CN109761873A - 非活化烯烃苄基化合成苄基化吲哚啉类化合物的方法 - Google Patents
非活化烯烃苄基化合成苄基化吲哚啉类化合物的方法 Download PDFInfo
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Abstract
本发明提供一种非活化烯烃苄基化合成苄基化吲哚啉类化合物的方法,该方法可以实现以非环原料合成吲哚啉,同时官能团耐受性能好。本发明的方法是首例实现甲苯与非活化双键的苄氢C‑H键官能团化反应。本发明的方法在廉价MnCl2·4H2O和二叔丁基过氧化物(DTBP)的作用下,N‑烯丙基苯胺类化合物发生串联的苄基化/环化反应,生成苄基化吲哚啉,并呈现exo选择性。本发明的方法为苄基化吲哚啉的合成提供了简单、直接的合成方法,且具有底物范围广和操作简单等优点。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种非活化烯烃苄基化合成 苄基化吲哚啉类化合物的方法。
背景技术
吲哚啉是一类非常重要的含氮杂环化合物,普遍存在于生物碱和其他 天然产物中,其在染料工业、香料、有机中间体合成、医药、农药合成方 面有着巨大的应用。由于以吲哚啉为母核结构化合物多样的生物活性和临 床应用,反过来又要求科学家合成更多结构多样的吲哚啉衍生物作为药物 先导分子。然而,吲哚化学中,吲哚啉骨架要比其它吲哚类结构(如氧化 吲哚)难构建的多(文献1:K.Nagarajua,D.Ma,Chem.Soc.Rev.2018,47,8018-8029;文献2:Z.Xu,Q.Wang,J.Zhu,Chem.Soc.Rev.2018,47, 7882-7898)。氧化吲哚既可以由它的母体吲哚对应物衍生化得到(文献3: Y.Zhou,L.Lin,X.Liu,X.Hu,Y.Lu,X.Zhang,X.Feng,Angew.Chem.Int.Ed. 2018,57,9113–9116;Angew.Chem.2018,130,9251–9254;文献4:X.Chen, J.Xiong,Q.Liu,S.Li,H.Sheng,C.von Essen,K.Rissanen,D.Enders,Angew. Chem.Int.Ed.2018,57,300–304;Angew.Chem.2018,130,306–310),也可以通过N-芳基丙烯酰胺化学合成(文献5:Z.Li,Y.Zhang,L.Zhang,Z.Liu, Org.Lett.2014,16,382-385;文献6:S.Zhou,L.Guo,H.Wang,X.Duan, Chem.Eur.J.2013,19,12970–12973),而吲哚啉合成则主要局限于吲哚的 去芳香化反应(文献7:C.Zheng,S.You,Chem 2016,1,830-857;文献8: C.Zhuo,C.Zheng,S.You,Acc.Chem.Res.2014,47,2558–2573)。
从非环原料合成吲哚啉的例子很少,而将氧化吲哚还原为吲哚啉的反 应由于需要强还原条件面临严重的官能团不耐受问题。
发明内容
为了解决现有技术中的问题,本发明的目的在于提供一种非活化烯烃 苄基化合成苄基化吲哚啉类化合物的方法,该方法以非环原料合成吲哚啉, 官能团耐受性能好。
本发明的目的是这样实现的:
一种非活化烯烃苄基化合成苄基化吲哚啉类化合物(式II化合物)的 方法,其特征在于,反应路线如下:
其中:
A为C或N;
R1是氢、卤素、C1-6烷基或苯基;
R2是氢或C1-6烷基;
R3是COR5、SO2R6、C1-6烷基;
R4是氢、卤素或C1-6烷基;
R5是C1-17烷基或-O-C1-6烷基;
R6是C1-6烷基;
所述催化剂包含催化剂1或/和催化剂2,所述催化剂1选自TBAI、CuBr、 Cu(OAc)2、AgNO3、FeCl3·6H2O、FeCl2·4H2O、CoCl2·6H2O、NiCl2·6H2O、 MnCl2·4H2O、Mn(OAc)3·2H2O、MnO2、KMnO4或MnCl2·4H2O;所述催化 剂2选自DTBP、TBHP、DCP、BPO、TBPB或K2S2O8。
本文所用的术语“卤素”是指氟、氯、溴或碘,优选为氟、氯或溴。
本文所用的术语“C1-6烷基”是指具有1-6个碳原子的饱和的直链或支 链烃基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔 丁基、正戊基、异戊基、新戊基、正己基、异己基等,优选甲基、乙基、 丙基、异丙基、叔丁基或异丁基。
本发明所用的术语“-O-C1-6烷基”,是指具有1-6个碳原子的饱和的 直链或支链烷氧基,例如甲氧基、乙氧基、叔丁氧基等。
进一步,本发明中R1选自氢、甲基、氟、氯、溴或苯基;R2选自氢或 甲基;R4是氢、卤素或甲基;R5选自甲基、乙基、n-C7H15、n-C9H19、n-C11H23、 n-C17H35、t-Bu或叔丁氧基;R6选自甲基或乙基。
进一步,本发明所述催化剂1优选MnCl2·4H2O、Mn(OAc)3·2H2O、 MnO2、KMnO4或MnCl2·4H2O;所述催化剂2优选DTBP。
本文式I化合物中,R1可以独立的为邻位、间位或对位,可以邻位、 间位或/和对位同时取代,也可以单独取代。
本文式II化合物和式III化合物中,R4可以独立的为邻位、间位或对 位,可以邻位、间位或/和对位同时取代,也可以单独取代。
本发明式II化合物选自2a1-4e化合物,具体如下表1。
表1 2a1-4e化合物
本发明式I化合物可以参照文献(文献9:D.Liang,Q.Dong,P.Xu,Y. Dong,W.Li,Y.Ma,J.Org.Chem.2018,83,11978-11986.;文献10:S. O'Sullivan,E.Doni,T.Tuttle,J.A.Murphy.Angew.Chem.Int.Ed.2014,53, 474–478;Angew.Chem.2014,126,484–488;文献11:Z.Wu,S.Li,H.Xu. Angew.Chem.Int.Ed.2018,57,14070–14074;Angew.Chem.2018,130,14266–14270.)制备得到,也可以自制,如采用以下方法:
有益效果
脱氢C-H键官能团化反应由于具有高度的原子和步骤经济性,过去的 十年里已成为构建C-C键的一个强力工具。廉价且来源丰富的烃类原料是 理想的C-H源。不意图为任何理论所束缚,认为尽管甲苯的苄基C-H键官 能团化反应已被广泛研究,它的偶联对象涵盖芳香、杂芳、醛基、活化烷 基和活化烯基C-H键,以及C-卤、C-B、C-NO2、C-CO2H、C-COMe键和CuIIIbpy(CF3)3,但是甲苯与非活化烯烃的苄基化偶联或加成反应从未实现, 这可以解释为极性不匹配。苄基和非活化烯烃都被认为是亲核性的,它们 都倾向于与缺电子物种发生反应,甲苯与富电子体系的偶联反应则是巨大 的挑战。
本发明人进行了非活化烯烃苄基化合成苄基化吲哚啉类化合物的实 验,并且出人意料地发现,使用特定的催化剂组合,可以实现以非环原料 合成吲哚啉,同时官能团耐受性能好。本发明的方法是首例实现甲苯与非 活化双键的苄氢C-H键官能团化反应。本发明的方法在廉价MnCl2·4H2O 和二叔丁基过氧化物(DTBP)的作用下,N-烯丙基苯胺类化合物发生串联 的苄基化/环化反应,生成苄基化吲哚啉,并呈现exo选择性。本发明的方 法为苄基化吲哚啉的合成提供了简单、直接的合成方法,且具有底物范围 广和操作简单等优点。
具体实施方式
为了使本发明的目的和技术方案更加清楚,下面对本发明的优选实施 例进行详细的描述。要说明的是:以下实施例只用于对本发明进行进一步 的说明,而不能理解为对本发明保护范围的限制。本领域的技术人员根据 本发明的上述内容做出的一些非本质的改进和调整均属于本发明的保护范 围。
实施例1
非活化烯烃类式I化合物的合成(以1a2合成为例),反应路线如下:
操作步骤:向一个放有磁力搅拌子的100mL圆底烧瓶中依次加入对甲 苯胺(1.607g,15.0mmol)、CH2Cl2(50.0mL),和Et3N(4.170mL, 30.0mmol),最后加入乙酰氯(1.273mL,18.0mmol)。反应混合液在室 温用磁力搅拌器进行搅拌。TLC显示原料对甲苯胺消耗完毕后,用饱和 NaHCO3溶液(100mL)淬灭反应,然后用CH2Cl2(100.0mL)萃取3次。 合并的有机相用食盐水(50mL)洗涤2次。蒸除有机溶剂得到的固体用石 油醚/乙酸乙酯(5:1,体积比)混合液洗涤,得到白色固体对甲基乙酰苯 胺(2.104g,94%产率)。向保持搅拌的对甲基乙酰苯胺(1.492g,10.0mmol) 和NaOH(600mg,15.0mmol)的DMF(30mL)溶液中加入2-甲基-3- 溴丙烯(1.311mL,13.0mmol),得到的混合液用磁力搅拌器在室温搅拌反 应。TLC显示对甲基乙酰苯胺消耗完毕后,用食盐水(60mL)淬灭反应 并用CH2Cl2(100.0mL)萃取3次。蒸除有机溶剂得到的残留物用硅胶进 行柱层析(石油醚-乙酸乙酯=20:1,体积比),得到无色油状物N-(2-甲 基烯丙基)-N-对甲苯基乙酰胺1a2(1.830g,90%产率)。
参照上述实施例1,制备得到以下式I化合物。
实施例2
非活化烯烃苄基化合成苄基化吲哚啉类化合物(以2a1的合成为例), 反应路线如下:
操作步骤:向装有磁力搅拌子和四氟螺口塞的耐压管中加入N-烯丙基 苯胺1a1(0.25mmol),MnCl2·4H2O(5mg,0.025mmol),DTBP(73mg, 0.50mmol)和溶剂甲苯(5.0mL)。该混合液在140℃反应6h,然后用 饱和Na2S2O3(1.0mL)和水(10.0mL)淬灭,再用二氯甲烷(10.0mL) 萃取三次。对蒸除有机溶剂得到的残留物进行柱层析(硅胶作为固定相, 石油醚和乙酸乙酯作为洗脱剂),得到苄基化吲哚啉产物2a1。
参照上述实施例2,考察催化剂对反应的影响,具体情况见下表2。
表2催化剂对反应的影响考察[a]
[a]反应条件:1a1(0.25mmol),催化剂1(0.25mmol),催化剂2(0.5mmol),甲 苯(5.0mL),140℃,6h。
[b]5.0-6.0mol/L的癸烷溶液。
[c]反应的其它条件相同,但MnCl2·4H2O用量为5mol%,或DTBP用量为1.5当量, 或在120℃进行。
发明人使用N-(2-甲基烯丙基)-N-苯基乙酰苯胺1a1作为模型底物开始 本研究(表2)。令人高兴的是,在二叔丁基过氧化物(DTBP)的作用下, 1a1在140℃的甲苯中顺利发生苄基化/环化反应,生成苄基化吲哚啉2a1, 不过产率很低(序号1)。为了提升反应效率,发明人对一些催化剂进行了 筛选。使用四丁基碘化铵(TBAI,序号2)和多种金属盐,包括CuBr(序 号3)、AgNO3(序号5)、FeCl3·6H2O(序号6),FeCl2·4H2O(序号7) 和NiCl2·6H2O(序号9),都能使吲哚啉2a1的产率升高,而Cu(OAc)2(序 号4)和CoCl2·6H2O(序号8)则对反应没有帮助。锰盐是更好的催化剂 (序号10-13),而使用MnCl2·4H2O时产率最高,为70%(序号10)。接 下来发明人使用无水过氧化叔丁醇(TBHP,序号14)、过氧化二异丙苯(DCP,序号15)或过氧化苯甲酰(BPO,序号16)都会导致吲哚啉2a1 的产率变得很低,而过氧化苯甲酸叔丁酯(TBPB,序号17)和K2S2O8(序 号18)则对该反应基本无效。降低催化剂或DCP的用量,或降低反应温度, 都会导致产率下降(序号19)。
参照上述实施例2,在最优条件下对底物适用范围进行了研究,具体情 况见下表3;其中反应路线如下:
表3苄基化吲哚啉合成[a]
[a]反应条件:1(0.25mmol),MnCl2·4H2O(0.025mmol),DTBP(0.5mmol),溶 剂(5.0mL),140℃,6h。
结果表明,5-位取代的吲哚啉2a2-5以46-68%的产率从N-芳基对位有 甲基、溴原子、氯原子或苯基的N-(2-甲基烯丙基)乙酰苯胺合成得到。令人 意外的是,该反应可以兼容烯丙化的4-乙酰氨基吡啶,对应2,3-二氢吡咯 并[3,2-c]吡啶产物2b以53%的产率生成。丙酰基保护的吲哚啉2c也以较 高的产率生成,而特戊酰基和长链N-保护基(R3),如辛酰基、癸酰基、 十二烷酰基和硬脂酰基,吲哚啉2d1-5的产率只有中等。带有叔丁氧羰基 R3的烯丙基化苯胺与甲苯反应以中等产率生成吲哚啉2e,而N-乙磺酰基吲 哚啉2f仅以很低的产率生成。从3,5-二氯苯胺合成的酰胺底物也可以被本 反应兼容,虽然目标苄基化吲哚啉2g的产率只有41%。C-H键偶联对象方 面,邻位、间位或对位带有供电子基或吸电子基的甲苯衍生物都可以与烯 丙基化酰基苯胺反应,生成对应苄基化吲哚啉2h-i。邻位取代甲苯溶剂中 进行的反应产率最高,对位取代的甲苯则是最不利的偶联对象,目前尚不 清楚导致这种反应活性的原因。使用均三甲苯和2,3,4,5,6-五氟甲苯作为溶 剂的反应也能顺利发生,对应吲哚啉2j,k分别以中等和较高的产率生成。
然而,使用芳酰基保护的烯丙基苯胺作为底物时即使升高温度也没有 反应发生(下式a),这可能是由于苯环共轭效应的影响,自由基捕获步骤 中N-芳基与加成得到的自由基的电性不再匹配导致。这些结果进一步表明, 电性匹配的内置捕获基团是分子内自由基被迅速捕获和反应顺利进行的关 键。不过,烯丙基化的N-甲基苯甲酰胺可以发生类似的苄基化/环化串联反 应,生成3,4-二氢异喹啉-1-酮3a,b,虽然产率略低(下式b)。
根据鲍德温规则(Baldwin's rules),exo和endo模式环合过程在本反 应中都是有利的。因此,初期发明人都使用2-甲基烯丙基底物开展研究, 以避免endo模式的环合反应。在以上反应中全部实现了exo选择性后,发 明人又对无甲基取代烯丙基酰基苯胺苄基化/环化反应进行了进一步研究, 研究结果见下表4。
表4无甲基取代烯丙基酰基苯胺苄基化/环化反应[a]
[a]反应条件:底物(0.25mmol),MnCl2·4H2O(0.025mmol),DTBP(0.5mmol), 甲苯(5.0mL),140℃,6h。
令人惊奇的发现,带有电中性、富电子或贫电子N-芳基基团的这类烯 烃在最优反应条件下也都能顺利和甲苯类溶剂发生相同的苄基化/环化反 应,并以46-62%的产率生成苄基化吲哚啉4a-e,而形式的6-endo-trig产物 仍然没有观察到。
目标产物的核磁数据
2a1,1-(3-甲基-3-苯乙基吲哚啉-1-基)-1-乙酮,1:5旋转异构体(由N–(CO)键的缓慢旋 转引起),浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.42(s,3H),1.90-2.03(m,2H),2.17(s,3H),2.39-2.46(m,1H),2.52-2.60(m,1H),3.71(d,J=10.3Hz,1H),3.89(d,J=10.3Hz,1H),7.06-7.27(m,8H),8.22(d,J=8.0Hz,1H);13C NMR(100MHz,CDCl3)δ=168.67,142.27,141.76,138.62,128.47,128.25,127.99,125.99,123.87,122.34,116.99,61.22,43.70,43.40,31.11,27.25,24.26;HRMS(ESI-TOF)Calcd for C19H22NO+([M+H]+)280.1696.Found 280.1695.
2a2,1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-乙酮,1:4旋转异构体,无色油状物.1H NMR (400MHz,CDCl3)δ=1.40(s,3H),1.88-2.01(m,2H),2.15(s,3H),2.33(s,3H),2.39-2.48 (m,1H),2.52-2.60(m,1H),3.68(d,J=10.3Hz,1H),3.87(d,J=10.3Hz,1H),6.93(s,1H), 7.02(d,J=8.5Hz,1H),7.10(d,J=7.2Hz,2H),7.16(dd,J=7.2,7.2Hz,1H),7.25(dd,J=7.5,7.3Hz,2H),8.09(d,J=8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=168.30,141.80, 139.99,138.73,133.43,128.45,128.44,128.23,125.95,122.91,116.68,61.35,43.63,43.32, 31.08,27.21,24.14,21.17;HRMS(ESI-TOF)Calcd for C20H24NO+([M+H]+)294.1852. Found 294.1864.
2a3,1-(3-甲基-3-苯乙基-5-溴吲哚啉-1-基)-1-乙酮,无色油状物.1H NMR(400MHz, CDCl3)δ=1.41(s,3H),1.88-2.02(m,2H),2.15(s,3H),2.40-2.48(m,1H),2.52-2.60(m, 1H),3.70(d,J=10.3Hz,1H),3.88(d,J=10.3Hz,1H),7.11(d,J=7.1Hz,2H),7.18(dd,J =7.2,7.2Hz,1H),7.22-7.29(m,3H),7.33(dd,J=2.0,8.6Hz,1H),8.10(d,J=8.6Hz,1H); 13C NMR(100MHz,CDCl3)δ=168.69,141.37,141.34,140.99,130.88,128.51,128.22, 126.11,125.57,118.44,116.24,61.19,43.80,43.18,31.01,27.19,24.13;HRMS(ESI-TOF) Calcd for C19H21BrNO+([M+H]+)358.0801.Found 358.0799.
2a4,1-(3-甲基-3-苯乙基-5-氯吲哚啉-1-基)-1-乙酮,无色油状物.1H NMR(400MHz, CDCl3)δ=1.41(s,3H),1.89-2.02(m,2H),2.15(s,3H),2.40-2.48(m,1H),2.52-2.60(m, 1H),3.71(d,J=10.3Hz,1H),3.89(d,J=10.3Hz,1H),7.08(d,J=2.0Hz,1H),7.11(d,J =7.0Hz,2H),7.16-7.20(m,2H),7.25-7.28(m,2H),8.15(d,J=8.6Hz,1H);13CNMR(100 MHz,CDCl3)δ=168.65,141.36,140.90,140.62,128.74,128.52,128.22,127.96,126.12, 122.67,117.98,61.26,43.81,43.18,31.02,27.18,24.10;HRMS(ESI-TOF)Calcdfor C19H21ClNO+([M+H]+)314.1306.Found 314.1298.
2a5,1-(3-甲基-3-苯乙基-5-苯基吲哚啉-1-基)-1-乙酮,白色固体:mp 137-138℃.1H NMR (400MHz,CDCl3)δ=1.48(s,3H),1.95-2.08(m,2H),2.19(s,3H),2.45-2.53(m,1H), 2.57-2.65(m,1H),3.76(d,J=10.3Hz,1H),3.94(d,J=10.3Hz,1H),7.12(d,J=7.0Hz, 2H),7.17(dd,J=7.3,7.2Hz,1H),7.24-7.28(m,2H),7.30-7.35(m,2H),7.43(dd,J=7.8, 7.4Hz,2H),7.48(dd,J=1.8,8.4Hz,1H),7.58(d,J=7.4Hz,2H),8.27(d,J=8.4Hz,1H); 13C NMR(100MHz,CDCl3)δ=168.61,141.71,141.66,141.03,139.32,137.06,128.76, 128.47,128.25,127.00,126.96,126.92,126.01,121.00,117.12,61.49,43.79,43.42,31.14, 27.26,24.21;HRMS(ESI-TOF)Calcd for C25H26NO+([M+H]+)356.2009.Found356.2012.
2b,1-(3-甲基-3-苯乙基-2,3-二氢-1H-吡咯并[3,2-c]吡啶-1-基)-1-乙酮,黄色油状物.1H NMR(400MHz,CDCl3)δ=1.39(s,3H),1.87-1.99(m,2H),2.09(s,3H),2.35-2.53(m, 2H),3.64(d,J=10.2Hz,1H),3.81(d,J=10.2Hz,1H),7.02(d,J=7.1Hz,2H),7.09(dd,J =7.2,7.2Hz,1H),7.18(dd,J=7.5,7.2Hz,2H),7.94(d,J=4.9Hz,1H),8.28(s,1H),8.34 (d,J=5.3Hz,1H);13C NMR(100MHz,CDCl3)δ=168.73,148.89,147.81,143.30,140.14, 132.91,127.51,127.19,125.13,110.34,60.27,42.19,42.09,30.03,26.30,23.18;HRMS (ESI-TOF)Calcd for C18H21N2O+([M+H]+)281.1648.Found 281.1659.
2c,1-(3-甲基-3-苯乙基吲哚啉-1-基)-1-丙酮,浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.22(t,J=7.4Hz,3H),1.42(s,3H),1.89-2.00(m,2H),2.33-2.46(m,3H),2.51-2.59(m,1H),3.69(d,J=10.3Hz,1H),3.89(d,J=10.3Hz,1H),7.05-7.11(m,3H),7.13-7.18(m,2H),7.21-7.27(m,3H),8.25(d,J=8.1Hz,1H);13C NMR(100MHz,CDCl3) δ=171.99,142.51,141.79,138.48,128.45,128.24,128.00,125.95,123.71,122.30,116.93,60.26,43.69,43.46,31.11,29.21,27.23,8.73;HRMS(ESI-TOF)Calcd for C20H24NO+ ([M+H]+)294.1852.Found 294.1864.
2d1,1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-辛酮,无色油状物.1H NMR(400MHz, CDCl3)δ=0.88(t,J=6.8Hz,3H),1.26-1.36(m,8H),1.40(s,3H),1.68-1.75(m,2H), 1.87-2.00(m,2H),2.29-2.48(m,6H),2.52-2.60(m,1H),3.68(d,J=10.3Hz,1H),3.88(d,J =10.3Hz,1H),6.92(s,1H),7.02(d,J=8.5Hz,1H),7.10(d,J=7.1Hz,2H),7.16(dd,J= 7.4,7.2Hz,1H),7.25(dd,J=7.0,7.7Hz,2H),8.12(d,J=8.2Hz,1H);13C NMR(100MHz, CDCl3)δ=171.14,141.87,140.23,138.69,133.28,128.46,128.44,128.25,125.94,122.88, 116.74,60.59,43.61,43.38,35.99,31.78,31.11,29.43,29.20,27.15,24.67,22.68,21.18, 14.13;HRMS(ESI-TOF)Calcd for C26H36NO+([M+H]+)378.2791.Found378.2791.
2d2,1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-癸酮,无色油状物.1H NMR(400MHz, CDCl3)δ=0.88(t,J=7.0Hz,3H),1.27-1.36(m,12H),1.40(s,3H),1.68-1.75(m,2H), 1.87-2.00(m,2H),2.26-2.48(m,6H),2.52-2.60(m,1H),3.68(d,J=10.3Hz,1H),3.89(d,J =10.3Hz,1H),6.92(s,1H),7.03(d,J=8.4Hz,1H),7.11(d,J=7.0Hz,2H),7.16(dd,J= 7.3,7.3Hz,1H),7.25(dd,J=7.6,7.1Hz,2H),8.12(d,J=8.2Hz,1H);13C NMR(100MHz, CDCl3)δ=171.15,141.86,140.21,138.68,133.28,128.46,128.43,128.24,125.93,122.87, 116.73,60.58,43.60,43.37,36.00,31.90,31.10,29.52,29.46,29.32,27.14,24.65,22.69, 21.17,14.13;HRMS(ESI-TOF)Calcd for C28H40NO+([M+H]+)406.3104.Found 406.3108.
2d3,1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-十二酮,无色油状物.1H NMR(400MHz, CDCl3)δ=0.88(t,J=7.0Hz,3H),1.26-1.38(m,16H),1.40(s,3H),1.68-1.75(m,2H), 1.87-2.00(m,2H),2.27-2.46(m,6H),2.52-2.60(m,1H),3.68(d,J=10.3Hz,1H),3.89(d,J =10.3Hz,1H),6.92(s,1H),7.03(d,J=8.4Hz,1H),7.11(d,J=7.0Hz,2H),7.16(dd,J= 7.3,7.3Hz,1H),7.25(dd,J=7.6,7.2Hz,2H),8.11(d,J=8.2Hz,1H);13C NMR(100MHz, CDCl3)δ=171.15,141.86,140.21,138.68,133.28,128.46,128.43,128.24,125.93,122.87, 116.73,60.58,43.60,43.37,35.99,31.93,31.10,29.67,29.64,29.56,29.53,29.46,29.36, 27.14,24.65,22.70,21.17,14.14;HRMS(ESI-TOF)Calcd forC30H44NO+([M+H]+) 434.3417.Found 434.3419.
2d4,1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-十八酮,无色油状物.1H NMR(400MHz, CDCl3)δ=0.88(t,J=7.0Hz,3H),1.25-1.36(m,28H),1.40(s,3H),1.68-1.75(m,2H), 1.87-2.00(m,2H),2.29-2.49(m,6H),2.52-2.60(m,1H),3.68(d,J=10.3Hz,1H),3.89(d,J =10.3Hz,1H),6.92(s,1H),7.03(d,J=8.4Hz,1H),7.11(d,J=7.0Hz,2H),7.16(dd,J= 7.3,7.3Hz,1H),7.25(dd,J=7.6,7.1Hz,2H),8.11(d,J=8.2Hz,1H);13C NMR(100MHz, CDCl3)δ=171.14,141.85,140.21,138.66,133.27,128.45,128.42,128.23,125.93,122.86, 116.72,60.57,43.60,43.36,35.99,31.94,31.09,29.71,29.67,29.56,29.52,29.46,29.37, 27.13,24.65,22.70,21.16,14.13;HRMS(ESI-TOF)Calcd forC36H56NO+([M+H]+) 518.4356.Found 518.4352.
2d5,2,2-二甲基-1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-丙酮,白色固体:mp59-60℃.1H NMR(400MHz,CDCl3)δ=1.36(s,9H),1.38(s,3H),1.84-1.99(m,2H),2.33(s,3H), 2.44-2.51(m,1H),2.59-2.66(m,1H),3.85(d,J=10.2Hz,1H),4.11(d,J=10.2Hz,1H), 6.93(s,1H),7.02(d,J=7.8Hz,1H),7.11(d,J=7.2Hz,2H),7.16(dd,J=7.4,7.2Hz,1H), 7.25(dd,J=7.7,7.0Hz,2H),8.10(d,J=8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=176.08,141.90,141.62,138.50,133.44,128.46,128.28,128.24,125.95,122.64,118.20,61.89,44.24,42.51,40.05,31.16,27.70,25.37,21.13;HRMS(ESI-TOF)Calcd forC23H30NO+([M+H]+)336.2322.Found 336.2322.
2e,3,5-二甲基-3-苯乙基吲哚啉-1-甲酸叔丁酯,1:1旋转异构体,无色油状物.1HNMR (400MHz,CDCl3)δ=1.36(s,3H),1.57(s,9H),1.83-1.96(m,2H),2.31(s,3H),2.35-2.43 (m,1H),2.56-2.63(m,1H),3.64(brs,1H),3.86(brs,0.5H),3.94(brs,0.5H),6.90(s,1H), 6.99(d,J=7.7Hz,1H),7.12(d,J=7.2Hz,2H),7.15(dd,J=7.3,7.3Hz,1H),7.25(dd,J= 7.6,7.2Hz,2H),7.33(brs,不可交换,0.5H),7.73(brs,不可交换,0.5H);13C NMR(100 MHz,CDCl3)δ=152.51(br),142.18,139.97-138.41(brm),131.83,128.36,128.25,125.79, 123.34(br),123.05(br),114.41,81.39(br),80.35(br),60.10(br),59.78(br),43.58,42.88 (br),42.18(br),31.02,28.52,27.17,21.02;HRMS(ESI-TOF)Calcd forC23H30NO2 + ([M+H]+)352.2271.Found 352.2273.
2f,3-甲基-3-苯乙基-1-乙磺酰基-5-氯吲哚啉,无色油状物.1H NMR(400MHz,CDCl3)δ =1.41(s,3H),1.42(t,J=7.4Hz,3H),1.86-2.01(m,2H),2.40-2.47(m,1H),2.62-2.70(m, 1H),3.12(q,J=7.4Hz,2H),3.73(d,J=10.1Hz,1H),3.98(d,J=10.1Hz,1H),7.09(d,J =2.1Hz,1H),7.12(d,J=7.0Hz,2H),7.15-7.20(m,2H),7.25-7.27(m,2H),7.30(d,J= 8.5Hz,1H);13C NMR(100MHz,CDCl3)δ=141.28,140.38,140.13,128.54,128.45, 128.20,128.18,126.12,123.57,114.11,62.03,44.24,43.86,42.80,30.97,26.50,7.78; HRMS(ESI-TOF)Calcd for C19H23ClNO2S+([M+H]+)364.1133.Found364.1131.
2g,1-(3-甲基-3-苯乙基-4,6-二氯吲哚啉-1-基)-1-辛酮,无色油状物.1H NMR(400MHz, CDCl3)δ=0.89(t,J=7.0Hz,3H),1.30-1.37(m,8H),1.52(s,3H),1.67-1.74(m,2H), 1.89-1.99(m,1H),2.24-2.51(m,5H),3.70(d,J=10.3Hz,1H),3.93(d,J=10.3Hz,1H), 7.01(d,J=1.8Hz,1H),7.11(d,J=7.0Hz,2H),7.17(dd,J=7.3,7.3Hz,1H),7.26(dd,J= 7.3,7.3Hz,2H),8.31(s,1H);13C NMR(100MHz,CDCl3)δ=171.79,145.25,141.43,134.42,132.01,130.38,128.48,128.29,126.06,124.65,116.00,60.83,45.29,40.30,36.06, 31.74,31.51,29.29,29.16,26.42,24.35,22.66,14.11;HRMS(ESI-TOF)Calcd forC25H32Cl2NO+([M+H]+)432.1855.Found 432.1871.
2h1,1-(3,5-二甲基-3-(2-甲基苯乙基)吲哚啉-1-基)-1-辛酮,浅黄色油状物.1HNMR(400 MHz,CDCl3)δ=0.88(t,J=7.0Hz,3H),1.30-1.40(m,8H),1.41(s,3H),1.68-1.78(m, 2H),1.80-1.91(m,2H),2.20(s,3H),2.27-2.42(m,6H),2.52-2.59(m,1H),3.73(d,J=10.3 Hz,1H),3.95(d,J=10.3Hz,1H),6.94(s,1H),6.99-7.12(m,5H),8.12(d,J=8.2Hz,1H); 13C NMR(100MHz,CDCl3)δ=171.12,140.18,139.98,138.67,135.61,133.26,130.29,128.66,128.47,126.09,122.85,116.76,60.57,43.64,42.24,36.03,31.76,29.43,29.19,28.40,26.92,24.70,22.66,21.16,19.10,14.11;HRMS(ESI-TOF)Calcd for C27H38NO+ ([M+H]+)392.2948.Found 392.2949.
2h2,1-(3,5-二甲基-3-(3-甲基苯乙基)吲哚啉-1-基)-1-辛酮,无色油状物.1HNMR(400 MHz,CDCl3)δ=0.88(t,J=6.8Hz,3H),1.30-1.39(m,11H),1.68-1.75(m,2H),1.86-1.99(m,2H),2.30-2.43(m,9H),2.49-2.56(m,1H),3.68(d,J=10.3Hz,1H),3.89(d,J=10.3Hz,1H),6.90-7.03(m,5H),7.14(dd,J=7.8,7.8Hz,1H),8.11(d,J=8.2Hz,1H); 13CNMR(100MHz,CDCl3)δ=171.13,141.80,140.21,138.73,138.03,133.25,129.07, 128.43,128.33,126.66,125.23,122.89,116.72,60.59,43.60,43.41,35.99,31.77,31.00,29.42,29.19,27.12,24.66,22.66,21.37,21.17,14.11;HRMS(ESI-TOF)Calcd forC27H38NO+([M+H]+)392.2948.Found 392.2946.
2h3,1-(3,5-二甲基-3-(4-甲基苯乙基)吲哚啉-1-基)-1-辛酮,浅黄色油状物.1HNMR(400 MHz,CDCl3)δ=0.88(t,J=6.8Hz,3H),1.30-1.39(m,11H),1.68-1.75(m,2H),1.86-1.94(m,2H),2.30-2.42(m,9H),2.48-2.56(m,1H),3.67(d,J=10.3Hz,1H),3.88(d,J=10.3Hz,1H),6.92(s,1H),6.98-7.07(m,5H),8.11(d,J=8.2Hz,1H);13C NMR(100 MHz,CDCl3)δ=171.13,140.20,138.77,138.75,135.39,133.25,129.10,128.42,128.11,122.88,116.71,60.58,43.60,43.50,35.99,31.77,30.63,29.43,29.19,27.15,24.66,22.66, 21.17,20.97,14.11;HRMS(ESI-TOF)Calcd for C27H38NO+([M+H]+)392.2948.Found392.2940.
2i1,1-(3,5-二甲基-3-(2-氯苯乙基)吲哚啉-1-基)-1-丙酮,无色油状物.1H NMR(400MHz, CDCl3)δ=1.24(t,J=7.4Hz,3H),1.41(s,3H),1.82-1.95(m,2H),2.33(s,3H),2.41-2.53 (m,3H),2.65-2.73(m,1H),3.72(d,J=10.4Hz,1H),4.01(d,J=10.3Hz,1H),6.95(s,1H), 7.03(d,J=8.4Hz,1H),7.08-7.17(m,3H),7.31(dd,J=2.0,7.0Hz,1H),8.12(d,J=8.2 Hz,1H);13C NMR(100MHz,CDCl3)δ=171.66,140.19,139.41,138.48,133.69,133.26, 130.33,129.53,128.51,127.51,126.92,122.90,116.66,60.24,43.66,41.70,29.22,29.16, 26.96,21.16,8.79;HRMS(ESI-TOF)Calcd for C21H25ClNO+([M+H]+)342.1619.Found 342.1622.
2i2,1-(3,5-二甲基-3-(3-氯苯乙基)吲哚啉-1-基)-1-丙酮,无色油状物.1H NMR(400MHz, CDCl3)δ=1.23(t,J=7.4Hz,3H),1.40(s,3H),1.85-1.98(m,2H),2.33(s,3H),2.35-2.42 (m,3H),2.49-2.56(m,1H),3.70(d,J=10.4Hz,1H),3.88(d,J=10.4Hz,1H),6.91(s,1H), 6.96(d,J=6.9Hz,1H),7.04(d,J=8.4Hz,1H),7.09(s,1H),7.13-7.19(m,2H),8.12(d,J =8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=171.60,143.86,140.24,138.20,134.16, 133.34,129.66,128.61,128.34,126.49,126.12,122.85,116.68,60.39,43.59,43.24,30.81, 29.13,27.18,21.17,8.76;HRMS(ESI-TOF)Calcd for C21H25ClNO+([M+H]+)342.1619. Found 342.1634.
2i3,1-(3,5-二甲基-3-(4-氯苯乙基)吲哚啉-1-基)-1-丙酮,无色油状物.1H NMR(400MHz, CDCl3)δ=1.22(t,J=7.4Hz,3H),1.40(s,3H),1.83-1.97(m,2H),2.33(s,3H),2.35-2.43 (m,3H),2.45-2.56(m,1H),3.68(d,J=10.3Hz,1H),3.86(d,J=10.3Hz,1H),6.91(s,1H), 7.01-7.04(m,3H),7.21(d,J=8.3Hz,2H),8.12(d,J=8.2Hz,1H);13C NMR(100MHz, CDCl3)δ=171.61,140.25,138.25,133.32,131.65,129.59,128.57,128.48,122.86,116.67, 60.41,43.59,43.40,30.49,29.12,27.21,21.16,8.74;HRMS(ESI-TOF)Calcd for C21H25ClNO+([M+H]+)342.1619.Found 342.1618.
2i4,1-(3,5-二甲基-3-(4-氟苯乙基)吲哚啉-1-基)-1-丙酮,浅黄色油状物.1HNMR(400 MHz,CDCl3)δ=1.22(t,J=7.4Hz,3H),1.40(s,3H),1.84-1.97(m,2H),2.33-2.41(m, 6H),2.48-2.56(m,1H),3.68(d,J=10.3Hz,1H),3.87(d,J=10.3Hz,1H),6.91-6.95(m, 3H),7.02-7.06(m,3H),8.12(d,J=8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=171.61,162.26(d,1J(C–F)=242.2Hz),140.24,138.39,137.40(d,4J(C–F)=3.0Hz),133.30,129.55(d, 3J(C–F)=7.7Hz),128.53,122.87,116.66,115.13(d,2J(C–F)=21.0Hz),60.42,43.60,30.29, 29.12,27.18,21.16,8.75;19F NMR(376MHz,CDCl3)δ=-117.54(m,1F);HRMS (ESI-TOF)Calcd for C21H25FNO+([M+H]+)326.1915.Found 326.1919.
2j,1-(3,5-二甲基-3-(3,5-二甲基苯乙基)吲哚啉-1-基)-1-辛酮,浅黄色油状物.1H NMR (400MHz,CDCl3)δ=0.88(t,J=6.8Hz,3H),1.26-1.39(m,11H),1.68-1.76(m,2H), 1.85-1.97(m,2H),2.17-2.42(m,12H),2.45-2.52(m,1H),3.67(d,J=10.3Hz,1H),3.89(d, J=10.3Hz,1H),6.72(s,2H),6.80(s,1H),6.92(s,1H),7.02(d,J=8.4Hz,1H),8.11(d,J =8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=171.11,141.77,140.21,138.78,137.94, 133.23,128.41,127.55,126.08,122.90,116.70,60.60,43.60,43.46,35.99,31.77,30.90, 29.43,29.19,27.10,24.67,22.67,21.24,21.17,14.11;HRMS(ESI-TOF)Calcd for C28H40NO+([M+H]+)406.3104.Found 406.3108.
2k,1-(3,5-二甲基-3-(2-(全氟苯基)乙基吲哚啉-1-基)-1-丙酮,无色晶体:mp94-95℃.1H NMR(400MHz,CDCl3)δ=1.25(t,J=7.4Hz,3H),1.41(s,3H),1.80-1.92(m,2H),2.33 (s,3H),2.40-2.52(m,3H),2.59-2.69(m,1H),3.76(d,J=10.4Hz,1H),3.98(d,J=10.5Hz, 1H),6.92(s,1H),7.04(d,J=8.3Hz,1H),8.11(d,J=8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=171.63,140.21,137.37,133.51,128.80,122.71,116.74,59.91,43.61,40.74,29.21,27.22,21.10,17.99,8.78;19F NMR(376MHz,CDCl3)δ=-144.93(m,2F),-157.53 (m,1F),-162.59(m,2F);HRMS(ESI-TOF)Calcd for C21H21F5NO+([M+H]+)398.1538. Found398.1540.
3a,2,4-二甲基-4-苯乙基-3,4-二氢异喹啉-1(2H)-酮,黄色油状物.1H NMR(400MHz, CDCl3)δ=1.41(s,3H),1.86-2.02(m,2H),2.37-2.44(m,1H),2.55-2.62(m,1H),3.14(s, 3H),3.30(d,J=12.5Hz,1H),3.51(d,J=12.6Hz,1H),7.08(d,J=7.3Hz,2H),7.16(dd,J =7.4,7.4Hz,1H),7.23(dd,J=7.5,7.5Hz,2H),7.29(d,J=7.8Hz,1H),7.35(dd,J=7.5, 7.6Hz,1H),7.48(dd,J=7.5,7.5Hz,1H),8.13(d,J=7.7Hz,1H);13C NMR(100MHz, CDCl3)δ=164.54,145.13,141.82,131.72,128.68,128.48,128.31,128.24,126.88,125.98, 124.26,58.62,41.59,37.33,35.34,30.95,23.21;HRMS(ESI-TOF)Calcdfor C19H22NO+ ([M+H]+)280.1696.Found 280.1692.
3b,2,4-二甲基-4-(2-甲基苯乙基)-3,4-二氢异喹啉-1(2H)-酮,无色油状物.1HNMR(400 MHz,CDCl3)δ=1.44(s,3H),1.77-1.92(m,2H),2.13(s,3H),2.34-2.42(m,1H),2.53-2.61(m,1H),3.16(s,3H),3.31(d,J=12.5Hz,1H),3.55(d,J=12.5Hz,1H), 7.00-7.19(m,4H),7.31(d,J=7.7Hz,1H),7.36(dd,J=6.8,7.5Hz,1H),7.48(ddd,J=1.2, 7.6,7.4Hz,1H),8.14(d,J=6.8Hz,1H);13C NMR(100MHz,CDCl3)δ=164.52,145.11, 139.93,135.56,131.68,130.32,128.76,128.69,128.30,126.91,126.15,126.13,124.29, 58.70,40.52,37.32,35.37,28.24,22.91,18.95;HRMS(ESI-TOF)Calcd for C20H24NO+ ([M+H]+)294.1852.Found 294.1851.
4a,1-(3-苯乙基吲哚啉-1-基)-1-乙酮,无色油状物.1H NMR(400MHz,CDCl3)δ=1.86-1.95(m,1H),2.13-2.18(m,1H),2.20(s,3H),2.72(t,J=7.4Hz,2H),3.40-3.47(m,1H),3.68(dd,J=6.0,10.3Hz,1H),4.14(dd,J=9.9,9.9Hz,1H),7.03(dd,J=7.4,7.4Hz,1H),7.17-7.23(m,5H),7.31(dd,J=7.1,7.6Hz,2H),8.20(d,J=8.0Hz,1H);13C NMR(100MHz,CDCl3)δ=168.66,142.69,141.31,134.73,128.57,128.35,127.96,126.18,123.78,123.66,117.00,54.98,39.71,37.01,33.24,24.25;HRMS(ESI-TOF)Calcd forC18H20NO+([M+H]+)266.1539.Found 266.1538.
4b,1-(5-甲基-3-苯乙基吲哚啉-1-基)-1-乙酮,浅黄色油状物.1H NMR(400MHz,CDCl3)δ=1.84-1.93(m,1H),2.12-2.20(m,4H),2.31(s,3H),2.69-2.74(m,2H), 3.36-3.43(m,1H),3.66(dd,J=6.0,10.4Hz,1H),4.12(dd,J=9.9,9.9Hz,1H),6.98-7.02 (m,2H),7.19-7.23(m,3H),7.29-7.32(m,2H),8.07(d,J=8.2Hz,1H);13C NMR(100MHz, CDCl3)δ=168.31,141.35,140.40,134.85,133.26,128.55,128.39,128.35,126.15,124.39,116.69,55.09,39.69,36.99,33.28,24.14,21.08;HRMS(ESI-TOF)Calcd for C19H22NO+ ([M+H]+)280.1696.Found 280.1699.
4c,1-(3-苯乙基-5-氯吲哚啉-1-基)-1-乙酮,白色固体:mp 88-89℃.1H NMR(400MHz, CDCl3)δ=1.85-1.95(m,1H),2.10-2.23(m,4H),2.69-2.74(m,2H),3.37-3.44(m,1H), 3.69(dd,J=6.1,10.4Hz,1H),4.14(dd,J=9.9,9.9Hz,1H),7.13-7.24(m,5H),7.29-7.33 (m,2H),8.13(d,J=8.6Hz,1H);13C NMR(100MHz,CDCl3)δ=168.64,141.35,140.93, 136.69,128.63,128.52,128.33,127.88,126.31,123.99,117.88,55.05,39.50,36.80,33.12, 24.10;HRMS(ESI-TOF)Calcd for C18H19ClNO+([M+H]+)300.1150.Found300.1161.
4d,1-(5-甲基-3-苯乙基吲哚啉-1-基)-1-丙酮,白色固体:mp 83-84℃.1H NMR(400MHz, CDCl3)δ=1.22(t,J=7.4Hz,3H),1.83-1.92(m,1H),2.11-2.20(m,1H),2.31(s,3H), 2.40(q,J=7.4Hz,2H),2.69-2.73(m,2H),3.35-3.42(m,1H),3.66(dd,J=5.9,10.3Hz, 1H),4.11(dd,J=9.9,9.9Hz,1H),6.98-7.02(m,2H),7.19-7.22(m,3H),7.28-7.32(m,2H), 8.11(d,J=8.2Hz,1H);13C NMR(100MHz,CDCl3)δ=171.64,141.39,140.65,134.74, 133.08,128.54,128.40,128.35,126.13,124.37,116.64,54.11,39.72,37.04,33.27,29.08, 21.07,8.76;HRMS(ESI-TOF)Calcd for C20H24NO+([M+H]+)294.1852.Found294.1850.
4e,1-(5-甲基-3-苯乙基吲哚啉-1-基)-1-辛酮,无色油状物.1H NMR(400MHz,CDCl3)δ =0.89(t,J=6.8Hz,3H),1.29-1.40(m,8H),1.68-1.75(m,2H),1.83-1.92(m,1H), 2.11-2.19(m,1H),2.30(s,3H),2.36(t,J=7.6Hz,2H),2.71(t,J=6.9Hz,2H),3.34-3.41 (m,1H),3.66(dd,J=6.0,10.3Hz,1H),4.11(dd,J=9.8,9.9Hz,1H),6.97-7.01(m,2H), 7.19-7.22(m,3H),7.28-7.32(m,2H),8.10(d,J=8.1 Hz,1H);13C NMR(100 MHz,CDCl3) δ=171.14,141.41,140.64,134.80,133.09,128.54,128.38,128.36,126.13,124.35,116.73, 54.30,39.72,37.03,35.95,33.30,31.76,29.42,29.19,24.65,22.67,21.07,14.12;HRMS (ESI-TOF)Calcd for C25H34NO+([M+H]+)364.2635.Found 364.2628.
Claims (9)
1.一种非活化烯烃苄基化合成苄基化吲哚啉类化合物(式II化合物)的方法,其特征在于,反应路线如下:
其中:
A为C或N;
R1是氢、卤素、C1-6烷基或苯基;
R2是氢或C1-6烷基;
R3是COR5、SO2R6、C1-6烷基;
R4是氢、卤素或C1-6烷基;
R5是C1-17烷基或-O-C1-6烷基;
R6是C1-6烷基;
所述催化剂包含催化剂1或/和催化剂2,所述催化剂1选自TBAI、CuBr、Cu(OAc)2、AgNO3、FeCl3·6H2O、FeCl2·4H2O、CoCl2·6H2O、NiCl2·6H2O、MnCl2·4H2O、Mn(OAc)3·2H2O、MnO2、KMnO4或MnCl2·4H2O;所述催化剂2选自DTBP、TBHP、DCP、BPO、TBPB或K2S2O8。
2.如权利要求1所述的方法,其特征在于:所述卤素为氟、氯、溴或碘。
3.如权利要求2所述的方法,其特征在于:所述卤素为氟、氯或溴。
4.如权利要求1-3任一项所述的方法,其特征在于:所述C1-6烷基选自甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基或异己基。
5.如权利要求4所述的方法,其特征在于:所述C1-6烷基选自甲基、乙基、丙基、异丙基、叔丁基或异丁基。
6.如权利要求1-3任一项所述的方法,其特征在于:所述-O-C1-6烷基选自甲氧基、乙氧基或叔丁氧基。
7.如权利要求1-3任一项所述的方法,其特征在于:所述R1选自氢、甲基、氟、氯、溴或苯基;R2选自氢或甲基;R4是氢、卤素或甲基;R5选自甲基、乙基、n-C7H15、n-C9H19、n-C11H23、n-C17H35、t-Bu或叔丁氧基;R6选自甲基或乙基。
8.如权利要求1-3任一项所述的方法,其特征在于:所述催化剂1选自MnCl2·4H2O、Mn(OAc)3·2H2O、MnO2、KMnO4或MnCl2·4H2O;所述催化剂2为DTBP。
9.式II化合物选自:
1-(3-甲基-3-苯乙基吲哚啉-1-基)-1-乙酮;
1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-乙酮;
1-(3-甲基-3-苯乙基-5-溴吲哚啉-1-基)-1-乙酮;
1-(3-甲基-3-苯乙基-5-氯吲哚啉-1-基)-1-乙酮;
1-(3-甲基-3-苯乙基-5-苯基吲哚啉-1-基)-1-乙酮;
1-(3-甲基-3-苯乙基-2,3-二氢-1H-吡咯并[3,2-c]吡啶-1-基)-1-乙酮;
1-(3-甲基-3-苯乙基吲哚啉-1-基)-1-丙酮;
1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-辛酮;
1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-癸酮;
1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-十二酮;
1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-十八酮;
2,2-二甲基-1-(3,5-二甲基-3-苯乙基吲哚啉-1-基)-1-丙酮;
3,5-二甲基-3-苯乙基吲哚啉-1-甲酸叔丁酯;
3-甲基-3-苯乙基-1-乙磺酰基-5-氯吲哚啉;
1-(3-甲基-3-苯乙基-4,6-二氯吲哚啉-1-基)-1-辛酮;
1-(3,5-二甲基-3-(2-甲基苯乙基)吲哚啉-1-基)-1-辛酮;
1-(3,5-二甲基-3-(3-甲基苯乙基)吲哚啉-1-基)-1-辛酮;
1-(3,5-二甲基-3-(4-甲基苯乙基)吲哚啉-1-基)-1-辛酮;
1-(3,5-二甲基-3-(2-氯苯乙基)吲哚啉-1-基)-1-丙酮;
1-(3,5-二甲基-3-(3-氯苯乙基)吲哚啉-1-基)-1-丙酮;
1-(3,5-二甲基-3-(4-氯苯乙基)吲哚啉-1-基)-1-丙酮;
1-(3,5-二甲基-3-(4-氟苯乙基)吲哚啉-1-基)-1-丙酮;
1-(3,5-二甲基-3-(3,5-二甲基苯乙基)吲哚啉-1-基)-1-辛酮;
1-(3,5-二甲基-3-(2-(全氟苯基)乙基吲哚啉-1-基)-1-丙酮;
2,4-二甲基-4-苯乙基-3,4-二氢异喹啉-1(2H)-酮;
2,4-二甲基-4-(2-甲基苯乙基)-3,4-二氢异喹啉-1(2H)-酮;
1-(3-苯乙基吲哚啉-1-基)-1-乙酮;
1-(5-甲基-3-苯乙基吲哚啉-1-基)-1-乙酮;
1-(3-苯乙基-5-氯吲哚啉-1-基)-1-乙酮;
1-(5-甲基-3-苯乙基吲哚啉-1-基)-1-丙酮;
1-(5-甲基-3-苯乙基吲哚啉-1-基)-1-辛酮。
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