钠(72.1mg,0.75mmol),然后加热至60℃反应。反应结束后,用乙酸乙酯稀释,加入少量硅胶,减压除去溶剂残留物经柱层析分离获得目标产物I(乙酸乙酯/石油醚=1/10)。
以下实施例2-实施例38的化合物参照实施例1制备获得。
实施例2
(85.5mg,99%产率,95%ee).分析数据:[α]26D=-179.7(c=1.0,CHCl3,95%ee).1H NMR(400MHz,CDCl3).δ8.66(d,J=5.7Hz,1H),8.06(d,J=8.5Hz,1H),7.96(d,J=8.2Hz,1H),7.77(d,J=8.3Hz,1H),7.65(dd,J=13.8,7.1Hz,2H),7.53(t,J=7.5Hz,1H),7.49-7.39(m,2H),7.33-7.23(m,2H),7.19(d,J=8.5Hz,1H),7.09(d,J=8.1Hz,2H),6.84(d,J=7.9Hz,2H),2.14(s,3H).手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=10.79min,tR(major)=21.47min.
实施例3
(96.0mg,99%产率,93%ee).分析数据:[α]20D=-192.9(c=1.0,CHCl3,93%ee).1H NMR(400MHz,CDCl3).δ8.64(d,J=5.8Hz,1H),8.04(d,J=8.5Hz,1H),7.94(d,J=8.1Hz,1H),7.73(d,J=8.3Hz,1H),7.69(d,J=8.5Hz,1H),7.60(d,J=5.6Hz,1H),7.49(ddd,J=8.5,7.0,1.4Hz,1H),7.45(ddd,J=8.5,7.0,1.4Hz,1H),7.40(s,1H),7.33-7.26(m,1H),7.24(dt,J=7.5,1.3Hz,1H),7.20(d,J=9.0Hz,1H),7.15-7.08(m,2H),7.07-7.01(m,2H),1.15(s,9H).手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=8.66min,tR(major)=16.86min.
实施例4
(89.5mg,99%产率,92%ee).分析数据:[α]26D=-160.7(c=1.0,CHCl3,92%ee).1H NMR(400MHz,CDCl3).δ8.65(d,J=5.8Hz,1H),8.03(d,J=8.5Hz,1H),7.93(d,J=8.2Hz,1H),7.76(d,J=8.3Hz,1H),7.67-7.59(m,2H),7.52(ddd,J=8.1,6.9,1.1Hz,1H),7.44(ddd,J=8.1,6.9,1.1Hz,1H),7.40-7.33(m,1H),7.28(ddd,J=8.2,6.8,1.2Hz,1H),7.24(ddd,J=8.3,6.8,1.1Hz,1H),7.16(d,J=8.4Hz,1H),7.12-7.05(m,2H),6.59-6.51(m,2H),3.61(s,3H).手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=16.15min,tR(major)=30.96min.
实施例5
(93.0mg,99%产率,91%ee).分析数据:熔点:116-118℃.[α]22D=-211.3(c=1.0,CHCl3,91%ee).1H NMR(400MHz,CDCl3)δ8.69(d,J=5.7Hz,1H),8.03(d,J=8.5Hz,1H),7.93(d,J=8.1Hz,1H),7.75(d,J=8.2Hz,1H),7.69(d,J=8.5Hz,1H),7.63(d,J=5.7Hz,1H),7.50(ddd,J=8.2,6.9,1.3Hz,1H),7.47-7.38(m,2H),7.31-7.25(m,1H),7.25-7.20(m,1H),7.16(d,J=8.5Hz,1H),7.12-7.04(m,2H),6.46-6.35(m,2H),2.77(s,6H).13CNMR(101MHz,CDCl3)δ160.6,148.8,142.0,139.2,136.0,133.5,133.0,132.3,130.1,129.8,129.3,128.6,128.5,128.3,127.8,127.3,126.9,126.6,126.3,126.0,125.2,119.8,111.7,40.2.IR(ATR):νmax(cm-1)=2919,1647,1607,1553,1523,1499,1443,1353,1319,1229,1190,1166,1060,950,810,749,695,642.HRMS(ESI):计算值:C27H23N2[M+H]+:375.1856,实测值375.1858.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=80:20,1mL/min,检测波长=254nm,tR(minor)=13.62min,tR(major)=26.14min.
实施例6
(81.0mg,98%产率,94%ee).分析数据:[α]20D=-171.9(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3).δ8.65(d,J=5.7Hz,1H),8.07(d,J=8.5Hz,1H),7.97(d,J=8.2Hz,1H),7.77(d,J=8.3Hz,1H),7.67(d,J=8.5Hz,1H),7.63(d,J=5.7Hz,1H),7.53(td,J=7.5Hz,1.3Hz,1H),7.48(td,J=7.4,1.1Hz),7.41(d,J=8.4Hz,1H),7.31(td,J=7.6Hz,1.3Hz,1H),7.26(td,7.2Hz,1.0Hz,1H),7.21(d,J=8.6Hz,1H),7.19-7.12(m,2H),7.05-6.95(m,3H).手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=10.74min,tR(major)=17.74min.
实施例7
(86.2mg,99%产率,93%ee).分析数据:熔点:61-63℃.[α]25D=-149.9(c=1.0,CHCl3,93%ee).1H NMR(400MHz,CDCl3)δ8.64(d,J=5.7Hz,1H),8.05(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.76(d,J=8.3Hz,1H),7.62(dd,J=7.1,5.0Hz,2H),7.52(ddd,J=8.2,6.8,1.3Hz,1H),7.47(ddd,J=8.1,6.7,1.2Hz,1H),7.36(d,J=8.4Hz,1H),7.31(ddd,J=8.2,6.7,1.3Hz,1H),7.27-7.23(m,1H),7.21(d,J=9.0Hz,1H),7.17-7.09(m,2H),6.76-6.63(m,2H).13C NMR(101MHz,CDCl3)δ161.6(d,J=246.0Hz),159.9,142.1 138.3,137.4(d,J=3.3Hz),136.1,134.5,132.9,132.9,131.0(d,J=8.0Hz),130.1,129.0,128.5,128.0,127.9,127.2 127.1,126.9,126.8,126.3,126.0,120.2,114.6(d,J=21.2Hz).19F NMR(376MHz,CDCl3)δ-116.07.IR(ATR):νmax(cm-1)=2987,1602,1583,1555,1501,1315,1220,1158,1083,1045,1015,954,867,818,746,698.HRMS(ESI):计算值:C25H17FN[M+H]+:350.1340,实测值350.1343.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=9.67min,tR(major)=16.45min.
实施例8
(90.6mg,99%产率,94%ee).分析数据:熔点:92-94℃.[α]22D=-178.0(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.64(d,J=5.7Hz,1H),8.05(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.79(d,J=8.2Hz,1H),7.64(d,J=5.7Hz,1H),7.60(d,J=8.5Hz,1H),7.55(td,J=7.5,1.3Hz,1H),7.47(td,J=7.4Hz,1.2Hz,1H),7.35(d,J=8.4Hz,1H),7.33-7.25(m,2H),7.18(d,J=8.5Hz,1H),7.13-7.03(m,2H),7.01-6.94(m,2H).13C NMR(101MHz,CDCl3)δ159.7,142.1,139.9,138.0,136.1,134.5,132.9,132.8,132.6,130.7,130.2,129.0,128.6,128.0,127.8,127.7,127.3,127.0,126.9,126.8,126.3,126.1,120.2.IR(ATR):νmax(cm-1)=2987,1620,1583,1553,1492,1396,1315,1089,1011,951,867,814,746.HRMS(ESI):计算值:C25H17ClN[M+H]+:366.1044,实测值366.1045.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=9.00min,tR(major)=15.50min.
实施例9
(93.0mg,91%产率,94%ee).分析数据:熔点:104-106℃.[α]22D=-148.8(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.63(d,J=5.7Hz,1H),8.05(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.79(d,J=8.3Hz,1H),7.64(d,J=5.5Hz,1H),7.59(d,J=8.5Hz,1H),7.54(ddd,J=8.1,6.8,1.2Hz,1H),7.47(ddd,J=8.1,6.9,1.1Hz,1H),7.35(d,J=7.9Hz,1H),7.33-7.28(m,1H),7.26(ddd,J=8.2,6.9,1.2Hz,1H),7.17(d,J=8.6Hz,1H),7.15-7.11(m,2H),7.06-7.01(m,2H).13C NMR(101MHz,CDCl3)δ159.7,142.1,140.4,138.0,136.1,134.5,132.9,132.9,131.0,130.8,130.2,129.1,128.6,128.0,127.6,127.3,127.0,126.9,126.8,126.3,126.1,120.9,120.3.IR(ATR):νmax(cm-1)=2921,1620,1583,1533,1489,1392,1315,1259,1069,1007,951,866,812,746,686.HRMS(ESI):计算值:C25H17BrN[M+H]+:410.0539,实测值410.0540.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=9.26min,tR(major)=15.87min.
实施例10
(99.0mg,99%产率,94%ee).分析数据:熔点:120-122℃.[α]26D=-125.2(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.62(d,J=5.7Hz,1H),8.07(d,J=8.5Hz,1H),7.96(d,J=8.2Hz,1H),7.78(d,J=8.3Hz,1H),7.63(d,J=5.8Hz,1H),7.61(d,J=8.5Hz,1H),7.54(ddd,J=8.1,6.8,1.1Hz,1H),7.49(ddd,J=8.1,6.9,1.1Hz,1H),7.37(d,J=8.0Hz,1H),7.32(ddd,J=8.1,6.8,1.2Hz,1H),7.28(s,4H),7.24(d,J=1.1Hz,1H),7.19(d,J=8.4Hz,1H).13C NMR(101MHz,CDCl3)δ159.4,145.1,145.1,142.1,137.8,136.0,134.8,133.0,132.8,130.2,129.6,129.1,128.6,128.5(q,J=32.3Hz),128.0,127.5,127.3,126.9,126.9,126.4,126.3,124.5(q,J=3.7Hz),124.0(d,J=272.0Hz),120.3.19FNMR(376MHz,CDCl3)δ-62.56.IR(ATR):νmax(cm-1)=2969,1614,1586,1556,1500,1403,1319,1159,1120,1106,1087,1067,1015,954,845,821,743,683.HRMS(ESI):计算值:C26H17F3N[M+H]+:400.1308,实测值400.1309.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=6.73min,tR(major)=11.22min.
实施例11
(63.5mg,71%产率,79%ee).分析数据:熔点:112-114℃.[α]26D=-127.1(c=1.0,CHCl3,79%ee).1H NMR(400MHz,CDCl3)δ8.60(d,J=5.7Hz,1H),8.06(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.78(d,J=8.3Hz,1H),7.63(d,J=5.6Hz,1H),7.57(d,J=8.5Hz,1H),7.55-7.51(m,1H),7.48(ddd,J=8.0,6.7,1.1Hz,1H),7.34-7.28(m,2H),7.28-7.24(m,3H),7.24-7.21(m,2H),7.19(d,J=8.6Hz,1H).13C NMR(101MHz,CDCl3)δ159.1,146.3,142.1,137.4,136.0,134.9,133.2,132.7,131.4,130.3,130.0,129.3,128.5,128.1,127.5,127.1,127.0,126.7,126.6,126.5,120.5,118.8,110.3.IR(ATR):νmax(cm-1)=2920,2226,1604,1555,1498,1399,1316,1259,1044,1017,953,865,826,749,692.HRMS(ESI):计算值:C26H17N2[M+H]+:357.1386,实测值357.1389.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=80:20,1mL/min,检测波长=254nm,tR(minor)=20.11min,tR(major)=29.58min.
实施例12
(85.4mg,99%产率,95%ee).分析数据:熔点:124-126℃.[α]26D=-193.7(c=1.0,CHCl3,95%ee).1H NMR(400MHz,CDCl3)δ8.62(d,J=5.7Hz,1H),8.03(d,J=8.5Hz,1H),7.93(d,J=8.2Hz,1H),7.73(d,J=8.3Hz,1H),7.65(d,J=8.5Hz,1H),7.59(d,J=5.8Hz,1H),7.49(t,J=7.6Hz,1H),7.44(t,J=7.5Hz,1H),7.39(d,J=8.4Hz,1H),7.28(t,J=7.6Hz,1H),7.24(d,J=7.9Hz,1H),7.20(d,J=8.4Hz,1H),7.01(s,1H),6.96-6.82(m,2H),6.77(d,J=7.5Hz,1H),2.07(s,3H).13C NMR(101MHz,CDCl3)δ160.2,142.0,141.3,139.4,137.1,136.0,134.4,132.9,132.8,130.4,130.0,128.8,128.7,128.1,128.0,127.4,127.3,127.2,127.0,126.7,126.6,126.4,126.4,125.8,120.0,21.2.IR(ATR):νmax(cm-1)=2920,1550,1494,1451,1315,1257,1042,955,919,868,796,745,704.HRMS(ESI):计算值:C26H20N[M+H]+:346.1590,实测值346.1592.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=10.26min,tR(major)=16.23min.
实施例13
(86.5mg,99%产率,94%ee).分析数据:熔点:81-83℃.[α]25D=-142.0(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.70(d,J=5.7Hz,1H),8.10(d,J=8.5Hz,1H),8.00(d,J=8.2Hz,1H),7.81(d,J=8.3Hz,1H),7.70-7.64(m,2H),7.57(ddd,J=8.2,6.8,1.3Hz,1H),7.52(ddd,J=8.1,6.7,1.2Hz,1H),7.42(d,J=8.3Hz,1H),7.36(ddd,J=8.2,6.7,1.3Hz,1H),7.33-7.24(m,2H),7.04-6.92(m,3H),6.76-6.67(m,1H).13C NMR(101MHz,CDCl3)δ162.1(d,J=245.4Hz),159.6,143.6(d,J=7.9Hz),142.1,138.0(d,J=2.0Hz),136.1,134.6,133.0,132.8,130.2,129.1,129.0(d,J=8.1Hz),128.6,128.1,127.6,127.3,127.0,126.9,126.9,126.4,126.2,125.3(d,J=2.9Hz),120.3,116.4(d,J=22.0Hz),113.5(d,J=21.0Hz).19F NMR(376MHz,CDCl3)δ-114.01.IR(ATR):νmax(cm-1)=2920,1609,1582,1488,1421,1346,1316,1258,1188,1138,1075,1017,958,922,894,871,817,787,744.HRMS(ESI):实测值:C25H17FN[M+H]+:350.1340,计算值350.1343.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=9.22min,tR(major)=13.29min.
实施例14
(89.0mg,99%产率,96%ee).分析数据:熔点:156-158℃.[α]25D=-189.3(c=1.0,CHCl3,96%ee).1H NMR(400MHz,CDCl3)δ8.63(d,J=5.7Hz,1H),8.04(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.78(d,J=8.3Hz,1H),7.66(d,J=8.5Hz,1H),7.62(d,J=5.7Hz,1H),7.54(ddd,J=8.1,6.7,1.3Hz,1H),7.46(ddd,J=8.1,6.7,1.2Hz,1H),7.40(d,J=8.3Hz,1H),7.33-7.26(m,2H),7.23-7.16(m,1H),6.76(s,2H),6.61(s,1H),2.02(s,6H).13C NMR(101MHz,CDCl3)δ160.3,141.9,141.2,139.5,136.9,136.0,134.3,132.9,132.8,130.0,128.8,128.8,128.1,128.0,127.4,127.4,127.0,126.7,126.6,126.4,125.8,119.9,21.1.IR(ATR):νmax(cm-1)=2985,2904,1586,1555,1496,1449,1317,1256,1046,959,873,852,824,781,747,705,689.HRMS(ESI):计算值:C27H22N[M+H]+:360.1747,实测值360.1750.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=9.90min,tR(major)=13.37min.
实施例15
(89.5mg,94%产率,86%ee).分析数据:熔点:167-169℃.[α]25D=-213.5(c=1.0,CHCl3,86%ee).1H NMR(400MHz,CDCl3)δ8.62(d,J=5.7Hz,1H),8.06(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.73(d,J=8.5Hz,1H),7.69(s,1H),7.63(d,J=8.3Hz,1H),7.59-7.54(m,2H),7.52(d,J=5.7Hz,1H),7.48-7.42(m,3H),7.42-7.37(m,1H),7.34-7.24(m,4H),7.24-7.15(m,2H).13C NMR(101MHz,CDCl3)δ160.1,142.1,139.2,139.0,136.0,134.7,133.0,133.0,132.9,131.9,130.1,129.0,128.7,128.7,128.3,128.1,128.1,127.6,127.4,127.2,127.2,127.1,126.8,126.8,126.4,126.0,125.9,125.8,120.2.IR(ATR):νmax(cm-1)=2920,1585,1554,1499,1315,1257,1016,946,863,818,741,693.HRMS(ESI):计算值:C29H20N[M+H]+:382.1590,实测值382.1592.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=11.70min,tR(major)=19.14min.
实施例16
(91.0mg,97%产率,92%ee).分析数据:[α]25D=-143.7(c=1.0,CHCl3,92%ee).1H NMR(400MHz,CDCl3)δ8.68(d,J=5.7Hz,1H),8.04(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.78(d,J=8.2Hz,1H),7.64(t,J=7.4Hz,2H),7.54(ddd,J=8.2,6.7,1.2Hz,1H),7.46(ddd,J=8.1,6.8,1.2Hz,1H),7.39(d,J=8.4Hz,1H),7.35-7.28(m,1H),7.28-7.24(m,1H),7.18(d,J=8.5Hz,1H),6.72(d,J=1.7Hz,1H),6.66(dd,J=8.0,1.8Hz,1H),6.48(d,J=8.0Hz,1H),5.75(s,2H).手性柱Chiralpak IG column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=24.98min,tR(major)=29.74min.
实施例17
(96.0mg,99%产率,94%ee).分析数据:[α]25D=-166.5(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.65(d,J=5.7Hz,1H),8.00(d,J=8.5Hz,1H),7.91(d,J=8.1Hz,1H),7.75(d,J=8.2Hz,1H),7.66-7.58(m,2H),7.51(t,J=7.4Hz,1H),7.42(t,J=7.2Hz,1H),7.37(d,J=8.4Hz,1H),7.25(ddt,J=10.1,8.6,3.9Hz,2H),7.13(d,J=8.5Hz,1H),6.76(d,J=2.0Hz,1H),6.59(dd,J=8.4,2.0Hz,1H),6.47(d,J=8.4Hz,1H),4.04(s,4H).手性柱Chiralpak IG column(25cm),正己烷/异丙醇=90:10,0.7mL/min,检测波长=254nm,tR(major)=22.87min,tR(minor)=33.56min.
实施例18
(54.0mg,58%产率,88%ee).分析数据:熔点:150-152℃.[α]24D=-67.0(c=1.0,CHCl3,88%ee).1H NMR(400MHz,CDCl3)δ8.63(d,J=5.7Hz,1H),8.06(d,J=8.5Hz,1H),7.96(d,J=8.2Hz,1H),7.72(d,J=8.2Hz,1H),7.69(d,J=8.5Hz,1H),7.59(d,J=5.7Hz,1H),7.53-7.46(m,2H),7.45(d,J=2.1Hz,1H),7.44-7.39(m,2H),7.33-7.27(m,1H),7.25-7.21(m,1H),7.18(d,J=8.5Hz,1H),7.14-7.06(m,2H),6.54(dd,J=2.3,0.8Hz,1H).13C NMR(101MHz,CDCl3)δ160.2,153.7,145.0,142.0,139.5,136.3,136.0,134.4,132.9,132.7,130.0,128.8,128.6,128.5,128.0,127.2,127.1,126.9,126.7,126.7,126.3,126.0,125.8,122.2,120.0,110.4,106.6.IR(ATR):νmax(cm-1)=2920,1620,1583,1555,1497,1454,1258,1224,1128,1107,1025,957,934,867,812,771,742,703.HRMS(ESI):计算值C27H18NO[M+H]+:372.1383,实测值372.1380.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=14.54min,tR(major)=23.38min.
实施例19
(82.5mg,80%产率,88%ee).分析数据:熔点:129-131℃.[α]25D=-67.0(c=1.0,CHCl3,88%ee).1H NMR(400MHz,CDCl3)δ8.75(d,J=5.7Hz,1H),8.03(d,J=8.7Hz,1H),7.92(d,J=8.2Hz,1H),7.87(dd,J=8.5,5.8Hz,2H),7.77(d,J=5.8Hz,1H),7.58(t,J=7.5Hz,1H),7.46(d,J=7.2Hz,1H),7.42(d,J=9.3Hz,1H),7.35(d,J=7.6Hz,2H),7.31-7.24(m,4H),7.18(t,J=7.3Hz,1H),7.11(d,J=8.5Hz,1H),6.89(d,J=3.9Hz,1H),6.60(d,J=3.8Hz,1H).13C NMR(101MHz,CDCl3)δ159.8,144.6,142.5,142.2,136.3,134.1,133.7,133.2,132.9,131.5,130.4,129.1,128.9,128.8,128.0,128.0,127.5,127.4,127.3,126.9,126.9,126.8,126.5,126.1,125.5,123.0,120.7.IR(ATR):νmax(cm-1)=2919,1618,1581,1555,1494,1442,1316,1261,1072,954,864,826,807,746,688,628,598.HRMS(ESI):计算值C29H20NS[M+H]+:414.1311,实测值414.1311.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=17.28min,tR(major)=51.16min.
实施例20
(96.0mg,99%产率,92%ee).分析数据:熔点:154-156℃.[α]23D=-220.7(c=1.0,CHCl3,92%ee).1H NMR(400MHz,CDCl3)δ8.77(d,J=5.7Hz,1H),8.08(d,J=8.6Hz,1H),7.96(t,J=8.7Hz,2H),7.85(d,J=8.2Hz,1H),7.77(d,J=5.7Hz,1H),7.57(t,J=7.8Hz,2H),7.51(q,J=8.3,7.8Hz,2H),7.47(d,J=8.3Hz,1H),7.37-7.27(m,2H),7.23-7.11(m,3H),7.02(s,1H).13C NMR(101MHz,CDCl3)δ159.5,143.2,142.4,140.5,139.7,136.2,134.8,133.2,133.2,131.7,130.4,129.1,129.1,128.0,127.7,127.5,127.0,127.0,126.8,126.6,126.5,124.1,124.0,123.9,123.5,121.8,120.8.IR(ATR):νmax(cm-1)=2986,1554,1497,1423,1316,1258,1068,949,869,821,745,726,692.HRMS(ESI):计算值C27H18NS[M+H]+:388.1154,实测值388.1153.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=17.79min,tR(minor)=23.43min.
实施例21
(88.2mg,98%产率,96%ee).分析数据:熔点:152-154℃.[α]25D=-177.1(c=1.0,CHCl3,96%ee).1H NMR(400MHz,CDCl3)δ8.63(d,J=5.7Hz,1H),8.06(d,J=8.5Hz,1H),7.95(d,J=8.2Hz,1H),7.79(d,J=8.3Hz,1H),7.65(d,J=5.7Hz,1H),7.60(d,J=8.5Hz,1H),7.55(t,J=7.4Hz,1H),7.49(t,J=7.4Hz,1H),7.34(d,J=8.1Hz,1H),7.33-7.26(m,2H),7.22(d,J=8.5Hz,1H),6.74(s,2H),2.24(s,6H).13C NMR(101MHz,CDCl3)δ159.3,156.8,149.7,141.9,136.8,136.0,134.8,133.1,132.7,130.2,129.1,128.7,128.0,127.3,126.9,126.8,126.8,126.4,126.4,120.9,120.3,24.2.IR(ATR):νmax(cm-1)=2918,1603,1554,1499,1400,1369,1322,1257,1136,1046,956,917,873,820,779,749,691.HRMS(ESI):计算值C26H21N2[M+H]+:361.1699,实测值361.1699.手性柱Chiralpak ICcolumn(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=14.92min,tR(major)=19.83min.
实施例22
(89.0mg,99%产率,94%ee).分析数据:熔点:123-125℃.[α]24D=-159.4(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.62(d,J=5.7Hz,1H),8.08(d,J=8.4Hz,1H),7.73(d,J=8.2Hz,1H),7.59(d,J=5.7Hz,1H),7.53-7.44(m,3H),7.41(dd,J=8.5,1.0Hz,1H),7.27(ddd,J=8.2,6.7,1.2Hz,1H),7.24-7.20(m,1H),7.17(d,J=8.2Hz,1H),7.09-7.00(m,2H),6.80(d,J=7.9Hz,2H),2.82(d,J=1.0Hz,3H),2.11(s,3H).13C NMR(101MHz,CDCl3)δ160.5,142.1,138.9,138.6,136.0,136.0,135.1,133.1,132.6,131.9,129.9,129.2,129.0,128.8,128.4,127.5,127.0,126.9,126.7,126.2,125.6,124.1,119.9,21.0,19.7.IR(ATR):νmax(cm-1)=2920,1646,1617,1581,1554,1511,1400,1376,1331,1020,942,869,817,748,683,625.HRMS(ESI):计算值:C27H22N[M+H]+:360.1747,实测值360.1745.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=13.51min,tR(major)=33.22min.
实施例23
(83.6mg,92%产率,93%ee).分析数据:熔点:108-110℃.[α]24D=-143.1(c=1.0,CHCl3,93%ee).1H NMR(400MHz,CDCl3)δ8.64(d,J=5.7Hz,1H),8.21(d,J=8.3Hz,1H),7.76(d,J=8.2Hz,1H),7.62(d,J=5.7Hz,1H),7.51(q,J=6.7Hz,2H),7.38(d,J=8.8Hz,1H),7.37-7.27(m,2H),7.25(d,J=5.3Hz,1H),7.17(d,J=7.0Hz,1H),7.04(d,J=7.9Hz,2H),6.81(d,J=7.8Hz,2H),2.11(s,3H).13C NMR(101MHz,CDCl3)δ159.5,158.8(d,J=252.9Hz),142.1,139.7(d,J=8.1Hz),137.6(d,J=1.5Hz),136.5,136.0,134.4(d,J=5.3Hz),130.4(d,J=4.2Hz),130.0,129.2,128.7,128.5,127.5,127.2,127.1,126.8,126.2(d,J=2.9Hz),126.0(d,J=1.8Hz),122.9(d,J=16.4Hz),120.5(d,J=5.2Hz),120.1,111.7(d,J=20.1Hz),21.0.19F NMR(376MHz,CDCl3)δ-122.89.IR(ATR):νmax(cm-1)=2920,1624,1602,1556,1505,1451,1382,1332,1262,1198,1143,1056,1020,947,861,818,757,703,688.HRMS(ESI):计算值C26H19FN[M+H]+:364.1496,实测值364.1495.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=8.44min,tR(major)=12.04min.
实施例24
(92.0mg,99%产率,93%ee).分析数据:熔点:100-102℃.[α]24D=-146.6(c=1.0,CHCl3,93%ee).1H NMR(400MHz,CDCl3)δ8.61(d,J=5.7Hz,1H),7.74(d,J=8.2Hz,1H),7.58(d,J=5.6Hz,1H),7.53-7.48(m,1H),7.48-7.42(m,2H),7.33-7.26(m,2H),7.24-7.20(m,1H),7.10-7.03(m,2H),6.93(dd,J=6.7,2.3Hz,1H),6.80(d,J=7.8Hz,2H),3.54-3.46(m,4H),2.12(s,3H).13C NMR(101MHz,CDCl3)δ160.2,146.7,145.8,142.2,141.2,139.3,138.5,136.0,135.8,131.3,130.1,129.8,129.4,128.6,128.5,128.3,127.5,126.8,126.7,121.8,121.3,119.7,119.4,30.6,30.4,21.0.IR(ATR):νmax(cm-1)=2918,1614,1555,1496,1365,1308,1021,985,966,865,819,756,725,686.HRMS(ESI):计算值C28H22N[M+H]+:372.1747,实测值372.1752.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=20.34min,tR(major)=54.74min
实施例25
(104.0mg,99%产率,90%ee).分析数据:熔点:105-107℃.[α]24D=+64.7(c=1.0,CHCl3,90%ee).1H NMR(400MHz,CDCl3)δ8.69(d,J=5.7Hz,1H),8.31(s,1H),8.20(dd,J=7.7,1.1Hz,1H),8.14(d,J=1.8Hz,2H),8.11(dd,J=7.7,1.1Hz,1H),7.98(t,J=7.6Hz,1H),7.87(d,J=9.3Hz,1H),7.77(d,J=8.3Hz,1H),7.65(d,J=5.7Hz,1H),7.51(ddd,J=8.2,6.8,1.2Hz,1H),7.43(d,J=9.3Hz,1H),7.32(dt,J=8.5,1.1Hz,1H),7.22-7.19(m,1H),7.19-7.15(m,2H),6.86(d,J=7.9Hz,2H),2.15(s,3H).13C NMR(101MHz,CDCl3)δ160.5,142.1,139.9,138.8,136.1,136.0,132.7,131.5,131.3,130.8,130.4,130.0,129.7,129.1,128.4,128.2,128.1,127.5,127.2,126.8,126.6,126.1,125.5,125.5,125.3,124.6,124.0,120.1,21.0.IR(ATR):νmax(cm-1)=2900,1583,1557,1510,1452,1437,1395,1320,1243,1080,1048,974,880,825,747.HRMS(ESI):计算值C32H22N[M+H]+:420.1747,实测值420.1750.手性柱Chiralpak IG column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=41.06min,tR(minor)=46.73min.
实施例26
(58.0mg,89%产率,82%ee).分析数据:[α]30D=-151.7(c=1.0,CHCl3,82%ee).1H NMR(400MHz,CDCl3)δ8.55(d,J=5.6Hz,1H),7.72(d,J=8.2Hz,1H),7.53(t,J=6.5Hz,2H),7.47(d,J=8.4Hz,1H),7.42(d,J=7.6Hz,1H),7.37-7.29(m,3H),6.98(d,J=8.2Hz,2H),6.49(d,J=8.3Hz,2H),3.59(s,3H),1.99(s,3H).13C NMR(101MHz,CDCl3)δ161.1,158.0,142.0,141.5,137.4,137.1,136.0,134.0,130.2,129.9,129.0,128.4,127.8,127.6,127.0,126.9,126.8,119.7,112.9,55.0,20.2.IR(ATR):νmax(cm-1)=2920,1609,1584,1557,1512,1457,1377,1352,1288,1245,1177,1095,1030,972,865,826,789,749,685.HRMS(ESI):计算值C23H20NO[M+H]+:326.1539,实测值326.1544.手性柱ChiralpakIC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=10.59min,tR(minor)=13.93min.
实施例27
(75.0mg,92%产率,72%ee).分析数据:熔点:146-148℃.[α]26D=-99.9(c=1.0,CHCl3,72%ee).1H NMR(400MHz,CDCl3)δ8.51(d,J=5.7Hz,1H),7.72(d,J=8.2Hz,1H),7.60(d,J=8.4Hz,1H),7.57-7.46(m,3H),7.37(t,J=7.6Hz,1H),7.13(d,J=7.7Hz,1H),7.04(d,J=8.3Hz,1H),6.95(d,J=8.0Hz,2H),6.78(d,J=7.9Hz,2H),3.66(s,3H),2.12(s,3H).13C NMR(101MHz,CDCl3)δ158.6,157.7,143.4,142.0,137.9,135.9,135.8,129.6,129.5,128.8,128.6,128.2,127.2,127.0,126.8,126.6,122.6,119.6,109.8,55.9,20.9.IR(ATR):νmax(cm-1)=2920,1620,1581,1558,1515,1462,1436,1380,1353,1306,1254,1110,1029,1014,973,819,790,748,684.HRMS(ESI):计算值C23H20NO[M+H]+:326.1539,实测值326.1540.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=13.03min,tR(minor)=22.42min.
实施例28
(76.0mg,99%产率,94%ee).分析数据:[α]26D=+2.3(c=1.0,CHCl3,94%ee).1HNMR(400MHz,CDCl3).δ8.60(d,J=4.3Hz,1H),7.95(d,J=8.5Hz,1H),7.90(d,J=8.1Hz,1H),7.59(d,J=8.5Hz,1H),7.46(t,J=7.4Hz,1H),7.37(t,J=8.0Hz,2H),7.28(d,J=8.4Hz,1H),7.20-7.14(m,1H),7.13(d,J=8.2Hz,2H),6.99(d,J=7.9Hz,2H),2.27(s,3H),1.73(s,3H).HRMS(ESI):计算值:C23H20N[M+H]+:310.1590,实测值310.1590.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=9.21min,tR(major)=16.31min.
实施例29
(74.5mg,91%产率,91%ee).分析数据:熔点:63-65℃.[α]26D=+4.4(c=1.0,CHCl3,91%ee).1H NMR(400MHz,CDCl3)δ8.60(t,J=6.8Hz,1H),8.01(d,J=8.5Hz,1H),7.95(d,J=8.1Hz,1H),7.63(d,J=8.5Hz,1H),7.51(t,J=7.5Hz,1H),7.44(t,J=7.6Hz,1H),7.33(d,J=8.5Hz,1H),7.17(d,J=7.7Hz,2H),7.06(d,J=7.8Hz,2H),6.99(dd,J=9.0,5.7Hz,1H),2.32(s,3H),1.72(s,3H).13C NMR(101MHz,CDCl3)δ167.4(d,J=260.7Hz),161.4(d,J=5.0Hz),148.4(d,J=8.1Hz),138.5,138.2,136.5,134.1(d,J=3.6Hz),132.9,132.0,129.6,128.9,128.7,128.2,128.1,126.8,125.9,125.7,121.6(d,J=12.8Hz),109.8(d,J=18.0Hz),21.2,10.6(d,J=4.2Hz).19F NMR(376MHz,CDCl3)δ-106.35.IR(ATR):νmax(cm-1)=1597,1562,1503,1461,1360,1262,1143,1117,1069,960,886,865,831,811,745,722,682.HRMS(ESI):计算值:C23H19NF[M+H]+:328.1496,实测值328.1501.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=95:5,1mL/min,检测波长=254nm,tR(minor)=9.74min,tR(major)=18.11min.
实施例30
(83.0mg,95%产率,94%ee).分析数据:熔点:52-54℃.[α]26D=-88.2(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.44(d,J=5.0Hz,1H),7.94(d,J=8.5Hz,1H),7.90(d,J=8.1Hz,1H),7.58(d,J=8.5Hz,1H),7.46(td,J=7.4Hz,1.3Hz,1H),7.38(td,J=7.5Hz,1.4Hz,1H),7.28(d,J=8.5Hz,1H),7.18-7.10(m,2H),7.04-6.94(m,3H),2.86-2.55(m,2H),2.29(s,3H),2.01(t,J=6.0Hz,2H),1.69-1.34(m,1H),1.53-1.35(m,3H).13CNMR(101MHz,CDCl3)δ157.9,146.6,145.5,138.5,137.9,136.1,135.4,132.9,132.6,132.2,129.6,128.4,128.2,128.1,127.9,126.4,125.9,125.6,123.1,29.2,25.7,22.5,22.1,21.1.IR(ATR):νmax(cm-1)=2925,1580,1502,1430,1372,1315,1241,1185,1023,946,905,835,809,747,688.HRMS(ESI):计算值:C26H24N[M+H]+:350.1903,实测值350.1908.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=11.66min,tR(major)=27.87min.
实施例31
(61.5mg,71%产率,81%ee).分析数据:熔点:116-118℃.[α]30D=-113.3(c=1.0,CHCl3,81%ee).1H NMR(400MHz,CDCl3)δ8.58(d,J=5.3Hz,1H),8.02(d,J=8.5Hz,1H),7.94(d,J=8.2Hz,1H),7.77(d,J=5.2Hz,1H),7.64(d,J=8.5Hz,1H),7.47(ddd,J=8.1,5.6,2.3Hz,1H),7.34(d,J=5.0Hz,2H),7.18(d,J=5.5Hz,1H),7.05(d,J=7.7Hz,2H),6.87(d,J=7.7Hz,2H),6.75(d,J=5.5Hz,1H),2.19(s,3H).13C NMR(101MHz,CDCl3)δ155.0,147.2,142.0,138.9,138.4,136.3,136.2,134.4,132.8,132.5,129.4,129.0,128.5,128.2,128.0,126.7,126.6,126.2,125.8,123.4,116.3,21.1.IR(ATR):νmax(cm-1)=2918,2850,1557,1537,1502,1433,1405,1374,1306,1022,870,810,746,709,687,638.HRMS(ESI):计算值:C24H18NS[M+H]+:352.1154,实测值352.1169.手性柱Chiralpak ICcolumn(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(minor)=13.34min,tR(major)=29.23min.
实施例32
(82.5mg,95%产率,86%ee).分析数据:[α]26D=-180.4(c=1.0,CHCl3,86%ee).1H NMR(400MHz,CDCl3).δ9.45(s,1H),8.08(d,J=8.5Hz,1H),8.02(d,J=8.5Hz,1H),7.96(d,J=8.2Hz,1H),7.75(t,J=7.5Hz,1H),7.65(d,J=8.5Hz,1H),7.49(t,J=7.4Hz,1H),7.41(d,J=8.2Hz,1H),7.33(q,J=8.8,8.3Hz,2H),7.20(d,J=8.5Hz,1H),7.06(d,J=7.7Hz,2H),6.85(d,J=7.6Hz,2H),2.14(s,3H).HRMS(ESI):计算值:C25H19N2[M+H]+:347.1543,实测值347.1542.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=95:5,1mL/min,检测波长=254nm,tR(major)=20.22min,tR(minor)=24.40min.
实施例33
(97.5mg,99%产率,94%ee).分析数据:熔点:146-148℃.[α]26D=-397.8(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.77(d,J=5.2Hz,1H),8.09(d,J=8.5Hz,1H),7.99(d,J=8.2Hz,1H),7.81(d,J=8.8Hz,1H),7.75(dd,J=7.9,1.5Hz,1H),7.69(d,J=5.2Hz,1H),7.63(t,J=8.5Hz,2H),7.55(d,J=8.7Hz,1H),7.48(ddd,J=8.1,6.7,1.2Hz,1H),7.43-7.37(m,2H),7.32-7.27(m,1H),7.06(ddd,J=8.6,7.0,1.5Hz,1H),6.75(d,J=8.0Hz,2H),6.65(d,J=7.8Hz,2H),2.07(s,3H).13C NMR(101MHz,CDCl3)δ157.2,143.5,138.7,138.2,137.8,137.6,135.7,133.3,132.9,131.8,131.7,129.2,128.8,128.7,128.6,128.6,128.0,127.9,127.0,126.8,126.6,126.4,126.1,126.1,125.9,125.4,120.8,20.8.IR(ATR):νmax(cm-1)=2918,1581,1551,1502,1359,1299,1233,1187,1024,988,920,873,852,830,808,748,719.HRMS(ESI):计算值for:C30H22N[M+H]+:396.1747,实测值396.1747.手性柱Chiralpak IG column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=26.47min,tR(minor)=29.49min.
实施例34
(101.4mg,99%产率,97%ee).分析数据:熔点:204-206℃.[α]22D=-316.2(c=1.0,CHCl3,97%ee).1H NMR(400MHz,CDCl3)δ8.78(d,J=5.2Hz,1H),8.16(d,J=8.4Hz,1H),7.77(d,J=8.8Hz,1H),7.74(d,J=7.8Hz,1H),7.70(d,J=8.7Hz,1H),7.65(d,J=5.2Hz,1H),7.61(d,J=8.8Hz,1H),7.53(q,J=5.8,4.4Hz,2H),7.46(d,J=8.5Hz,1H),7.40(t,J=7.4Hz,1H),7.31(t,J=7.6Hz,1H),7.09(t,J=7.7Hz,1H),6.81(d,J=7.8Hz,2H),6.67(d,J=7.7Hz,2H),2.89(s,3H),2.07(s,3H).13C NMR(101MHz,CDCl3)δ157.4,143.5,138.3,137.5,137.3,137.1,135.6,134.8,132.9,132.5,131.8,131.8,129.6,129.3,128.7,128.6,127.9,126.9,126.6,126.5,126.5,126.3,126.2,125.7,125.4,124.2,120.7,20.8,19.7.IR(ATR):νmax(cm-1)=2919,1580,1550,1507,1415,1376,1260,1230,1187,1023,985,903,874,854,818,754.HRMS(ESI):计算值C31H24N[M+H]+:410.1903,实测值410.1906.手性柱Chiralpak IG column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=17.02min,tR(minor)=37.02min.
实施例35
(105.3mg,99%产率,96%ee).分析数据:熔点:167-169℃.[α]22D=-381.2(c=1.0,CHCl3,96%ee).1H NMR(400MHz,CDCl3)δ8.77(d,J=5.2Hz,1H),8.44(d,J=8.4Hz,1H),7.77(d,J=8.8Hz,1H),7.74(dt,J=8.3,2.1Hz,2H),7.64(d,J=5.2Hz,1H),7.60(d,J=8.8Hz,1H),7.49(t,J=7.5Hz,1H),7.44-7.38(m,2H),7.32(t,J=7.6Hz,1H),7.11(t,J=7.8Hz,1H),6.98(s,1H),6.81(d,J=8.1Hz,2H),6.68(d,J=7.8Hz,2H),4.12(s,3H),2.08(s,3H).13C NMR(101MHz,CDCl3)δ157.3,155.4,143.5,138.6,138.0,137.5,135.7,132.9,132.7,131.7,131.4,129.4,128.6,128.5,127.9,127.3,126.9,126.7,126.5,126.1,125.8,125.4,125.4,125.3,121.9,120.6,107.0,55.6,20.8.IR(ATR):νmax(cm-1)=2920,1592,1553,1506,1444,1417,1377,1302,1260,1229,1159,1111,1089,1043,907,854,824,801,766,754.HRMS(ESI):计算值C31H24NO[M+H]+:426.1852,实测值426.1849.手性柱Chiralpak IG column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=24.28min,tR(minor)=41.53min.
实施例36
(101.0mg,98%产率,94%ee).分析数据:熔点:124-126℃.[α]22D=-307.4(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.76(d,J=5.2Hz,1H),8.26(d,J=8.4Hz,1H),7.80(d,J=8.8Hz,1H),7.76(d,J=7.8Hz,1H),7.69(d,J=5.2Hz,1H),7.64(d,J=8.8Hz,1H),7.54(dd,J=7.8,5.9Hz,2H),7.45-7.38(m,2H),7.38-7.30(m,2H),7.10(ddd,J=8.6,7.0,1.5Hz,1H),6.71(d,J=7.9Hz,2H),6.64(d,J=8.0Hz,2H),2.06(s,3H).13C NMR(101MHz,CDCl3)δ158.8(d,J=252.9Hz),156.6,143.7,138.3(d,J=8.0Hz),137.8,137.4,136.3,135.1(d,J=4.0Hz),133.3(d,J=4.9Hz),133.1,132.1,129.20,128.8,128.7,128.2,127.9,127.2,126.8,126.7,126.4,126.2,126.2,126.0,125.5,123.6(d,J=16.6Hz),121.1,120.7(d,J=5.1Hz),112.5(d,J=20.1Hz),20.9.19F NMR(376MHz,CDCl3)δ-122.98.IR(ATR):νmax(cm-1)=2917,1628,1601,1581,1505,1417,1383,1355,1299,1233,1186,1059,988,906,870,853,818,754,701,655.HRMS(ESI):计算值C30H21FN[M+H]+:414.1653,实测值414.1650.手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=20.99min,tR(minor)=26.60min.
实施例37
(101.8mg,97%产率,97%ee).分析数据:熔点:100-102℃.[α]22D=-362.2(c=1.0,CHCl3,97%ee).1H NMR(400MHz,CDCl3)δ8.74(d,J=5.2Hz,1H),7.78(d,J=8.9Hz,1H),7.76-7.72(m,2H),7.64(d,J=5.5Hz,2H),7.44-7.37(m,2H),7.31-7.26(m,2H),7.15-7.05(m,2H),6.75(d,J=7.9Hz,2H),6.63(d,J=8.1Hz,2H),3.66-3.42(m,4H),2.06(s,3H).13C NMR(101MHz,CDCl3)δ157.3,146.6,145.9,143.7,139.8,139.2,139.1,137.6,135.5,134.8,133.0,131.7,130.0,129.6,129.0,128.7,128.6,127.9,126.9,126.5,126.5,126.3,125.5,122.5,121.2,120.6,119.6,30.7,30.4,20.9.IR(ATR):νmax(cm-1)=2915,1608,1582,1552,1511,1444,1415,1364,1299,1234,1048,990,855,838,818,747.HRMS(ESI):计算值C32H24N[M+H]+:422.1903,实测值422.1902.手性柱Chiralpak ICcolumn(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=27.60min,tR(minor)=31.82min.
实施例38
(111.5mg,95%产率,94%ee).分析数据:熔点:112-114℃.[α]22D=+78.2(c=1.0,CHCl3,94%ee).1H NMR(400MHz,CDCl3)δ8.84(d,J=5.2Hz,1H),8.31(s,1H),8.25(dd,J=7.7,1.2Hz,1H),8.19(d,J=1.2Hz,2H),8.14(d,J=7.3Hz,1H),8.02(t,J=7.6Hz,1H),7.91(d,J=9.2Hz,1H),7.82(d,J=8.8Hz,1H),7.77-7.74(m,1H),7.74-7.69(m,2H),7.67(d,J=8.8Hz,1H),7.34(td,J=6.7Hz,1.5Hz,2H),6.90-6.83(m,3H),6.70(d,J=7.9Hz,2H),2.11(s,3H).13C NMR(101MHz,CDCl3)δ157.5,143.5,138.7,138.4,137.6,137.3,135.7,133.0,131.9,131.3,131.3,131.0,129.4,129.2,129.0,128.6,128.3,128.0,127.9,127.5,127.4,127.0,126.7,126.5,126.1,126.0,125.4,125.3,125.3,125.2,124.7,124.6,120.9,20.9.IR(ATR):νmax(cm-1)=2920,1583,1553,1509,1444,1414,1383,1299,1259,1182,1085,1019,989,931,888,820,748,689.HRMS(ESI):计算值C36H24N[M+H]+:470.1903,实测值470.1900.手性柱Chiralpak IG column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=25.81min,tR(minor)=46.75min.
实施例39
除配体不同外,其他条件和操作均同实施例1。其中,配体为L4。
(85.5mg,99%产率,95%ee).分析数据:[α]26 D=+179.7(c=1.0,CHCl3,95%ee).1H NMR(400MHz,CDCl3).δ8.66(d,J=5.7Hz,1H),8.06(d,J=8.5Hz,1H),7.96(d,J=8.2Hz,1H),7.77(d,J=8.3Hz,1H),7.65(dd,J=13.8,7.1Hz,2H),7.53(t,J=7.5Hz,1H),7.49-7.39(m,2H),7.33-7.23(m,2H),7.19(d,J=8.5Hz,1H),7.09(d,J=8.1Hz,2H),6.84(d,J=7.9Hz,2H),2.14(s,3H).手性柱Chiralpak IC column(25cm),正己烷/异丙醇=90:10,1mL/min,检测波长=254nm,tR(major)=10.79min,tR(minor)=21.47min.
实施例40
除下表1中特别指明的条件外,其余条件和操作均同实施例1。
表1
注:a通过1H NMR(以1,3,5-三甲氧基苯作为内标)分析粗反应混合物;b手性HPLC分析确定;c重复结果;d重复两次的结果;e括号内为分离收率。
实施例41:轴手性吡啶氮氧化合物的合成
在单口烧瓶中加入取代异喹啉I-13(54.0mg,0.15mmmol)和二氯甲烷(1.5mL)。在0℃下,加入间氯过氧苯甲酸(52mg,0.30mmol)。然后在室温下搅拌4小时,反应混合物用饱和的碳酸钠溶液淬灭,二氯甲烷萃取,有机相使用饱和食盐水洗涤,无水硫酸钠干燥,过滤。减压旋除溶剂,柱层析纯化(CH2Cl2/EtOAc=1/1,v/v),得到目标产物IV(53.5mg,95%收率,95%ee).分析数据:熔点=218-220℃.[α]28D=-97.2(c=1.0,CHCl3,95%ee).1H NMR(400MHz,CDCl3)δ8.34(d,J=7.2Hz,1H),8.09(d,J=8.5Hz,1H),7.97(d,J=8.2Hz,1H),7.71(d,J=8.5Hz,1H),7.66(t,J=7.6Hz,2H),7.49(t,J=7.5Hz,1H),7.41-7.34(m,2H),7.25-7.15(m,2H),7.02(s,2H),6.92(d,J=8.5Hz,1H),6.69(s,1H),2.12(s,6H).13C NMR(101MHz,CDCl3)δ145.9,140.9,140.6,137.3,136.8,132.8,131.5,129.9,129.8,128.9,128.8,128.4,128.0,127.9,127.4,126.5,126.4,126.3,126.1,126.0,125.1,125.1,123.6,21.1.IR(ATR):νmax(cm-1)=1593,1552,1495,1452,1400,1316,1275,1217,1130,1025,984,951,856,817,782,743,708,677.HRMS(ESI):计算值C27H22NO[M+H]+:376.1696,实测值376.1702.手性柱Chiralpak AD-H column(25cm),正己烷/异丙醇=80:20,1mL/min,检测波长=254nm,tR(minor)=9.06min,tR(major)=10.27min.
实施例42:烯丙基三氯硅烷和醛的不对称加成反应
在氩气保护下,向干燥的Schlenk管中加入催化剂Sa-IV(15mg,0.04mmol),iPr2NEt(82.6μL,0.5mmol),苯甲醛(41μL,0.4mmol)以及乙腈(2mL),将得到的反应混合物冷却至-40℃。将烯丙基三氯硅烷(69.5μL,0.48mmol)逐滴加入到上述溶液中,然后在-40℃反应48小时。反应混合液用饱和的碳酸氢钠溶液淬灭反应,水稀释,二氯甲烷萃取,有机相使用饱和食盐水洗涤,无水硫酸钠干燥,过滤。减压旋除溶剂,柱层析纯化(石油醚/乙酸乙酯=20/1,v/v),得到目标产物V(31.0mg,52%yield,91%ee)。分析数据:[α]25D=-33.7(c=0.1,CHCl3,91%ee).1H NMR(400MHz,CDCl3)δ7.34(d,J=4.4Hz,4H),7.28(dt,J=8.5,4.1Hz,1H),5.85-5.74(m,1H),5.23-5.07(m,2H),4.71(dd,J=7.5,5.4Hz,1H),2.57-2.44(m,2H),2.15(s,1H).手性柱Daicel Chiralpak OD-H column,正己烷/异丙醇=99:1,1mL/min,检测波长=254nm,tR(minor)=22.48min,tR(major)=28.27min.
实施例43:化合物IV的单晶衍射实验
1.单晶培养:将实施例41中得到的主要组分化合物IV(50mg)溶于无水石油醚和乙酸乙酯的混合溶剂中,于4℃静置3天,有单晶析出,收集单晶进行单晶衍射测试。
2.测试参数如下表所示:
3.测定结果:化合物IV的构型由单晶衍射确定为Sa构型。
Claims (19)
1.一种化合物1的制备方法,其特征在于,其包括以下步骤:在保护气体氛围下,有机溶剂中,在铑催化剂、膦配体和碱的存在下,将如式II所示化合物与如式III所示化合物进行如下所示的芳基化反应,即可;所述的化合物1为如式I和/或式I’所示化合物:
其中,X为卤素;
Z为CH或N;
R2、R5和R6独立地为氢、卤素、C1-10的烷基或C1-10的烷氧基;
R3和R4独立地为C1-10的烷基或C1-10的烷氧基;
R7为未取代或R7-1取代的C6-10的芳基、未取代或R7-2取代的“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基或未取代或R7-3取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基;
R7-1、R7-2和R7-3独立地为氢、氰基、卤素、C1-6的卤代烷基、C1-10的烷基、C1-10的烷氧基、C6-10的芳基或NR7-1-1R7-1-2;
R7-1-1和R7-1-2独立地为氢或C1-6的烷基;
或者,R2、R3与其间的碳原子一起形成C6-10的芳基、“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基或C3-7的环烯基;
或者,R4、R5与其间的碳原子一起形成C6-10的芳基;
或者,R5、R6与其间的碳原子一起形成C6-10的芳基或C3-7的环烯基;
或者,R4、R5、R6与其间的碳原子一起形成C10-20的芳基或C9-10的芳基并环烯基;
所述铑催化剂为[Rh(C2H4)2Cl]2、[Rh(CO)2Cl]和[Rh(cod)Cl]中的一种或多种;
所述碱为叔丁醇钠、叔丁醇钾、碳酸钾和碳酸铯中的一种或多种。
2.如权利要求1所述的化合物1的制备方法,其特征在于,X为卤素,卤素为氯、溴或碘;
和/或,当R2为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R2为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R2为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R5为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R5为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R5为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R6为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R6为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R6为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R3为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R3为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R4为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R4为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R7为未取代或R7-1取代的C6-10的芳基时,所述的R7-1的个数为一个或多个,当存在多个R7-1时,所述的R7-1相同或不同;
和/或,当R7为未取代或R7-1取代的C6-10的芳基时,所述的C6-10的芳基为苯基或萘基;
和/或,当R7为未取代或R7-2取代的“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基时,所述的R7-2的个数为一个或多个,当存在多个R7-2时,所述的R7-2相同或不同;
和/或,当R7为未取代或R7-2取代的“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基时,所述的杂芳基为“杂原子选自N、O和S,杂原子个数为1-3个”的5-6元的单环杂芳基或“杂原子选自N、O和S,杂原子个数为1-3个”的9-10元的双环杂芳基;
和/或,当R7为未取代或R7-3取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基时,所述的R7-3的个数为一个或多个,当存在多个R7-3时,所述的R7-3相同或不同;
和/或,当R7为未取代或R7-3取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基时,所述的芳基并杂环烯基为“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的苯并杂环烯基;
和/或,当R7-1为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R7-1为C1-6的卤代烷基时,所述的C1-6的卤代烷基为C1-3的卤代烷基;
和/或,当R7-1为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R7-1为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R7-1为C6-10的芳基时,所述的C6-10的芳基为苯基或萘基;
和/或,当R7-2为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R7-2为C1-6的卤代烷基时,所述的C1-6的卤代烷基为C1-3的卤代烷基;
和/或,当R7-2为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R7-2为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R7-2为C6-10的芳基时,所述的C6-10的芳基为苯基或萘基;
和/或,当R7-3为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R7-3为C1-6的卤代烷基时,所述的C1-6的卤代烷基为C1-3的卤代烷基;
和/或,当R7-3为C1-10的烷基时,所述的C1-10的烷基为C1-4的烷基;
和/或,当R7-3为C1-10的烷氧基时,所述的C1-10的烷氧基为C1-4的烷氧基;
和/或,当R7-3为C6-10的芳基时,所述的C6-10的芳基为苯基或萘基;
和/或,当R7-1-1为C1-6的烷基时,所述的C1-6的烷基为C1-4的烷基;
和/或,当R7-1-2为C1-6的烷基时,所述的C1-6的烷基为C1-4的烷基;
和/或,当R2、R3与其间的碳原子一起形成C6-10的芳基时,所述的C6-10的芳基为苯基或萘基;
和/或,当R2、R3与其间的碳原子一起形成“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基,所述的杂芳基为“杂原子选自N、O和S,杂原子个数为1-3个”的5-6元的杂芳基;
和/或,当R2、R3与其间的碳原子一起形成C3-7的环烯基时,所述的环烯基为环丙烯基、环丁烯基、环戊烯基或环己烯基;
和/或,当R4、R5与其间的碳原子一起形成C6-10的芳基时,所述的C6-10的芳基为苯基或萘基;
和/或,当R5、R6与其间的碳原子一起形成C6-10的芳基时,所述的C6-10的芳基为苯基或萘基;
和/或,当R5、R6与其间的碳原子一起形成C3-7的环烯基时,所述的C3-7的环烯基为环丙烯基、环丁烯基、环戊烯基或环己烯基;
和/或,当R4、R5、R6与其间的碳原子一起形成C10-20的芳基时,所述的C10-20的芳基为C10-15的芳基;
和/或,当R4、R5、R6与其间的碳原子一起形成C9-10的芳基并环烯基时,所述的C9-10的芳基并环烯基为C9-10的苯并环烯基。
3.如权利要求2所述的化合物1的制备方法,其特征在于,X为卤素,所述的卤素为溴;
和/或,当R2为卤素时,所述的卤素为氟;
和/或,当R2为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R2为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R5为卤素时,所述的卤素为氟;
和/或,当R5为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R5为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R6为卤素时,所述的卤素为氟;
和/或,当R6为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R6为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R3为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R3为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R4为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R4为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R7为未取代或R7-1取代的C6-10的芳基时,所述的R7-1的个数为1、2、3或4个;
和/或,当R7为未取代或R7-2取代的“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基时,所述的R7-2的个数为1、2或3个;
和/或,当R7为未取代或R7-2取代的“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基时,所述的杂芳基为呋喃基、吡咯基、噻吩基、吡喃基、吡啶基、苯并呋喃基或苯并噻吩基;
和/或,当R7为未取代或R7-3取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基时,所述的R7-3的个数为1、2或3个;
和/或,当R7为未取代或R7-3取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基时,所述的芳基并杂环烯基为苯并二氧戊环烯基或苯并二氧六环烯基;
和/或,当R7-1为卤素时,所述的卤素为氟、氯或溴;
和/或,当R7-1为C1-6的卤代烷基时,所述的C1-6的卤代烷基为三氟甲基;
和/或,当R7-1为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R7-1为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R7-2为卤素时,所述的卤素为氟、氯或溴;
和/或,当R7-2为C1-6的卤代烷基时,所述的C1-6的卤代烷基为三氟甲基;
和/或,当R7-2为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R7-2为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R7-3为卤素时,所述的卤素为氟、氯或溴;
和/或,当R7-3为C1-6的卤代烷基时,所述的C1-6的卤代烷基为三氟甲基;
和/或,当R7-3为C1-10的烷基时,所述的C1-10的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R7-3为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基;
和/或,当R7-1-1为C1-6的烷基时,所述的C1-6的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R7-1-2为C1-6的烷基时,所述的C1-6的烷基为甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基;
和/或,当R2、R3与其间的碳原子一起形成“杂原子选自N、O和S,杂原子个数为1-3个的5-10元”的杂芳基,所述的杂芳基为呋喃基、吡咯基、噻吩基、吡喃基或吡啶基;
和/或,当R2、R3与其间的碳原子一起形成C3-7的环烯基时,所述的环烯基为环己烯基;
和/或,当R5、R6与其间的碳原子一起形成C3-7的环烯基时,所述的C3-7的环烯基为环戊烯基;
和/或,当R4、R5、R6与其间的碳原子一起形成C9-10的芳基并环烯基时,所述的C9-10的芳基并环烯基为苯并环戊烯基。
4.如权利要求3所述的化合物1的制备方法,其特征在于,所述的化合物1为如式I或式I’所示化合物;
和/或,当R2为C1-10的烷基时,所述的C1-10的烷基为甲基;
和/或,当R2为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R5为C1-10的烷基时,所述的C1-10的烷基为甲基;
和/或,当R5为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R6为C1-10的烷基时,所述的C1-10的烷基为甲基;
和/或,当R6为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R3为C1-10的烷基时,所述的C1-10的烷基为甲基;
和/或,当R3为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R4为C1-10的烷基时,所述的C1-10的烷基为甲基;
和/或,当R4为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R7-1为C1-10的烷基时,所述的C1-10的烷基为甲基或叔丁基;
和/或,当R7-1为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R7-2为C1-10的烷基时,所述的C1-10的烷基为甲基或叔丁基;
和/或,当R7-2为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R7-3为C1-10的烷基时,所述的C1-10的烷基为甲基或叔丁基;
和/或,当R7-3为C1-10的烷氧基时,所述的C1-10的烷氧基为甲氧基;
和/或,当R7-1-1为C1-6的烷基时,所述的C1-6的烷基为甲基;
和/或,当R7-1-2为C1-6的烷基时,所述的C1-6的烷基为甲基;
5.如权利要求1所述的化合物1的制备方法,其特征在于,所述的如式I或式I’所示化合物的某些基团的定义为以下任一方案:
(1)Z为CH;
(2)X为卤素;
Z为CH;
R2、R5和R6独立地为氢、卤素、C1-10的烷基或C1-10的烷氧基;
R3为C1-10的烷基或C1-10的烷氧基;
R4为C1-10的烷氧基;
R7为未取代或R7-1为取代的C6-10的芳基、未取代或R7-2为取代的“杂原子为N,杂原子个数为1-3个的5-10元”的杂芳基或未取代或R7-3为取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基;
R7-1、R7-2和R7-3独立地为氢、卤素、C1-6的卤代烷基、C1-10的烷基、C1-10的烷氧基、C6-10的芳基或NR7-1-1R7-1-2;
R7-1-1和R7-1-2独立地为氢或C1-6的烷基;
或者,R2、R3与其间的碳原子一起形成C6-10的芳基或C3-7的环烯基;
或者,R4、R5与其间的碳原子一起形成C6-10的芳基;
或者,R5、R6与其间的碳原子一起形成C6-10的芳基或C3-7的环烯基;
或者,R4、R5、R6与其间的碳原子一起形成C10-20的芳基或C9-10的芳基并环烯基。
6.如权利要求1所述的化合物1的制备方法,其特征在于,Z为CH;
和/或,R3为C1-10的烷基或C1-10的烷氧基;
和/或,R4为C1-10的烷氧基;
和/或,R7为未取代或R7-1为取代的C6-10的芳基、未取代或R7-2为取代的“杂原子为N,杂原子个数为1-3个的5-10元”的杂芳基或未取代或R7-3为取代的“杂原子选自N、O和S,杂原子个数为1-3个的9-10元”的芳基并杂环烯基;
和/或,R7-1、R7-2和R7-3独立地为氢、卤素、C1-6的卤代烷基、C1-10的烷基、C1-10的烷氧基、C6-10的芳基或NR7-1-1R7-1-2;
和/或,R2、R3与其间的碳原子一起形成C6-10的芳基或C3-7的环烯基。
8.如权利要求1所述的化合物1的制备方法,其特征在于,所述的保护气体为氦气、氖气、氮气和氩气中的一种或多种;
和/或,所述的有机溶剂为芳烃类溶剂和/或醚类溶剂;
和/或,所述的如式II所示化合物在所述的有机溶剂中的摩尔浓度为0.1-0.8mol/L;
和/或,所述的如式III所示化合物与所述的如式II所示化合物的摩尔比为1:1-8:1;
和/或,所述的铑催化剂与所述的如式II所示化合物的摩尔比为0.04:1-0.2:1;
和/或,所述的膦配体与所述的如式II所示化合物的摩尔比为0.05:1-0.35:1;
和/或,所述的碱与所述的如式II所示化合物的摩尔比为1:1-5:1;
和/或,所述的芳基化反应的温度为0-100℃;
和/或,所述芳基化反应的时间为0.5-12h。
9.如权利要求8所述的化合物1的制备方法,其特征在于,所述的保护气体为氩气;
和/或,当所述的有机溶剂为芳烃类溶剂时,所述的芳烃类溶剂为甲苯、对二甲苯和1,3,5-三甲基苯中的一种或多种;
和/或,当所述的有机溶剂为醚类溶剂,所述的醚类溶剂为甲基叔丁基醚;
和/或,所述的如式II所示化合物在所述的有机溶剂中的摩尔浓度为0.4-0.6mol/L;
和/或,所述的如式III所示化合物与所述的如式II所示化合物的摩尔比为2:1-4:1;
和/或,所述的铑催化剂为[Rh(C2H4)2Cl]2;
和/或,所述的铑催化剂与所述的如式II所示化合物的摩尔比为0.05:1-0.07:1;
和/或,所述的膦配体与所述的如式II所示化合物的摩尔比为0.05:1-0.2:1;
和/或,所述的碱为叔丁醇钠;
和/或,所述的碱与所述的如式II所示化合物的摩尔比为2:1-4:1。
13.如权利要求1所述的化合物1的制备方法,其特征在于,所述的制备方法为以下任一方案:
(1)在保护气体氛围下,有机溶剂中,在铑催化剂、膦配体和碱的存在下,将如式II所示化合物与如式III所示化合物进行芳基化反应;所述的有机溶剂为芳烃类溶剂;所述的铑催化剂为[Rh(C2H4)2Cl]2、[Rh(CO)2Cl]和[Rh(cod)Cl]中的一种或多种;所述的膦配体为R8和R8’独立地为C6-C10的芳基,R9和R9’独立地为未取代或R9-1取代的C6-C10的芳基,R9-1为C1-3卤代烷基、C1-4烷基或C1-4烷氧基;所述的碱为叔丁醇钠、叔丁醇钾、碳酸钾和碳酸铯中的一种或多种;
(2)所述的化合物1的制备方法包括以下步骤:将铑催化剂、膦配体和有机溶剂混合,加热至70-90℃反应0.5-3h,冷却至20-30℃,再加入如式II、如式III所示化合物和碱,在40-80℃进行所述的芳基化反应,即可。
14.如权利要求1所述的化合物1的制备方法,其特征在于,所述的制备方法为
在保护气体氛围下,有机溶剂中,在铑催化剂、膦配体和碱的存在下,将如式II所示化合物与如式III所示化合物进行芳基化反应;所述的有机溶剂为芳烃类溶剂;所述的铑催化剂为[Rh(C2H4)2Cl]2、[Rh(CO)2Cl]和[Rh(cod)Cl]中的一种或多种;所述的膦配体为R8和R8’独立地为C6-C10的芳基,R9和R9’独立地为未取代或R9-1取代的C6-C10的芳基,R9-1为C1-3卤代烷基、C1-4烷基或C1-4烷氧基;所述的碱为叔丁醇钠、叔丁醇钾、碳酸钾和碳酸铯中的一种或多种;所述的如式II所示化合物在所述的有机溶剂中的摩尔浓度为0.4-0.6mol/L;所述的如式III所示化合物与所述的如式II所示化合物的摩尔比为2:1-4:1;所述的铑催化剂与所述的如式II所示化合物的摩尔比为0.05:1-0.07:1;所述的膦配体与所述的如式II所示化合物的摩尔比为0.05:1-0.35:1;所述的碱与所述的如式II所示化合物的摩尔比为2-4:1。
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