Formation Of Indolines Research Articles

Synthesis of Substituted Indolines through Photocatalyzed Decarboxylative Radical Arylation.

We report a new photocatalyzed remote alkyl radical generation and cyclization to prepare substituted indolines in a green, metal-free procedure. This method complements the Fischer indolization, metal-catalyzed couplings, and photocatalyzed radical addition and cyclization. A wide range of functional groups is tolerated, including aryl halides, that would not be compatible with most existing methods. Electronic bias and substitution were studied to demonstrate complete regiocontrol and high chemocontrol in the indoline formation.

Iron-Catalyzed Divergent Tandem Radical Annulation of Aldehydes with Olefins toward Indolines and Dihydropyrans.

Iron-catalyzed divergent tandem radical annulations of aldehydes with olefins are reported. The new strategy allows the rapid and efficient construction of various multifunctionlized indolines (R = Ar) and dihydropyrans (R = Me), which are significant skeletons in bioactive natural products and pharmaceuticals. The substituents of tertiary amines play vital roles to facilitate the desired transformation. Mechanistic studies on indoline formation disclose that the homolytic cleavage of the carbonyl C-H bond might be involved in the rate-determining step, while dissociation of the aromatic C-H bond was most likely included in the product-determining step.

Merging C–H Activation and Alkene Difunctionalization at Room Temperature: A Palladium-Catalyzed Divergent Synthesis of Indoles and Indolines

A palladium-catalyzed 1,2-carboamination through C-H activation at room temperature is reported for the synthesis of 2-arylindoles, and indolines from readily available, inexpensive aryl ureas and vinyl arenes. The reaction initiates with a urea-directed electrophilic ortho palladation, alkene insertion, and β-hydride elimination sequences to provide the Fujiwara-Moritani arylation product. Subsequently, aza-Wacker cyclization, and β-hydride elimination provide the 2-arylindoles in high yields. Intercepting the common σ-alkyl-Pd intermediate, corresponding indolines are also achieved. The indoline formation is attributed to the generation of stabilized, cationic π-benzyl-Pd species to suppress β-hydride elimination.

An Unexpected Inversion of Enantioselectivity in a Copper-Catalyzed Intramolecular­ Desymmetric Aryl C–N Coupling Reaction

Enantioselective formation of indolines was achieved through desymmetrization of α,α-bis(2-iodobenzyl)glycines under the catalysis of copper(I) iodide and (2<i>S</i>,3a<i>S</i>,7a<i>S</i>)-octahydro-1<i>H</i>-­indole-2-carboxylic acid. An unexpected inversion of enantioselectivity was observed when achiral additives such as 4-(<i>N</i>,<i>N</i>-dimethylamino)pyridine were added which work together with the ligand. The configuration-reversed products were obtained in moderate yields as well as moderate ee values.

Formal Synthesis of Hepatitis C Virus NS5B Polymerase Inhibitor

A formal synthesis of a hepatitis C virus (HCV) inhibitor is described. The synthesis features a benzyne-mediated one-pot indoline formation–methylation sequence and an In(OTf) 3 -mediated mild oxa-Pictet–Spengler reaction for the synthesis of substituted electron-rich pyranoindole.

One-Point Binding Ligands for Asymmetric Gold Catalysis: Phosphoramidites with a TADDOL-Related but Acyclic Backbone

Readily available phosphoramidites incorporating TADDOL-related diols with an acyclic backbone turned out to be excellent ligands for asymmetric gold catalysis, allowing a number of mechanistically different transformations to be performed with good to outstanding enantioselectivities. This includes [2 + 2] and [4 + 2] cycloadditions of ene-allenes, cycloisomerizations of enynes, hydroarylation reactions with formation of indolines, as well as intramolecular hydroaminations and hydroalkoxylations of allenes. Their preparative relevance is underscored by an application to an efficient synthesis of the antidepressive drug candidate (-)-GSK 1360707. The distinctive design element of the new ligands is their acyclic dimethyl ether backbone in lieu of the (isopropylidene) acetal moiety characteristic for traditional TADDOL's. Crystallographic data in combination with computational studies allow the efficiency of the gold complexes endowed with such one-point binding ligands to be rationalized.

Copper-Catalyzed Desymmetric Intramolecular Ullmann C–N Coupling: An Enantioselective Preparation of Indolines

The first highly enantioselective copper-catalyzed intramolecular Ullmann C-N coupling reaction has been developed. The asymmetric desymmetrization of 1,3-bis(2-iodoaryl)propan-2-amines catalyzed by CuI/(R)-BINOL-derived ligands led to the enantioselective formation of indolines in high yields and excellent enantiomeric excesses. This method was also applied to the formation of 1,2,3,4-tetrahydroquinolines in high yields and excellent enantioselectivity.

Control over the Chemoselectivity of Pd‐Catalyzed Cyclization Reactions of (2‐Iodoanilino)carbonyl Compounds

The factors that control the chemoselectivity of palladium-catalyzed cyclization reactions of (2-iodoanilino)carbonyl compounds have been explored by an extensive experimental computational (DFT) study. It was found that the selectivity of the process, that is, the formation of fused six- versus five-membered rings, can be controlled by the proper selection of the initial reactant, reaction conditions, and additives. Thus, esters or amides produce ketones by a nucleophilic addition process, whereas the addition of PhO(-) ions leads to the formation of indolines by an α-arylation reaction. In contrast, the corresponding ketone reactants yield a mixture of both reaction products, the ratio of which depends on the base used, in the presence of phenol. The outcome of the processes can be explained by the formation of a common four-membered palladacycle intermediate from which the competitive nucleophilic addition and α-arylation reactions occur. The remarkable effect of phenol in the process, which makes the α-arylation reaction easier, favored the formation of enol complexes, which are stabilized by an intramolecular hydrogen bond between the hydroxy group of the enol moiety and the oxygen atom of the phenoxy ligand. Moreover, the chemoselectivy of the process can be also controlled by the addition of bidendate ligands that lead to the almost exclusive formation of indoles at expenses of the corresponding alcohols.

Alkoxyamine‐Mediated Radical Synthesis of Indolinones and Indolines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Alkoxyamine-Mediated Radical Synthesis of Indolinones and Indolines

Thermolysis of alpha-alkoxyamino propionanilides produces indolinones, whereas thermal reaction of N-allylaniline derivatives with various Tordo-type alkoxyamines results in formation of indolines in the radical regime. [reaction: see text]

Stereoselectivity in the reduction of chiral indoles to indolines

The reduction of 2-alkylindoles containing a chiral substituent at the nitrogen atom by sodium cyanoborohydride in an acidic medium at -80°C is accompanied by the formation of indolines with S-configuration of the new chiral site at C(2). An AMI quantum chemical calculation showed that the major diastereomer has greater thermodynamic stability. However, the high diastereoselectivity of this reduction may be attributed only to the relative stability of the different conformations of the intermediate indoleninium cations leading to different diastereomers.

ChemInform Abstract: Indoline Formation by Regioselective Aryl Radical Cyclization to Azomethine Bond.

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Indoline Formation by Regioselective Aryl Radical Cyclization to Azomethine Bond

Aryl radical-initiated cyclization of the ketimines derived from acetophenone and benzophenone occurred exclusively at the nitrogen end of the azomethine bond in an exo-5 mode to yield the corresponding indoline derivatives

Darstellung und Oxidation von 2-(2,5-Dihydroxy-phenyl)-ethylamin-Derivaten, II / Synthesis and Oxidation of 2-(2,5-Dihydroxyphenyl)-ethylamine Derivatives, II

Abstract 2,5-Dihydroxyphenylethylamine derivatives 8a,b; 14; 19a,b and 25a,b,c are synthesized and oxidized to indole 9a, indolines 15 and 18a,b as well as 24a,b,c. Quantitative oxidation of hydroquinones yields the 2-(aminoethyl)quinones 30a as free base and 30d-f; 27a,b and the hydrochlorides 28a,b. Quinone 30a is reduced to indoline 29 and acetylated to 3-acylindole 32, transformed by heating to indole 23 and in acetic acid to the dimeric indole 31. 32 is synthesized unequivocally from 33 and 34. The course of the reaction is discussed and the formation of indolines is explained by cyclisation of a semiquinone precursor (43).