CN111233743A - 一种2,3-二取代吲哚啉类化合物及其制备方法和应用 - Google Patents
一种2,3-二取代吲哚啉类化合物及其制备方法和应用 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
本发明公开了一种2,3‑二取代吲哚啉类化合物及其制备方法和应用，式I所示的叔丁磺酰基(Bus)保护的亚胺‑炔胺类化合物和芳基硼酸为原料，在廉价的铜催化剂和温和的反应条件下，实现高区域选择性芳基化环化，以中等到优异的产率便捷地制备各种2,3‑二取代吲哚啉类化合物，具有宽泛的底物适应范围和基团耐受性。本发明的2,3‑二取代吲哚啉类化合物可以进一步方便地制备获得各种有用的2‑二苯甲基‑1H‑吲哚类化合物和吲哚基甲醇类化合物。
Description
技术领域
本申请属于有机合成方法学技术领域，具体涉及一种2,3-二取代吲哚啉类化合物及其制备方法和应用。
背景技术
过渡金属催化的炔类化合物与不饱和有机硼酸的碳金属化/环化串联反应已经是有机合成领域应用于快速构建复杂的杂环/碳环类分子结构的有效策略之一。然而，相对于含有羰基结构单元炔类底物，过渡金属催化的芳基化环化含有亚胺结构的炔类底物很少被报道，并且这类的芳基化环化反应往往受限于贵金属催化剂例如铑(Rh)和钯(Pd)，或者基于偕二甲基效应(Thorpe-Ingoldeffect)而只能使用特定的反应底物例如2-亚氨基芳基硼酸类化合物和二甲基系亚胺-炔类底物。其中可能的原因在于有机硼酸类化合物对高亲电性亚胺结构单元的进攻所导致。
炔胺类化合物已被证明是有机合成中功能强大且用途广泛的试剂，并且在过去十年中建立了各种有效的合成方法。尽管已经取得了许多重大的进步，但是前述提到的基于炔胺类化合物的芳基化环化反应仍然很少被现有技术所披露。Lam和他的同事报道了唯一的例子，即通过铑催化的炔胺类化合物与含亲电性官能团的芳基硼酸或其酯进行的铑催化环合反应，合成了茚的衍生物(Gourdet,B.；Rudkin,M.E.；Lam,H.W.Org.Lett.2010,12,2554.)。值得注意的是，反应底物仅限于咪唑啉酮和恶唑烷酮衍生的炔胺，因为这些底物的羰基与金属催化剂形成配位，从而实现良好的区域选择性。作为发明人课题组对于炔胺化学和杂环合成工作的深入，在本发明中，发明人报道了一种有效的铜催化的亚胺基炔胺类化合物和芳基硼酸的高区域选择性芳基化环化，以中等到优异的产率便捷地制备各种2,3-二取代吲哚类化合物，具有宽泛的底物适应范围和基团耐受性。
发明内容
本发明的目的在于克服现有技术的不足，通过对反应底物结构的精准设计而提供一种全新的合成策略，即以下文式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物和芳基硼酸为原料，在廉价的铜催化剂和温和的反应条件下，实现高区域选择性芳基化环化，以中等到优异的产率便捷地制备各种2,3-二取代吲哚啉类化合物，具有宽泛的底物适应范围和基团耐受性。
作为本发明首要目的，提供了一种式III所示的2,3-二取代吲哚啉类化合物，其结构如下：
式III中，R1、R2分别表示所连接苯环上的一个或多个取代基，取代基的最大数量取决于所连接的苯环具有的可被取代的碳原子的数目，例如可以具有1,2,3,4或5个取代基。各个取代基彼此独立地选自氢、卤素、C1-20烷基、C1-20卤代烷基、C1-20烷氧基、C1-20卤代氧烷基、C1-20烷硫基、C1-20酰基、C1-20烷氧基羰基、C6-20芳基、三(C1-20烷基)硅基、-CHO、C6-20芳基-C1-20烷氧基、HO-C1-20烷基-、氰基、硝基。
PG表示氨基保护基团，氨基保护基选自本领域公知的种类，例如可以选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种。
Ar表示取代或未取代的C6-20芳基、取代或未取代的C2-20杂芳基；其中所述“取代或未取代的C6-20芳基和取代或未取代的C2-20杂芳基”中的取代基个数为一个或多个，取代基的最大数量取决于所述芳基或杂芳基的可被取代的碳原子数目，例如具有1,2,3,4,5个取代基，并且各个取代基彼此独立选自卤素、C1-20烷基、C1-20卤代烷基、C1-20烷氧基、C1-20卤代卤代烷基、C1-20烷硫基、C1-20酰基、C1-20烷氧基羰基、C6-20芳基、三(C1-20烷基)硅基、-CHO、C6-20芳基-C1-20烷氧基、HO-C1-20烷基-、氰基、硝基。
优选地，式III中，R1、R2分别表示所连接苯环上的一个或多个取代基，各个取代基彼此独立地选自氢、卤素、C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代烷氧基、C1-6烷硫基、C1-6酰基、C1-6烷氧基羰基、C6-14芳基、三(C1-6烷基)硅基、-CHO、C6-14芳基-C1-6烷氧基、HO-C1-6烷基-、氰基、硝基。
PG表示氨基保护基团，选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种。
Ar表示取代或未取代的C6-14芳基、取代或未取代的C2-14杂芳基；其中所述“取代或未取代的C6-14芳基和取代或未取代的C2-14杂芳基”中的取代基个数为一个或多个，各个取代基彼此独立选自卤素、C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代卤代烷基、C1-6烷硫基、C1-6酰基、C1-6烷氧基羰基、C6-14芳基、三(C1-6烷基)硅基、-CHO、C6-14芳基-C1-6烷氧基、HO-C1-6烷基-、氰基、硝基。
进一步优选地，式III中，R1、R2分别表示所连接苯环上的一个或多个取代基，各个取代基彼此独立地选自氢、氟、氯、溴、碘、-CO2Me、乙酰基、三氟甲基、甲基、甲氧基、三氟甲氧基、甲硫基、苯基、三甲基硅基、醛基、苄氧基、羟甲基、氰基、硝基。
PG表示氨基保护基团，选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种。
Ar表示取代或未取代的苯基、吲哚基；其中所述“取代或未取代苯基”中的取代基个数为一个或多个，各个取代基彼此独立选自氟、氯、溴、碘、-CO2Me、乙酰基、三氟甲基、甲基、甲氧基、三氟甲氧基、甲硫基、苯基、三甲基硅基、醛基、苄氧基、羟甲基、氰基、硝基。
作为本发明的另一目的，提供一种2,3-二取代吲哚啉类化合物的制备方法，包括如下步骤：
向Schlenk封管反应器中，依次加入式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物和式II所示的硼酸类化合物，铜催化剂，将反应器用惰性气氛保护，随后在惰性气氛条件下加入有机溶剂，置于室温～50℃条件下搅拌反应0.5～120h，经TLC监测原料消耗完全，再经后处理得到式III所示的2,3-二取代吲哚啉类化合物。反应式如下(反应式一)：
在上述反应式中，R1、R2分别表示所连接苯环上的一个或多个取代基，取代基的最大数量取决于所连接的苯环具有的可被取代的碳原子的数目，例如可以具有1,2,3,4或5个取代基。各个取代基彼此独立地选自氢、卤素、C1-20烷基、C1-20卤代烷基、C1-20烷氧基、C1-20卤代氧烷基、C1-20烷硫基、C1-20酰基、C1-20烷氧基羰基、C6-20芳基、三(C1-20烷基)硅基、-CHO、C6-20芳基-C1-20烷氧基、HO-C1-20烷基-、氰基、硝基。
PG表示氨基保护基团，氨基保护基选自本领域公知的种类，例如可以选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种。
Ar表示取代或未取代的C6-20芳基、取代或未取代的C2-20杂芳基；其中所述“取代或未取代的C6-20芳基和取代或未取代的C2-20杂芳基”中的取代基个数为一个或多个，取代基的最大数量取决于所述芳基或杂芳基的可被取代的碳原子数目，例如具有1,2,3,4,5个取代基，并且各个取代基彼此独立选自卤素、C1-20烷基、C1-20卤代烷基、C1-20烷氧基、C1-20卤代卤代烷基、C1-20烷硫基、C1-20酰基、C1-20烷氧基羰基、C6-20芳基、三(C1-20烷基)硅基、-CHO、C6-20芳基-C1-20烷氧基、HO-C1-20烷基-、氰基、硝基。
优选地，R1、R2分别表示所连接苯环上的一个或多个取代基，各个取代基彼此独立地选自氢、卤素、C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代烷氧基、C1-6烷硫基、C1-6酰基、C1-6烷氧基羰基、C6-14芳基、三(C1-6烷基)硅基、-CHO、C6-14芳基-C1-6烷氧基、HO-C1-6烷基-、氰基、硝基。
PG表示氨基保护基团，选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种。
Ar表示取代或未取代的C6-14芳基、取代或未取代的C2-14杂芳基；其中所述“取代或未取代的C6-14芳基和取代或未取代的C2-14杂芳基”中的取代基个数为一个或多个，各个取代基彼此独立选自卤素、C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代卤代烷基、C1-6烷硫基、C1-6酰基、C1-6烷氧基羰基、C6-14芳基、三(C1-6烷基)硅基、-CHO、C6-14芳基-C1-6烷氧基、HO-C1-6烷基-、氰基、硝基。
进一步优选地，R1、R2分别表示所连接苯环上的一个或多个取代基，各个取代基彼此独立地选自氢、氟、氯、溴、碘、-CO2Me、乙酰基、三氟甲基、甲基、甲氧基、三氟甲氧基、甲硫基、苯基、三甲基硅基、醛基、苄氧基、羟甲基、氰基、硝基。
PG表示氨基保护基团，选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种。
Ar表示取代或未取代的苯基、吲哚基；其中所述“取代或未取代苯基”中的取代基个数为一个或多个，各个取代基彼此独立选自氟、氯、溴、碘、-CO2Me、乙酰基、三氟甲基、甲基、甲氧基、三氟甲氧基、甲硫基、苯基、三甲基硅基、醛基、苄氧基、羟甲基、氰基、硝基。
根据本发明前述的制备方法，其中，所述的铜催化剂选自CuOTf，CuOAc中的任意一种；优选地，所述铜催化剂选自CuOAc。
根据本发明前述的制备方法，其中，所述的有机溶剂选自无水甲醇、无水乙醇中的任意一种；优选地，所述有机溶剂选自无水甲醇。
根据本发明前述的制备方法，其中，反应温度优选为50℃；反应时间优选为0.5～1h。
根据本发明前述的制备方法，其中，所述的惰性气氛为氩气气氛或氮气气氛，优选为氩气气氛。
根据本发明前述的制备方法，其中，式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物、式II所示的硼酸类化合物和铜催化剂投料摩尔比为1:(1.5～3):(0.05～0.2)；优选地，式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物、式II所示的硼酸类化合物和铜催化剂投料摩尔比为1:2～3:0.1。
根据本发明前述的制备方法，其中，所述的后处理操作如下：经TLC监测原料消耗反应完全，冷却至室温，加入二氯甲烷淬灭，随后将混合溶液真空浓缩，随后将得到的残余物经硅胶柱层析分离(洗脱溶剂为石油醚/乙酸乙酯)得到式III所示的2,3-二取代吲哚啉类化合物。
根据本发明前述的制备方法，其反应机理如下(方案一)：
作为本发明的另一目的，本发明提供了所述式III所示的2,3-二取代吲哚啉类化合物的应用方法。
(1)式III所示的2,3-二取代吲哚啉类化合物在制备式IV所示的2-二苯甲基-1H-吲哚类化合物中的用途(反应式二)：
其中，R1,R2,PG,Ar具有与本文前述相同的定义。
具体应用方法如下：向配备磁粒搅拌子的干燥反应器中，加入钠和萘，抽真空并立即充入氮气保护，将无水THF加入反应瓶中，对混合物进行超声处理30分钟，得到萘钠。随后在-78℃条件下加入化合物III的无水THF溶液。将反应混合物在该温度下搅拌20分钟后，用饱和氯化铵和饱和碳酸氢钠溶液淬灭，乙酸乙酯萃取，合并有机相并用无水硫酸镁干燥，过滤，滤液经减压浓缩得到粗产物，再经硅胶柱层析分离得到式IV所示的2-二苯甲基-1H-吲哚类化合物。
(2)式III所示的2,3-二取代吲哚啉类化合物在制备式V所示的吲哚基甲醇类化合物的用途(反应式三)：
其中，R1,R2,PG,Ar具有与本文前述相同的定义。
具体应用方法如下：将化合物III和苯甲醚溶于无水二氯甲烷中，分批次加入AlCl3，室温下搅拌2小时，将得到的深红色溶液用二氯甲烷稀释，随后在搅拌下滴加10％的NaOH溶液直至固体消失。水相用二氯甲烷萃取4次，合并有机相并用无水硫酸镁干燥，过滤并真空浓缩，将粗产物经硅胶柱层析分离得到式V的目标产物。
本发明的合成方法取得了如下有益效果：
1)本发明首次报道了式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物和芳基硼酸为原料，在廉价的铜催化剂和温和的反应条件下，实现高区域选择性芳基化环化的合成策略，克服了现有技术在该类反应中需要使用贵金属催化剂和/或特定反应底物的不足，丰富了现有技术制备2,3-二取代吲哚啉类化合物的合成途径。
2)由本发明的制备方法(详见具体实施例)可以看出，该方法具有非常广泛的基团底物适应范围和基团耐受性，普适性高，以中等到优异(高达98％)的产率制备获得一系列各种不同的2,3-二取代吲哚啉类化合物。
3)本发明所述的2,3-二取代吲哚啉类化合物可经进一步还原制备式IV所示的2-二苯甲基-1H-吲哚类化合物、和/或在AlCl3/苯甲醚条件下转化为式V所示吲哚基甲醇类化合物。
具体实施方式
以下结合具体实施例，对本发明作进一步详述。在下文中，如无特殊说明，所述方法均为本领域常规方法，所用试剂均可以通过常规的商业途径购得。各反应底物均可以根据现有技术已知的制备方法和现有的合成条件制备获得。
反应条件优化实施例
以式I-1的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物及式II-1的苯硼酸为模板，探讨了不同合成条件下对目标产物III-1产率的影响，结果如下：
反应式四
实施例1
在室温下向Schlenk封管反应器中，依次加入式I-1所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物(0.1mmol)和式II所示的苯硼酸(0.2mmol)，CuOTf(0.01mmol)，将反应器用氩气保护，用注射器加入无水甲醇(0.25mL)，然后将反应器置于50℃(油浴)条件下搅拌反应19h，经TLC监测反应完全，随后向反应液中加入0.01mol的邻苯二甲酸二乙酯作为内标，将反应液浓缩，取样进行核磁检测计算产率III-1为50％，原料水解产物﹤1％。
实施例2
替换催化剂为CuI，反应时间为48h至原料消耗完全，其余条件同实施例1，III-1核磁产率为20％，原料水解产物产率28％。
实施例3
替换催化剂为Cu(MeCN)4PF6，反应时间为44h至原料消耗完全，其余条件同实施例1，III-1核磁产率为14％，原料水解产物产率﹤1％。
实施例4
替换催化剂为CuOAc，反应时间为0.5h即原料消耗完全，其余条件同实施例1，III-1核磁产率为90％，原料水解产物产率﹤1％。
实施例5
替换催化剂为Cu(OAc)2，反应时间为98h至原料消耗完全，其余条件同实施例1，III-1核磁产率为19％，原料水解产物产率12％。
实施例6
替换反应温度为室温，反应时间为120h至原料消耗完全，其余条件同实施例4，III-1核磁产率为28％，原料水解产物产率20％。
实施例7
式II-1的苯硼酸投料量为1.5当量(0.15mmol)，其余条件同实施例4，III-1核磁产率为44％，原料水解产物产率7％。其中式I-1的原料仍然剩余22％未反应。
实施例8
替换溶剂为无水乙醇，反应时间为15小至原料消耗完全，其余条件同实施例4，III-1核磁产率为17％，原料水解产物产率42％。
底物拓展实施例
在确定获得最佳条件的基础上(实施例4)，以实施例4的反应条件为模板，计算分离产率，探讨了不同类型底物对于反应体系的适应性，制备获得了一系列的2,3-二取代吲哚啉类化合物(反应式一)：
实施例9化合物III-1
的制备
向Schlenk封管反应器中，依次加入式I-1所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物(0.1mmol)和苯硼酸(0.2mmol)，CuOAc(0.01mmol)，将反应器用氩气保护，用注射器加入无水甲醇(0.5mL)，然后将反应器置于50℃(油浴)条件下搅拌反应0.5h，经TLC监测反应完全，冷却至室温，加入二氯甲烷淬灭，随后将混合溶液真空浓缩，随后将得到的残余物经硅胶柱层析分离(洗脱溶剂为石油醚/乙酸乙酯＝5:1,v/v)得到式III-1所示的2,3-二取代吲哚啉类化合物。分离产率89％。1H NMR(400MHz,CDCl3)δ7.67(d,J＝7.6Hz,1H),7.57(d,J＝8.0Hz,1H),7.47(d,J＝8.4Hz,2H),7.42–7.30(m,4H),7.28–7.19(m,8H),7.16(d,J＝8.0Hz,2H),4.94(d,J＝8.8Hz,1H),3.46(d,J＝9.2Hz,1H),2.36(s,3H),1.12(s,9H)；13C NMR(100MHz,CDCl3)δ145.2,142.6,141.5,140.0,139.0,134.4,134.1,133.7,129.8,129.7,129.5,128.7,128.4,127.9,127.7,127.5,127.1,126.5,119.5,59.8,56.2,23.8,21.5；IR(neat):2923,1647(s),1540,1463,1372,1318,1173,1126,704,661,556；HRESIMS Calcd for[C32H32N2NaO4S2]+(M+Na+)595.1696,found 595.1698。
实施例10-37
按实施例9的操作及工艺参数条件，替换式II所示的硼酸类化合物，考察本发明最佳催化反应条件下对于不同取代基的芳基(杂芳基)硼酸类底物的普适性，结果如下(表1)：
表1：
上表中，b表示该实施例中反应时间为1h；c表示该实施例中，式II的硼酸类化合物的投料量为3摩尔当量。
实施例38-54
按实施例9的操作及工艺参数条件，替换式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物，考察本发明最佳催化反应条件下对于不同取代基的普适性，结果如下(表2)。
表2：
化合物III-2～III-45结构表征数据如下：
III-2:Pale yellow soild(mp 173–174℃).1H NMR(400MHz,CDCl3)δ7.65–7.63(m,1H),7.51(d,J＝8.0Hz,1H),7.45(d,J＝8.4Hz,2H),7.40–7.35(m,1H),7.28–7.23(m,6H),7.18–7.15(m,4H),7.03–7.08(m,2H),4.97(d,J＝8.8Hz,1H),3.68(d,J＝8.8Hz,1H),2.37(s,3H),1.18(s,9H)；13C NMR(150MHz,CDCl3)δ162.8(d,J＝246.0Hz),145.2,141.6,141.5,140.0,135.0(d,J＝3.0Hz),134.4,133.7,131.7(d,J＝7.5Hz),129.9,129.8,129.6,128.0,127.8,127.7,126.9,126.6,119.5,115.7(d,J＝21.0Hz),59.9,56.1,23.9,21.6；IR(neat):2922,1632,1465,1370,1309,1174,1127,1090,749,665,561；HRESIMSCalcd for[C32H31FN2NaO4S2]+(M+Na+)613.1601,found 613.1617。
III-3.Pale yellow soild(mp 105–106℃).1H NMR(400MHz,CDCl3)δ7.65(d,J＝7.2Hz,1H),7.50(d,J＝8.0Hz,1H),7.44(d,J＝8.0Hz,2H),7.40–7.31(m,3H),7.26–7.13(m,10H),4.96(d,J＝9.2Hz,1H),3.63(d,J＝9.2Hz,1H),2.37(s,3H),1.18(s,9H)；13C NMR(150MHz,CDCl3)δ145.3,141.5,141.4,139.7,137.5,134.7,134.6,134.4,133.8,131.3,129.9,129.8,129.6,128.9,128.1,127.9,127.8,127.0,126.7,119.5,59.9,56.1,23.9,21.6；IR(neat):2921,1595,1463,1371,1307,1173,1174,1127,1090,749,665,561；HRESIMS Calcd for[C32H31ClN2NaO4S2]+(M+Na+)629.1306,found 629.1310。
III-4.Pale yellow oil.1H NMR(400MHz,CDCl3)δ7.66(d,J＝7.6Hz,1H),7.51–7.48(m,3H),7.44(d,J＝8.4 Hz,2H),7.35–7.39(m,1H),7.26–7.11(m,10H),4.96(d,J＝9.0 Hz,1H),3.62(d,J＝9.0 Hz,1H),2.36(s,3H),1.17(s,9H)；13C NMR(100 MHz,CDCl3)δ145.3,141.4,141.3,139.6,137.9,134.6,134.3,133.7,131.9,131.5,129.9,129.8,129.6,128.0,127.9,127.8,127.0,126.7,122.8,119.5,59.9,56.1,23.8,21.6；IR(neat):2921,1595,1463,1371,1308,1173,1127,1088,694,665,557；HRESIMS Calcd for[C32H31BrN2NaO4S2]+(M+Na+)673.0801,found 673.0808。
III-5.Pale pink oil.1H NMR(400 MHz,CDCl3)δ7.70–7.66(m,3H),7.50(d,J＝8.0 Hz,1H),7.43(d,J＝8.0 Hz,2H),7.39–7.34(m,1H),7.26–7.13(m,8H),7.03(d,J＝8.4Hz,2H),4.95(d,J＝9.2 Hz,1H),3.59(d,J＝8.8 Hz,1H),2.36(s,3H),1.16(s,9H)；13C NMR(100 MHz,CDCl3)δ145.3,141.5,141.4,139.6,138.6,137.8,134.6,134.3,133.8,131.6,129.9,129.8,129.6,128.0,127.9,127.7,127.1,126.6,119.4,94.5,59.9,56.1,23.8,21.6；IR(neat):2926,1648,1463,1371,1318,1173,1172,1126,1090,1009,849,755,663,586；HRESIMS Calcd for[C32H31IN2NaO4S2]+(M+Na+)721.0662,found 721.0670。
III-6.Pale yellow soild(mp 109–110℃).1H NMR(400 MHz,CDCl3)δ8.04(d,J＝8.4 Hz,2H),7.65(d,J＝7.6 Hz,1H),7.56–7.34(m,7H),7.26–7.13(m,7H),4.94(d,J＝9.2Hz,1H),3.92(s,3H),3.55(d,J＝9.2 Hz,1H),2.37(s,3H),1.15(s,9H)；13C NMR(100 MHz,CDCl3)δ166.6,145.3,143.7,141.6,141.5,139.5,135.1,134.2,133.8,130.1,129.9(4),129.9(2),129.8(9),129.8(4),129.7,128.0,127.9,127.8,127.1,126.7,119.4,59.9,56.1,52.2,23.9,21.6；IR(neat):2923,1723,1636,1278,1173,1127,1019,701,665,557；HRESIMS Calcd for[C34H34N2NaO6S2]+(M+Na+)653.1750,found 653.1773。
III-7.Pale yellow soild(mp 105–106℃).1H NMR(400 MHz,CDCl3)δ7.95(d,J＝8.4 Hz,2H),7.63(d,J＝7.6 Hz,1H),7.56–7.32(m,7H),7.26–7.15(m,7H),4.96(d,J＝9.2Hz,1H),3.64(d,J＝9.2 Hz,1H),2.60(s,3H),2.37(s,3H),1.16(s,9H)；13C NMR(100 MHz,CDCl3)δ197.5,145.3,143.8,141.5,141.4,139.5,136.8,135.2,134.2,133.8,130.2,129.9,129.8,129.7,128.6,128.1,127.9,127.8,127.0,126.7,119.5,59.9,56.0,26.7,23.9,21.6；IR(neat):2919,1683,1645,1368,1307,1173,1126,1089,665,574；HRESIMSCalcdfor[C34H34N2NaO5S2]+(M+Na+)637.1801,found 637.1807。
III-8.Pale yellow soild(mp 102–103℃).1H NMR(400 MHz,CDCl3)δ7.69–7.60(m,3H),7.53(d,J＝8.0 Hz,1H),7.47–7.37(m,5H),7.28–7.15(m,8H),4.92(d,J＝9.2 Hz,1H),3.49(d,J＝9.2 Hz,1H),2.37(s,3H),1.13(s,9H)；13C NMR(150 MHz,CDCl3)δ145.4,142.7,141.5,141.1,139.4,135.3,134.1,133.7,130.7(q,J＝33.0 Hz),130.2,129.9,129.8,129.8,128.0,127.9,127.1,126.8,125.8(q,J＝3.0 Hz),124.8(q,J＝270.0 Hz),119.5,59.9,56.1,23.8,21.6；IR(neat):2926,1597,1463,1370,1325,1171,1126,1067,846,664,576；HRESIMS Calcd for[C33H31F3N2NaO4S2]+(M+Na+)663.1570,found 663.1591。
III-9.Pale yellow soild(mp 147–148℃).1H NMR(400 MHz,CDCl3)δ7.68(d,J＝7.6 Hz,1H),7.53(d,J＝7.6 Hz,1H),7.45(d,J＝8.4 Hz,2H),7.39–7.35(m,1H),7.25–7.18(m,6H),7.17–7.13(m,6H),4.96(d,J＝8.8 Hz,1H),3.58(d,J＝8.8 Hz,1H),2.36(s,3H),2.35(s,3H),1.15(s,9H)；13C NMR(100 MHz,CDCl3)δ145.1,142.7,141.6,140.3,138.3,136.2,134.7,133.9,133.8,129.9,129.8,129.7,129.5,129.3,128.1,127.7,127.5,127.2,126.5,119.5,59.9,56.4,23.9,21.6,21.3；IR(neat):2922,1634,1463,1371,1318,1173,1127,1089,1017,664,561；HRESIMS Calcd for[C33H34N2NaO4S2]+(M+Na+)609.1852,found 609.1843。
III-10.Pale yellow soild(mp 137–138℃).1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.2 Hz,1H),7.49(d,J＝8.0 Hz,1H),7.44(d,J＝8.0 Hz,2H),7.39–7.33(m,1H),7.25–7.12(m,10H),6.87(d,J＝8.8 Hz,2H),5.00(d,J＝8.8 Hz,1H),3.81(s,3H),3.73(d,J＝8.4 Hz,1H),2.36(s,3H),1.19(s,9H)；13C NMR(100Hz,CDCl3)δ159.8,145.1,142.5,141.6,140.4,134.8,134.0,133.4,131.5,131.2,130.0,129.8,129.4,128.1,127.7,127.5,127.1,126.5,119.4,114.1,59.9,56.4,55.3,23.9,21.6；IR(neat):2922,1606,1492,1367,1306,1249,1126,1032,695,562；HRESIMS Calcd for[C33H34N2NaO5S2]+(M+Na+)625.1801,found 625.1798。
III-11.Pale yellow oil.1H NMR(400 MHz,CDCl3)δ7.66(d,J＝7.6 Hz,1H),7.53(d,J＝8.0 Hz,1H),7.45(d,J＝8.4 Hz,2H),7.40–7.36(m,1H),7.32(d,J＝8.8 Hz,2H),7.26–7.14(m,10H),4.95(d,J＝9.2Hz,1H),3.53(d,J＝9.2 Hz,1H),2.36(s,3H),1.15(s,9H)；13C NMR(213 MHz,CDCl3)δ149.2,145.3,141.5,141.2,139.7,137.6,134.8,134.1,133.7,133.4,131.4,129.9,129.8,129.7,128.3(q,J＝25.6 Hz),128.0,127.9,127.8,121.1,120.3(q,J＝213.0 Hz),119.5,59.8,56.1,23.8,21.6；IR(neat):2925,1698,1597,1506,1463,1372,1257,1170,1125,1090,706；HRESIMS Calcd for[C33H31F3N2NaO5S2]+(M+Na+)679.1519,found 679.1523。
III-12.Pale pink oil.1H NMR(400 MHz,CDCl3)δ7.68(d,J＝7.6 Hz,1H),7.51(d,J＝8.0 Hz,1H),7.44(d,J＝8.4 Hz,2H),7.39–7.35(m,1H),7.24–7.14(m,12H),4.98(d,J＝8.8 Hz,1H),3.62(d,J＝8.8Hz,1H),2.48(s,3H),2.37(s,3H),1.17(s,9H)；13C NMR(214 MHz,CDCl3)δ145.2,142.2,141.5,140.0,139.3,135.6,134.6,134.0,133.8,130.2,130.0,129.8,129.5,128.0,127.8,127.6,127.1,126.6,126.3,119.4,59.9,56.3,23.9,21.6,15.4；IR(neat):2923,1646,1464,1307,1172,1126,1090,1033,762,664,560；HRESIMS Calcd for[C33H34N2NaO4S3]+(M+Na+)641.1573,found 641.1578。
III-13.Colorless oil.1H NMR(400 MHz,CDCl3)δ7.71(d,J＝7.6 Hz,1H),7.57(m,5H),7.50–7.32(m,9H),7.30–7.26(m,4H),7.24–7.14(m,3H),5.01(d,J＝9.2 Hz,1H),3.49(d,J＝9.2 Hz,1H),2.37(s,3H),1.13(s,9H)；13C NMR(100 MHz,CDCl3)δ145.3,142.3,141.6,141.3,140.5,140.1,138.1,134.5,134.2,133.9,130.2,130.0,129.9,129.6,128.8,128.0,127.8,127.6,127.5,127.4,127.3,127.1,126.6,119.5,59.9,56.5,23.8,21.6；IR(neat):2920,1635,1463,1370,1318,1126,1089,763,696,558；HRESIMS Calcdfor[C38H36N2NaO4S2]+(M+Na+)671.2009,found 671.2030。
III-14.Pale yellow soild(mp 158–159℃).1H NMR(400 MHz,CDCl3)δ7.73(d,J＝7.6 Hz,1H),7.58(d,J＝8.0 Hz,1H),7.51–7.44(m,5H),7.28–7.13(m,10H),4.90(d,J＝9.2 Hz,1H),3.27(d,J＝9.2 Hz,1H),2.35(s,3H),1.08(s,9H),0.26(s,9H)；13C NMR(100MHz,CDCl3)δ145.2,142.6,141.6,140.6,140.1,139.5,134.4,133.9,133.8,133.7,129.8,129.7,129.5,128.7,127.9,127.7,127.5,127.4,126.6,119.4,59.8,56.5,23.8,21.6,-1.2；IR(neat):2955,1698,1597,1463,1372,1320,1249,1173,1127,1090,848,759,664,574；HRESIMS Calcd for[C35H40N2NaO4S2Si]+(M+Na+)667.2091,found 667.2089。
III-15.Pale yellow oil.1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.6 Hz,1H),7.56(d,J＝8.0 Hz,1H),7.46(d,J＝8.4 Hz,2H),7.42–7.30(m,3H),7.24–7.14(m,7H),7.09–7.03(m,2H),6.99–6.97(m,1H),4.93(d,J＝9.2 Hz,1H),3.42(d,J＝9.2 Hz,1H),2.37(s,3H),1.16(s,9H)；13C NMR(100 MHz,CDCl3)δ162.6(d,J＝246.0 Hz),145.3,141.5,141.3(d,J＝2.0 Hz),141.0(d,J＝7.0 Hz),139.5,134.8,130.4(d,J＝9.0 Hz),134.2,133.7,129.9,129.8,129.7,128.0,127.9,127.8,127.1,126.7,125.5(d,J＝3.0 Hz),119.5,117.1(d,J＝22.0 Hz),115.4(d,J＝21.0 Hz),59.9,56.1,23.8,21.6；IR(neat):2924,1610,1582,1463,1370,1308,1172,1127,706,662,559；HRESIMS Calcd for[C32H31FN2NaO4S2]+(M+Na+)613.1601,found 613.1607。
III-16.Pale yellow soild(mp 163–164℃).1H NMR(400 MHz,CDCl3)δ7.68(d,J＝7.6 Hz,1H),7.58(d,J＝8.0 Hz,1H),7.46(d,J＝8.0 Hz,2H),7.41–7.37(m,1H),7.34–7.30(m,2H),7.28–7.16(m,10H),4.89(d,J＝9.2 Hz,1H),3.30(d,J＝9.2 Hz,1H),2.37(s,3H),1.13(s,9H)；13C NMR(100 MHz,CDCl3)δ145.4,141.5,141.0,140.8,139.5,134.9,134.6,134.1,133.7,130.2,129.9,129.7(3),129.7(1),129.6(8),128.6,127.9,127.9,127.8,127.2,126.7,119.5,59.8,56.2,23.8,21.6；IR(neat):2922,1595,1463,1372,1318,1173,1126,1089,704,664,557；HRESIMS Calcd for[C32H31ClN2NaO4S2]+(M+Na+)629.1306,found 629.1304。
III-17.Pale yellow oil.1H NMR(400 MHz,CDCl3)δ7.68(d,J＝7.6 Hz,1H),7.58(d,J＝8.0 Hz,1H),7.49–7.34(m,5H),7.30–7.17(m,12H),4.89(d,J＝9.2 Hz,1H),3.27(d,J＝9.2 Hz,1H),2.37(s,3H),1.12(s,9H)；13C NMR(100 MHz,CDCl3)δ145.4,141.6,141.1,140.9,139.5,135.0,134.1,133.7,132.5,131.5,130.5,129.9,129.7,128.4,128.0,127.9,127.8,127.2,126.7,122.9,119.5,59.8,56.2,23.8,21.6；IR(neat):2923,1594,1463,1372,1318,1174,1127,1090,704,664,557；HRESIMS Calcd for[C32H31BrN2NaO4S2]+(M+Na+)673.0801,found 673.0799。
III-18.Colorless oil.1H NMR(400 MHz,CDCl3)δ10.02(s,1H),7.91–7.85(m,1H),7.77(s,1H),7.61–7.47(m,6H),7.43–7.32(m,2H),7.27–7.17(m,7H),4.92(d,J＝8.8Hz,1H),3.55(d,J＝8.8 Hz,1H),2.37(s,3H),1.10(s,9H)；13C NMR(213 MHz,CDCl3)δ192.0,145.3,141.5,141.0,139.9,136.6,135.6,135.3,134.0,133.6,131.2,129.9,129.8,129.7,129.6,129.4,128.0,127.9,127.9,126.8,126.7,119.6,59.7,55.9,23.8,21.6；IR(neat):2925,1748,1668,1558,1385,1033,967,833,660；HRESIMS Calcd for[C33H32N2NaO5S2]+(M+Na+)623.1645,found 623.1655。
III-19.White soild(mp 88–89℃).1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.6 Hz,1H),7.58(d,J＝8.0 Hz,1H),7.46(d,J＝8.0 Hz,2H),7.40–7.36(m,1H),7.25–7.21(m,6H),7.17–7.13(m,4H),7.05(d,J＝8.8 Hz,2H),4.92(d,J＝8.8 Hz,1H),3.39(d,J＝8.8Hz,1H),2.36(s,3H),2.34(s,3H),1.09(s,9H)；13CNMR(100 MHz,CDCl3)δ145.2,142.6,141.7,140.1,139.0,138.4,134.5,134.0,133.9,130.1,129.8,129.8,129.5,129.2,128.7,128.0,127.8,127.5,127.2,126.8,126.5,119.5,59.8,56.3,23.8,21.6,21.4；IR(neat):2923,1598,1463,1376,1307,1172,1127,1090,662,558；HRESIMS Calcd for[C33H34N2NaO4S2]+(M+Na+)609.1852,found 609.1848。
III-20.Pale pink oil.1H NMR(400 MHz,CDCl3)δ7.71(d,J＝7.6 Hz,1H),7.61(d,J＝8.0 Hz,1H),7.46(d,J＝8.0 Hz,2H),7.40–7.37(m,1H),7.27–7.23(m,7H),7.16(d,J＝8.0 Hz,2H),6.91–6.83(m,2H),6.71(s,1H),4.91(d,J＝9.2 Hz,1H),3.76(s,3H),3.24(d,J＝9.0 Hz,1H),2.36(s,3H),1.09(s,9H)；13CNMR(125 MHz,CDCl3)δ159.7,145.3,142.2,141.7,140.3,139.9,134.3,134.1,133.8,129.9,129.8,129.7,129.5,127.9,127.8,127.6,127.3,126.6,122.0,119.5,115.7,113.3,59.8,56.3,55.2,23.7,21.6；IR(neat):2926,1637,1463,1367,1276,1171,1126,750,664,474；HRESIMS Calcd for[C33H34N2NaO5S2]+(M+Na+)625.1801,found 625.1797。
III-21.White soild(mp 179–180℃).1H NMR(400 MHz,CDCl3)δ7.70(d,J＝7.6Hz,1H),7.59(d,J＝8.0 Hz,1H),7.45(d,J＝8.4 Hz,2H),7.41–7.19(m,13H),7.15(d,J＝8.0 Hz,2H),6.95–6.90(m,2H),6.82–6.76(m,1H),5.05–4.97(m,2H),4.93(d,J＝9.2 Hz,1H),3.30(d,J＝9.2 Hz,1H),2.35(s,3H),1.09(s,9H)；13C NMR(100 MHz,CDCl3)δ158.9,145.2,142.2,141.6,140.3,139.8,136.7,134.4,134.1,133.7,129.9,129.8,129.7,129.5,128.5,128.0,127.9,127.8,127.6,127.3,126.6,122.4,119.5,116.5,114.3,70.0,59.8,56.3,23.8,21.6；IR(neat):2982,1637,1597,1463,1370,1318,1172,1126,1089,738,697,663；HRESIMS Calcdfor[C39H38N2NaO5S2]+(M+Na+)701.2114,found 701.2116。
III-22.Pale yellow oil.1H NMR(500 MHz,CDCl3)δ7.61(s,1H),7.58(d,J＝8.0Hz,1H),7.51(d,J＝8.5 Hz,2H),7.46(d,J＝7.5 Hz,1H),7.41–7.37(m,1H),7.28(d,J＝7.0 Hz,2H),7.23–7.18(m,4H),7.16–7.14(m,4H),6.85–6.83(m,1H),5.01(d,J＝7.5 Hz,1H),4.77(d,J＝5.5 Hz,2H),4.15(d,J＝7.5 Hz,1H),3.29(s,1H),2.35(s,3H),1.16(s,9H)；13C NMR(214 MHz,CDCl3)δ145.0,142.0,141.8,139.0,134.3,133.8,129.9,129.8,129.6,128.7,128.4,128.3,127.9,127.7,127.6,127.1,126.3,126.2,119.9,64.7,59.9,55.7,24.0,21.6；IR(neat):2965,1647,1558,1276,1028,834,751,697,629；HRESIMSCalcd for[C33H34N2NaO5S2]+(M+Na+)625.1801,found 625.1793。
III-23.Pale yellow soild(mp 150–151℃).1H NMR(500 MHz,CDCl3)δ10.34(s,1H),7.69(dd,J＝6.4,2.4 Hz,1H),7.59–7.56(m,3H),7.48(d,J＝8.0 Hz,2H),7.41–7.38(m,1H),7.26–7.17(m,9H),4.90(d,J＝9.2 Hz,1H),3.51(d,J＝9.2 Hz,1H),2.36(s,3H),1.13(s,9H)；13C NMR(125 MHz,CDCl3)δ186.8,164.3(d,J＝258.8 Hz),145.4,141.5,140.1,139.3,137.8(d,J＝8.8 Hz),135.7,135.6,133.7(d,J＝26.3 Hz),130.3,129.9,129.8,129.7,128.0,128.0,126.7,126.7,124.2(d,J＝8.8 Hz),119.6,117.3(d,J＝21.3Hz),59.7,55.8,23.8,21.6；IR(neat):2359,1959,1634,1464,1371,1313,1126,1090,953,699,665；HRESIMSCalcd for[C33H31FN2NaO5S2]+(M+Na+)641.1551,found 641.1560。
III-24.Pale yellow soild(mp 138–139℃).1H NMR(500 MHz,CDCl3)δ7.66(d,J＝7.5 Hz,1H),7.56(d,J＝8.0 Hz,1H),7.44(d,J＝8.0 Hz,2H),7.41–7.35(m,2H),7.28–7.21(m,6H),7.16(d,J＝8.0 Hz,2H),6.94(d,J＝8.0 Hz,1H),6.65(s,1H),4.96(d,J＝9.0Hz,1H),3.81(s,3H),3.47(d,J＝8.5 Hz,1H),2.36(s,3H),1.11(s,9H)；13C NMR(125 MHz,CDCl3)δ155.2,145.3,141.6,141.2,139.5,138.7,134.8,134.2,133.8,130.4,129.8,129.7,129.6,127.9,127.8,127.7,127.1,126.6,123.0,119.5,113.0,59.8,56.2,23.7,21.6；IR(neat):2931,1959,1645,1596,1463,1398,1370,1173,1091,1064,817,665；HRESIMS Calcd for[C33H33ClN2NaO5S2]+(M+Na+)659.1412,found 659.1420。
III-25.Pale yellow soild(mp 132–133℃).1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.2 Hz,1H),7.52(d,J＝8.0 Hz,1H),7.44(d,J＝8.0 Hz,2H),7.39–7.33(m,1H),7.25–7.09(m,9H),6.96(s,1H),6.79(d,J＝8.4 Hz,1H),4.98(d,J＝8.4 Hz,1H),3.82(s,3H),3.61(d,J＝8.4 Hz,1H),2.36(s,3H),2.18(s,3H),1.13(s,9H)；13C NMR(125 MHz,CDCl3)δ158.0,145.0,142.6,141.7,140.5,134.8,134.0,133.4,131.8,131.0,129.9,129.8,129.4,128.5,128.0,127.7,127.4,127.1,126.9,126.4,119.4,109.9,59.7,56.4,55.3,23.8,21.6,16.2；IR(neat):2928,1605,1503,1464,1369,1319,1248,1172,1128,1089,1032,814,695,664；HRESIMS Calcd for[C34H36N2NaO5S2]+(M+Na+)639.1958,found639.1956。
III-26.Pale yellow soild(mp 159–160℃).1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.6 Hz,1H),7.59(d,J＝8.0 Hz,1H),7.46(d,J＝8.4 Hz,2H),7.41–7.35(m,1H),7.25–7.15(m,8H),6.95(s,1H),6.83(s,2H),4.91(d,J＝8.6 Hz,1H),3.31(d,J＝8.6 Hz,1H),2.36(s,3H),2.30(s,6H),1.05(s,9H)；13C NMR(150MHz,CDCl3)δ145.2,142.6,141.8,140.2,138.9,138.3,134.5,133.9,133.8,130.1,129.8,129.7,129.5,127.9,127.8,127.5,127.2,127.1,126.5,119.5,59.6,56.3,23.6,21.6,21.3；IR(neat):2922,1598,1463,1370,1320,1172,1127,1090,705,664,574,558；HRESIMS Calcd for[C34H36N2NaO4S2]+(M+Na+)623.2009,found623.2011。
III-27.Pale yellow soild(mp 185–186℃).1H NMR(400 MHz,CDCl3)δ7.90–7.88(m,2H),7.82–7.77(m,2H),7.67(d,J＝7.6 Hz,1H),7.60(d,J＝8.0 Hz,1H),7.52–7.50(m,4H),7.42–7.35(m,1H),7.26–7.18(m,9H),4.97(d,J＝8.8 Hz,1H),3.47(d,J＝8.8 Hz,1H),2.37(s,3H),0.94(s,9H)；13C NMR(150MHz,CDCl3)δ145.3,142.4,141.7,140.0,136.4,134.5,134.3,133.8,133.2,133.1,130.0,129.9,129.6,129.3,128.6,128.4,128.0,127.9,127.7,127.2,126.9,126.6,126.5,126.4,119.5,59.7,56.6,23.6,21.6；IR(neat):2922,1597,1463,1369,1318,1173,1126,1089,818,664,558；HRESIMS Calcd for[C36H34N2NaO4S2]+(M+Na+)645.1852,found 645.1861。
III-28.Pale pink soild(mp 160–161℃).1H NMR(400 MHz,CDCl3)δ8.32(s,1H),7.70(d,J＝7.6 Hz,1H),7.59(d,J＝7.6 Hz,2H),7.49(d,J＝8.4 Hz,2H),7.39–7.34(m,1H),7.30–7.13(m,10H),6.92(dd,J＝8.4,1.4 Hz,1H),6.59–6.44(m,1H),4.95(d,J＝9.0Hz,1H),3.50(d,J＝9.0 Hz,1H),2.36(s,3H),1.01(s,9H)；13C NMR(213 MHz,CDCl3)δ145.2,141.6,135.7,134.9,133.8,132.9,130.6,130.0,129.8,129.4,128.0,127.8,127.6,127.3,127.2,126.5,125.0,123.4,122.6,119.5,111.5,102.9,59.8,56.8,23.6,21.6；IR(neat):2925,1683,1595,1490,1463,1360,1166,1025,813,763,665,579；HRESIMSCalcd for[C34H33N3NaO4S2]+(M+Na+)634.1805,found 634.1809。
III-29.Pale yellow soild(mp 162–163℃).1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.2 Hz,1H),7.58–7.49(m,3H),7.40–7.33(m,4H),7.25–7.18(m,8H),6.85–6.78(m,2H),4.94(d,J＝9.0 Hz,1H),3.82(s,3H),3.61(d,J＝9.0 Hz,1H),1.15(s,9H)；13C NMR(100MHz,CDCl3)δ163.8,142.5,141.7,140.0,139.0,134.6,134.2,130.2,129.8,129.7,129.5,128.7,128.4,128.0,127.7,127.5,127.2,126.5,119.6,114.4,59.9,56.2,55.6,23.8；IR(neat):2980,1593,1496,1367,1312,1167,1148,1023,735,699,558；HRESIMS Calcdfor[C32H32N2NaO5S2]+(M+Na+)611.1645,found 611.1650。
III-30.Pale yellow oil.1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.6 Hz,1H),7.59–7.50(m,5H),7.40–7.34(m,6H),7.28–7.22(m,7H),4.97(d,J＝8.8 Hz,1H),3.58(d,J＝8.8 Hz,1H),1.14(s,9H)；13C NMR(100 MHz,CDCl3)δ142.7,141.5,140.0,139.0,137.0,134.5,134.1,134.0,129.9,129.7,129.5,129.2,128.7,128.5,128.0,127.9,127.6,127.2,126.6,119.3,60.0,56.2,24.0；IR(neat):2980,1577,1489,1365,1305,1177,1033,1012,745,687,543；HRESIMS Calcd for[C31H30N2NaO4S2]+(M+Na+)581.1539,found581.1540。
III-31.Pale yellow soild(mp 152–153℃).1H NMR(400 MHz,CDCl3)δ7.66(d,J＝7.6 Hz,1H),7.52–7.33(m,9H),7.24–7.20(m,6H),7.09–7.06(m,2H),5.04(d,J＝8.4Hz,1H),4.26(d,J＝8.0 Hz,1H),1.24(s,9H)；13C NMR(100 MHz,CDCl3)δ142.7,141.1,139.6,138.8,135.9,135.1,134.4,132.3,129.9,129.8,129.7,129.6,129.4,128.7,127.9,127.7,127.1,126.8,119.7,59.9,56.0,24.0；IR(neat):2923,1573,1463,1373,1309,1173,1126,1087,742,613,559；HRESIMS Calcd for[C31H29BrN2NaO4S2]+(M+Na+)659.0644,found 659.0650。
III-32.Pale yellow soild(mp 108–109℃).1H NMR(400 MHz,CDCl3)δ7.64(d,J＝7.6 Hz,1H),7.43–7.29(m,12H),7.21–7.17(m,1H),5.18(d,J＝5.6 Hz,1H),5.11(d,J＝5.6 Hz,1H),2.40(s,3H),1.26(s,9H)；13C NMR(100 MHz,CDCl3)δ141.7,139.7,139.6,138.3,136.5,134.5,130.1,129.5,129.3,128.7,128.6,128.5,128.2,126.9,125.9,119.4,59.9,55.4,41.5,24.0；IR(neat):2928,1602,1464,1338,1305,1149,1126,966,699,650,541 HRESIMS Calcd for[C26H28N2NaO4S2]+(M+Na+)519.1383,found 519.1394。
III-33.Pale yellow soild(mp 183–184℃).1H NMR(400 MHz,CDCl3)δ7.64(dd,J＝18.8 Hz,7.6 Hz,2H),7.49(d,J＝8.0 Hz,2H),7.39–7.34(m,5H),7.24–7.16(m,6H),6.94–6.90(m,2H),4.91(d,J＝9.2Hz,1H),3.38(d,J＝8.8 Hz,1H),2.36(s,3H),1.11(s,9H)；13C NMR(100 MHz,CDCl3)δ161.9(d,J＝247.0),145.4,141.5,141.4,138.8,136.1,136.0,134.2,134.2,133.7,131.6(d,J＝8.0),129.8,129.7,129.6,128.8,128.5,127.9,127.1,126.6,119.5,114.7(d,J＝21.0),59.8,56.2,23.8,21.6；IR(neat):2983,1601,1506,1464,1369,1227,1174,1126,836,737,583；HRESIMS Calcd for[C32H31FN2NaO4S2]+(M+Na+)613.1601,found 613.1606。
III-34.Pale yellow soild(mp 180–181℃).1H NMR(400 MHz,CDCl3)δ7.64(dd,J＝18.8 Hz,7.6 Hz,2H),7.48(d,J＝8.0 Hz,2H),7.41–7.36(m,4H),7.25–7.11(m,9H),4.92(d,J＝8.8 Hz,1H),3.47(d,J＝8.8 Hz,1H),2.38(s,3H),1.11(s,9H)；13C NMR(100MHz,CDCl3)δ145.4,141.4,141.2,138.5,138.5,134.7,134.2,133.7,133.4,131.2,129.9,129.7,129.6,128.8,128.6,128.0,127.9,127.1,126.6,119.6,59.8,56.2,23.8,21.6；IR(neat):2981,1596,1463,1369,1311,1173,1126,1014,711,671,593,557；HRESIMS Calcdfor[C32H31ClN2NaO4S2]+(M+Na+)629.1306,found 629.1307。
III-35.Pale yellow oil.1H NMR(400 MHz,CDCl3)δ7.66(d,J＝7.2 Hz,1H),7.61(d,J＝8.0 Hz,1H),7.47(d,J＝8.0 Hz,2H),7.42–7.31(m,6H),7.27–7.16(m,5H),7.07(d,J＝8.4 Hz,2H),4.93(d,J＝8.8 Hz,1H),3.51(d,J＝8.8 Hz,1H),2.38(s,3H),1.12(s,9H)；13C NMR(125 MHz,CDCl3)δ145.4,141.4,141.1,138.9,138.5,134.8,134.3,133.7,131.5,130.9,129.9,129.7,129.6,128.8,128.6,127.9,127.1,126.6,121.8,119.6,59.8,56.2,23.8,21.6；IR(neat):2924,1639,1486,1463,1370,1319,1173,1126,1091,1011,703,670,557；HRESIMS Calcd for[C32H31BrN2NaO4S2]+(M+Na+)673.0801,found 673.0809。
III-36.Pale yellow oil.1H NMR(400 MHz,CDCl3)δ7.65(dd,J＝13.2,7.6 Hz,2H),7.55(d,J＝8.4 Hz,2H),7.47(d,J＝8.4 Hz,2H),7.39(d,J＝7.6 Hz,6H),7.28–7.19(m,5H),4.93(d,J＝9.2 Hz,1H),3.05(d,J＝9.2 Hz,1H),2.39(s,3H),1.07(s,9H)；13C NMR(213 MHz,CDCl3)δ145.8,145.1,141.2,140.4,137.8,136.1,133.6,133.5,131.6,130.4,130.1,129.8,129.6,129.1,128.9,127.7,127.2,126.9,119.4,118.8,110.9,59.9,56.1,23.7,21.6；IR(neat):2324,1636,1370,1316,1173,1126,1091,1018,706,672,661；HRESIMSCalcd for[C33H31N3NaO4S2]+(M+Na+)620.1648,found 620.1652。
III-37.Pale yellow soild(mp 159–160℃).1H NMR(400 MHz,CDCl3)δ7.64(dd,J＝17.2,7.6 Hz,2H),7.48(d,J＝8.0 Hz,2H),7.42–7.30(m,4H),7.25–7.19(m,3H),7.18–7.01(m,6H),4.91(d,J＝8.8 Hz,1H),3.39(d,J＝8.8 Hz,1H),2.36(s,3H),2.33(s,3H),1.10(s,9H)；13C NMR(100 MHz,CDCl3)δ145.1,142.6,141.6,139.2,137.4,137.2,134.4,133.8,133.6,129.7,129.6(9),129.6(8),129.5,128.7,128.5,128.3,127.9,127.1,126.5,119.5,59.8,56.3,23.8,21.6,21.3；IR(neat):2923,1597,1463,1369,1307,1173,1126,817,737,703,584；HRESIMS Calcd for[C33H34N2NaO4S2]+(M+Na+)609.1852,found609.1850。
III-38.Pale yellow soild(mp 151–152℃).1H NMR(400 MHz,CDCl3)δ7.67(d,J＝7.6 Hz,1H),7.60(d,J＝8.0 Hz,1H),7.49(d,J＝8.4 Hz,2H),7.42–7.33(m,4H),7.24–7.17(m,6H),7.06(d,J＝8.0 Hz,1H),6.95–6.80(m,2H),4.93(d,J＝9.0 Hz,1H),3.52(d,J＝9.0 Hz,1H),2.37(s,3H),1.12(s,9H)；13C NMR(100 MHz,CDCl3)δ162.3(d,J＝243.0Hz),145.5,142.1(d,J＝8.0 Hz),141.3,141.2,138.4,135.0,134.3,133.5,129.9,129.6,129.1(d,J＝9.0 Hz),128.9,128.6,128.0,127.1,126.7,125.6(d,J＝3.0 Hz),119.7,116.8(d,J＝22.0 Hz),114.4(d,J＝20.0 Hz),59.8,56.2,23.8,21.6；IR(neat):2923,1583,1463,1369,1308,1172,1126,1089,737,706,661,568；HRESIMS Calcd for[C32H31FN2NaO4S2]+(M+Na+)613.1601,found613.1608。
III-39.Pale orange soild(mp 109–110℃).1H NMR(400 MHz,CDCl3)δ7.66(d,J＝7.6 Hz,1H),7.50(d,J＝8.0 Hz,3H),7.44–7.30(m,6H),7.28–7.16(m,6H),7.13(d,J＝7.6 Hz,1H),4.95(d,J＝8.8 Hz,1H),3.76(d,J＝8.8 Hz,1H),2.40(s,3H),1.16(s,9H)；13CNMR(100 MHz,CDCl3)δ145.5,142.0,141.4,140.9,138.3,135.3,134.5,133.7,132.7,130.5,129.9,129.7,129.6,129.3,128.9,128.7,128.6,128.2,127.1,126.7,121.9,119.7,59.9,56.1,23.9,21.7；IR(neat):2982,1595,1471,1369,1308,1173,1126,1089,735,704,670,557；HRESIMS Calcd for[C32H31BrN2NaO4S2]+(M+Na+)673.0801,found673.0803。
III-40.Pale yellow soild(mp 158–159℃).1H NMR(400 MHz,CDCl3)δ7.66(d,J＝7.6 Hz,1H),7.56(d,J＝8.0 Hz,1H),7.50(d,J＝8.4 Hz,2H),7.43–7.35(m,4H),7.30(d,J＝2.0 Hz,1H),7.27–7.20(m,2H),7.17–7.12(m,3H),7.03(d,J＝8.0 Hz,2H),6.97(s,1H),4.93(d,J＝8.4 Hz,1H),3.61(d,J＝8.8 Hz,1H),2.37(s,3H),2.26(s,3H),1.14(s,9H)；13C NMR(100 MHz,CDCl3)δ145.0,142.6,141.6,139.9,139.1,137.1,134.5,134.0,133.9,130.4,129.7,129.6,129.4,128.6,128.3,128.0,127.6,127.1,127.0,126.4,119.4,59.8,56.2,23.8,21.6,21.4；IR(neat):2922,1599,1463,1370,1318,1172,1127,1089,705,661,557；HRESIMSCalcd for[C33H34N2NaO4S2]+(M+Na+)609.1852,found609.1848。
III-41.Pale yellow soild(mp 180–181℃).1H NMR(400 MHz,CDCl3)δ7.65(dd,J＝8.4,5.6 Hz,1H),7.49(d,J＝8.0 Hz,2H),7.40–7.30(m,4H),7.26–7.18(m,9H),6.94–6.89(m,1H),4.87(d,J＝9.2 Hz,1H),3.30(d,J＝9.2 Hz,1H),2.37(s,3H),1.10(s,9H)；13CNMR(100 MHz,CDCl3)δ163.1(d,J＝246.0 Hz),145.5,143.1,142.9(d,J＝9.0 Hz),139.9,138.9,134.0,133.5,130.1(d,J＝3.0 Hz),130.0,129.7,129.6,128.7,128.5(d,J＝9.0Hz),128.4,127.9,127.8,127.7,113.6(d,J＝23.0 Hz),107.3(d,J＝26.0 Hz),59.8,55.9,23.7,21.6；IR(neat):2983,1602,1489,1373,1314,1174,1126,1090,695,664,586,540；HRESIMS Calcd for[C32H31FN2NaO4S2]+(M+Na+)613.1601,found 613.1618。
III-42.Pale yellow oil.1H NMR(400MHz,CDCl3)δ7.61(dd,J＝5.2,3.2Hz,2H),7.49(d,J＝8.4Hz,2H),7.34–7.36(m,3H),7.27–7.22(m,5H),7.25–7.17(m,5H),4.88(d,J＝9.2Hz,1H),3.40(d,J＝9.2Hz,1H),2.37(s,3H),1.11(s,9H)；13C NMR(100MHz,CDCl3)δ145.6,143.1,142.7,139.8,138.9,135.2,133.6,133.5,132.9,130.0,129.8,129.7,128.8,128.5,128.1,128.0,127.8,127.7,126.8,119.9,59.9,55.9,23.8,21.6；IR(neat):2924,1597,1492,1368,1125,1033,752,664,591,473；HRESIMS Calcd for[C32H31ClN2NaO4S2]+(M+Na+)629.1306,found 629.1311。
III-43.Pale yellow oil.1H NMR(400MHz,CDCl3)δ7.47(d,J＝8.0Hz,3H),7.41(d,J＝8.0Hz,1H),7.36–7.32(m,3H),7.25–7.14(m,10H),4.89(d,J＝9.2Hz,1H),3.49(d,J＝9.0Hz,1H),2.36(s,3H),2.35(s,3H),1.13(s,9H)；13C NMR(100MHz,CDCl3)δ145.1,142.4,140.1,139.1,136.5,134.5,134.4,133.8,130.3,129.9,129.8,129.7,128.7,128.4,128.1,127.7,127.6,127.5,119.2,59.8,56.3,23.9,21.6,21.3；IR(neat):2923,1597,1453,1377,1313,1176,1128,1090,708,662,556；HRESIMS Calcd for[C33H34N2NaO4S2]+(M+Na+)609.1852,found 609.1843。
III-44.Pale yellow oil.1H NMR(400MHz,CDCl3)δ7.69(d,J＝2.0Hz,1H),7.52(d,J＝8.8Hz,1H),7.47(d,J＝8.4Hz,2H),7.38–7.33(m,4H),7.25–7.23(m,5H),7.21–7.16(m,4H),4.88(d,J＝9.2Hz,1H),3.42(d,J＝9.2Hz,1H),2.37(s,3H),1.11(s,9H)；13C NMR(100MHz,CDCl3)δ145.5,143.2,140.2,139.8,138.8,136.1,133.6,133.5,132.0,130.0,129.8,129.7,129.6,128.8,128.5,128.0,127.8,127.7,127.5,120.6,59.9,56.2,23.8,21.6；IR(neat):2102,1636,1463,1373,1313,1171,1126,661,579,468；HRESIMSCalcd for[C32H31ClN2NaO4S2]+(M+Na+)629.1306,found 629.1301。
III-45.Pale yellow oil.1H NMR(400MHz,CDCl3)δ7.54(d,J＝7.6Hz,1H),7.48(d,J＝8.0Hz,2H),7.43(s,1H),7.35–7.32(m,3H),7.27–7.15(m,9H),7.04(d,J＝7.6Hz,1H),4.88(d,J＝9.2Hz,1H),3.42(d,J＝9.2Hz,1H),2.42(s,3H),2.35(s,3H),1.11(s,9H)；13C NMR(100MHz,CDCl3)δ145.1,142.4,141.6,140.1,139.8,139.1,134.4,133.9,131.5,129.9,129.8,129.7,128.7,128.3,128.0,127.7,127.5,127.4,126.7,120.0,59.7,56.2,23.8,21.7,21.6；IR(neat):2926,1597,1492,1368,1307,1171,1125,1089,814,778,664,587；HRESIMS Calcd for[C33H34N2NaO4S2]+(M+Na+)609.1852,found 609.1855。
实施例55
本发明的2,3-二取代吲哚啉类化合物在制备式IV所示的2-二苯甲基-1H-吲哚类化合物中的应用示例，反应式如下：
具体操作如下：向配备磁粒搅拌子的干燥反应器中，加入钠(30mg,1.3mmol)、萘(167mg,1.3mmol)，抽真空并立即充入氮气保护，将无水THF(5mL)加入反应瓶中，对混合物进行超声处理30分钟，得到萘钠。随后在-78℃条件下加入化合物III-1(74.5mg,0.13mmol)的无水THF(2mL)溶液。将反应混合物在该温度下搅拌20分钟后，用饱和氯化铵和饱和碳酸氢钠溶液淬灭，乙酸乙酯萃取，合并有机相并用无水硫酸镁干燥，过滤，滤液经减压浓缩得到粗产物，再经硅胶柱层析分离(洗脱溶剂为石油醚/乙酸乙酯＝10:1,v/v)得到式IV-1所示的2-二苯甲基-1H-吲哚类化合物。产率76％。1H NMR(400MHz,CDCl3)δ7.77(s,1H),7.49(d,J＝7.6Hz,1H),7.35–7.16(m,11H),7.12–7.03(m,2H),6.08(s,1H),5.56(s,1H)；13C NMR(100MHz,CDCl3)δ142.1,140.8,136.2,129.0,128.6,126.9,121.5,120.2,119.7,110.6,102.8,51.0；IR(neat):1635,1494,1456,1290,1181,1030,747,610,594,427；HRESIMSCalcd for[C21H17NNa]+(M+Na+)306.1253,found 306.1257。
实施例56
本发明的2,3-二取代吲哚啉类化合物在制备式V所示的吲哚基甲醇类化合物中的应用示例，反应式如下：
具体操作如下：
将化合物III-1(0.1mmol,57.3mg)和苯甲醚(0.13mmol,14uL)溶于无水二氯甲烷中(2mL)，分批次加入AlCl3(0.2mmol,26.7mg)，室温下搅拌2小时，将得到的深红色溶液用二氯甲烷稀释，随后在搅拌下滴加10％的NaOH溶液直至固体消失。水相用二氯甲烷萃取4次，合并有机相并用无水硫酸镁干燥，过滤并真空浓缩，将粗产物经硅胶柱层析分离(石油醚/乙酸乙酯＝3:1，v/v)得到式V-1的目标产物。产率57％。1H NMR(400MHz,CDCl3)δ7.96(d,J＝8.4Hz,1H),7.57(d,J＝8.4Hz,2H),7.35–7.30(m,10H),7.27–7.21(m,2H),7.18–7.11(m,3H),5.96(s,1H),5.87(d,J＝0.8Hz,1H),2.31(s,3H)；13C NMR(100MHz,CDCl3)δ146.6,145.9,144.8,137.7,135.7,129.7,127.9,127.8,127.5,126.7,125.2,123.7,121.3,116.3,115.0,79.0,21.5；IR(neat):1637,1449,1349,1173,1146,1015,750,702,672,585；HRESIMS Calcd for[C28H23NNaO3S]+(M+Na+)476.1291,found 476.1289。
以上所述实施例仅为本发明的优选实施例，而并非本发明可行实施的穷举。对于本领域技术人员而言，在不背离本发明原理和精神的前提下，对其所作出的任何显而易见的改动，都应当被认为包含在本发明的权利要求保护范围之内。
Claims (10)
1.一种式III所示的2,3-二取代吲哚啉类化合物，其结构如下：
式III中，R1、R2分别表示所连接苯环上的一个或多个取代基，各个取代基彼此独立地选自氢、卤素、C1-20烷基、C1-20卤代烷基、C1-20烷氧基、C1-20卤代氧烷基、C1-20烷硫基、C1-20酰基、C1-20烷氧基羰基、C6-20芳基、三(C1-20烷基)硅基、-CHO、C6-20芳基-C1-20烷氧基、HO-C1-20烷基-、氰基、硝基；
PG表示氨基保护基团；
Ar表示取代或未取代的C6-20芳基、取代或未取代的C2-20杂芳基；其中所述“取代或未取代的C6-20芳基和取代或未取代的C2-20杂芳基”中的取代基个数为一个或多个，并且各个取代基彼此独立选自卤素、C1-20烷基、C1-20卤代烷基、C1-20烷氧基、C1-20卤代卤代烷基、C1-20烷硫基、C1-20酰基、C1-20烷氧基羰基、C6-20芳基、三(C1-20烷基)硅基、-CHO、C6-20芳基-C1-20烷氧基、HO-C1-20烷基-、氰基、硝基。
2.根据权利要求1所述的式III所示的2,3-二取代吲哚啉类化合物，R1、R2分别表示所连接苯环上的一个或多个取代基，各个取代基彼此独立地选自氢、卤素、C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代烷氧基、C1-6烷硫基、C1-6酰基、C1-6烷氧基羰基、C6-14芳基、三(C1-6烷基)硅基、-CHO、C6-14芳基-C1-6烷氧基、HO-C1-6烷基-、氰基、硝基；
PG表示氨基保护基团，选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种；
Ar表示取代或未取代的C6-14芳基、取代或未取代的C2-14杂芳基；其中所述“取代或未取代的C6-14芳基和取代或未取代的C2-14杂芳基”中的取代基个数为一个或多个，各个取代基彼此独立选自卤素、C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代卤代烷基、C1-6烷硫基、C1-6酰基、C1-6烷氧基羰基、C6-14芳基、三(C1-6烷基)硅基、-CHO、C6-14芳基-C1-6烷氧基、HO-C1-6烷基-、氰基、硝基。
3.根据权利要求1所述的式III所示的2,3-二取代吲哚啉类化合物，R1、R2分别表示所连接苯环上的一个或多个取代基，各个取代基彼此独立地选自氢、氟、氯、溴、碘、-CO2Me、乙酰基、三氟甲基、甲基、甲氧基、三氟甲氧基、甲硫基、苯基、三甲基硅基、醛基、苄氧基、羟甲基、氰基、硝基；
PG表示氨基保护基团，选自Ts(对甲苯磺酰基),MBS(对甲氧基苯磺酰基),SO2Ph,Bs(对溴苯磺酰基),Ms(甲基磺酰基)中的任意一种；
Ar表示取代或未取代的苯基、吲哚基；其中所述“取代或未取代苯基”中的取代基个数为一个或多个，各个取代基彼此独立选自氟、氯、溴、碘、-CO2Me、乙酰基、三氟甲基、甲基、甲氧基、三氟甲氧基、甲硫基、苯基、三甲基硅基、醛基、苄氧基、羟甲基、氰基、硝基。
4.根据权利要求1～3任意一项所述的式III所示的2,3-二取代吲哚啉类化合物的制备方法，其特征在于，包括如下步骤：
向Schlenk封管反应器中，依次加入式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物和式II所示的硼酸类化合物，铜催化剂，将反应器用惰性气氛保护，随后在惰性气氛条件下加入有机溶剂，置于室温～50℃条件下搅拌反应0.5～120h，经TLC监测原料消耗完全，再经后处理得到式III所示的2,3-二取代吲哚啉类化合物，反应式如下：
其中，R1,R2,PG,Ar具有与权利要求1～3任意一项相同的定义；
所述的铜催化剂选自CuOTf，CuOAc中的任意一种；
所述的有机溶剂选自无水甲醇、无水乙醇中的任意一种。
5.根据权利要求4所述的制备方法，其特征在于，所述铜催化剂选自CuOAc；所述有机溶剂选自无水甲醇。
6.根据权利要求4所述的制备方法，其特征在于，反应温度优选为50℃；惰性气氛为氩气气氛或氮气气氛，优选为氩气气氛。
7.根据权利要求4～6任意一项所述的制备方法，其特征在于，式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物、式II所示的硼酸类化合物和铜催化剂投料摩尔比为1:(1.5～3):(0.05～0.2)；优选地，式I所示的叔丁磺酰基(Bus)保护的亚胺-炔胺类化合物、式II所示的硼酸类化合物和铜催化剂投料摩尔比为1:2～3:0.1。
8.根据权利要求4～7任意一项所述的制备方法，其特征在于，所述的后处理操作如下：经TLC监测原料消耗反应完全，冷却至室温，加入二氯甲烷淬灭，随后将混合溶液真空浓缩，随后将得到的残余物经硅胶柱层析分离(洗脱溶剂为石油醚/乙酸乙酯)得到式III所示的2,3-二取代吲哚啉类化合物。
9.根据权利要求1～3任意一项所述的式III所示的2,3-二取代吲哚啉类化合物在制备式IV所示的2-二苯甲基-1H-吲哚类化合物中的应用，其特征在于，反应式如下：
其中，R1,R2,PG,Ar具有与权利要求1～3任意一项相同的定义；
应用方法如下：向配备磁粒搅拌子的干燥反应器中，加入钠和萘，抽真空并立即充入氮气保护，将无水THF加入反应瓶中，对混合物进行超声处理30分钟，得到萘钠；随后在-78℃条件下加入化合物III的无水THF溶液；将反应混合物在该温度下搅拌20分钟后，用饱和氯化铵和饱和碳酸氢钠溶液淬灭，乙酸乙酯萃取，合并有机相并用无水硫酸镁干燥，过滤，滤液经减压浓缩得到粗产物，再经硅胶柱层析分离得到式IV所示的2-二苯甲基-1H-吲哚类化合物。
10.根据权利要求1～3任意一项所述的式III所示的2,3-二取代吲哚啉类化合物在制备式V所示的吲哚基甲醇类化合物的应用，其特征在于，反应式如下：
其中，R1,R2,PG,Ar具有与权利要求1～3任意一项相同的定义。
应用方法如下：将化合物III和苯甲醚溶于无水二氯甲烷中，分批次加入AlCl3，室温下搅拌2小时，将得到的深红色溶液用二氯甲烷稀释，随后在搅拌下滴加10％的NaOH溶液直至固体消失；水相用二氯甲烷萃取4次，合并有机相并用无水硫酸镁干燥，过滤并真空浓缩，将粗产物经硅胶柱层析分离得到式V的目标产物。
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