CN115772171A - Method for synthesizing spiro [ indoline-3, 3' -piperidine ] skeleton under catalysis of monovalent gold - Google Patents
Method for synthesizing spiro [ indoline-3, 3' -piperidine ] skeleton under catalysis of monovalent gold Download PDFInfo
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- CN115772171A CN115772171A CN202111055275.1A CN202111055275A CN115772171A CN 115772171 A CN115772171 A CN 115772171A CN 202111055275 A CN202111055275 A CN 202111055275A CN 115772171 A CN115772171 A CN 115772171A
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- indole
- indoline
- piperidine
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- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 229910052737 gold Inorganic materials 0.000 title claims abstract description 54
- 239000010931 gold Substances 0.000 title claims abstract description 54
- GNBNUSQSICJAFE-UHFFFAOYSA-N spiro[1,2-dihydroindole-3,3'-piperidine] Chemical group C1NC2=CC=CC=C2C11CCCNC1 GNBNUSQSICJAFE-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 title claims description 8
- 238000006555 catalytic reaction Methods 0.000 title description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 49
- 239000000758 substrate Substances 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- -1 N-propargyl methylene indole Chemical compound 0.000 claims abstract description 21
- 239000012434 nucleophilic reagent Substances 0.000 claims abstract description 7
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 4
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 153
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 52
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 29
- 238000003756 stirring Methods 0.000 claims description 28
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 27
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 26
- 150000002475 indoles Chemical class 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 229940054051 antipsychotic indole derivative Drugs 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000012038 nucleophile Substances 0.000 claims description 4
- 239000012041 precatalyst Substances 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- CGLATYVMTSUOJA-UHFFFAOYSA-N [Au+2].[N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.[N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [Au+2].[N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.[N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1 CGLATYVMTSUOJA-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- IFPWCRBNZXUWGC-UHFFFAOYSA-M gold(1+);triphenylphosphane;chloride Chemical group [Cl-].[Au+].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 IFPWCRBNZXUWGC-UHFFFAOYSA-M 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- ZXMGHDIOOHOAAE-UHFFFAOYSA-N 1,1,1-trifluoro-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical group FC(F)(F)S(=O)(=O)NS(=O)(=O)C(F)(F)F ZXMGHDIOOHOAAE-UHFFFAOYSA-N 0.000 claims 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims 1
- 229910052709 silver Inorganic materials 0.000 claims 1
- 239000004332 silver Substances 0.000 claims 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000001308 synthesis method Methods 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- 239000000203 mixture Substances 0.000 description 37
- 229910003771 Gold(I) chloride Inorganic materials 0.000 description 34
- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 description 34
- 238000004809 thin layer chromatography Methods 0.000 description 34
- 229910052757 nitrogen Inorganic materials 0.000 description 33
- 230000003595 spectral effect Effects 0.000 description 33
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 32
- 239000007858 starting material Substances 0.000 description 32
- 238000001914 filtration Methods 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 25
- 238000010898 silica gel chromatography Methods 0.000 description 25
- 238000002156 mixing Methods 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 235000002597 Solanum melongena Nutrition 0.000 description 2
- 244000061458 Solanum melongena Species 0.000 description 2
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 description 1
- QJRWYBIKLXNYLF-UHFFFAOYSA-N 6-methoxy-1h-indole Chemical compound COC1=CC=C2C=CNC2=C1 QJRWYBIKLXNYLF-UHFFFAOYSA-N 0.000 description 1
- KGWPHCDTOLQQEP-UHFFFAOYSA-N 7-methylindole Chemical compound CC1=CC=CC2=C1NC=C2 KGWPHCDTOLQQEP-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- URGUJYLTSUVAFP-UHFFFAOYSA-N [N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.[N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.[Ag+2] Chemical group [N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.[N-](S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F.[Ag+2] URGUJYLTSUVAFP-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001361 allenes Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- LJXTYJXBORAIHX-UHFFFAOYSA-N diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1 LJXTYJXBORAIHX-UHFFFAOYSA-N 0.000 description 1
- 229930005303 indole alkaloid Natural products 0.000 description 1
- 238000001871 ion mobility spectroscopy Methods 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
Classifications
-
- 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
- Y02P20/584—Recycling of catalysts
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
A synthesis method of spiro [ indoline-3, 3' -piperidine ] skeleton catalyzed by monovalent gold belongs to the field of organic chemical synthesis, wherein the monovalent gold is used as a catalyst, an N-propargyl methylene indole substrate directly generates intramolecular cyclization reaction under mild conditions, and an obtained intermediate is rapidly captured by a nucleophilic reagent to generate the spiro [ indoline-3, 3-piperidine ] skeleton. From the chemical perspective, the method has the advantages of good atom economy, mild reaction conditions and simple operation; from the industrial and environmental perspectives, the catalyst is low in price, simple in post-treatment, green and environment-friendly, high in product purity and good in yield.
Description
Technical Field
The invention belongs to the field of organic chemical synthesis, and particularly relates to a method for constructing a spiro [ indoline-3, 3' -piperidine ] skeleton by using a monovalent gold catalysis N-propargyl methylene indole cascade cyclization strategy.
Background
The spiro [ indoline-3, 3' -piperidine ] skeleton is a very important structure which is commonly present in natural products and active molecules of some indole alkaloids. (J.org.chem., 2010,75,7026, tetrahedron Lett.,1991,32, 3859) but because of the structural particularity, the synthesis has certain difficulty, so that the search for a simple and efficient synthesis method is always a focus of attention of organic chemists. At present, the reported methods for synthesizing spiro [ indoline-3, 3' -piperidine ] skeleton mainly include:
in 1.2001, the Ronald group utilized Pd-catalyzed cascade cyclization to construct spiro [ indoline-3, 3' -piperidine ] skeleton. (J.org.chem., 2010,75, 7026.)
According to the method, allene and aniline derivatives are used as initial raw materials, and a cascade cyclization reaction is carried out under the condition of palladium catalysis, so that a spiro [ indoline-3, 3' -piperidine ] skeleton is constructed, but the yield of the product prepared by the method is low.
In 1991, ronald topic group utilizes aniline derivatives to perform cascade cyclization under the action of Pd catalysis to obtain spiro [ indoline-3, 3' -piperidine ] skeleton. (Tetrahedron Lett.,1991,32, 3859.)
The disadvantage of this reaction is that it is carried out at elevated temperature and that (Me) is used 3 Sn) 2 It will cause some damage to human body.
In 3.2008, jeffrey A subject group successfully constructed spiro [ indoline-3, 3' -piperidine ] skeleton by utilizing Pd catalytic cascade cyclization reaction. (Tetrahedron Lett.,2008,49, 4372.)
The disadvantage of this reaction is the need to use Pd (OAc) at elevated temperatures 2 、(C 6 H 11 ) 3 P and tBuOK, and strong base.
In view of the above, in the known synthesis method of spiro [ indoline-3, 3' -piperidine ] skeleton compounds, strong alkali is required for the reaction conditions, the temperature required for the reaction is high, the required reagents are expensive, or the post-treatment is troublesome and has an influence on the environment.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a simple, green and mild synthesis method of a spiro [ indoline-3, 3' -piperidine ] skeleton compound.
The invention is realized by the following technical scheme:
the invention provides a new method for synthesizing a spiro [ indoline-3, 3-piperidine ] skeleton from an N-propargyl methylene indole substrate by utilizing the characteristic that a monovalent gold catalyst can activate a triple bond, namely, monovalent gold is used as the catalyst, the N-propargyl methylene indole substrate directly generates intramolecular cyclization reaction under mild conditions, and the obtained intermediate is rapidly captured by a nucleophilic reagent to generate the spiro [ indoline-3, 3-piperidine ] skeleton.
The synthesis method specifically comprises the following steps:
hans' ester (diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate, abbreviated as HEH) as nucleophile: sequentially adding an N-propargyl methylene indole substrate and hans ester into a reaction vessel, adding a solvent, adding a monovalent gold catalyst, heating and stirring, after monitoring the reaction, evaporating the solvent, and separating and purifying a concentrate to obtain a spiro [ indoline-3, 3-piperidine ] skeleton;
or
Indole or indole derivatives are used as nucleophilic reagents: adding an N-propargyl methylene indole substrate and indole or indole derivatives into a reaction vessel, adding a solvent, adding a monovalent gold catalyst, stirring at room temperature, after monitoring the reaction, evaporating the solvent, and separating and purifying a concentrate to obtain a spiro [ indoline-3, 3-piperidine ] skeleton.
The reaction formula is as follows:
or
Wherein R is 1 Is a hydrogen atom, a methyl, methoxy, fluorine, chlorine or bromine atom, R 2 Is hydrogen atom, methyl, benzyl or tert-butyloxycarbonyl radical, R 3 Is p-toluenesulfonyl (Ts), benzenesulfonyl (SO) 2 Ph), p-bromophenylsulfonyl (Bs) or methylsulfonyl (Ms), R 4 And R is each independently a methyl group, a methoxy group, an ester group, fluorine, chlorine or bromine atom.
In the preparation process:
the molar ratio of the N-propargylmethyleneindole substrate to the hans-ester, or to the indole or indole derivative is 1-1.
In the reaction using Hans ester as nucleophilic reagent, the reaction temperature is heated to 60-80 ℃, and the stirring time is 12-48h.
In the reaction taking indole or indole derivatives as nucleophilic reagent, stirring for 2-8h at room temperature.
The univalent gold catalyst used in the reaction is triphenylphosphine bis (trifluoromethanesulfonimide) gold (PPh) 3 AuNTf 2 ) When in use, the catalyst is prepared by a pre-catalyst and an additive, wherein the pre-catalyst is triphenylphosphine gold chloride or 1, 3-bis (2, 6-di-isopropylphenyl) imidazole-2-subunit gold (I) chloride, and the additive is bis (trifluoromethanesulfonimide) silver, silver hexafluoroantimonate and silver trifluoromethanesulfonate. The addition amount of the monovalent gold catalyst is 5-20mol% of the N-propargyl methylene indole substrate.
The progress of the reaction was monitored by thin layer chromatography.
The reaction solvent is dichloromethane, tetrahydrofuran, toluene, 1, 2-dichloroethane, methanol or acetonitrile.
The method has the advantages that from the chemical perspective, the method has good atom economy, mild reaction conditions and simple operation; from the industrial and environmental perspectives, the catalyst is low in price, simple in post-treatment, green and environment-friendly, high in product purity and good in yield.
Detailed Description
In the following embodiments, the developing agent used in the TLC monitoring process is petroleum ether, ethyl acetate, n-hexane, or a mixture of two or three of them, after the reaction is completed, the reaction solution is filtered through diatomaceous earth, and then concentrated by using a rotary evaporator, and the developing agent used for performing column chromatography on the concentrate is petroleum ether, ethyl acetate, n-hexane, or a mixture of two or three of them.
Example 1
PPh is mixed 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was charged into a dry eggplant-shaped bottle (25 mL), and anhydrous 1, 2-dichloroethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a1 (414mg, 1mmol) and hansidyl ester (1.27g, 5mmol) were added to a dry sealed tube (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution (5), stirred at 80 ℃ for 12h, monitored by TLC until no more starting material remained, filtered through celite, and the reaction was concentrated. Flash silica gel column chromatography gave b1 in 66% yield.
The spectral data of the product b1 are: ESI-MS (m/z) 439 (m/z) Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ7.69(d,J＝8.3Hz,2H),7.49(d,J＝8.0Hz,2H),7.16–7.18(m,3H),7.03–6.99(m,2H),6.95(td,J＝7.6,1.3Hz,1H),6.80(dd,J＝7.4,1.3Hz,1H),6.52(d,J＝7.8Hz,1H),6.46(t,J＝7.3Hz,1H),6.00(t,J＝3.5Hz,1H),5.75(s,1H),3.75–3.65(m,2H),3.54(d,J＝10.1Hz,1H),3.42(d,J＝10.1Hz,1H),3.09(d,J＝11.2Hz,1H),2.92(d,J＝11.2Hz,1H),2.41(s,3H)。
Example 2
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was charged into a dry eggplant-shaped bottle (25 mL), and anhydrous 1, 2-dichloroethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a2 (428mg, 1mmol) and hanster (1.27g, 5mmol) were added to a dry lock tube (50 mL)Anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution was stirred at 80 ℃ for 12h, TLC was carried out until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b2 in 69% yield.
The spectral data of the product b2 are: ESI-MS (m/z): 453[ M ] +Na ]] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ7.65(d,J＝8.3Hz,2H),7.45(d,J＝8.1Hz,2H),7.14–7.12(m,3H),7.06(td,J＝7.6,1.3Hz,1H),6.98–6.95(m,2H),6.85(dd,J＝7.6,1.3Hz,1H),6.58–6.53(m,2H),6.00(t,J＝3.5Hz,1H),3.78–3.74(m,1H),3.68–3.63(m,1H),3.38(d,J＝9.9Hz,1H),3.27(d,J＝9.7Hz,1H),3.04(d,J＝5.2Hz,2H),2.70(s,3H),2.41(s,3H)。
Example 3
Mixing PPh 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous 1, 2-dichloroethane (10 mL) was added under nitrogen protection, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a3 (338mg, 1mmol) and hanster (1.27g, 5mmol) were added to a dry lock (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution (5), stirred at 80 ℃ for 12h, monitored by TLC until no more starting material remained, filtered through celite, and the reaction was concentrated. Flash silica gel column chromatography gave b3 in 72% yield.
The spectral data for product b3 are: ESI-MS (m/z) 363[ m ] +Na] + ； 1 H-NMR(600MHz,CDCl 3 )δ7.10–7.07(m,3H),7.02–6.95(m,3H),6.90(d,J＝7.2Hz,1H),6.58(t,J＝7.3Hz,1H),6.54(d,J＝7.8Hz,1H),5.96(t,J＝3.4Hz,1H),3.96(qd,J＝17.0,3.5Hz,2H),3.62(d,J＝10.1Hz,1H),3.45(d,J＝10.1Hz,1H),3.36(d,J＝11.7Hz,1H),3.24(d,J＝11.6Hz,1H),2.67(s,3H)。
Example 4
PPh is mixed 3 AuCl (99.2mg, 0.2mmol) and AgNTf 2 (77.6mg, 0.2mmol) is added into a dried eggplant-shaped bottle (25 mL), anhydrous 1, 2-dichloroethane (10 mL) is added under the protection of nitrogen, and the mixture is stirred for 30min at room temperature to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a4 (432mg, 1mmol) and hansixan (1.27g, 5mmol) were added to a dry sealed tube (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution (5), stirred at 80 ℃ for 12h, monitored by TLC until no more starting material remained, filtered through celite, and the reaction was concentrated. Flash silica gel column chromatography gave b4 in 65% yield.
The spectral data of the product b4 are: ESI-MS (m/z) 457[ m ] +Na] + ； 1 H-NMR(600MHz,CDCl 3 )δ7.68–7.63(m,2H),7.31(d,J＝8.0Hz,2H),7.04(td,J＝7.6,1.3Hz,1H),7.01–6.97(m,2H),6.87–6.84(m,1H),6.83–6.79(m,2H),6.63(d,J＝7.6Hz,2H),5.91(t,J＝3.5Hz,1H),3.96(dd,J＝16.8,3.9Hz,1H),3.68(d,J＝2.8Hz,2H),3.43(d,J＝11.4Hz,1H),2.95(d,J＝11.3Hz,1H),2.43(s,3H)。
Example 5
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous 1, 2-dichloroethane (10 mL) was added under nitrogen protection, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a5 (448mg, 1mmol) and hanster (1.27g, 5mmol) were added to a dry lock (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution was stirred at 80 ℃ for 12h, TLC was carried out until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash column chromatography on silica gel afforded b5 in 62% yield.
The spectral data of product b5 are: ESI-MS (m/z) 474[ 2 ], [ M ] +Na] + ； 1 H NMR(600MHz,CDCl 3 )δ7.57(d,J＝8.3Hz,2H),7.24(d,J＝8.2Hz,2H),7.01(d,J＝8.6Hz,2H),6.96(td,J＝7.6,1.3Hz,1H),6.89(d,J＝8.6Hz,2H),6.75(dd,J＝7.4,1.3Hz,1H),6.56–6.51(m,2H),5.89–5.85(m,1H),3.90(dd,J＝16.9,4.0Hz,1H),3.66–3.55(m,3H),3.37(d,J＝11.4Hz,1H),2.85(d,J＝11.4Hz,1H),2.35(s,3H)。
Example 6
Mixing PPh 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous 1, 2-dichloroethane (10 mL) was added under nitrogen protection, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a6 (428mg, 1mmol) and hanster (1.27g, 5mmol) were added to a dry sealed tube (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution (5), stirred at 80 ℃ for 12h, monitored by TLC until no more starting material remained, filtered through celite, and the reaction was concentrated. Flash silica gel column chromatography gave b6 in 68% yield.
The spectral data of the product b6 are: ESI-MS (m/z) 453[ 2 ] M + H] + ； 1 H-NMR(600MHz,CDCl 3 )δ7.65(d,J＝8.3Hz,2H),7.31(d,J＝8.0Hz,2H),7.04(td,J＝7.6,1.3Hz,1H),6.86(d,J＝7.2Hz,1H),6.62(d,J＝7.9Hz,2H),5.93(t,J＝3.5Hz,1H),3.95(dd,J＝16.7,3.9Hz,1H),3.75–3.62(m,3H),3.42(d,J＝11.4Hz,1H),2.94(d,J＝11.3Hz,1H),2.42(s,3H),2.22(s,3H)。
Example 7
PPh is mixed 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was charged in a dry eggplant type bottle (25 mL), and the solution was charged under nitrogen atmosphereAnhydrous 1, 2-dichloroethane (10 mL) was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a7 (444mg, 1mmol) and hansenoate (2.54g, 10mmol) were added to a dry sealed tube (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution was stirred at 80 ℃ for 12h, TLC was carried out until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b7 in 77% yield.
The spectral data of the product b7 are: ESI-MS (m/z) 469[ 2 ], [ M + Na ]] + ； 1 H-NMR(600MHz,CDCl 3 )δ7.65(d,J＝7.9Hz,2H),7.31(d,J＝7.9Hz,2H),7.03(t,J＝7.6Hz,1H),6.99(t,J＝7.6Hz,1H),6.94(d,J＝7.5Hz,1H),6.88(d,J＝7.4Hz,1H),6.85(s,1H),6.78(d,J＝7.7Hz,1H),6.62(t,J＝7.4Hz,2H),5.93(d,J＝3.5Hz,1H),3.93(dd,J＝16.8,3.9Hz,1H),3.72–3.67(m,2H),3.64(d,J＝10.0Hz,1H),3.39(d,J＝11.3Hz,1H),2.98(d,J＝11.3Hz,1H),2.43(s,3H),2.19(s,3H)。
Example 8
PPh is mixed 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous 1, 2-dichloroethane (10 mL) was added under nitrogen protection, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a8 (404mg, 1mmol) and hansidyl ester (1.27g, 5mmol) were added to a dry sealed tube (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution (g) was stirred at 60 ℃ for 24h, TLC was monitored until no more starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b8 in 66% yield.
The spectral data for product b8 are: ES (ES)I-MS(m/z):429[M+Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ7.64(d,J＝8.4Hz,2H),7.51(d,J＝1.7Hz,1H),7.43(d,J＝8.1Hz,2H),6.99(td,J＝7.6,1.3Hz,1H),6.65(d,J＝7.3Hz,1H),6.60(d,J＝7.8Hz,1H),6.45(d,J＝7.3Hz,1H),6.42(dd,J＝5.2,2.7Hz,1H),6.26(dd,J＝3.4,1.8Hz,1H),5.86(s,1H),5.44(d,J＝3.3Hz,1H),4.08–4.04(m,1H),3.57(d,J＝9.7Hz,1H),3.50(d,J＝10.4Hz,2H),3.39(dd,J＝17.6,2.6Hz,1H),2.39(s,3H),2.36(dd,J＝11.5,1.3Hz,1H)。
Example 9
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was charged into a dry eggplant-shaped bottle (25 mL), and anhydrous 1, 2-dichloroethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a9 (420mg, 1mmol) and hanster (1.27g, 5mmol) were added to a dry sealed tube (50 mL), anhydrous 1, 2-dichloroethane (10 mL) was added, and the addition of the solution containing PPh was continued 3 AuNTf 2 1, 2-dichloroethane solution, stirred at 80 ℃ for 169h, monitored by TLC until no more starting material remained, filtered through Celite, and the reaction was concentrated. Flash silica gel column chromatography gave b9 in 69% yield.
The spectral data of the product b9 are: ESI-MS (m/z): 445[ M ] +Na ]] + ； 1 H-NMR(600MHz,CDCl 3 )δ7.65(d,J＝8.3Hz,2H),7.31(d,J＝8.0Hz,2H),7.26(s,1H),7.10(t,J＝7.5Hz,1H),7.04(d,J＝4.8Hz,1H),6.82(d,J＝7.2Hz,1H),6.77(dd,J＝5.1,3.7Hz,1H),6.68(d,J＝7.9Hz,1H),6.63(t,J＝7.3Hz,1H),6.60(d,J＝3.7Hz,1H),6.24(dd,J＝5.1,2.6Hz,1H),4.15(dd,J＝17.1,4.6Hz,1H),3.83(d,J＝10.0Hz,1H),3.78(d,J＝11.7Hz,1H),3.70(d,J＝10.6Hz,1H),3.42(dd,J＝17.1,2.6Hz,1H),2.51(d,J＝11.6Hz,1H),2.42(s,3H)。
Example 10
Mixing PPh 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and the mixture was added under nitrogen atmosphereAnhydrous dichloromethane (10 mL) is stirred for 30min at room temperature to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a10 (414mg, 1mmol) and indole (586mg, 5mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 8 hours, followed by TLC until no more starting material remained, filtration through Celite, and concentration of the reaction mixture. Flash silica gel column chromatography gave b10 in 72% yield.
Spectral data for product b10 were: ESI-MS (m/z) 554[ 2 ] M + Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.92(s,1H),7.33–7.25(m,7H),7.16–7.10(m,4H),7.08(t,J＝8.1Hz,1H),7.05–7.02(m,2H),6.96–6.92(m,2H),6.74–6.67(m,2H),6.16(d,J＝3.3Hz,1H),5.97(dd,J＝4.7,2.2Hz,1H),5.29(d,J＝3.2Hz,1H),4.03(dd,J＝17.2,1.3Hz,1H),3.64(d,J＝11.3Hz,1H),2.81(dd,J＝17.1,2.2Hz,1H),2.27(s,3H),1.90(d,J＝11.3Hz,1H)。
Example 11
PPh is mixed 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a11 (338mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b11 in 72% yield.
The spectral data of the product b11 are: ESI-MS (m/z) 478[ 2 ], [ M ] +Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ11.00(s,1H),7.35–7.27(m,4H),7.18(d,J＝2.5Hz,1H),7.13(d,J＝7.4Hz,2H),7.09(q,J＝6.6,6.2Hz,3H),7.03(t,J＝7.6Hz,1H),6.85(t,J＝7.5Hz,1H),6.68(t,J＝7.0Hz,2H),6.15(d,J＝3.2Hz,1H),6.13(dd,J＝4.7,2.2Hz,1H),5.42(d,J＝3.0Hz,1H),4.04(dd,J＝17.1,4.4Hz,1H),3.55(dd,J＝17.3,2.3Hz,1H),3.50(d,J＝11.6Hz,1H),2.59(s,3H),2.52(d,J＝11.6Hz,1H)。
Example 12
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a12 (400mg, 1mmol) and indole (1.76g, 15mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash column chromatography on silica gel gave b12 in 71% yield.
Spectral data for product b12 were: ESI-MS (m/z) 540[ 2 ], [ M ] +Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.92(s,1H),7.53(t,J＝7.4Hz,1H),7.40(d,J＝7.4Hz,2H),7.35–7.27(m,7H),7.15–7.12(m,2H),7.08(t,J＝7.4Hz,1H),7.04(d,J＝7.7Hz,2H),6.95(t,J＝8.0Hz,1H),6.93(d,J＝2.5Hz,1H),6.73(t,J＝7.4Hz,1H),6.71(d,J＝2.5Hz,1H),6.16(d,J＝3.3Hz,1H),5.98(dd,J＝4.7,2.2Hz,1H),5.30(d,J＝2.0Hz,1H),4.06(dd,J＝17.2,4.7Hz,1H),3.67(d,J＝11.5Hz,1H),2.84(dd,J＝17.1,2.2Hz,1H),1.93(d,J＝11.3Hz,1H)。
Example 13
Mixing PPh 3 AuCl (24.8mg, 0.05mmol) and AgNTf 2 (19.4mg, 0.05mmol) was put into a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a13 (478mg, 1mmol) and indole (586mg, 5mmol) were put in a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The dichloromethane solution was stirred at room temperature for 4h, monitored by tlc until no starting material remained, filtered through celite, and the reaction was concentrated. Flash silica gel column chromatography gave b13 in 23% yield.
The spectral data of the product b13 are: ESI-MS (m/z): 618[ 2 ], [ M ] +Na ]] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.95(s,1H),7.52(d,J＝8.7Hz,2H),7.08(d,J＝8.7Hz,2H),7.38–7.25(m,5H),7.16–7.12(m,2H),7.09(t,J＝8.2Hz,1H),7.05(d,J＝8.7Hz,2H),6.98–6.90(m,2H),6.74–6.67(m,2H),6.18(d,J＝3.2Hz,1H),5.99(dd,J＝4.7,2.3Hz,1H),5.30(d,J＝3.0Hz,1H),4.07(dd,J＝17.2,1.3Hz,1H),3.64(d,J＝11.3Hz,1H),2.91(dd,J＝17.1,2.2Hz,1H),1.94(d,J＝11.3Hz,1H)。
Example 14
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and under nitrogen protection, anhydrous dichloromethane (10 mL) was added, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a14 (432mg, 1mmol) and indole (586mg, 5mmol) were put in a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b14 in 69% yield.
The spectral data of the product b14 are: ESI-MS (m/z) 572[ M + [ Na ]] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.95(s,1H),7.37–7.26(m,7H),7.13(d,J＝7.9Hz,2H),7.08(t,J＝7.5Hz,1H),7.05(d,J＝7.6Hz,2H),6.99–6.91(m,4H),6.69(dd,J＝8.5,4.4Hz,1H),6.13(s,1H),6.00(dd,J＝4.7,2.2Hz,1H),5.35(s,1H),4.09(dd,J＝17.1,4.7Hz,1H),3.68(d,J＝11.4Hz,1H),2.84(dd,J＝17.2,2.3Hz,1H),2.27(s,3H),1.93(d,J＝11.4Hz,1H)。
Example 15
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a15 (448mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b15 in 64% yield.
The spectral data of product b15 are: ESI-MS (m/z) 588[ 2 ], [ M + [ Na ]] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.96(s,1H),7.33(d,J＝7.6Hz,2H),7.32–7.28(m,3H),7.25(s,1H),7.18–7.11(m,3H),7.11–7.06(m,2H),7.07–7.03(m,2H),6.97(d,J＝2.5Hz,1H),6.94(t,J＝7.5Hz,1H),6.70(d,J＝8.3Hz,1H),6.38(d,J＝3.0Hz,1H),6.01(dd,J＝4.7,2.3Hz,1H),5.75(s,1H),5.34(d,J＝3.0Hz,1H),4.07(dd,J＝17.3,4.9Hz,1H),3.64(d,J＝11.4Hz,1H),2.85(dd,J＝17.2,2.2Hz,1H),2.28(s,3H),1.90(d,J＝11.5Hz,1H)。
Example 16
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Adding substrate a16 (428mg, 1mmol) and indole (586mg, 5mmol) into a dry eggplant-shaped bottle(50 mL), dry dichloromethane (10 mL) was added and the addition of the solution containing PPh was continued 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash column chromatography on silica gel gave b16 in 75% yield.
The spectral data of the product b16 are: ESI-MS (m/z) 569[ 2 ], [ M + Na ]] + ； 1 H NMR(600MHz,DMSO-d 6 ))δ10.92(d,J＝2.5Hz,1H),7.35–7.25(m,7H),7.13(d,J＝7.9Hz,2H),7.09(t,J＝7.6Hz,1H),7.07–7.04(m,2H),6.99–6.89(m,4H),6.64(d,J＝7.9Hz,1H),5.99(dd,J＝4.7,2.3Hz,2H),5.31(s,1H),4.07–4.00(m,1H),3.66(d,J＝11.3Hz,1H),2.85(dd,J＝17.2,2.3Hz,1H),2.28(s,3H),2.27(s,3H),1.96(d,J＝11.3Hz,1H)。
Example 17
PPh is mixed 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and under nitrogen protection, anhydrous dichloromethane (10 mL) was added, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a17 (444mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b17 in 76% yield.
The spectral data of product b17 are: ESI-MS (m/z) 584[ M + Na ]] + ； 1 H-NMR(600MHz,CDCl 3 )δ8.12(s1H),7.50(d,J＝8.0Hz,1H),7.35–7.32(m,2H),7.30–7.26(m,2H),7.16(q,J＝7.7Hz,2H),7.11(t,J＝7.6Hz,1H),7.07–7.03(m,1H),7.01(dd,J＝9.4,7.5Hz,2H),6.89(d,J＝2.5Hz,1H),6.88(s,1H),6.84–6.79(m,2H),6.70(d,J＝7.7Hz,1H),5.88(dd,J＝4.6,2.3Hz,1H),5.41(s,1H),4.09–4.02(m,1H),3.81–3.75(m,1H),3.02(dd,J＝16.8,2.4Hz,1H),2.31(d,J＝11.3Hz,1H),2.28(s,3H),2.27(s,3H)。
Example 18
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a18 (428mg, 1mmol) and indole (586mg, 5mmol) were put in a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b18 in 70% yield.
The spectral data of the product b18 are: ESI-MS (m/z) 569[ 2 ], [ M + Na ]] + ； 1 H NMR(600MHz,DMSO-d 6 )δ10.93(s,1H),7.79(s,1H),7.39–7.31(m,1H),7.30–7.23(m,5H),7.22–7.12(m,4H),7.02–6.89(m,3H),6.85(d,J＝7.4Hz,1H),6.79(d,J＝7.8Hz,1H),6.53(d,J＝31.6Hz,1H),5.95(s,1H),4.63(s,1H),4.03(dd,J＝17.4,4.6Hz,1H),3.76–3.64(m,1H),2.77(d,J＝16.8Hz,1H),2.24(s,4H),1.88(s,1H)。
Example 19
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a19 (504mg, 1mmol) and indole (586mg, 5mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 Was stirred at room temperature for 6h, monitored by TLC until no starting material remained, and purified by CeliteThe mixture was filtered through a soil filter, and the reaction mixture was concentrated. Flash silica gel column chromatography gave b19 in 68% yield.
The spectral data of the product b19 are: ESI-MS (m/z): 645[ M ] +Na ]] + ； 1 H NMR(600MHz,DMSO-d 6 ))δ11.23(s,1H),10.95(s,2H),7.80(d,J＝8.0Hz,2H),7.62(s,1H),7.60–7.53(m,2H),7.40(d,J＝8.1Hz,2H),7.34(d,J＝7.8Hz,2H),7.29(d,J＝7.5Hz,0H),7.22(d,J＝6.2Hz,2H),7.20–7.14(m,6H),7.11(d,J＝8.9Hz,8H),7.05–7.02(m,2H),6.99(d,J＝7.8Hz,4H),6.96–6.91(m,6H),6.85(d,J＝7.4Hz,7H),6.78(d,J＝8.0Hz,6H),6.64(s,1H),6.50–6.44(m,2H),6.15(d,J＝7.9Hz,1H),5.96(s,1H),5.91(s,2H),5.32(s,1H),5.02(s,2H),4.64(d,J＝16.2Hz,2H),4.51(d,J＝15.8Hz,1H),4.02(dd,J＝17.1,4.6Hz,3H),3.93(d,J＝15.5Hz,1H),3.77(t,J＝14.3Hz,4H),3.63(d,J＝11.4Hz,1H),2.84(d,J＝17.3Hz,1H),2.77(d,J＝17.0Hz,2H),2.34(s,3H),2.24(s,6H),2.03(d,J＝11.3Hz,1H),1.86(d,J＝11.2Hz,2H)。
Example 20
PPh is mixed 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a20 (514mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous methylene chloride (10 mL) was added thereto, followed by addition of a solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b20 in 68% yield.
Spectral data for product b20 were: ESI-MS (m/z): 655[ M ] +Na ]] + ； 1 H NMR(600MHz,DMSO-d 6 ))δ11.02(s,1H),7.69(d,J＝8.2Hz,1H),7.65(s,1H),7.44(d,J＝8.1Hz,1H),7.39(t,J＝7.9Hz,1H),7.22–6.84(m,8H),6.79–6.71(m,2H),5.67(s,1H),5.37(s,1H),3.99(s,1H),3.50(s,1H),2.99(s,1H),2.31(s,3H),2.14(d,J＝11.8Hz,1H),1.00(s,9H)。
Example 21
PPh is mixed 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and under nitrogen protection, anhydrous dichloromethane (10 mL) was added, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a21 (432mg, 1mmol) and indole (586mg, 5mmol) were put in a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b21 in 72% yield.
Spectral data for product b21 were: ESI-MS (m/z) 573[ m ] +Na] + ； 1 H NMR(600MHz,DMSO-d 6 )δ10.94(s,1H),7.32(dd,J＝8.2,5.3Hz,2H),7.27(d,J＝8.1Hz,2H),7.18–7.09(m,7H),7.05(dd,J＝8.7,5.6Hz,2H),6.98–6.95(m,2H),6.73(t,J＝7.4Hz,1H),6.71(d,J＝7.9Hz,1H),6.18(d,J＝3.1Hz,1H),5.98–5.97(m,1H),5.24(s,1H),4.02(dd,J＝16.9,4.6Hz,1H),3.63(d,J＝11.3Hz,1H),2.81(d,J＝16.0Hz,1H),2.28(s,3H),1.91(d,J＝11.3Hz,1H)。
Example 22
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a22 (448mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, and TLC was carried out until no starting material remained, followed by filtration through Celite and concentration of the reaction mixture. Flash silica gel column chromatography gave b22 in 70% yield.
Spectral data for product b22 were: ESI-MS (m/z) 589[ m + Na ]] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.94(s,1H),7.39(d,J＝8.6Hz,2H),7.33(dd,J＝8.1,3.0Hz,2H),7.26(d,J＝8.2Hz,2H),7.15–7.09(m,5H),7.04(d,J＝8.6Hz,2H),6.97(t,J＝7.5Hz,1H),6.94(d,J＝2.4Hz,1H),6.75–6.72(m,1H),6.71(d,J＝7.7Hz,1H),6.18(d,J＝3.2Hz,1H),6.00(dd,J＝4.8,2.2Hz,1H),5.22(d,J＝3.1Hz,1H),4.03(dd,J＝17.3,4.7Hz,1H),3.63(d,J＝11.3Hz,1H),2.81(dd,J＝17.3,2.2Hz,1H),2.27(s,3H),1.90(d,J＝11.4Hz,1H)。
Example 23
PPh is mixed 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a23 (472mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue adding the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, and TLC was carried out until no starting material remained, followed by filtration through Celite and concentration of the reaction mixture. Flash silica gel column chromatography gave b23 in 68% yield.
The spectral data of the product b23 are: ESI-MS (m/z) 613[ m ] +Na] + ； 1 H NMR(600MHz,DMSO-d 6 ))δ10.94(d,J＝2.6Hz,1H),7.88(d,J＝8.6Hz,2H),7.30(dd,J＝25.8,8.3Hz,4H),7.19–7.11(m,6H),7.09(t,J＝7.7Hz,1H),6.95(t,J＝7.4Hz,1H),6.93(d,J＝2.5Hz,1H),6.77–6.70(m,2H),6.19(s,1H),6.08(dd,J＝4.7,2.3Hz,1H),5.22(s,1H),4.06(dd,J＝17.5,4.7Hz,1H),3.82(s,3H),3.65(d,J＝11.2Hz,1H),2.85(dd,J＝17.4,2.3Hz,1H),2.27(s,3H),1.93(d,J＝11.4Hz,1H)。
Example 24
Mixing PPh 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and under nitrogen protection, anhydrous dichloromethane (10 mL) was added, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a24 (428mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b24 in 75% yield.
Spectral data for product b24 were: ESI-MS (m/z) 569[ 2 ], [ M + Na ]] + ； 1 H NMR(600MHz,DMSO-d 6 )δ10.92(s,1H),7.36(d,J＝8.1Hz,1H),7.32(d,J＝8.2Hz,1H),7.26(d,J＝7.8Hz,2H),7.15–7.08(m,7H),7.00–6.87(m,4H),6.75–6.68(m,2H),6.16(s,1H),5.93(dd,J＝4.7,2.2Hz,1H),5.29(s,1H),4.01(dd,J＝17.1,4.8Hz,1H),3.62(d,J＝11.3Hz,1H),2.80(d,J＝16.9Hz,1H),2.26(s,6H),1.89(d,J＝11.4Hz,1H))。
Example 25
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a25 (444mg, 1mmol) and indole (586mg, 5mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 Stirring the mixture at room temperature for 6 hours, monitoring by TLC until no raw material remains, filtering the mixture through celite, and reacting the mixtureAnd (5) concentrating. Flash silica gel column chromatography gave b25 in 76% yield.
The spectral data for product b25 are: ESI-MS (m/z) 585[ M ] +Na] + ； 1 H NMR(600MHz,CDCl 3 )δ8.12(s1H),7.50(d,J＝8.0Hz,1H),7.35–7.32(m,2H),7.30–7.26(m,2H),7.16(q,J＝7.7Hz,2H),7.11(t,J＝7.6Hz,1H),7.07–7.03(m,1H),7.01(dd,J＝9.4,7.5Hz,2H),6.89(d,J＝2.5Hz,1H),6.88(s,1H),6.84–6.79(m,2H),6.70(d,J＝7.7Hz,1H),5.88(dd,J＝4.6,2.3Hz,1H),5.41(s,1H),4.09–4.02(m,1H),3.81–3.75(m,1H),3.02(dd,J＝16.8,2.4Hz,1H),2.31(d,J＝11.3Hz,1H),2.28(s,3H),2.27(s,3H)。
Example 26
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a26 (404mg, 1mmol) and indole (586mg, 5mmol) were charged into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added thereto, followed by addition of a solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, and TLC was carried out until no starting material remained, followed by filtration through Celite and concentration of the reaction mixture. Flash silica gel column chromatography gave b26 in 70% yield.
The spectral data of the product b26 are: ESI-MS (m/z): 545[ M ] +Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.97(s,1H),7.65(d,J＝1.8Hz,1H),7.32(d,J＝8.1Hz,1H),7.28(d,J＝2.4Hz,1H),7.25(d,J＝8.2Hz,2H),7.18(d,J＝8.0Hz,2H),7.10–7.05(m,2H),7.03(t,J＝8.1Hz,1H),6.90(d,J＝7.3Hz,1H),6.84(t,J＝7.5Hz,1H),6.70(d,J＝7.7Hz,1H),6.59(td,J＝7.4,1.1Hz,1H),6.43(dd,J＝3.3,1.8Hz,1H),6.37(dd,J＝4.7,3.1Hz,1H),6.25(s,1H),5.88(d,J＝3.4Hz,1H),5.64(s,1H),3.72(dd,J＝17.5,4.8Hz,1H),3.10(d,J＝11.6Hz,1H),2.88(dd,J＝17.5,3.1Hz,1H),2.44(d,J＝11.6Hz,1H),2.29(s,3H)。
Example 27
PPh is mixed 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a27 (420mg, 1mmol) and indole (586 mg, 5mmol) were charged in a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash column chromatography on silica gel afforded b27 in 71% yield.
The spectral data of product b27 are: ESI-MS (m/z) 561[ 2 ], [ M ] +Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.95(s,1H),7.42(dd,J＝5.1,1.2Hz,1H),7.34(d,J＝8.1Hz,1H),7.32(d,J＝8.1Hz,1H),7.25(d,J＝8.1Hz,2H),7.16–7.10(m,4H),7.06(ddd,J＝8.1,7.0,1.2Hz,1H),7.04(d,J＝6.1Hz,1H),6.98(dd,J＝5.1,3.6Hz,1H),6.92(ddd,J＝8.0,7.0,1.0Hz,1H),6.71(dd,J＝3.6,1.2Hz,1H),6.69(d,J＝7.8Hz,1H),6.66(td,J＝7.4,1.0Hz,1H),6.23(d,J＝3.3Hz,1H),6.18(dd,J＝4.9,2.5Hz,1H),5.51(d,J＝2.9Hz,1H),3.87(dd,J＝17.2,5.1Hz,1H),3.40(d,J＝11.5Hz,1H),2.78(dd,J＝17.3,2.5Hz,1H),2.28(s,3H),2.13(d,J＝11.6Hz,1H)。
Example 28
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Adding substrate a28 (414mg, 1mmol) and 5-methoxyindole (736mg, 5mmol) to a dried eggplant shapeTo a bottle (50 mL), anhydrous dichloromethane (10 mL) was added and the addition of the solution containing PPh was continued 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash column chromatography on silica gel afforded b28 in 74% yield.
The spectral data for product b28 are: ESI-MS (m/z) 585[ M ] +Na] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ10.82(s,1H),7.32(d,J＝7.9Hz,2H),7.29–7.25(m,3H),7.22(d,J＝8.8Hz,1H),7.16–7.13(m,4H),7.07(d,J＝7.5Hz,2H),7.01(d,J＝2.7Hz,1H),6.75–6.70(m,3H),6.65(s,1H),6.15(d,J＝3.3Hz,1H),6.00(dd,J＝4.7,2.3Hz,1H),5.30(d,J＝3.2Hz,1H),4.05(dd,J＝17.1,4.8Hz,1H),3.67(s,1H),3.64(s,3H),2.87(dd,J＝17.2,2.4Hz,1H),2.29(s,3H),1.98(d,J＝11.3Hz,1H)。
Example 29:
mixing PPh 3 AuCl (49.6 mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a29 (414mg, 1mmol) and 5-methyl indole formate (876mg, 5mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash silica gel column chromatography gave b29 in 65% yield.
The spectral data of the product b29 are: ESI-MS (m/z) 613[ m ] +Na] + ； 1 H NMR(600MHz,DMSO-d 6 )δ11.40(s,1H),8.15(s,1H),7.77(dd,J＝8.6,1.7Hz,1H),7.44(d,J＝8.6Hz,1H),7.40–7.31(m,5H),7.24–7.18(m,2H),7.16–7.10(m,5H),6.84–6.78(m,2H),6.28(d,J＝3.4Hz,1H),6.06(dd,J＝4.8,2.3Hz,1H),5.36(d,J＝3.4Hz,1H),4.13–4.04(m,1H),3.93(s,3H),3.61(d,J＝11.2Hz,1H),2.89(dd,J＝17.2,2.2Hz,1H),2.30(s,3H),1.89(d,J＝11.2Hz,1H)。
Example 30
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and under nitrogen protection, anhydrous dichloromethane (10 mL) was added, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a30 (414mg, 1mmol) and 5-bromoindole (980mg, 5mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, and TLC was carried out until no starting material remained, followed by filtration through Celite and concentration of the reaction mixture. Flash column chromatography on silica gel gave b30 in 56% yield.
The spectral data for product b30 were: ESI-MS (m/z): 634[ 2 ], [ M ] +Na ]] + ； 1 H-NMR(600MHz,DMSO-d 6 )δ11.16(s,1H),7.45(s,1H),7.34(d,J＝8.0Hz,2H),7.33–7.27(m,4H),7.22(dd,J＝8.7,1.9Hz,1H),7.21–7.14(m,4H),7.05–7.02(m,2H),6.99(d,J＝2.5Hz,1H),6.81–6.72(m,2H),5.25(s,1H),6.32(s,1H),4.06(dd,J＝17.1,4.7Hz,1H),3.61(d,J＝11.2Hz,1H),3,18(s,1H),2.86(dd,J＝17.2,2.3Hz,1H),2.29(s,3H),1.85(d,J＝11.2Hz,1H)。
Example 31
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8 mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and under nitrogen protection, anhydrous dichloromethane (10 mL) was added, and the mixture was stirred at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a31 (414mg, 1mmol) and 6-methoxyindole (736mg, 5mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 2 ofThe methyl chloride solution was stirred at room temperature for 6h, monitored by TLC until no starting material remained, filtered through Celite, and the reaction was concentrated. Flash silica gel column chromatography gave b31 in 76% yield.
The spectral data of the product b31 are: ESI-MS (m/z) 585[ M ] +Na] + ； 1 H NMR(600MHz,DMSO-d 6 )δ10.69(s,1H),7.32–7.24(m,5H).,7.20(d,J＝8.7Hz,1H),7.16–7.10(m,4H),7.07(d,J＝7.5Hz,2H),6.80(dd,J＝14.1,2.3Hz,2H),6.75–6.68(m,2H),6.63(dd,J＝8.7,2.3Hz,1H),6.14(d,J＝3.3Hz,1H),5.97(dd,J＝4.7,2.3Hz,1H),5.23(d,J＝2.7Hz,1H),4.04(dd,J＝17.1,4.7Hz,1H),3.78(s,3H),3.59(d,J＝11.3Hz,1H),2.83(dd,J＝17.1,2.2Hz,1H),2.28(s,3H),1.88(d,J＝11.3Hz,1H)。
Example 32
Mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a The substrate a32 (414mg, 1mmol) and 7-methylindole (656mg, 5mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, monitored by TLC until no starting material remained, and the reaction mixture was concentrated by filtration through Celite. Flash column chromatography on silica gel afforded b32 in 71% yield.
Spectral data for product b32 were: ESI-MS (m/z) 569[ 2 ], [ M + Na ]] + ； 1 H NMR(600MHz,DMSO-d 6 )δ10.91(s,1H),7.33–7.26(m,5H),7.16–7.11(m,5H),7.07(d,J＝7.5Hz,2H),6.94(d,J＝2.5Hz,1H),6.90(d,J＝7.0Hz,1H),6.86(t,J＝7.4Hz,1H),6.77–6.70(m,2H),6.16(d,J＝3.3Hz,1H),5.99(dd,J＝4.7,2.3Hz,1H),5.31(d,J＝3.2Hz,1H),4.04(dd,J＝17.1,4.8Hz,1H),3.63(d,J＝11.3Hz,1H),2.82(dd,J＝17.2,2.2Hz,1H),2.43(s,3H),2.28(s,3H),1.87(d,J＝11.3Hz,1H)。
Example 33:
mixing PPh 3 AuCl (49.6mg, 0.1mmol) and AgNTf 2 (38.8mg, 0.1mmol) was put in a dry eggplant-shaped bottle (25 mL), and anhydrous dichloromethane (10 mL) was added under nitrogen protection, followed by stirring at room temperature for 30min to prepare a monovalent gold catalyst PPh 3 AuNTf 2 (ii) a Substrate a33 (414mg, 1mmol) and 1-methylindole (131mg, 1mmol) were put into a dry eggplant-shaped bottle (50 mL), and anhydrous dichloromethane (10 mL) was added to continue the addition of the solution containing PPh 3 AuNTf 2 The mixture was stirred at room temperature for 6 hours, and TLC was carried out until no starting material remained, followed by filtration through Celite and concentration of the reaction mixture. Flash column chromatography on silica gel afforded b33 in 31% yield.
The spectral data of product b33 are: ESI-MS (m/z) 569[ 2 ], [ M + Na ]] + ； 1 H NMR(600MHz,DMSO-d 6 )δ7.34(d,J＝8.0Hz,3H),7.29–7.25(m,3H),7.13–7.10(m,7H),7.05(d,J＝7.4Hz,2H),6.93(t,J＝7.5Hz,1H),6.76–6.68(m,2H),6.16(s,1H),5.97(dd,J＝4.8,2.3Hz,1H),5.32(s,1H),4.03(dd,J＝17.2,4.8Hz,1H),3.71(s,3H),3.62(d,J＝11.3Hz,1H),2.84(dd,J＝17.1,2.2Hz,1H),2.29(s,3H),1.92(d,J＝11.3Hz,1H)。
Claims (6)
1. A method for synthesizing a spiro [ indoline-3, 3 '-piperidine ] skeleton catalyzed by monovalent gold is characterized in that the monovalent gold is used as a catalyst, an N-propargyl methylene indole substrate is directly subjected to intramolecular cyclization reaction, and an obtained intermediate is captured by a nucleophilic reagent to generate the spiro [ indoline-3, 3' -piperidine ] skeleton; the method specifically comprises the following steps:
hans esters are used as nucleophiles: sequentially adding an N-propargyl methylene indole substrate and hans ester into a reaction vessel, adding a solvent, adding a monovalent gold catalyst, heating and stirring, after the monitoring reaction is finished, evaporating the solvent, and separating and purifying a concentrate to obtain a spiro [ indoline-3, 3-piperidine ] skeleton;
or alternatively
Indole or indole derivatives are used as nucleophilic reagents: adding an N-propargyl methylene indole substrate and indole or indole derivatives into a reaction vessel, adding a solvent, adding a monovalent gold catalyst, stirring at room temperature, after monitoring the reaction, evaporating the solvent, and separating and purifying a concentrate to obtain a spiro [ indoline-3, 3-piperidine ] skeleton;
wherein R is 1 Is a hydrogen atom, a methyl, methoxy, fluorine, chlorine or bromine atom, R 2 Is a hydrogen atom, methyl, benzyl or tert-butoxycarbonyl, R 3 Is p-toluenesulfonyl (Ts), benzenesulfonyl (SO) 2 Ph), p-bromophenylsulfonyl (Bs) or methylsulfonyl (Ms), R 4 And R is independently methyl, methoxy, ester group, fluorine, chlorine or bromine atom.
2. The monovalent gold-catalyzed synthesis of a spiro [ indoline-3, 3' -piperidine ] scaffold according to claim 1, wherein the molar ratio of the N-propargylmethyleneindole substrate to hans-ester, or to indole or indole derivative is 1-1.
3. The method for synthesizing a spiro [ indoline-3, 3' -piperidine ] skeleton catalyzed by monovalent gold according to claim 1, wherein the reaction temperature is 60-80 ℃ and the stirring time is 12-48h in the reaction using hans ester as a nucleophile.
4. The method for synthesizing a spiro [ indoline-3, 3' -piperidine ] skeleton catalyzed by monovalent gold according to claim 1, wherein the reaction using indole or an indole derivative as a nucleophile is stirred at room temperature for 2 to 8 hours.
5. The method for synthesizing the spiro [ indoline-3, 3' -piperidine ] skeleton catalyzed by monovalent gold according to claim 1, wherein the monovalent gold catalyst used in the reaction is triphenylphosphine bis (trifluoromethanesulfonimide) gold, and the monovalent gold catalyst is prepared by a pre-catalyst and an additive when used, the pre-catalyst is triphenylphosphine gold chloride or 1, 3-bis (2, 6-di-isopropylphenyl) imidazole-2-ylidenegold (I) chloride, and the additive is bistrifluoromethanesulfonimide silver, hexafluoroantimonate silver, trifluoromethanesulfonate silver; the addition amount of the monovalent gold catalyst is 5-20mol% of the N-propargyl methylene indole substrate.
6. The method of claim 1, wherein the reaction solvent is dichloromethane, tetrahydrofuran, toluene, 1, 2-dichloroethane, methanol, or acetonitrile.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001005790A1 (en) * | 1999-07-21 | 2001-01-25 | Astrazeneca Ab | New compounds |
| WO2010094622A1 (en) * | 2009-02-17 | 2010-08-26 | F. Hoffmann-La Roche Ag | 3, 3' -spiroindolinone derivatives as anticancer agents |
| CN109384789A (en) * | 2017-08-08 | 2019-02-26 | 沈阳药科大学 | A kind of synthetic method for the indoles and azepine heptatomic ring that monovalence silver is catalyzed |
-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001005790A1 (en) * | 1999-07-21 | 2001-01-25 | Astrazeneca Ab | New compounds |
| WO2010094622A1 (en) * | 2009-02-17 | 2010-08-26 | F. Hoffmann-La Roche Ag | 3, 3' -spiroindolinone derivatives as anticancer agents |
| CN102356082A (en) * | 2009-02-17 | 2012-02-15 | 霍夫曼-拉罗奇有限公司 | 3, 3' -spiroindolinone derivatives as anticancer agents |
| CN109384789A (en) * | 2017-08-08 | 2019-02-26 | 沈阳药科大学 | A kind of synthetic method for the indoles and azepine heptatomic ring that monovalence silver is catalyzed |
Non-Patent Citations (3)
| Title |
|---|
| LONG LI等: "Reversal of Regioselectivity in Catalytic Arene-Ynamide Cyclization:Direct Synthesis of Valuable Azepino[4, 5-b]indoles and β-Carbolines and DFT Calculations", ACS CATAL., vol. 7, pages 4004 - 4010 * |
| LUO, JIAJUN等: "Visible-Light-Induced [2+2+1] Dearomative Cascade Cyclization of Indole/Furan Alkynes to Synthesize Sulfonyl Polycycles", ADVANCED SYNTHESIS & CATALYSIS, vol. 364, no. 13, pages 2197 - 2204 * |
| ZHU, JIANG等: "Gold(I)-Catalyzed Substitution-Controlled Syntheses of Spiro[indoline-3, 3\'-pyrrolidine] and Spiro[indoline-3, 3\'-piperidine] Derivatives", JOURNAL OF ORGANIC CHEMISTRY, vol. 88, no. 15, pages 10586 - 10598 * |
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