Access to Indoles via Diels–Alder Reactions of 5‐Methylthio‐2‐vinylpyrroles with Maleimides

Diels–Alder reactions of 5‐methylthio‐2‐vinyl‐1H‐pyrroles with maleimides followed by isomerization gave tetrahydroindoles in moderate to good yield. Aromatization using activated MnO₂ in refluxing toluene gave the corresponding 2‐methylthioindoles in good yields, and demethylthioation using Raney nickel gave the 2‐H indoles in excellent yields. The protection of the adducts produced aromatization in improved yield, demonstrating the effectiveness of the methylthio group as a protecting group for pyrroles; however, 5‐methylthio‐2‐vinylpyrrole was shown to perform with slightly less efficiency than 2‐vinylpyrrole in Diels–Alder reactions, indicating the protective group was more deactivating than desired. This route toward indoles offers high convergency and conveniently available starting materials that are easily purified. Bis‐methylthioated vinylpyrroles were shown to have potential as highly activated Diels–Alder dienes.     

Latent Nucleophiles in Lewis Base Catalyzed Enantioselective N‐Allylations of N‐Heterocycles

Latent nucleophiles are compounds that are themselves not nucleophilic but can produce a strong nucleophile when activated. Such nucleophiles can expand the scope of Lewis base catalyzed reactions. As a proof of concept, we report that N‐silyl pyrroles, indoles, and carbazoles serve as latent N‐centered nucleophiles in substitution reactions of allylic fluorides catalyzed by Lewis bases. The reactions feature broad scopes for both reaction partners, excellent regioselectivities, and produce enantioenriched N‐allyl pyrroles, indoles, and carbazoles when chiral cinchona alkaloid catalysts are used.     

Arylsulfenylation of heterocyclic compounds with arylsulfenamides in the presence of phosphorus(V) oxochloride

The electrophilic sulfenylation of a series of indoles and pyrroles with arylsulfenamides in the presence of phophorus(V) oxohalide has been studied. It has been shown that arylsulfenylation of indoles led to products with substitution at position 3, while in the case of pyrrole it occurred at position 2.     

Formal [4+2] Reaction between 1,3‐Diynes and Pyrroles: Gold(I)‐Catalyzed Indole Synthesis by Double Hydroarylation

Indole synthesis by a gold(I)‐catalyzed intermolecular formal [4+2] reaction between 1,3‐diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3‐diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7‐disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.     

Easy formation of SNH products in reactions of indoles and pyrroles with 3-aryl-1,2,4-triazin-5(2H)-ones in the presence of tosyl chloride

The reactions of 3-aryl-1,2,4-triazin-5(2H)-ones with indoles and pyrroles in the presence of p-toluenesulfonyl chloride afforded 3-aryl-6-hetaryl-1,2,4-triazin-5(2H)-ones in high yields. The latter are products of the nucleophilic substitution of hydrogen.     

Synthesis of 9,9‐Disubstituted 9H‐Pyrrolo[1,2‐a]indoles by Hydriodic Acid‐Catalyzed Cyclization of 1‐[2‐(1‐Aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles

A novel method is reported for the synthesis of 9,9‐disubstituted 9H‐pyrrolo[1,2‐a]indoles. Cyclization of 1‐[2‐(1‐aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles, which can be easily prepared from 2‐(1‐aryl(or methyl)ethenyl)anilines, proceeds smoothly, in general, at 0° in the presence of a catalytic (or an equimolar) amount of HI in MeCN to provide the desired products.     

Lewis acid catalyzed direct cyanation of indoles and pyrroles with N-cyano-N-phenyl-p-toluenesulfonamide (NCTS)

BF(3)·OEt(2)-catalyzed direct cyanation of indoles and pyrroles using a less toxic, bench-stable, and easily handled electrophilic cyanating agent N-cyano-N-phenyl-para-toluenesulfonamide (NCTS) affords 3-cyanoindoles and 2-cyanopyrroles in good yields with excellent regioselectivity. The substrate scope is broad with respect to indoles and pyrroles.     

Ru‐Catalysed CH Arylation of Indoles and Pyrroles with Boronic Acids: Scope and Mechanistic Studies

The Ru‐catalysed C2?H arylation of indoles and pyrroles by using boronic acids under oxidative conditions is reported. This reaction can be applied to tryptophan derivatives and tolerates a wide range of functional groups on both coupling partners, including bromides and iodides, which can be further derivatised selectively. New indole‐based ruthenacyclic complexes are described and investigated as possible intermediates in the reaction. Mechanistic studies suggest the on‐cycle intermediates do not possess a para‐cymene ligand and that the on‐cycle metalation occurs through an electrophilic attack by the Ru centre.     

Visible‐Light‐Accelerated C−H Sulfinylation of Heteroarenes

Heteroaromatic sulfoxides are a frequent structural motif in natural products, drugs, catalysts, and materials. We report a metal‐free visible‐light‐accelerated synthesis of heteroaromatic sulfoxides from sulfinamides and peroxodisulfate. The reaction proceeds at room temperature with blue‐light irradiation and allows the C−H sulfinylation of electron‐rich heteroarenes, such as pyrroles and indoles. An electrophilic aromatic substitution mechanism is proposed based on the substrate scope, substitution selectivity, and competition experiments with different nucleophiles.     

Ruthenium-catalyzed functionalization of pyrroles and indoles with propargyl alcohols

Several ruthenium-catalyzed atom-economic transformations of propargyl alcohols with pyrroles or indoles leading to alkylated, propargylated, or annulated heteroaromatics are reported. The mechanistically distinct reactions are catalyzed by a single ruthenium(0) complex containing a redox-coupled dienone ligand. The mode of activation regarding the propargyl alcohols determines the reaction pathway and depends on the alcohols' substitution pattern. Secondary substrates form alkenyl complexes by a 1,2-hydrogen shift, whereas the transformation of tertiary substrates involves allenylidene intermediates. 1-Vinyl propargyl alcohols are converted by a cascade allylation/cyclization sequence. The environmentally benign processes are of broad scope and allow the selective synthesis of highly functionalized pyrroles and indoles generating water as the only waste product.     

Metal‐Free Enantioselective Electrophilic Activation of Allenamides: Stereoselective Dearomatization of Indoles

The effective and unprecedented chiral BINOL phosphoric acid catalyzed (1–10 mol %) dearomatization of indoles through electrophilic activation of allenamides (ee up to 94 %), is documented. Besides the synthesis of 3,3‐disubstituted indolenine cores, a dearomatization/hydrogen transfer cascade sequence is also presented as a new synthetic shortcut toward highly enantiomerically enriched indolines.     

Ruthenium‐Catalyzed Functionalization of Pyrroles and Indoles with Propargyl Alcohols

Several ruthenium‐catalyzed atom‐economic transformations of propargyl alcohols with pyrroles or indoles leading to alkylated, propargylated, or annulated heteroaromatics are reported. The mechanistically distinct reactions are catalyzed by a single ruthenium(0) complex containing a redox‐coupled dienone ligand. The mode of activation regarding the propargyl alcohols determines the reaction pathway and depends on the alcohols’ substitution pattern. Secondary substrates form alkenyl complexes by a 1,2‐hydrogen shift, whereas the transformation of tertiary substrates involves allenylidene intermediates. 1‐Vinyl propargyl alcohols are converted by a cascade allylation/cyclization sequence. The environmentally benign processes are of broad scope and allow the selective synthesis of highly functionalized pyrroles and indoles generating water as the only waste product.     

Sythesis of methylthiomaleimides for the preparation of pyridazines and related comopounds

New functionalized maleimides (3‐methylthio‐2,5‐dioxo‐1H‐pyrroles) were obtained by the reaction of ketene dithioacetals with nitromethane or the reaction of nitro ketene dithioacetal with active methylene compounds in the presence of the appropriate base in dimethyl sulfoxide followed by treatment with methanol. These nakeunudes reacted with various nucleophilic reagents such as election‐rich aromatic and heteroaromatic compounds like dialkylanilines, aminophenols, indoles, indolizines, and cyalazines to give the corresponding 3‐aryl‐ or heteroaryl‐ 1H‐pyrole‐2,5‐diones. Styryl and merocyanie dyes, and polycyclic pyridazine‐diones as chemiluminophors and succinimides were also obtained from these maleimides with good results.     

Facile synthesis of bis(indolyl)methanes using catalytic amount of iodine at room temperature under solvent-free conditions

Efficient electrophilic substitution reactions of indoles with various aromatic aldehydes were carried out using a catalytic amount of I₂ under solvent-free conditions to afford the corresponding bis(indolyl)methanes in excellent yields.     

Fixation of Atmospheric Nitrogen: Synthesis of Heterocycles with Atmospheric Nitrogen as the Nitrogen Source

Dry air is the source of molecular nitrogen for reactions with TiL₄, Li, and TMSCl (L = Cl, OiPr; TMS = trimethylsilyl). The nitrogen–titanium complexes thus prepared can be used to synthesize indoles, pyrroles, and lactams from carbonyl compounds. Applying this method to 1 provides access to 2 , the key compound in the synthesis of (±)-lycopodine.     

Direct Trifluoromethylthiolation and Perfluoroalkylthiolation of C(sp2)?H Bonds with CF3SO2Na and RfSO2Na

A new method for CF₃SO₂Na‐based direct trifluoromethylthiolation of C(sp²) H bonds has been developed. CF₃SSCF₃ is generated in situ from cheap and easy‐to‐handle CF₃SO₂Na, and in the presence of CuCl can be used for electrophilic trifluoromethylthiolation of indoles, pyrroles, and enamines. The method has been extended to perfluoroalkylthiolation reactions using R_fSO₂Na.     

Direct Trifluoromethylthiolation and Perfluoroalkylthiolation of C(sp2)H Bonds with CF3SO2Na and RfSO2Na

A new method for CF₃SO₂Na‐based direct trifluoromethylthiolation of C(sp²)? H bonds has been developed. CF₃SSCF₃ is generated in situ from cheap and easy‐to‐handle CF₃SO₂Na, and in the presence of CuCl can be used for electrophilic trifluoromethylthiolation of indoles, pyrroles, and enamines. The method has been extended to perfluoroalkylthiolation reactions using R_fSO₂Na.     

Aktivierte Chinone: Substitution von Azulenen,Benzofuran und Indolen durch 2-Methoxycarbonyl-1,4-benzochinon. Regiospezifische Synthesen von Polymethoxy-fluorenonen und eine neue Synthese des 2,6-Dihydro-naphtho[1,2,3-cd]indol-6-on-Systems

Activated quinones: substitution reactions by methoxy-carbonyl-1,4-benzoquinone of azulenes, benzofuran and indoles; regiospecific syntheses of polymethoxy-fluorenones; a new synthesis of the 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one system. We present new electrophilic substitution reactions of azulenes and 5-membered heterocyclics by methoxy-carbonyl-1,4-benzoquinone. Hydroquinones 3a and 5 are prepared from azulene, and 3b from guaiazulene (see Scheme 1). Benzofuran undergoes α- and β-substitution (hydroquinones 9 10 ) (see Scheme 2). Only β-substitution is observed with indole (hydroquinone 20 ) (see Scheme 4). After methylation, saponification and intramolecular acylation of the substituted indoles 22c, 22d , derivatives of 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one have been obtained. Spectral data prove the presence of the methylidenequinone tautomer. By protonation or alkylation at the carbonyl group of 23 , the violet, highly delocalized 16π-electron systems 25 are generated. Analogously, polymethoxy-fluorenones have been prepared from methoxylated diphenylquinones 15 (see Scheme 3). They also are transformed by protonation and alkylation to the highly coloured and delocalized 12 π-electron systems 18 . By contrast, anthracene is not substituted by methoxycarbonyl-1,4-benzoquinone, but undergoes cycloaddition to the triptycene derivative 1 (see Scheme 1). A summary is presented of previously described reactions of activated quinones.     

Molecular iodine-catalyzed efficient and highly rapid synthesis of bis(indolyl)methanes under mild conditions

Highly rapid and efficient electrophilic substitution reactions of indoles with various aldehydes and ketones were carried out using I₂ in CH₃CN to afford the corresponding bis(indolyl)methanes in excellent yields.     

Facile,efficient and eco-friendly synthesis of 5-sulfenyl tetrazole derivatives of indoles and pyrroles

A concise, two-step eco-friendly approach towards the synthesis of 5-sulfenyl tetrazole derivatives of indoles and pyrroles, is reported. The synthesis comprises the oxone-mediated thiocyanation of the starting heterocycles towards intermediate 3-thiocyanato indoles and 2-thiocyanato pyrroles, and their subsequent treatment with sodium azide in 2-propanol/water under zinc bromide promotion.