CN112778328B - 一种氮杂环卡宾催化官能化亚胺作为新型1，4-偶极合成子及其合成应用 - Google Patents
一种氮杂环卡宾催化官能化亚胺作为新型1，4-偶极合成子及其合成应用 Download PDFInfo
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- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
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Abstract
本发明涉及一种氮杂环卡宾催化官能化亚胺作为新型1，4‑偶极合成子及其应用，本发明属于化学合成领域。本发明在温和的反应条件下，使用手性氮杂环卡宾催化剂催化活化醛亚胺，在氧化的条件下得到一种新型的氮杂1，4‑偶极合成子，这种新型的有机合成子可以进一步与三氟苯乙酮，靛红及靛红衍生的亚胺类底物发生4+2环合反应，生成结构新颖的带有手性季碳中心的杂环化合物；使用同种手性构型的氮杂环卡宾催化剂和非手性的硫脲催化剂共催化可以实现三氟苯乙酮类化合物的立体多样性合成；反应高效，具有很好的底物普适性，醛亚胺衍生的1，4‑氮杂偶极合成子为合成多种多样的功能氮杂环类化合物提供了重要的方法，有应用于工业生产的潜力。
Description
技术领域
本发明属于化学合成领域，特别涉及氮杂环卡宾催化官能化的醛亚胺作为新型的1，4-偶极合成子及其应用于4+2环合反应制备手性氮杂环化合物的方法。
背景技术
不对称催化是制备手性化合物最重要的方法。氮杂环卡宾作为一类重要的有机小分子催化剂，近年来在催化合成手性分子领域发挥了重要的作用，获得了较快的发展。但是已经报道的反应类型大多基于氮杂环卡宾催化活化醛类化合物及其酯类衍生物。而催化与醛具有相似电子性质的亚胺类化合物的反应则鲜有报道，亚胺的不对称催化活化更是一个巨大挑战。而亚胺作为非常重要的一种官能团是合成含氮化合物的重要原料，开发和发展亚胺的新的活化模式并将其运用到有机合成中将为氮杂环化学提供新的机遇，合成的含氮化合物尤其是手性氮杂环化合物将为药物发现和筛选提供新的可能。
发明内容
本发明解决的技术问题是：提出一种氮杂环卡宾催化官能化的醛亚胺作为新型的1，4-偶极合成子并将其应用于4+2环合反应制备手性氮杂环化合物的方法。为了解决上述技术问题，本发明提出的技术方案是：一种氮杂环卡宾催化得到的醛亚胺I衍生的1，4-氮杂偶极合成子，该化合物II结构式如下：
所述化合物II具体为下列结构中的一种：
其中：R为取代的芳香基,R1为甲基或卤素原子；
NHC为下列结构中的一种：
进一步的，其中：R为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-三氟甲基苯基，4-甲氧酰基苯基，4-氰基苯基，3-氟苯基，3-甲基苯基，3-三氟甲基苯基，3-氯苯基，3-溴苯基，3，4-二甲基苯基，2-萘基，3-吡啶，2-噻吩或2-呋喃；卤素原子为F、Cl或Br，X为碳原子或氮原子。
进一步的，所述反应式如下：
所述化合物I为下列结构中的一种：
其中：R为取代的芳香基,R1为甲基或卤素原子；X为碳原子或氮原子；
所使用的碱为下列所述中的一种：碳酸钾，4-二甲氨基吡啶，碳酸铯，乙酸钠，1,8-二氮杂二环十一碳-7-烯，三乙胺，磷酸钾，1,4-二氮杂二环[2.2.2]辛烷，叔丁醇钾或N,N-二异丙基乙胺；
所使用的溶剂为下列所述中的一种：1，4-二氧六环，二氯甲烷，甲苯，1，3，5-均三甲苯，N,N-二甲基甲酰胺，乙腈，三氯甲烷，四氯化碳，甲基叔丁基醚或三氟甲基苯；
所述干燥剂为
MS或无水硫酸镁；
所述氧化剂为3,3',5,5'-四叔丁基-4,4'-联苯醌(DQ)或二氧化锰。
本发明提出的另一技术方案是：所述的醛亚胺衍生的1，4-偶极合成子的应用，所述醛亚胺衍生的1，4-偶极合成子与三氟苯乙酮类化合物III反应合成S构型的含有三氟季碳手性季碳中心的杂环化合物的方法，使用结构式I的醛亚胺和结构式为III的三氟苯乙酮衍生物为原料，在NHC B作为催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷作溶剂及
MS作为干燥剂的条件下于室温反应48-72小时至反应完成，反应液经硅胶柱纯化得到结构式为(S)-VI的目标产物；
其中，R为各种取代的芳香环，具体为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-三氟甲基苯基，4-甲氧酰基苯基，4-氰基苯基，3-氟苯基，3-甲基苯基，3-三氟甲基苯基，3-氯苯基，3-溴苯基，3，4-二甲基苯基，2-萘基，3-吡啶，2-噻吩或2-呋喃；
R1为甲基或卤素原子；X为碳原子或氮原子；
当Y＝F时，R2为4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-苯基苯，3-甲氧基苯基，2-萘基，2-苯并呋喃，2-苯并噻吩，2-吡啶，9-甲基咔唑或苯乙基，当R2为苯基，Y＝H，Br或Cl。
进一步的，所述化合物(S)-VI的结构式如下：
本发明提出的另一技术方案是：所述的醛亚胺衍生的1，4-偶极合成子的应用，所述醛亚胺衍生的1，4-偶极合成子与三氟苯乙酮类化合物III反应合成R构型的含有三氟季碳手性季碳中心的杂环化合物的方法，，使用结构式I的醛亚胺和结构式为III的三氟苯乙酮衍生物为原料，在NHC C和非手性硫脲V作为共催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷/正己烷作溶剂及
MS作为干燥剂的条件下于0℃反应48-72小时至反应完成，反应液经硅胶柱纯化得到结构式为(R)-VI的目标产物；
其中，R为各种取代的芳香环，具体为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-三氟甲基苯基，4-甲氧酰基苯基，4-氰基苯基，3-氟苯基，3-甲基苯基，3-三氟甲基苯基，3-氯苯基，3-溴苯基，3，4-二甲基苯基，2-萘基，3-吡啶，2-噻吩或2-呋喃；
R1为甲基或卤素原子；X为碳原子或氮原子；当Y＝F时，R2为4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-苯基苯，3-甲氧基苯基，2-萘基，2-苯并呋喃，2-苯并噻吩，2-吡啶，9-甲基咔唑或苯乙基，当R2为苯基，Y＝H，Br或Cl。
进一步的，所述的醛亚胺衍生的1，4-偶极合成子的应用，所述化合物(R)-VI的结构式如下：
本发明提出的另一技术方案是：所述的醛亚胺衍生的1，4-偶极合成子的应用，所述醛亚胺衍生的1，4-偶极合成子与靛红类化合物VI反应合成手性螺环化合物的方法，使用结构式I的醛亚胺和结构式为VI的靛红衍生物为原料，在NHC C和非手性硫脲V作为共催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷/正己烷作溶剂及
MS作为干燥剂的条件下于0℃反应48小时至反应完成，反应液经硅胶柱纯化得到结构式为VII的目标产物；
其中，R为各种取代的芳香环，具体为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-三氟甲基苯基，4-甲氧酰基苯基，4-氰基苯基，3-氟苯基，3-甲基苯基，3-三氟甲基苯基，3-氯苯基，3-溴苯基，3，4-二甲基苯基，2-萘基，3-吡啶，2-噻吩或2-呋喃；
R1为甲基或卤素原子；Y为碳原子或氮原子；R2为苄基和甲基；R3为4，6-二氟，5-甲基，5-甲氧基，5-氟，5-氯，5-溴，5-碘，6-甲氧基，6-氯，7-溴，7-三氟甲基或5，7-二甲基。
进一步的，所述化合物VII的结构式如下：
本发明提出的另一技术方案是：所述的醛亚胺衍生的1，4-偶极合成子的应用，所述的醛亚胺衍生的1，4-偶极合成子与靛红衍生的亚胺类化合物VIII反应合成手性螺环化合物的方法，使用结构式I的醛亚胺和结构式为VIII的靛红衍生的亚胺类化合物为原料，在NHC C作为催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷/正己烷作溶剂及
MS作为干燥剂的条件下于0℃反应48小时至反应完成，反应液经硅胶柱纯化得到结构式为IX的目标产物；
进一步的，所述氮杂环卡宾催化剂NHC B的用量是式I01化合物用量的20mol％；所述氮杂环卡宾催化剂NHC C的用量是式I化合物用量的10mol％；硫脲共催化剂Urea V的用量是式I化合物用量的20mol％；所述式I化合物和式Ⅲ化合物的摩尔比是1.2:1；所述式I化合物和式VI化合物的摩尔比是1:1；所述式I化合物和式VIII化合物的摩尔比是1:1；所述碱K3PO4的用量是式I化合物用量的150mol％；，所述干燥剂
MS K3PO4的用量是1000mg/mmol。
本发明的有益效果是：本发明公开了氮杂环卡宾催化官能化的醛亚胺作为新型的1，4-偶极合成子的新方法。本发明在温和的反应条件下，使用手性氮杂环卡宾催化剂催化活化醛亚胺，在氧化的条件下得到一种新型的氮杂1，4-偶极合成子，这种新型的有机合成子可以进一步与三氟苯乙酮，靛红及靛红衍生的亚胺类底物发生4+2环合反应，生成结构新颖的带有手性季碳中心的杂环化合物；本发明方法中，使用同种手性构型的氮杂环卡宾催化剂和非手性的硫脲催化剂共催化可以实现三氟苯乙酮类化合物的立体多样性合成，这种创新的手性催化方法将有助于简化手性化合物的合成方案，降低手性化合物的合成成本；本发明方法条件温和，反应高效，具有很好的底物普适性，所报道的醛亚胺衍生的1，4-氮杂偶极合成子为合成多种多样的功能氮杂环类化合物提供了重要的方法，有应用于工业生产的潜力。
附图说明
下面结合附图对本发明的作进一步说明。
图1是化合物(S)-IV01的氢谱；
图2是化合物(S)-IV01的氟谱；
图3化合物是(S)-IV01的碳谱；
图4是化合物VII01的氢谱；
图5是化合物VII01的碳谱；
图6是化合物IX的氢谱；
图7是化合物IX的碳谱。
具体实施方式
为了使本技术领域的人员更好地理解本申请方案，下面将结合本申请的实施例，对本申请的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分的实施例，而不是全部的实施例。基于本申请中的实施例，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，都应当属于本申请保护的范围。
需要说明的是，本申请的说明书和权利要求书的术语“包括”和“具有”以及他们的任何变形，意图在于覆盖不排他的包含，例如，包含了一系列步骤或单元的过程、方法、系统、产品或设备不必限于清楚地列出的那些步骤或单元，而是可包括没有清楚地列出的或对于这些过程、方法、产品或设备固有的其它步骤或单元。
以下所用化学试剂均购自商业化产品。溶剂为购自商业化的超干溶剂。薄层色谱分析(TLC)使用60F254硅胶板，在254nm的UV光下显色。1H NMR和13C NMR使用Bruker 400M核磁共振仪表征，溶剂为氘代氯仿。耦合常数的单位是Hz.。旋光度用Jasco P-1030polarimeter旋光仪测量。对映体过量用Shimadzu LC-20AD HPLC测定.高分辨质谱(HRMS)使用Waters Q-TOF Permier Spectrometer测定。
通过以下实施例有助于进一步理解本发明,但并不限制本发明的内容。
实施例1
向干燥的试管中加入醛亚胺I(0.12mmol)，NHC B(4.8mg,20mol％),K3PO4(31.8mg,0.15mmol),DQ(44.8mg,0.11mmol),
MS(100mg)，然后向混合物中加入1mL二氯甲烷作溶剂，最后向体系中加入1.0倍量的三氟苯乙酮。反应体系在室温下搅拌48小时，TLC监测反应完全后，反应混合物使用硅胶柱分离纯化，洗脱剂为乙酸乙酯/石油醚/二氯甲烷＝1：8：1，产物为白色固体。(S)-2,4-二苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪:85％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝17.7min,tR(minor)＝16.3min.
1H NMR(400MHz,CDCl3)δ8.24(d,J＝7.2Hz,2H),7.77(d,J＝7.6Hz,1H),7.73(d,J＝7.6Hz,2H),7.63-7.59(m,2H),7.55-7.48(m,4H),7.27-7.22(m,1H),7.03(t,J＝7.2Hz,1H),6.43(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ158.6,146.5,142.8,133.7,131.8,131.2,130.9,129.4,129.3,129.0,128.8,127.8,124.1,123.6,123.1(q,J＝290.5Hz),120.4,111.4,90.6(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.30；HRMS(ESI)Calcd forC22H15F3N3O+[M+H]+394.1162；Found:394.1164.
(S)-4-苯基-2-(对甲苯基)-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，87％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝30.0min,tR(minor)＝35.7min.
1H NMR(400MHz,CDCl3)δ8.12(d,J＝7.2Hz,2H),7.74(d,J＝8.4Hz,1H),7.70(d,J＝7.6Hz,2H),7.60-7.51(m,3H),7.30-7.20(m,3H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.0Hz,1H),2.43(s,3H)；13C NMR(100MHz,CDCl3)δ158.8,146.7,144.8,142.9,131.8,131.3,131.0,129.6,129.4,129.0,127.8,127.8,126.5,123.9,123.5,120.3,111.4,21.9,123.2(q,J＝290.7Hz),90.5(q,J＝33.1Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C23H17F3N3O+[M+H]+408.1318；Found:408.1311.
(S)-2-(4-甲氧基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，68％yield,89:11er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝53.4min,tR(minor)＝31.6min.
1H NMR(400MHz,CDCl3)δ8.18(d,J＝9.4Hz,2H),7.75-7.70(m,3H),7.58(t,J＝7.2Hz,1H),7.52(t,J＝8.0Hz,2H),7.26-7.19(m,1H),7.02-6.96(m,3H),6.41(d,J＝8.4Hz,1H),3.87(s,3H)；13C NMR(100MHz,CDCl3)δ164.2,158.5,146.9,142.9,131.8,131.4,131.1,131.0,129.4,127.8,127.5,123.8,123.4,121.5,120.2,114.3,111.3,124.0(q,J＝290.7Hz),90.4(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcdfor C23H16F3N3NaO2 +[M+Na]+446.1087；Found:446.1090.
(S)-2-(4-氟苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，83％yield,94:6er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝22.0min,tR(minor)＝19.3min.
1H NMR(400MHz,CDCl3)δ8.27-8.23(m,2H),7.76(d,J＝8.0Hz,1H),7.72(d,J＝7.6Hz,2H),7.63-7.52(m,3H),7.27-7.15(m,3H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)167.5,165.0,157.7,146.3,142.8,131.9,131.5,131.4,131.0,130.9,129.5,127.8,125.5,125.5,124.2,123.6,120.4,116.3,116.1,111.4,123.1(q,J＝290.5Hz),90.7(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.33,-103.73；HRMS(ESI)Calcd for C22H13F4N3NaO+[M+Na]+434.0887；Found:434.0883.
(S)-2-(4-氯苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，81％yield,91:9er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝31.6min,tR(minor)＝25.5min.
1H NMR(400MHz,CDCl3)δ8.15(d,J＝8.8Hz,2H),7.76-7.70(m,3H),7.60-7.50(m,3H),7.44(d,J＝8.4Hz,2H),7.26-7.19(m,1H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.7,146.2,142.8,140.2,132.0,131.0,130.9,130.2,129.5,129.2,127.8,127.8,124.3,123.7,120.5,111.5,123.1(q,J＝290.5Hz),90.7(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C22H13ClF3N3NaO+[M+Na]+450.0591；Found:450.0597.
(S)-2-(4-溴苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，72％yield,92:8er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝37.7min,tR(minor)＝28.2min.
1H NMR(400MHz,CDCl3)δ8.07(d,J＝8.4Hz,2H),7.76-7.70(m,3H),7.62-7.50(m,5H),7.27-7.19(m,1H),7.02(t,J＝8.0Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.9,146.2,142.8,132.2,132.0,130.9,130.3,129.5,129.0,128.2,127.8,124.3,123.7,120.5,111.5,123.1(q,J＝290.5Hz),90.7(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C22H13BrF3N3NaO+[M+Na]+494.0086；Found:494.0084.
(S)-4-苯基-4-(三氟甲基)-2-(4-(三氟甲基)苯基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，75％yield,85:15er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝26.2min,tR(minor)＝23.1min.
1H NMR(400MHz,CDCl3)δ8.34(d,J＝8.0Hz,2H),7.85-7.72(m,5H),7.63-7.53(m,3H),7.24(t,J＝7.6Hz,1H),7.04(t,J＝8.0Hz,1H),6.42(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)δ157.2,145.9,142.8,132.6,132.1,130.9,130.8,129.6,129.2,127.8,125.8,125.8,124.6,123.8,121.6,120.7,111.5,134.9(q,J＝32.6Hz),123.6(q,J＝271.3Hz),90.9(q,J＝33.4Hz)；19F NMR(376MHz,CDCl3)δ-63.08,-75.33；HRMS(ESI)Calcdfor C23H14F6N3O+[M+H]+462.1036；Found:462.1026.
(S)-4-(4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪-2-基)苯甲酸甲酯，81％yield,95:5er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝38.0min,tR(minor)＝24.5min.1H NMR(400MHz,CDCl3)δ8.29(d,J＝8.4Hz,2H),8.14(d,J＝8.8Hz,2H),7.78-7.72(m,3H),7.61(t,J＝7.6Hz,1H),7.54(t,J＝7.6Hz,2H),7.24(t,J＝9.2Hz,1H),7.03(t,J＝6.0Hz,1H),6.41(d,J＝8.0Hz,1H),3.95(s,3H)；13C NMR(100MHz,CDCl3)δ166.2,157.6,146.1,142.8,134.4,1332,132.0,130.9,129.9,129.5,128.9,1279,124.5,123.8,123.1(q,J＝290.3Hz),120.6,111.5,90.8(q,J＝33.1Hz),52.7.19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C24H17F3N3O3 +[M+H]+452.1217；Found:452.1219.
(S)-4-(4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪-2-基)苄腈，87％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝44.0min,tR(minor)＝55.8min.
1H NMR(400MHz,CDCl3)δ8.33(d,J＝8.8Hz,2H),7.80-7.77(m,3H),7.73(d,J＝8.8Hz,2H),7.65-7.61(m,1H),7.58-7.54(m,2H),7.27-7.23(m,1H),7.06(t,J＝8.4Hz,1H),6.41(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)δ156.7,145.7,142.8,133.3,132.6,132.1,130.7,130.6,129.6,129.2,127.8,124.8,123.9,120.6,118.0,116.7,111.5,77.5,77.4,77.2,76.8,123.0(q,J＝290.5Hz),91.0(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.29；HRMS(ESI)Calcd for C23H13F3N4NaO+[M+Na]+441.0934；Found:441.0932.
(S)-2-(3-氟苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，78％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝11.8min,tR(minor)＝10.1min.
1H NMR(400MHz,CDCl3)δ8.03(d,J＝7.6Hz,1H),7.89(d,J＝9.2Hz,1H),7.77(d,J＝8.0Hz,1H),7.72(d,J＝7.6Hz,2H),7.61(t,J＝7.6Hz,1H),7.54(t,J＝8.0Hz,2H),7.50-7.44(m,1H),7.32-7.22(m,2H),7.04(t,J＝8.0Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ164.0,161.5,157.4,146.1,142.8,132.0,131.5(d,J＝8.1Hz),130.9,130.5(d,J＝7.9Hz),129.5,127.8,124.7,124.7,124.4,123.7,120.8,120.6,120.6,115.7(d,J＝24Hz),111.5,123.1(q,J＝290.4Hz),90.8(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.31,-111.41；HRMS(ESI)Calcd for C22H13F4N3NaO+[M+Na]+434.0887；Found:434.0886.
(S)-2-(3-氯苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，75％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝95/5,1.0mL/min,tR(major)＝26.5min,tR(minor)＝25.0min.
1H NMR(400MHz,CDCl3)δ8.18(s,1H),8.13(d,J＝8.0Hz,1H),7.77(d,J＝8.0Hz,1H),7.72(d,J＝6.8Hz,2H),7.64-7.53(m,4H),7.44(t,J＝8.0Hz,1H),7.24(t,J＝9.2Hz,1H),7.04(t,J＝8.0Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.3,146.0,142.8,135.0,133.6,132.0,131.1,130.9,130.2,129.5,128.7,127.8,127.1,124.4,123.7,120.6,111.5,123.1(q,J＝290.6Hz),90.8(q,J＝33.1Hz)；19F NMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C22H14ClF3N3O+[M+H]+428.0772；Found:428.0778.
(S)-2-(3-溴苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，81％yield,93:7er.HPLC condition:Chiralpak IC(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝17.0min,tR(minor)＝12.7min
1H NMR(400MHz,CDCl3)δ8.34(s,1H),8.17(d,J＝8.0Hz,1H),7.77(d,J＝8.8Hz,1H),7.72(d,J＝8.8Hz,3H),7.62(t,J＝7.6Hz,1H),7.55(t,J＝8.0Hz,2H),7.37(t,J＝8.0Hz,1H),7.27-7.22(m,1H),7.04(t,J＝9.6Hz,1H),6.41(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)δ157.2,146.0,142.8,136.5,132.0,131.6,131.3,130.9,130.4,129.5,127.8,127.5,124.4,123.7,122.9,120.6,111.5,123.04(q,J＝290.6Hz),90.81(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C22H13BrF3N3NaO+[M+Na]+494.0086；Found:494.0096.
(S)-2-(3-甲基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，68％yield,89:11er.HPLC condition:Chiralpak IA(Hex/iPrOH＝90/10,1.0mL/min,tR(major)＝14.7min,tR(minor)＝15.6min.1H NMR(400MHz,CDCl3)δ8.03(d,J＝11.6Hz,2H),7.76-7.70(m,3H),7.60-7.50(m,3H),7.40-7.34(m,2H),7.25-7.19(m,1H),7.00(t,J＝8.0Hz,1H),6.40(d,J＝8.4Hz,1H),2.40(s,3H)；13C NMR(100MHz,CDCl3)δ158.8,146.6,142.9,138.7,134.6,131.8,131.2,131.0,129.5,129.2,128.8,127.9,126.2,124.0,123.6,120.4,111.4,21.4,123.2(q,J＝291.8Hz),90.6(q,J＝33.6Hz)；19FNMR(376MHz,CDCl3)δ-75.30；HRMS(ESI)Calcd for C23H17F3N3O+[M+H]+408.1318；Found:408.1311.
(S)-2-(3-三氟甲基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，73％yield,92:8er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝8.1min,tR(minor)＝7.4min.
1H NMR(400MHz,CDCl3)δ8.48(s,1H),8.40(d,J＝8.0Hz,1H),7.85(d,J＝7.6Hz,1H),7.78(d,J＝8.0Hz,1H),7.73(d,J＝5.6Hz,2H),7.66-7.61(m,2H),7.56(t,J＝8.0Hz,2H),7.23(t,J＝6.8Hz,1H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.2,145.9,142.8,132.1,131.9,131.7,131.4,130.9,130.8,130.2,130.0,130.0,129.6,127.7,125.7,125.7,124.5,123.8,120.6,111.5,122.62(q,J＝75.9Hz),90.93(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-62.74,-75.31；HRMS(ESI)Calcdfor C23H14F6N3O+[M+H]+462.1036；Found:462.1039.
(S)-2-(3,4-二甲基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，51％yield,92:8er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝14.6min,tR(minor)＝17.1min.
1H NMR(400MHz,CDCl3)δ8.02(s,1H),7.95(d,J＝8.0Hz,1H),7.76-7.72(m,3H),7.59(t,J＝7.6Hz,1H),7.53(t,J＝7.6Hz,2H),7.26-7.20(m,2H),7.00(t,J＝7.6Hz,1H),6.41(d,J＝8.4Hz,1H),2.33(d,J＝5.6Hz,6H)；13C NMR(100MHz,CDCl3)δ159.0,146.8,143.6,142.9,137.4,131.8,131.4,131.0,130.1,130.0,129.4,127.9,126.8,126.6,123.9,123.4,123.2(q,J＝290.7Hz),120.3,111.4,90.5(q,J＝33.2Hz),20.3,19.9,19FNMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C24H19F3N3O+[M+H]+422.1475；Found:422.1480.
(S)-2-(萘-2-基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪85％yield,92:8er.HPLC condition:Chiralpak IA(Hex/iPrOH＝90/10,1.0mL/min,tR(major)＝31.1min,tR(minor)＝29.2min.
1H NMR(400MHz,CDCl3)δ8.72(s,1H),8.35-8.33(m,1H),7.94-7.87(m,3H),7.80(t,J＝8.4Hz,3H),7.63-7.52(m,5H),7.25(t,J＝7.2Hz,1H),7.04(t,J＝6.8Hz,1H),6.45(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ158.8,146.6,143.0,135.9,132.6,131.9,131.2,131.0,130.5,129.6,129.5,128.9,128.7,128.0,127.9,127.1,126.6,124.4,124.2,123.6,120.5,111.5,123.2(q,J＝290.5Hz),91.0(q,J＝33.1Hz)；19F NMR(376MHz,CDCl3)δ-75.20；HRMS(ESI)Calcd for C26H17F3N3O+[M+H]+444.1318；Found:444.1322.
(S)-4-苯基-2-(吡啶-3-基)-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，83％yield,94:6er.HPLC condition:Chiralpak IA(Hex/iPrOH＝80/20,1.0mL/min,tR(major)＝16.2min,tR(minor)＝11.8min.
1H NMR(400MHz,CDCl3)δ9.38(s,1H),8.83-8.81(m,1H),8.52-8.49(m,1H),7.79-7.72(m,3H),7.64-7.54(m,3H),7.47-7.44(m,1H),7.25(t,J＝6.8Hz,1H),7.05(t,J＝7.2Hz,1H),6.42(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.0,154.0,150.0,145.8,142.7,136.2,132.1,130.9,130.7,129.6,127.8,127.8,125.8,125.6,124.5,123.8,123.7,120.7,111.5,123.7(q,J＝290.6Hz),90.9(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C21H14F3N4O+[M+H]+395.1114；Found:395.1109.
(S)-7,8-二甲基-2,4-二苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，53％yield,90:10er.HPLC condition:Chiralpak IC(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝19.3min,tR(minor)＝12.7min.1H NMR(400MHz,CDCl3)δ8.21(d,J＝7.2Hz,2H),7.71(d,J＝8.0Hz,2H),7.62-7.57(m,2H),7.55-7.46(m,5H),6.20(s,1H),2.30(s,3H),2.14(s,3H)；13C NMR(100MHz,CDCl3)δ157.9,145.9,141.4,133.5,133.4,132.6,131.7,131.5,129.5,129.4,128.8,128.8,127.8,127.8,123.1(q,J＝290.5Hz),120.6,111.7,90.6(q,J＝33.0Hz),20.7,20.2.19F NMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C24H19F3N3O+[M+H]+422.1475；Found:422.1469.
实施例2
向干燥的试管中加入醛亚胺I(0.12mmol)，NHC C(4.8mg,10mol％),Urea V(9.8mg,20mol％),K3PO4(31.8mg,0.15mmol),DQ(44.8mg,0.11mmol),
MS(100mg)，然后向混合物中加入二氯甲烷/正己烷＝(v/v＝1：1，0.1M)作溶剂，最后向体系中加入1.0倍量的三氟苯乙酮。反应体系在0℃下搅拌48小时，TLC监测反应完全后，反应混合物使用硅胶柱分离纯化，洗脱剂为石油醚/二氯甲烷＝1：6，产物为白色固体。
(R)-2,4-二苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪:91％yield,94:6er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝16.6min,tR(minor)＝17.9min.[α]D 25(c 1.0,CHCl3)＝-53.3.
1H NMR(400MHz,CDCl3)δ8.24(d,J＝7.2Hz,2H),7.77(d,J＝7.6Hz,1H),7.73(d,J＝7.6Hz,2H),7.63-7.59(m,2H),7.55-7.48(m,4H),7.27-7.22(m,1H),7.03(t,J＝7.2Hz,1H),6.43(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ158.6,146.5,142.8,133.7,131.8,131.2,130.9,129.4,129.3,129.0,128.8,127.8,124.1,123.6,123.1(q,J＝290.5Hz),120.4,111.4,90.6(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.30；HRMS(ESI)Calcd forC22H15F3N3O+[M+H]+394.1162；Found:394.1164.
(R)-4-苯基-2-(对甲苯基)-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，72％yield,96:4er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝30.7min,tR(minor)＝35.8min.[α]D 25(c 1.0,CHCl3)＝-28.9。
1H NMR(400MHz,CDCl3)δ8.12(d,J＝7.2Hz,2H),7.74(d,J＝8.4Hz,1H),7.70(d,J＝7.6Hz,2H),7.60-7.51(m,3H),7.30-7.20(m,3H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.0Hz,1H),2.43(s,3H)；13C NMR(100MHz,CDCl3)δ158.8,146.7,144.8,142.9,131.8,131.3,131.0,129.6,129.4,129.0,127.8,127.8,126.5,123.9,123.5,120.3,111.4,21.9,123.2(q,J＝290.7Hz),90.5(q,J＝33.1Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C23H17F3N3O+[M+H]+408.1318；Found:408.1311.
(R)-2-(4-甲氧基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，76％yield,94:6er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝31.7min,tR(minor)＝54.2min.[α]D 25(c 1.0,CHCl3)＝-19.7。
1H NMR(400MHz,CDCl3)δ8.18(d,J＝9.4Hz,2H),7.75-7.70(m,3H),7.58(t,J＝7.2Hz,1H),7.52(t,J＝8.0Hz,2H),7.26-7.19(m,1H),7.02-6.96(m,3H),6.41(d,J＝8.4Hz,1H),3.87(s,3H)；13C NMR(100MHz,CDCl3)δ164.2,158.5,146.9,142.9,131.8,131.4,131.1,131.0,129.4,127.8,127.5,123.8,123.4,121.5,120.2,114.3,111.3,124.0(q,J＝290.7Hz),90.4(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcdfor C23H16F3N3NaO2 +[M+Na]+446.1087；Found:446.1090.
(R)-2-(4-氟苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，81％yield,94:6er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝20.0min,tR(minor)＝22.4min.[α]D 25(c 1.0,CHCl3)＝-46.9.
1H NMR(400MHz,CDCl3)δ8.27-8.23(m,2H),7.76(d,J＝8.0Hz,1H),7.72(d,J＝7.6Hz,2H),7.63-7.52(m,3H),7.27-7.15(m,3H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)167.5,165.0,157.7,146.3,142.8,131.9,131.5,131.4,131.0,130.9,129.5,127.8,125.5,125.5,124.2,123.6,120.4,116.3,116.1,111.4,123.1(q,J＝290.5Hz),90.7(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.33,-103.73；HRMS(ESI)Calcd for C22H13F4N3NaO+[M+Na]+434.0887；Found:434.0883.
(R)-2-(4-氯苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，88％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝27.2min,tR(minor)＝31.8min.[α]D 25(c 1.0,CHCl3)＝-29.4。
1H NMR(400MHz,CDCl3)δ8.15(d,J＝8.8Hz,2H),7.76-7.70(m,3H),7.60-7.50(m,3H),7.44(d,J＝8.4Hz,2H),7.26-7.19(m,1H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.7,146.2,142.8,140.2,132.0,131.0,130.9,130.2,129.5,129.2,127.8,127.8,124.3,123.7,120.5,111.5,123.1(q,J＝290.5Hz),90.7(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C22H13ClF3N3NaO+[M+Na]+450.0591；Found:450.0597.
(R)-2-(4-溴苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，90％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝29.6min,tR(minor)＝37.8min).[α]D 25(c 1.0,CHCl3)＝-3.3.
1H NMR(400MHz,CDCl3)δ8.07(d,J＝8.4Hz,2H),7.76-7.70(m,3H),7.62-7.50(m,5H),7.27-7.19(m,1H),7.02(t,J＝8.0Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.9,146.2,142.8,132.2,132.0,130.9,130.3,129.5,129.0,128.2,127.8,124.3,123.7,120.5,111.5,123.1(q,J＝290.5Hz),90.7(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C22H13BrF3N3NaO+[M+Na]+494.0086；Found:494.0084.
(R)-4-苯基-4-(三氟甲基)-2-(4-(三氟甲基)苯基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，86％yield,96:4er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝25.3min,tR(minor)＝26.5min).[α]D 25(c 1.0,CHCl3)＝-33.5。1HNMR(400MHz,CDCl3)δ8.34(d,J＝8.0Hz,2H),7.85-7.72(m,5H),7.63-7.53(m,3H),7.24(t,J＝7.6Hz,1H),7.04(t,J＝8.0Hz,1H),6.42(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)δ157.2,145.9,142.8,132.6,132.1,130.9,130.8,129.6,129.2,127.8,125.8,125.8,124.6,123.8,121.6,120.7,111.5,134.9(q,J＝32.6Hz),123.6(q,J＝271.3Hz),90.9(q,J＝33.4Hz)；19F NMR(376MHz,CDCl3)δ-63.08,-75.33；HRMS(ESI)Calcd for C23H14F6N3O+[M+H]+462.1036；Found:462.1026.
(R)-4-(4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪-2-基)苯甲酸甲酯，91％yield,96:4er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝25.5min,tR(minor)＝38.2min.[α]D 25(c 1.0,CHCl3)＝-30.8。
1H NMR(400MHz,CDCl3)δ8.29(d,J＝8.4Hz,2H),8.14(d,J＝8.8Hz,2H),7.78-7.72(m,3H),7.61(t,J＝7.6Hz,1H),7.54(t,J＝7.6Hz,2H),7.24(t,J＝9.2Hz,1H),7.03(t,J＝6.0Hz,1H),6.41(d,J＝8.0Hz,1H),3.95(s,3H)；13C NMR(100MHz,CDCl3)δ166.2,157.6,146.1,142.8,134.4,1332,132.0,130.9,129.9,129.5,128.9,1279,124.5,123.8,123.1(q,J＝290.3Hz),120.6,111.5,90.8(q,J＝33.1Hz),52.7.19F NMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C24H17F3N3O3 +[M+H]+452.1217；Found:452.1219.
(R)-4-(4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪-2-基)苄腈，90％yield,96:4er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝57.9min,tR(minor)＝43.6min.[α]D 25(c 1.0,CHCl3)＝-30.9.
1H NMR(400MHz,CDCl3)δ8.33(d,J＝8.8Hz,2H),7.80-7.77(m,3H),7.73(d,J＝8.8Hz,2H),7.65-7.61(m,1H),7.58-7.54(m,2H),7.27-7.23(m,1H),7.06(t,J＝8.4Hz,1H),6.41(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)δ156.7,145.7,142.8,133.3,132.6,132.1,130.7,130.6,129.6,129.2,127.8,124.8,123.9,120.6,118.0,116.7,111.5,77.5,77.4,77.2,76.8,123.0(q,J＝290.5Hz),91.0(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.29；HRMS(ESI)Calcd for C23H13F3N4NaO+[M+Na]+441.0934；Found:441.0932.
(R)-2-(3-氟苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，90％yield,95:5er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝10.4min,tR(minor)＝11.9min.[α]D 25(c 1.0,CHCl3)＝-43.3.
1H NMR(400MHz,CDCl3)δ8.03(d,J＝7.6Hz,1H),7.89(d,J＝9.2Hz,1H),7.77(d,J＝8.0Hz,1H),7.72(d,J＝7.6Hz,2H),7.61(t,J＝7.6Hz,1H),7.54(t,J＝8.0Hz,2H),7.50-7.44(m,1H),7.32-7.22(m,2H),7.04(t,J＝8.0Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ164.0,161.5,157.4,146.1,142.8,132.0,131.5(d,J＝8.1Hz),130.9,130.5(d,J＝7.9Hz),129.5,127.8,124.7,124.7,124.4,123.7,120.8,120.6,120.6,115.7(d,J＝24Hz),111.5,123.1(q,J＝290.4Hz),90.8(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.31,-111.41；HRMS(ESI)Calcd for C22H13F4N3NaO+[M+Na]+434.0887；Found:434.0886.
(R)-2-(3-氯苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，43％yield,92:8er.HPLC condition:Chiralpak IA(Hex/iPrOH＝95/5,1.0mL/min,tR(major)＝25.1min,tR(minor)＝26.7min.[α]D 25(c 0.5,CHCl3)＝-17.3.
1H NMR(400MHz,CDCl3)δ8.18(s,1H),8.13(d,J＝8.0Hz,1H),7.77(d,J＝8.0Hz,1H),7.72(d,J＝6.8Hz,2H),7.64-7.53(m,4H),7.44(t,J＝8.0Hz,1H),7.24(t,J＝9.2Hz,1H),7.04(t,J＝8.0Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.3,146.0,142.8,135.0,133.6,132.0,131.1,130.9,130.2,129.5,128.7,127.8,127.1,124.4,123.7,120.6,111.5,123.1(q,J＝290.6Hz),90.8(q,J＝33.1Hz)；19F NMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C22H14ClF3N3O+[M+H]+428.0772；Found:428.0778.
(R)-2-(3-溴苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，86％yield,94:6er.HPLC condition:Chiralpak IC(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝12..7min,tR(minor)＝17.0min.[α]D 25(c 1.0,CHCl3)＝-20.4。
1H NMR(400MHz,CDCl3)δ8.34(s,1H),8.17(d,J＝8.0Hz,1H),7.77(d,J＝8.8Hz,1H),7.72(d,J＝8.8Hz,3H),7.62(t,J＝7.6Hz,1H),7.55(t,J＝8.0Hz,2H),7.37(t,J＝8.0Hz,1H),7.27-7.22(m,1H),7.04(t,J＝9.6Hz,1H),6.41(d,J＝8.4Hz,1H)；13C NMR(100MHz,CDCl3)δ157.2,146.0,142.8,136.5,132.0,131.6,131.3,130.9,130.4,129.5,127.8,127.5,124.4,123.7,122.9,120.6,111.5,123.04(q,J＝290.6Hz),90.81(q,J＝33.5Hz)；19F NMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C22H13BrF3N3NaO+[M+Na]+494.0086；Found:494.0096.
(R)-2-(3-甲基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，82％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝90/10,1.0mL/min,tR(major)＝15.6min,tR(minor)＝14.8min.[α]D 25(c 1.0,CHCl3)＝-35.9。
1H NMR(400MHz,CDCl3)δ8.03(d,J＝11.6Hz,2H),7.76-7.70(m,3H),7.60-7.50(m,3H),7.40-7.34(m,2H),7.25-7.19(m,1H),7.00(t,J＝8.0Hz,1H),6.40(d,J＝8.4Hz,1H),2.40(s,3H)；13C NMR(100MHz,CDCl3)δ158.8,146.6,142.9,138.7,134.6,131.8,131.2,131.0,129.5,129.2,128.8,127.9,126.2,124.0,123.6,120.4,111.4,21.4,123.2(q,J＝291.8Hz),90.6(q,J＝33.6Hz)；19F NMR(376MHz,CDCl3)δ-75.30；HRMS(ESI)Calcd forC23H17F3N3O+[M+H]+408.1318；Found:408.1311.
(R)-2-(3-三氟甲基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，81％yield,95:5er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝7.3min,tR(minor)＝8.0min.[α]D 25(c 1.0,CHCl3)＝-33.4。
1H NMR(400MHz,CDCl3)δ8.48(s,1H),8.40(d,J＝8.0Hz,1H),7.85(d,J＝7.6Hz,1H),7.78(d,J＝8.0Hz,1H),7.73(d,J＝5.6Hz,2H),7.66-7.61(m,2H),7.56(t,J＝8.0Hz,2H),7.23(t,J＝6.8Hz,1H),7.03(t,J＝7.2Hz,1H),6.41(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.2,145.9,142.8,132.1,131.9,131.7,131.4,130.9,130.8,130.2,130.0,130.0,129.6,127.7,125.7,125.7,124.5,123.8,120.6,111.5,122.62(q,J＝75.9Hz),90.93(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-62.74,-75.31；HRMS(ESI)Calcdfor C23H14F6N3O+[M+H]+462.1036；Found:462.1039.
(R)-2-(3,4-二甲基苯基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，73％yield,93:7er.HPLC condition:Chiralpak IA(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝17.4min,tR(minor)＝14.6min.[α]D 25(c 1.0,CHCl3)＝-19.5。
1H NMR(400MHz,CDCl3)δ8.02(s,1H),7.95(d,J＝8.0Hz,1H),7.76-7.72(m,3H),7.59(t,J＝7.6Hz,1H),7.53(t,J＝7.6Hz,2H),7.26-7.20(m,2H),7.00(t,J＝7.6Hz,1H),6.41(d,J＝8.4Hz,1H),2.33(d,J＝5.6Hz,6H)；13C NMR(100MHz,CDCl3)δ159.0,146.8,143.6,142.9,137.4,131.8,131.4,131.0,130.1,130.0,129.4,127.9,126.8,126.6,123.9,123.4,123.2(q,J＝290.7Hz),120.3,111.4,90.5(q,J＝33.2Hz),20.3,19.9,19FNMR(376MHz,CDCl3)δ-75.33；HRMS(ESI)Calcd for C24H19F3N3O+[M+H]+422.1475；Found:422.1480.
(R)-2-(萘-2-基)-4-苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪86％yield,94:6er.HPLC condition:Chiralpak IA(Hex/iPrOH＝90/10,1.0mL/min,tR(major)＝29.8min,tR(minor)＝31.1min.[α]D 25(c 1.0,CHCl3)＝+14.1。
1H NMR(400MHz,CDCl3)δ8.72(s,1H),8.35-8.33(m,1H),7.94-7.87(m,3H),7.80(t,J＝8.4Hz,3H),7.63-7.52(m,5H),7.25(t,J＝7.2Hz,1H),7.04(t,J＝6.8Hz,1H),6.45(d,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ158.8,146.6,143.0,135.9,132.6,131.9,131.2,131.0,130.5,129.6,129.5,128.9,128.7,128.0,127.9,127.1,126.6,124.4,124.2,123.6,120.5,111.5,123.2(q,J＝290.5Hz),91.0(q,J＝33.1Hz)；19F NMR(376MHz,CDCl3)δ-75.20；HRMS(ESI)Calcd for C26H17F3N3O+[M+H]+444.1318；Found:444.1322.
(R)-4-苯基-2-(吡啶-3-基)-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，87％yield,91:9er.HPLC condition:Chiralpak IA(Hex/iPrOH＝80/20,1.0mL/min,tR(major)＝11.8min,tR(minor)＝16.3min.[α]D 25(c 1.0,CHCl3)＝-37.0。
1H NMR(400MHz,CDCl3)δ9.38(s,1H),8.83-8.81(m,1H),8.52-8.49(m,1H),7.79-7.72(m,3H),7.64-7.54(m,3H),7.47-7.44(m,1H),7.25(t,J＝6.8Hz,1H),7.05(t,J＝7.2Hz,1H),6.42(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ157.0,154.0,150.0,145.8,142.7,136.2,132.1,130.9,130.7,129.6,127.8,127.8,125.8,125.6,124.5,123.8,123.7,120.7,111.5,123.7(q,J＝290.6Hz),90.9(q,J＝33.3Hz)；19F NMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C21H14F3N4O+[M+H]+395.1114；Found:395.1109.
(S)-7,8-二甲基-2,4-二苯基-4-(三氟甲基)-4H-苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪，71％yield,95:5er.HPLC condition:Chiralpak IC(Hex/iPrOH＝85/15,1.0mL/min,tR(major)＝12.7min,tR(minor)＝19.4min.[α]D 25(c 1.0,CHCl3)＝-88.6。
1H NMR(400MHz,CDCl3)δ8.21(d,J＝7.2Hz,2H),7.71(d,J＝8.0Hz,2H),7.62-7.57(m,2H),7.55-7.46(m,5H),6.20(s,1H),2.30(s,3H),2.14(s,3H)；13C NMR(100MHz,CDCl3)δ157.9,145.9,141.4,133.5,133.4,132.6,131.7,131.5,129.5,129.4,128.8,128.8,127.8,127.8,123.1(q,J＝290.5Hz),120.6,111.7,90.6(q,J＝33.0Hz),20.7,20.2.19FNMR(376MHz,CDCl3)δ-75.27；HRMS(ESI)Calcd for C24H19F3N3O+[M+H]+422.1475；Found:422.1469.
实施例3
向干燥的试管中加入醛亚胺I(0.12mmol)，NHC C(4.8mg,10mol％),Urea V(9.8mg,20mol％),K3PO4(31.8mg,0.15mmol),DQ(44.8mg,0.11mmol),
MS(100mg)和N-Bn靛红0.1mmol，然后向混合物中加入二氯甲烷/正己烷＝(v/v＝1：1，0.1M)作溶剂，反应体系在0℃下搅拌48小时，TLC监测反应完全后，反应混合物使用硅胶柱分离纯化，洗脱剂为石乙酸乙酯/石油醚/二氯甲烷＝1：4：1，产物为白色固体。
(R)-1'-苄基-2-苯基螺[苯并[4,5]咪唑[1,2-c][1,3,5]恶二嗪-4,3'-吲哚]-2'-酮:96％yield,99:1er.[α]D 25(c 1.0,CHCl3)＝-64.8，HPLC condition:Chiralpak IA(Hex/iPrOH＝70/30,1.0mL/min,tR(major)＝42.0min,tR(minor)＝20.5min).
1H NMR(400MHz,CDCl3)δ8.23(d,J＝8.0Hz,2H),7.77(d,J＝8.0Hz,1H),7.60-7.45(m,5H),7.32-7.18(m,7H),6.97(d,J＝7.6Hz,1H),6.92(t,J＝8.0Hz,1H),5.98(d,J＝8.0Hz,1H),5.05(d,J＝15.6Hz,1H),4.78(t,J＝15.6Hz,1H)；13C NMR(100MHz,CDCl3)δ169.0,159.7,147.7,143.7,143.5,134.4,133.8,133.4,130.2,129.2,129.0,128.6,128.4,127.6,126.9,124.5,123.6,123.5,122.0,120.6,111.1,109.7,44.4；HRMS(ESI)Calcd for C29H21N4O2 +[M+H]+457.1659；Found:457.1660.
采用与VII01相同的制备方法进行制备VII02。
(R)-1'-苄基-2-(对甲苯基)螺[benzo[4,5]咪唑[1,2-c][1,3,5]恶二嗪-4,3'-吲哚]-2'-酮95％yield,99:1er.[α]D 25(c 1.0,CHCl3)＝-68.4HPLC condition:ChiralpakIA(Hex/iPrOH＝70/30,1.0mL/min,tR(major)＝52.2min,tR(minor)＝34.8min).1H NMR(400MHz,CDCl3)δ8.12(d,J＝8.0Hz,2H),7.76(d,J＝8.0Hz,1H),7.56-7.49(m,2H),7.31-7.26(m,7H),7.22-7.17(m,2H),6.98(d,J＝8.0Hz,1H),6.91(t,J＝8.4Hz,1H),5.99(d,J＝8.0Hz,1H),5.04(d,J＝15.6Hz,1H),4.78(d,J＝15.6Hz,1H),2.42(s,3H)；13C NMR(100MHz,CDCl3)δ169.0,159.9,147.9,144.3,143.7,143.5,134.4,133.8,130.2,129.4,129.1,129.0,128.4,127.6,127.4,126.8,124.5,123.4,122.1,120.4,111.1,109.7,87.0,44.4,21.9；HRMS(ESI)Calcd for C30H23N4O2 +[M+H]+471.1816；Found:471.1811.
(R)-1'-苄基-2-(对氟苯基)螺[benzo[4,5]咪唑[1,2-c][1,3,5]恶二嗪-4,3'-吲哚]-2'-酮96％yield,99:1er.[α]D 25(c 1.0,CHCl3)＝-60.9.HPLC condition:ChiralpakIA(Hex/iPrOH＝70/30,1.0mL/min,tR(major)＝46.4min,tR(minor)＝21.3min).1H NMR(400MHz,CDCl3)δ8.26-8.22(m,2H),7.76(d,J＝8.0Hz,1H),7.58-7.51(m,2H),7.31-7.19(m,7H),7.14(t,J＝8.4Hz,2H),6.99(t,J＝8.0Hz,1H),6.92(t,J＝7.2Hz,1H),5.98(d,J＝8.0Hz,1H),5.05(d,J＝15.6Hz,1H),4.77(d,J＝15.6Hz,1H)；13C NMR(100MHz,CDCl3)δ169.0,167.4,164.8,158.7,147.6,143.6(d,J＝26.0Hz),134.3,133.9,131.5(d,J＝9.2Hz),130.2,129.2,128.4,127.6,126.9,126.4,126.4,124.5,123.6(d,J＝10.4Hz),121.8,120.6,116.1,115.8,111.2,109.7,87.2,44.4.19F NMR(376MHz,CDCl3)δ-104.53；HRMS(ESI)Calcd for C29H20FN4O2 +[M+H]+475.1565；Found:475.1575.
(R)-1'-苄基-2-(对氯苯基)螺[benzo[4,5]咪唑[1,2-c][1,3,5]恶二嗪-4,3'-吲哚]-2'-酮，93％yield,99:1er.[α]D 25(c 1.0,CHCl3)＝-37.4，HPLC condition:ChiralpakIA(Hex/iPrOH＝70/30,1.0mL/min,tR(major)＝64.7min,tR(minor)＝27.7min).，1H NMR(400MHz,CDCl3)δ8.15(d,J＝8.8Hz,2H),7.76(d,J＝8.6Hz,1H),7.58-7.51(m,2H),7.43(d,J＝8.8Hz,2H),7.30-7.19(m,7H),6.99(d,J＝8.0Hz,1H),6.92(t,J＝8.4Hz,1H),5.98(d,J＝8.0Hz,1H),5.04(d,J＝15.6Hz,1H),4.77(d,J＝15.6Hz,1H)；13C NMR(100MHz,CDCl3)δ168.9,158.8,147.5,143.7,143.5,139.8,134.3,134.0,130.2,130.2,129.2,129.0,128.7,128.4,127.6,126.9,124.6,123.8,123.6,121.8,120.6,111.2,109.7,87.2,44.4；HRMS(ESI)Calcd for C29H19ClN4NaO2 +[M+Na]+513.1089；Found:513.1097.
(R)-1'-苄基-2-(对三氟甲基苯基)螺[benzo[4,5]咪唑[1,2-c][1,3,5]恶二嗪-4,3'-吲哚]-2'-酮，93％yield,98:2er.[α]D 25(c 1.0,CHCl3)＝-42.3，HPLC condition:Chiralpak IA(Hex/iPrOH＝70/30,1.0mL/min,tR(major)＝63.3min,tR(minor)＝23.3min).，1H NMR(400MHz,CDCl3)δ8.34(d,J＝8.0Hz,2H),7.79-7.72(m,3H),7.60-7.53(m,2H),7.31-7.20(m,7H),7.01(d,J＝8.0Hz,1H),6.95(t,J＝8.0Hz,1H),5.99(d,J＝8.0Hz,1H),5.06(d,J＝15.6Hz,1H),4.78(d,J＝15.6Hz,1H)；13C NMR(100MHz,CDCl3)δ168.9,158.3,147.2,143.8,143.4,134.5(d,J＝32.7Hz),134.3,134.1,133.5,130.2,129.2,129.2,128.4,127.6,126.9,125.6,125.6,125.6,124.6,124.1,123.8,123.7(q,J＝271.3Hz),121.6,120.8,111.3,109.8,87.4,44.4；19F NMR(376MHz,CDCl3)δ-62.92；HRMS(ESI)Calcd for C30H19F3N4NaO2 +[M+Na]+547.1352；Found:547.1354.
(R)-1'-苄基-2-(间甲苯基)螺[苯并[4,5]咪唑并[1,2-c][1,3,5]恶二嗪-4,3'-吲哚]-2'-酮，93％yield,99:1er.[α]D 25(c 1.0,CHCl3)＝-69.6，HPLC condition:Chiralpak IA(Hex/iPrOH＝70/30,1.0mL/min,tR(major)＝34.6min,tR(minor)＝14.5min).1H NMR(400MHz,CDCl3)δ8.03(t,J＝7.2Hz,2H),7.76(d,J＝8.0Hz,1H),7.58-7.52(m,2H),7.39-7.27(m,7H),7.22-7.17(m,2H),7.00(d,J＝12.0Hz,1H),6.93(t,J＝7.6Hz,1H),6.00(d,J＝15.2Hz,1H),5.06(d,J＝15.6Hz,1H),4.80(d,J＝15.6Hz,1H),2.42(s,3H)；13C NMR(100MHz,CDCl3)δ169.0,159.9,147.8,143.7,143.5,138.5,134.4,134.2,133.8,130.2,130.1,129.5,129.1,128.6,128.4,127.6,126.8,126.2,124.5,123.6,123.5,122.0,120.5,111.2,109.7,87.1,44.4,21.4；HRMS(ESI)Calcd for C30H23N4O2 +[M+H]+471.1816；Found:471.1826.
实施例4
向干燥的试管中加入醛亚胺I(0.12mmol)，NHC C(4.8mg,10mol％),K3PO4(31.8mg,0.15mmol),DQ(44.8mg,0.11mmol),
MS(100mg)和N-Bn靛红亚胺VIII 0.1mmol，然后向混合物中加入二氯甲烷/正己烷＝(v/v＝1：1，0.1M)作溶剂，反应体系在0℃下搅拌48小时，TLC监测反应完全后，反应混合物使用硅胶柱分离纯化，洗脱剂为石乙酸乙酯/石油醚/二氯甲烷＝1：3：1，产物为白色固体。
叔丁基(R)-1'-苄基-2'-氧代-2-苯基-3H-螺环[苯并[4,5]咪唑[1,2-a][1,3,5]三嗪-4,3'-吲哚]-3-羧酸盐:73％yield,58:42er.HPLC condition:Chiralpak IA(Hex/iPrOH＝80/20,1.0mL/min,tR(major)＝65.0min,tR(minor)＝21.2min).
1H NMR(400MHz,CDCl3)δ7.73-7.70(m,3H),7.55-7.50(m,3H),7.47-7.44(m,2H),7.41-7.35(m,4H),7.29(d,J＝6.8Hz,1H),7.15(t,J＝7.2Hz,1H),7.02(t,J＝7.6Hz,1H),6.98(d,J＝7.6Hz,1H),6.87(t,J＝7.2Hz,1H),6.30(d,J＝8.0Hz,1H),5.12(s,2H),1.02(s,9H)；13C NMR(100MHz,CDCl3)δ169.4,156.8,150.7,147.8,143.4,142.8,136.9,134.6,132.2,131.2,130.3,129.1,128.7,128.4,128.3,127.8,125.0,124.3,124.3,123.4,123.1,120.4,110.5,109.9,85.8,74.6,45.2,27.1；HRMS(ESI)Calcd for C34H30N5O3 +[M+H]+556.2343；Found:556.2346.
本发明的不局限于上述实施例所述的具体技术方案，凡采用等同替换形成的技术方案均为本发明要求的保护范围。
Claims (5)
1.一种结构式为(S)-IV的目标产物的制备方法，其特征在于:醛亚胺衍生的1，4-偶极合成子与三氟苯乙酮类化合物III反应合成S构型的含有三氟季碳手性季碳中心的杂环化合物的方法，使用结构式I的醛亚胺和结构式为III的三氟苯乙酮衍生物为原料，在NHC B作为催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷作溶剂及
MS作为干燥剂的条件下于室温反应48-72小时至反应完成，反应液经硅胶柱纯化得到结构式为(S)-IV的目标产物；
其中，R为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-三氟甲基苯基，4-甲氧酰基苯基，4-氰基苯基，3-氟苯基，3-甲基苯基，3-三氟甲基苯基，3-氯苯基，3-溴苯基，3，4-二甲基苯基，2-萘基，3-吡啶，2-噻吩或2-呋喃；
R1为甲基或卤素原子；X为碳原子或氮原子；
当Y＝F时，R2为4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-苯基苯，3-甲氧基苯基，2-萘基，2-苯并呋喃，2-苯并噻吩，2-吡啶，9-甲基咔唑或苯乙基，当R2为苯基时，Y＝H，Br或Cl。
2.一种结构式为(S)-IV的目标产物的制备方法，其特征在于：
醛亚胺衍生的1，4-偶极合成子与三氟苯乙酮类化合物III反应合成S构型的含有三氟季碳手性季碳中心的杂环化合物的方法，使用结构式I的醛亚胺和结构式为III的三氟苯乙酮衍生物为原料，在NHC B作为催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷作溶剂及
MS作为干燥剂的条件下于室温反应48-72小时至反应完成，反应液经硅胶柱纯化得到结构式为(S)-IV的目标产物；
所述化合物(S)-IV的结构式如下：
3.一种结构式为(R)-IV的目标产物的制备方法，其特征在于:所述醛亚胺衍生的1，4-偶极合成子与三氟苯乙酮类化合物III反应合成R构型的含有三氟季碳手性季碳中心的杂环化合物的方法，，使用结构式I的醛亚胺和结构式为III的三氟苯乙酮衍生物为原料，在NHC C和非手性硫脲V作为共催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷/正己烷作溶剂及
MS作为干燥剂的条件下于0℃反应48-72小时至反应完成，反应液经硅胶柱纯化得到结构式为(R)-IV的目标产物；
其中，R为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-三氟甲基苯基，4-甲氧酰基苯基，4-氰基苯基，3-氟苯基，3-甲基苯基，3-三氟甲基苯基，3-氯苯基，3-溴苯基，3，4-二甲基苯基，2-萘基，3-吡啶，2-噻吩或2-呋喃；
R1为甲基或卤素原子；X为碳原子或氮原子；当Y＝F时，R2为4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-苯基苯，3-甲氧基苯基，2-萘基，2-苯并呋喃，2-苯并噻吩，2-吡啶，9-甲基咔唑或苯乙基，当R2为苯基时，Y＝H，Br或Cl。
4.一种结构式为(R)-IV的目标产物的制备方法，其特征在于：
醛亚胺衍生的1，4-偶极合成子与三氟苯乙酮类化合物III反应合成R构型的含有三氟季碳手性季碳中心的杂环化合物的方法，，使用结构式I的醛亚胺和结构式为III的三氟苯乙酮衍生物为原料，在NHC C和非手性硫脲V作为共催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷/正己烷作溶剂及
MS作为干燥剂的条件下于0℃反应48-72小时至反应完成，反应液经硅胶柱纯化得到结构式为(R)-IV的目标产物；
所述化合物(R)-IV的结构式如下：
5.一种结构式为IX的目标产物的制备方法，其特征在于:醛亚胺衍生的1，4-偶极合成子与靛红衍生的亚胺类化合物VIII反应合成手性螺环化合物的方法，使用结构式I的醛亚胺和结构式为VIII的靛红衍生的亚胺类化合物为原料，在NHC C作为催化剂，3,3',5,5'-四叔丁基-4,4'-联苯醌DQ作为氧化剂，K3PO4作为碱，二氯甲烷/正己烷作溶剂及
MS作为干燥剂的条件下于0℃反应48小时至反应完成，反应液经硅胶柱纯化得到结构式为IX的目标产物；
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107936025A (zh) * | 2017-10-24 | 2018-04-20 | 浙江理工大学 | 一种手性反‑2,3‑二取代的二环吡唑烷酮化合物的制备方法 |
| CN110551136A (zh) * | 2019-09-16 | 2019-12-10 | 贵州大学 | 一种氮杂环卡宾催化的含吲哚骨架手性螺环化合物的制备方法及用途 |
| CN112174842A (zh) * | 2020-11-02 | 2021-01-05 | 苏州山青竹生物医药有限公司 | 一种制备(s)-3-氨基-2-苄基丙酸的方法 |
| CN112209850A (zh) * | 2020-11-02 | 2021-01-12 | 苏州山青竹生物医药有限公司 | 一种制备(s)-3-氨基-2-苄基丙酸甲酯的方法 |
| CN114516881A (zh) * | 2022-03-08 | 2022-05-20 | 贵州大学 | 一种氮杂环卡宾催化的含吡唑并吡喃骨架手性化合物及制备方法 |
-
2021
- 2021-01-04 CN CN202110003575.9A patent/CN112778328B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107936025A (zh) * | 2017-10-24 | 2018-04-20 | 浙江理工大学 | 一种手性反‑2,3‑二取代的二环吡唑烷酮化合物的制备方法 |
| CN110551136A (zh) * | 2019-09-16 | 2019-12-10 | 贵州大学 | 一种氮杂环卡宾催化的含吲哚骨架手性螺环化合物的制备方法及用途 |
| CN112174842A (zh) * | 2020-11-02 | 2021-01-05 | 苏州山青竹生物医药有限公司 | 一种制备(s)-3-氨基-2-苄基丙酸的方法 |
| CN112209850A (zh) * | 2020-11-02 | 2021-01-12 | 苏州山青竹生物医药有限公司 | 一种制备(s)-3-氨基-2-苄基丙酸甲酯的方法 |
| CN114516881A (zh) * | 2022-03-08 | 2022-05-20 | 贵州大学 | 一种氮杂环卡宾催化的含吡唑并吡喃骨架手性化合物及制备方法 |
Non-Patent Citations (6)
| Title |
|---|
| Chengyuan Wang et al..Asymmetric N-alkylation of indoles with isatins catalyzed by N-heterocyclic carbene: efficient synthesis of functionalized cyclic N,O-aminal indole derivatives.《Org. Chem. Front》.2020,第1647-1652页. * |
| Dustin E. A. Raup et al..Cooperative catalysis by carbenes and Lewis acids in a highly stereoselective route to γ-lactams.《NATURE CHEMISTRY》.2010,第766-771页. * |
| Guanjie Wang et al..Asymmetric Carbene-Catalyzed Oxidation of Functionalized Aldimines as 1,4-Dipoles.《Angew. Chem. Int. Ed》.2021,第7913-7919页. * |
| Kuruva Balanna et al..N-Heterocyclic Carbene-Catalyzed Formal [6+2] Annulation Reaction via Cross-Conjugated Aza-Trienolate Intermediates.《Chem. Eur. J.》.2019,第818-822页. * |
| Xing Yang et al..Carbene-Catalyzed Activation of Remote Nitrogen Atoms of (Benz)imidazole-Derived Aldimines for Enantioselective Synthesis of Heterocycles.《Angew. Chem. Int. Ed.》.2021,第7906-7912页. * |
| Yonggui Liu et al..Carbene-Catalyzed Enantioselective Aromatic N-Nucleophilic Addition of Heteroarenes to Ketones.《Angew. Chem. Int. Ed.》.2019,第442-448页. * |
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