Synthesis of fused indoles by sequential palladium-catalyzed Heck reaction and N-heteroannulation

A route to 3,4-fused indoles via two consecutive palladium-catalyzed reactions; an intramolecular Heck reaction followed by a reductive N-heteroannulation is described. Using this route, a number of indoles have been prepared having a variety of ring sizes anchored to the 3- and 4-position of the indole nucleus. Furthermore, a number of functional groups, both carbon and heteroatom substituents can be introduced in (and on) the additional ring without any detrimental effects on the two reactions.     

Furan ring opening–indole ring closure: recyclization of 2-(2-aminophenyl)furans into 2-(2-oxoalkyl)indoles

The acid-catalyzed rearrangement of 5-alkyl-2-[2-(sulfonylamino)phenyl]furans into 2-(2-oxoalkyl)indoles is described. When the N-sulfonyl group in the starting compounds was displaced by an N-acyl group, the corresponding indoles were not formed under the same reaction conditions due to the in situ indole deacylation and decomposition. The presence of an alkyl group at the C5 position of the furan ring is also crucial for the efficiency of the process. The discussed rearrangement provides a simple and efficient approach to 2-(2-oxoalkyl)indoles.     

Introduction of the pyrazolidine ring into the pyrrole ring of indole

The reaction of indoles with 1-acyl-5-hydroxypyrazolidines under heterogeneous catalysis conditions leads, depending on the structure of indole, to 2- and/or 3-(1-acyl-5-pyrazolidinyl)indoles. Thus, the formation of 2-pyrazolidinylindoles is the results of an unco-substitution at the 3-position of the indole, followed by migration of the pyrazolidine ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1207–1213, September, 1990.     

Parallel synthesis of an indole-based library via an iterative Mannich reaction sequence

A library of 1,3-disubstituted indoles has been prepared via an iterative Mannich reaction sequence. The first Mannich reaction with secondary amines and formaldehyde preferentially yields 3-aminomethyl indoles, while the second Mannich reaction introduces an additional aminomethyl group at the N1-position of the indole ring. A library of 25 substituted indoles has thus been prepared in moderate to good yields with purity.     

Highly efficient construction of benzene ring in carbazoles by palladium-catalyzed endo-mode oxidative cyclization of 3-(3'-alkenyl)indoles

[reaction: see text] A highly efficient construction of the benzene ring in carbazoles by palladium-catalyzed endo-mode oxidative cyclization of 3-(3'-alkenyl)indoles was developed. The reaction utilizes benzoquinone as the stoichiometric oxidant and is conducted under mild conditions.     

CAN-catalyzed microwave promoted reaction of indole with Betti bases under solvent-free condition and evaluation of antibacterial activity of the products

CAN-catalyzed reaction of Betti bases with indoles under microwave irradiation gives 3-(α,α-diarylmethyl)indoles. Better yield of the products, especially when one of the aryl ring is phenol were achieved. The reaction is performed in solvent-free condition. The antibacterial studies of the synthesized compounds were performed and some of the compounds showed good activity against Methicillin-resistant Staphylococcus aureus bacteria.     

Tandem Approach to Functionalized Pyrrolo[3,4-α]carbazole-1,3-diones via a Pd-catalyzed Indole-to-carbazole Transformation

A one-pot and efficient tliree-component reaction of indoles, acrylates and maleimides for the synthesis of pyrrolo[3,4-α]carbazole-1,3-dione derivatives was developed. Three C-C bonds and one ring were created in a single step via an indole-to-carbazole transformation triggered by Pd(II)-catalyzed direct C3-alkenylation of indoles.     

Synthesis of 2,2′-Biindolyls; Potential Intermediates for Indolocarbazole Alkaloids

The synthesis of 2,2′-biindolyls oxygenated in the benzenoid ring is reported. Wittig-Horner reaction of the phosphonate esters of 1-benzenesulfonyl-2- bromomethyl-3-substituted indoles with o-nitrobenzaldehydes followed by deoxygenation with triethyl phosphite gave 2,2′-biindolyls.     

A one-pot access to cycloalkano[1,2-a]indoles through an intramolecular alkyl migration reaction in indolylborates

A novel one-pot protocol for the preparation of cycloalkano[1,2-a]indoles by way of an intramolecular alkyl migration reaction in cyclic indolylborates is described. NaOMe was found to act as a successful trialkylboryl-protecting group against to the lithiation at the C2 of the indole ring. Treatment of cyclic indolylborates with electrophiles produced cycloalkano-[1,2-a]indoles.     

Asymmetric synthesis of the highly methylated tryptophan portion of the hemiasterlin tripeptides

[reaction: see text] The asymmetric synthesis of the methylated tryptophan portion of hemiasterlin peptides is described. The key reactions are a SnCl4-mediated ring opening of epoxynitriles or epoxysulfones by N-methylindole followed by an asymmetric Strecker reaction. A second approach involving opening of glycidic esters by indoles is also described.     

The Witkop-Winterfeldt oxidation converts tetrahydropyridoindoles into pyrroloquinolones and cinnolines by an unprecedented scaffold rearrangement

The Fischer indole reaction between phenylhydrazines and tosyl-4-piperidone furnishes tetrahydropyrido[4,3-b]indoles. In a Witkop-Winterfeldt-oxidation using ozone such indole derivatives are converted into medium-sized dicarbonyl ring systems, which cyclize to pyrroloquinolones. A detailed study of the reaction intermediates and the characterization of a cinnoline betaine side product formed by an unprecedented ring closure mechanism are reported.     

Base-promoted three-component cascade approach to unsymmetrical bis(indolyl)methanes

Here we report a base-catalyzed reaction of two different indoles with aldehydes under heating to produce unsymmetrical bis(indolyl)methanes (BIMs), in which one of the indole ring must be N-substituted. Mixture of EtOH-H₂O is used as solvent. The reaction did not give symmetrical BIMs of N-substituted indoles or N–H indoles. However, traces of latter were formed in few cases, especially when electron-rich aldehydes were used. Diversely substituted indoles and aldehydes were used for the reaction. The reaction proceeds via 3-indolylalcohol, which we confirmed through isolation. The method also gives good yield on multigram scale reaction.     

Efficient photochemical synthesis of tricyclic keto‐indoles

Tricyclic keto‐indoles were synthesized by photocyclization of easily obtained enaminones in an electro‐cyclic photochemical reaction. The three methods reported were chosen according to the enaminone structure. The most general procedure using one‐step synthesis was carried out in a benzene‐methanol solution in the presence of sodium methylate. In the case of base sensitive substrates, the best method was photocyclization followed by oxidation. Besides, N‐unsubstituted indoles with a five‐membered ring were prepared by a photolysis reaction. All three methods are efficient and easy to perform.     

Thermolysis of benzannulated enyne-carbodiimides. Application in the synthesis of pyrido[1',2':1,2]pyrimido[4,5-b]indoles and related heteroaromatic compounds

Several derivatives of the pyrido[1',2':1,2]pyrimido[4,5-b]indoles 4 and the pyrazino[1',2':1,2]pyrimido[4,5-b]indoles 14 were synthesized by treatment of the benzannulated enyne-isocyanates 8 with the iminophosphoranes 9 and 13, respectively, for the aza-Wittig reaction followed by thermolysis. The reaction presumably proceeds through an initial formation of the corresponding benzannulated enyne-carbodiimides, such as 10, followed by a formal intramolecular hetero Diels-Alder reaction. Surprisingly, when the iminophosphorane 17 was used for condensation with 8, the expected pyrimido[1',6':1,2]pyrimido[4,5-b]indoles 16 were not obtained. Instead, the isomeric pyrimido[6',1':2,3]pyrimido[4,5-b]indoles 21 were isolated. Presumably, an alternative reaction pathway involving an initial [2 + 2] cycloaddition reaction to form 19 followed by ring opening could lead to 20 and, after an intramolecular radical-radical coupling, 21. Treatment of the urea derivatives 24 with dibromotriphenylphosphorane also produced in situ the benzannulated enyne-carbodiimides 25, which on thermolysis gave the isoquinolino[2',1':1,2]pyrimido[4,5-b]indoles 26. Methylation of 4a, 14a, and 26a with methyl iodide occurred exclusively at the site of the indolo nitrogen. The planar geometry of those novel heteroaromatic compounds, resembling many DNA-binding agents, makes them potential candidates as DNA intercalators.     

有机催化吲哚碳环上的不对称Friedel⁃Crafts烷基化反应

将金鸡纳碱衍生物双功能催化剂用于有机催化羟基吲哚与靛红的不对称Friedel-Crafts反应, 筛选出最佳反应条件: 催化剂为5%(摩尔分数)6′-脱甲基奎尼丁(1b), 溶剂为四氢呋喃, 反应温度 0 ℃. 以67%~91%的产率和最高达97%的对映选择性获得了苯环上取代的羟基烷基化产品. 拓宽了该反应的催化剂类型和底物范围.     

Studies on the reactivity of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone: reactions with indole derivatives and other C-nucleophiles

[reaction: see text] Thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone) in the presence of indole derivatives affords 3-acylated indoles existing in their enol forms, through a ring contraction and alpha,alpha'-dioxoketene formation reaction. The same reactants afford 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a copper-catalyzed reaction. Enamines, among other C-nucleophiles tested, give analogous results.     

Tandem cyclopropane ring-opening/Conia-ene reactions of 2-alkynyl indoles: a [3 + 3] annulative route to tetrahydrocarbazoles

A Zn(NTf(2))(2) catalyzed tandem reaction consisting of a nucelophilic ring opening of 1,1-cyclopropanediesters by 2-alkynyl indoles followed by a Conia-ene ring closure results in the efficient one-step synthesis of tetrahydrocarbazoles. The adducts may be further elaborated to carbazoles.     

Pyrrolo- and pyrido[1,2-a]indoles via an intramolecular wittig reaction

Several pyrrolo- and pyrido[1,2-a]indoles were prepared via an intramolecular Wittig reaction in good yields. This reaction sequence represents a facile entry into the mitosene ring system.     

A cascade reaction of azolopyrimidines. Synthesis of unusual indole and azaindole derivatives

The reaction of bromo substituted pyrido[3',2':4,5]pyrrolo-[1,2-c]pyrimidine and pyrimido[1,6-a]indole methyl carboxylates with primary amines is described. The expected amide formation occurs but it is followed by an unexpected cascade process involving attack of the amine to the pyrimidine ring, opening of the pyrimidine ring, loss of the bromine substituent and competitive cyclizations to afford unusual imidazolidene substituted indoles and azaindoles.     

Synthetic Applications of 2-(1,3-Dithian-2-yl)indoles. 7. Synthesis of Aspidospermidine

A new method of synthesizing the alkaloid aspidospermidine (1), based on building ring E on the pyridocarbazole [ABCD] ring structure, is reported. The preparation of the pyridocarbazole framework of Aspidosperma alkaloids is a new three-step synthetic application of 2-(1,3-dithian-2-yl)indoles. A tandem conjugate addition-alkylation reaction starting from indolyldithiane (4), 3-methylenelactam 6, and EtI yields the adduct 17. Treatment of lactam 17 with DIBALH leads to formation of the naphthyridoindole 18. Compound 18 isomerizes in aqueous AcOH to yield pyridocarbazole 3. Finally, closure of ring E and subsequent reduction of the dithiane ring produces aspidospermidine. Pyridocarbazoles 2 and 10 were prepared as models.