CN114436943A - 一种双重氧化脱氢芳构化合成螺环吲哚类化合物的方法 - Google Patents
一种双重氧化脱氢芳构化合成螺环吲哚类化合物的方法 Download PDFInfo
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 19
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims abstract description 15
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims abstract description 15
- -1 spiro indole compound Chemical class 0.000 title claims abstract description 15
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 9
- 230000001590 oxidative effect Effects 0.000 title claims description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052802 copper Inorganic materials 0.000 claims abstract description 10
- 239000010949 copper Substances 0.000 claims abstract description 10
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims abstract description 6
- 125000003003 spiro group Chemical group 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000012298 atmosphere Substances 0.000 claims abstract description 4
- 239000003960 organic solvent Substances 0.000 claims abstract description 4
- TXOLGHRJRRYOHA-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical class N1C2=CC=CC=C2C=C1C1=CC=CC=C1.N1C2=CC=CC=C2C=C1C1=CC=CC=C1 TXOLGHRJRRYOHA-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229940125782 compound 2 Drugs 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 150000002475 indoles Chemical class 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 239000007800 oxidant agent Substances 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 3
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 3
- 229940125904 compound 1 Drugs 0.000 claims description 3
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 3
- JIDMEYQIXXJQCC-UHFFFAOYSA-L copper;2,2,2-trifluoroacetate Chemical group [Cu+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F JIDMEYQIXXJQCC-UHFFFAOYSA-L 0.000 claims description 3
- ZKXWKVVCCTZOLD-UHFFFAOYSA-N copper;4-hydroxypent-3-en-2-one Chemical compound [Cu].CC(O)=CC(C)=O.CC(O)=CC(C)=O ZKXWKVVCCTZOLD-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 238000005899 aromatization reaction Methods 0.000 abstract description 4
- 230000007547 defect Effects 0.000 abstract description 4
- 238000005839 oxidative dehydrogenation reaction Methods 0.000 abstract description 4
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- 239000011261 inert gas Substances 0.000 abstract 1
- 229910000510 noble metal Inorganic materials 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 6
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical group [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- HUIJGZIKPZNLMP-UHFFFAOYSA-N C(C=C1)=CC=C1C(NC1=CC=CC=C11)=C1C(C=CC=C1)=C1C1=CC=CC=C1 Chemical compound C(C=C1)=CC=C1C(NC1=CC=CC=C11)=C1C(C=CC=C1)=C1C1=CC=CC=C1 HUIJGZIKPZNLMP-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- BSPJVRORVHKCQW-UHFFFAOYSA-N indeno[2,1-b]indole Chemical group C1=CC=C2C3=C4C=CC=CC4=CC3=NC2=C1 BSPJVRORVHKCQW-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- SVQQZZGNPVUCGR-UHFFFAOYSA-N C(C=C1)=CC=C1C(NC1=CC=CC=C11)=C1C(C=CC=C1)=C1C(C=C1)=CC=C1C1=CC=CC=C1 Chemical compound C(C=C1)=CC=C1C(NC1=CC=CC=C11)=C1C(C=CC=C1)=C1C(C=C1)=CC=C1C1=CC=CC=C1 SVQQZZGNPVUCGR-UHFFFAOYSA-N 0.000 description 1
- ABSBNHAOBRZLFM-UHFFFAOYSA-N C(C=C1)=CC=C1C(NC1=CC=CC=C11)=C1C(C=CC=C1)=C1C1=CC=CC2=C1OC1=C2C=CC=C1 Chemical compound C(C=C1)=CC=C1C(NC1=CC=CC=C11)=C1C(C=CC=C1)=C1C1=CC=CC2=C1OC1=C2C=CC=C1 ABSBNHAOBRZLFM-UHFFFAOYSA-N 0.000 description 1
- YPMYOMCWOHYVID-UHFFFAOYSA-N CC(C=C1)=CC=C1C(C=CC=C1)=C1C1=C(C2=CC=CC=C2)NC2=CC=CC=C12 Chemical compound CC(C=C1)=CC=C1C(C=CC=C1)=C1C1=C(C2=CC=CC=C2)NC2=CC=CC=C12 YPMYOMCWOHYVID-UHFFFAOYSA-N 0.000 description 1
- SZPFIMTWAAZWFY-UHFFFAOYSA-N COC(C=C1)=CC=C1C(C=CC=C1)=C1C1=C(C2=CC=CC=C2)NC2=CC=CC=C12 Chemical compound COC(C=C1)=CC=C1C(C=CC=C1)=C1C1=C(C2=CC=CC=C2)NC2=CC=CC=C12 SZPFIMTWAAZWFY-UHFFFAOYSA-N 0.000 description 1
- CCTLBLQFSLQOJL-UHFFFAOYSA-N ClC(C=C1)=CC=C1C(C=CC=C1)=C1C1=C(C2=CC=CC=C2)NC2=CC=CC=C12 Chemical compound ClC(C=C1)=CC=C1C(C=CC=C1)=C1C1=C(C2=CC=CC=C2)NC2=CC=CC=C12 CCTLBLQFSLQOJL-UHFFFAOYSA-N 0.000 description 1
- 229910002567 K2S2O8 Inorganic materials 0.000 description 1
- QFRGCXGKLNTZRG-UHFFFAOYSA-K [Cu+3].CC([O-])=O.CC([O-])=O.CC([O-])=O Chemical compound [Cu+3].CC([O-])=O.CC([O-])=O.CC([O-])=O QFRGCXGKLNTZRG-UHFFFAOYSA-K 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical group Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical group Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 238000005890 dearylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical group COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 238000007154 radical cyclization reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/96—Spiro-condensed ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
本发明公开了一种通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,属于有机化学技术领域。以取代2‑苯基1H‑吲哚1为原料,在铜催化剂和过硫酸钾存在下,惰性气体气氛下,有机溶剂中反应得到螺环吲哚化合物2。本发明采用非贵金属铜为催化剂,避免了传统制备方法中催化成本高的缺点;采用该方法可制备不同取代的螺环吲哚化合物,为该类化合物提供了一种简单、有效、便捷的合成方法。
Description
技术领域
本发明属于有机化学技术领域,具体涉及一种通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法。
背景技术
螺环二氢吲哚是药学相关化合物和生物活性天然产物中的重要核心结构骨架,此外,螺环吲哚独特的刚性结构也使其在有机光电子学中的应用中发挥着不可替代的作用。
在合成化学和材料科学中已经报道了许多方法构建功能化的螺环吲哚,如分子内Pd催化3-取代吲哚脱芳基化同时使用三苯基膦作为配体在C-3位生成含季碳中心的各种螺环吲哚;使用钯/降冰片烯(Pd/NBE)协同催化对吲哚基联芳基与溴烷基炔烃的高度化学选择性分子间环化;使用非手性Xantphos和手性亚磺酰胺膦配体(PC-Phos)作为共配体,钯催化3-芳基吲哚与内部炔烃分子间动力学不对称脱芳构化合成各种生物碱和含有手性的螺环吲哚药物骨架。
尽管取得了这些进展,但吲哚衍生物的氧化脱氢脱芳构化仍然报道较少,此外,构建这些化合物的经典方法通常需要涉及自由基引发、自由基加成和环化的多步步骤。特别值得注意的是,过渡金属催化的吲哚衍生物的脱氢芳构化已被认为是合成螺环吲哚的有前景的途径。
发明内容
为了克服上述所指出的诸多缺陷,进而寻求合成取代螺环吲哚类化合物的简便方法,本发明公开了一种简单、有效、便捷合成螺环吲哚类化合物的方法。从简单易得试剂出发,经由简便的操作步骤,在温和反应条件下,经过一步反应即可得到含有芴和茚并[2,1-b]吲哚基团的螺环吲哚,避免了传统合成方法原料复杂、催化成本高等弊端,成功合成了不同系列螺环吲哚类化合物。
通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,采用方程式表示为:
包括以下操作:以取代2-苯基1H-吲哚1为原料、在氧化剂和铜催化剂存在下,有机溶剂中反应,得到螺环吲哚类化合物2;
其中,R为氢、C1-C4烷基、C1-C4烷氧基、卤素或杂环取代基。
进一步地,上述取代基更具体而言,R选自氢、甲基、甲氧基、氯、苯基、苯并呋喃等。更具体地,化合物1为3-([1,1'-联苯]-2-基)-2-苯基-1H-吲哚,3-(4'-甲基-[1,1'-联苯]-2-基)-2-苯基-1H-吲哚,3-(4'-甲氧基-[1,1'-联苯]-2-基)-2-苯基-1H-吲哚,3-(4'-氯-[1,1'-联苯]-2-基)-2-苯基-1H-吲哚,3-([1,1':4',1”-三联苯]-2-基)-2-苯基-1H-吲哚,3-(2-(二苯并[b,d]呋喃-4-基)苯基)-2-苯基-1H-吲哚。
进一步地,在上述技术方案中,所述氧化剂选自过硫酸钠、过硫酸钾、过硫酸铵中的任意一种。优选氧化剂为过硫酸钾。
进一步地,在上述技术方案中,所述反应温度选自-10℃至25℃;更进一步地,优化温度为0℃。
进一步地,在上述技术方案中,所述反应溶剂选自TFA(三氟乙酸)、DCE(二氯乙烷)中的一种或两种;更进一步地,优选溶剂为DCE/TFA=1/1。
进一步地,在上述技术方案中,所述铜催化剂选自醋酸铜、三氟乙酸铜、三氟甲磺酸铜、乙酰丙酮铜。优选催化剂为醋酸铜铜;优选条件下,铜催化剂加入量为10mmol%。
进一步地,在上述技术方案中,所述吲哚类化合物1、氧化剂与铜催化剂摩尔比为1:1-1.2:0.05-0.1,在该比例下,反应效果最佳。
进一步地,在上述技术方案中,反应在惰性氛围下进行,优选在氮气保护下进行。
进一步地,为了更好的理解本发明,以3-([1,1'-联苯]-2-基)-2-苯基-1H-吲哚,以三醋酸铜为催化剂、DCE/TFA为溶剂和氮气条件为例,结果如下:在氮气保护下,将0.3mmol 3-([1,1'-联苯]-2-基)-2-苯基-1H-吲哚1、0.36mmol过硫酸钾、10mol%醋酸铜催化剂和2mL溶剂(DCE:TFA=1:1)依次加入到Schlenk反应管中,经液氮脱气处理后,在低温泵中0℃条件下搅拌反应24h。反应结束后,真空减压浓缩除去TFA,然后用二氯甲烷(3×20mL)和蒸馏水萃取。合并有机相并用无水硫酸钠干燥有机相。柱层析分离得到目标产物2a,收率为69%,改变其它反应条件时,结果如下:
1)将氧化剂更换为过硫酸钠或过硫酸铵,得到产物2a,收率为41%或40%。
2)将铜催化剂更换为三氟乙酸铜、氯化铜、溴化铜、三氟甲磺酸铜、乙酰丙酮铜,产物2a收率分别为67%,trace,trace,43%,49%。
3)将反应温度升高至25℃或降低至-10℃,产物2a收率为45%或65%。
4)将反应溶剂更换为TFA,产物2a收率为53%。
根据以上反应结果,推测反应机理为:
发明有益效果
本发明从简单易得试剂出发,经由简便的操作步骤,在温和反应条件下,经过一步反应即可得到含有芴和茚并[2,1-b]吲哚基团的螺环吲哚,避免了传统合成方法原料复杂、催化成本高等弊端,成功合成了不同系列螺环吲哚类化合物。
具体实施例
通过以下实例对本发明的上述内容做进一步详细说明,但不应该将此理解为本发明上述主题的范围仅限于以下实例,凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1-6
在氮气气氛下,将0.3mmol化合物1a-1f、0.36mmol过硫酸钾、10mol%醋酸铜催化剂和2mL溶剂(TFA/DCE=1/1)依次加入到Schlenk反应管中,经液氮脱气处理后在低温泵中0℃条件下搅拌反应24h。反应结束后,真空减压浓缩除去TFA,然后用二氯甲烷(3×20mL)和蒸馏水萃取。合并有机相并用无水硫酸钠干燥有机相。通过柱层析法分离得到目标产物2a-2f,结果如下:
Standaed condition:1(1.0equiv,0.3mmol),Cu(OAc)2(10mol%,0.03mmol),K2S2O8(1.2equiv,0.36mmol),Solvent(2mL),N2,0℃,24h.
化合物2a-2f表征数据如下:
6′-(3-([1,1′-Biphenyl]-4-yl)-2-phenyl-3H-indol-3-yl)-2′-phenylspiro[fluorene-9,3′-indole](2a),69%;1H NMR(400MHz,CDCl3)δ7.85(d,J=7.2Hz,5H),7.76(d,J=8.0Hz,1H),7.40-7.24(m,14H),6.18(t,J=7.2Hz,2H),7.13-7.05(m,4H),7.03-6.95(m,4H),6.84-6.76(m,3H),6.38(d,J=8.0Hz,1H);13C{1H}NMR(101MHz,CDCl3)δ180.3,178.5,155.9,144.6,144.6,143.3,142.2,141.7,141.7,139.6,138.4,132.6,132.3,130.9,130.7,129.7,129.6,128.5,128.4,128.3,128.2,128.1,128.0,127.5,127.2,126.8,126.2,124.3,124.1,124.1,122.6,121.8,121.4,120.9,71.4.HRMS,calculatedfor C52H35N2(M+H+):687.2795,found 687.2790.
2-Methyl-6′-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-2-phenyl-3H-indol-3-yl)-2′-phenylspiro[fluorene-9,3′-indole](2b),53%;1H NMR(400MHz,CDCl3)δ7.86-7.71(m,7H),7.41-7.26(m,14H),7.20-7.16(m,3H),7.09-7.04(m,3H),6.96(d,J=7.2Hz,1H),6.76(t,J=8.4Hz,1H),6.58(d,J=6.8Hz,2H),6.41-6.37(m,1H),2.20(s,6H);13C{1H}NMR(101MHz,CDCl3)δ180.3,178.6,156.8,155.8,154.3,148.0,145.0,144.8,144.7,144.5,144.5,143.4,142.6,142.3,141.9,141.8,141.0,139.2,139.1,139.0,138.6,138.4,138.4,136.7,136.1,134.7,132.7,132.3,130.8,130.8,130.7,130.4,129.6,129.4,129.4,128.8,128.5,128.4,128.3,128.2,128.1,128.1,127.9,127.8,127.8,127.3,127.1,126.1,125.8,124.6,124.5,124.3,124.0,123.9,122.5,122.4,122.3,121.6,121.4,120.7,120.6,120.5,119.7,71.2,21.6,21.6,21.3.HRMS,calculated forC54H39N2(M+H+):715.3108,found 715.3107.
2-Methoxy-6'-(3-(4'-methoxy-[1,1'-biphenyl]-4-yl)-2-phenyl-3H-indol-3-yl)-2'-phenylspiro[fluorene-9,3'-indole](2c),50%;1H NMR(400 MHz,CDCl3)δ7.85-7.79(m,3H),7.75(dd,J=8.4,2.4 Hz,3H),7.41-7.24(m,13H),7.19(t,J=7.2 Hz,2H),7.09-6.89(m,7H),6.76-6.71(m,1H),6.40(d,J=8.0 Hz,1H),6.30-6.27(m,2H),3.69(s,3H),3.60(s,3H);13C{1H}NMR(101 MHz,CDCl3)δ180.3,178.6,160.2,158.3,155.8,146.4,144.1,143.0,142.3,141.7,138.9,134.6,134.6,132.9,132.3,132.1,130.9,130.7,129.6,128.5,128.4,128.3,128.1,128.1,127.4,127.2,127.1,126.2,124.3,124.3,123.9,123.9,122.5,122.4,121.7,121.7,121.5,120.0,114.5,111.9,109.5,71.3,55.6,55.2.HRMS,calculated for C54H39N2O2(M+H+):747.3006,found 747.3006.
2-Chloro-6'-(3-(4'-chloro-[1,1'-biphenyl]-4-yl)-2-phenyl-3H-indol-3-yl)-2'-phenylspiro[fluorene-9,3'-indole](2d),60%;1H NMR(400 MHz,CDCl3)δ7.94(d,J=7.6Hz,2H),7.87(dd,J=8.4,2.8 Hz,1H),7.79(d,J=4.4 Hz,1H),7.60-7.51(m,1H),7.44-7.21(m,15H),7.16-7.02(m,5H),6.89(t,J=7.2 Hz,1H),6.82-6.75(m,4H),6.52(dd,J=18.4,8.0 Hz,2H);13C{1H}NMR(101 MHz,CDCl3)δ180.7,148.4,142.3,142.2,141.1,140.1,140.0,138.6,138.1,135.6,135.5,132.9,132.8,132.5,132.3,132.3,132.2,131.8,131.3,130.9,130.4,130.4,130.2,130.1,129.9,129.8,128.4,128.3,128.1,128.0,127.9,127.7,127.6,127.5,127.3,127.2,127.2,126.5,126.1,124.2,123.8,123.5,121.7,119.2,113.4,113.4,111.2,111.1,71.4,29.8.HRMS,calculated forC52H33Cl2N2(M+H+):755.2015,found 755.2015.
6'-(3-([1,1':4',1”-Terphenyl]-4-yl)-2-phenyl-3H-indol-3-yl)-2,2'-diphenylspiro[fluorene-9,3'-indole](2e),49%;1H NMR(400 MHz,CDCl3)δ8.00-7.83(m,6H),7.61(t,J=6.4 Hz,1H),7.50-7.20(m,22H),7.15-6.96(m,11H),6.77(s,1H),6.47-6.40(m,1H);13C{1H}NMR(101MHz,CDCl3)δ180.1,178.5,155.9,148.0,145.3,144.9,144.8,143.1,142.0,142.0,141.3,140.8,140.5,140.4,139.1,138.6,138.2,134.5,132.4,132.2,131.1,130.9,130.4,129.9,129.6,129.3,128.8,128.7,128.5,128.3,128.2,128.1,127.9,127.5,127.1,126.9,126.1,126.0,125.0,124.1,124.1,122.6,122.5,121.6,121.2,120.9,71.2.HRMS,calculated for C64H43N2(M+H+):839.3421,found839.3426.
6'-(3-(4-(Dibenzo[b,d]furan-2-yl)phenyl)-2-phenyl-3H-indol-3-yl)-2'-phenylspiro[fluoreno[2,3-b]benzofuran-7,3'-indole](2f),55%;1H NMR(400MHz,CDCl3)δ8.37-8.33(m 1H),8.07-8.04(m,3H),7.97(d,J=8.4Hz,1H),7.85-7.78(m,1H),7.74-7.62(m,3H),7.57(dd,J=14.4,7.6Hz,2H),7.49-7.16(m,15H),7.12-6.91(m,8H),6.84(d,J=8.0Hz,1H),6.77-6.67(m,2H),6.46-6.30(m,2H),6.19-6.00(m,1H);13C{1H}NMR(101MHz,CDCl3)δ180.0,179.9,178.2,178.1,156.8,156.0,155.9,155.5,153.4,152.6,152.4,150.8,148.1,146.2,144.5,144.4,144.0,143.9,142.3,141.7,141.4,139.5,139.2,138.4,137.7,136.9,134.5,133.2,132.6,132.2,131.3,130.9,130.5,129.9,129.7,129.2,128.8,128.8,128.6,128.5,128.4,128.4,128.2,128.1,128.0,127.9,127.4,127.4,127.3,127.0,126.6,126.4,126.2,125.9,125.1,124.9,124.5,124.5,124.4,124.2,124.1,124.0,124.0,123.8,123.2,123.2,122.5,122.4,122.3,121.7,121.6,121.4,121.3,121.2,120.7,120.4,120.3,120.1,119.9,118.4,112.0,111.8,111.6,71.9,71.4.HRMS,calculated for C64H38N2NaO2(M+Na+):889.2825,found889.2833.
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明原理的范围下,本发明还会有各种变化和改进,这些变化和改进均落入本发明保护的范围内。
Claims (8)
2.根据权利要求1所述通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,其特征在于:所述氧化剂选自过硫酸钾、过硫酸钠或过硫酸铵。
3.根据权利要求1所述通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,其特征在于:所述铜催化剂选自三氟乙酸铜、三氟甲磺酸铜或乙酰丙酮铜。
4.根据权利要求1所述通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,其特征在于:所述有机溶剂选自TFA或DCE/TFA。
5.根据权利要求1所述通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,其特征在于:所述取代吲哚类化合物1、氧化剂与铜催化剂摩尔比为1:1-1.2:0.05-0.1。
6.根据权利要求1所述通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,其特征在于:所述反应温度为-10℃至25℃。
7.根据权利要求1所述通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,其特征在于:反应在惰性氛围下进行。
8.根据权利要求1所述通过双重氧化脱氢芳构化合成螺环吲哚类化合物的方法,其特征在于:惰性氛围为氮气保护下。
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