Tandem Sulfonylation/Cyclization of Vinyl Azides with Aryldiazonium Tetrafluoroborates and SO2

An efficient and facile strategy for the synthesis of 6-(sulfonylmethyl)phenanthridines and its derivatives has been developed via tandem sulfonylation cyclization of vinyl azides under mild conditions in the absence of any catalysts and additives. The reaction simply utilizes easily accessible and cheap K₂S₂O₅ as the sulfur dioxide source, delivering functionalized phenanthridines in moderate to excellent yields with operational simplicity and gram-scale synthesis, as well as good functional-group tolerance.     

Palladium-catalyzed intramolecular C-H activation/C-C bond formation: a straightforward synthesis of phenanthridines

The palladium-catalyzed intramolecular C-H activation/C-C cross-coupling has been developed for a straightforward and efficient synthesis of phenanthridines. With Pd(OAc)(2) (4 mol %) as the catalyst, PCy(3) (8 mol %) as the ligand, and Cs(2)CO(3) as the base, this protocol was applied to synthesize a small library of phenanthridine derivatives in good yields in THF.     

Nitrenoid from Oxime: A Practical Synthesis of Planar Chiral Ferrocenyl Phenanthridines via Nitrene-Involved Ring-Expansion Reaction

Nitrenes and nitrenoids are highly reactive species and the proposed key intermediates in nitrogen-containing heterocyclic compound synthesis. In this work, we developed a practical method for the synthesis of phenanthridines by the reaction of oximes and Grignard reagents (with or without diethylzinc) via ring-expansion of magnesium coordinated nitrenoid complex as the key step. The method has been used to synthesize optically active planar chiral ferrocenyl phenanthridines.     

Synthesis of 6-carboxylated phenanthridines by oxidative alkoxycarbonylation–cyclization of 2-isocyanobiphenyls with carbazates

An iron-catalyzed synthesis of 6-carboxylated phenanthridines starting with readily prepared isocyanides and carbazates was developed. Reactions occurred via addition of alkoxycarbonyl radicals to the isocyanide group and subsequent intramolecular cyclization.     

Synthesis and physicochemical characterization of novel 6-aminopyrido[3,4-c][1,9]phenanthrolines as aza-analogs of benzo[c]phenanthridines

Based on the 6-aminobenzo[c]phenanthridines, a compound class showing noteworthy antitumor activity, an efficient one-step synthesis consisting of a base-catalyzed condensation of 2 equiv of 4-methylpyridine-3-carbonitrile and various aldehydes causing twofold ring closure is described. The obtained 6-amino-11,12-dihydropyrido[3,4-c][1,9]phenanthrolines could be aromatized with Pd/C at high temperatures to form 6-aminopyrido[3,4-c][1,9]phenanthrolines. All compounds were systematically characterized regarding both lipophilicity and solubility and a high cytotoxic potential was evaluated in preliminary in vitro studies. Compared to formerly described 6-aminobenzo[c]phenanthridines our newly developed phenanthrolines turned out to possess improved drugability, due to significantly increased water-solubility and decreased lipophilicity.     

Radical dearomatization of benzene leading to phenanthridine and phenanthridinone derivatives related to (±)-pancratistatin

The synthesis of the phenanthridinone nucleus common to the Amaryllidaceae series of natural products is achieved by a sequence involving tributylstannane-mediated, benzeneselenol-catalyzed addition of ortho-nitrogen functionalized aryl radicals to benzene, yielding aryl-substituted cyclohexadienes. These cyclohexadienes may be manipulated by oxidative ring closure sequences to generate functionalized phenanthridines. Beginning from 2-hydroxy-6-iodopiperonic acid a key intermediate in the Danishefsky synthesis of (±)-pancratistatin is achieved in two steps.     

Palladium-catalyzed tandem reaction to construct benzo[c]phenanthridine: application to the total synthesis of benzo[c]phenanthridine alkaloids

A concise and efficient synthesis of benzo[c]phenanthridines was accomplished by the palladium-catalyzed ring-opening coupling of azabicyclic alkene with o-iodobenzoates, followed by tandem cyclization. The strategy was successfully applied in the total synthesis of benzo[c]phenanthridine alkaloids such as sanguinarine, chelerythrine, nitidine and avicine.     

Expeditious synthesis of phenanthridines from benzylamines via dual palladium catalysis

A method for the synthesis of phenanthridines from benzylamines and aryl iodides which uses a dual palladium-catalyzed process is developed. The domino sequence ends via an intramolecular amination and an oxidative dehydrogenation. No protecting group or prefunctionalization of the amine is required, and the process uses dioxygen as the terminal oxidant.     

A one-pot access to 6-substituted phenanthridines from fluoroarenes and nitriles via 1,2-arynes

[reaction: see text] A one-pot, t-BuLi-induced synthesis of 6-substituted phenanthridines from fluoroarenes and nitriles via 1,2-arynes is reported. Aryl- and hetaryl nitriles, cyanamides, and trimethylacetonitrile gave phenanthridine products. The method was extended to provide bisphenanthridine 10 by a one-pot bis-cyclization, using 1,3-dicyanobenzene and PhF in 1:5 ratio. Reaction of 1-fluoronaphthalene and 4-chlorofluorobenzene with benzonitrile afforded the regioisomerically pure products 11 and 12, respectively.     

Phenanthridine synthesis via [2+2+2] cyclotrimerization reactions

A concise synthesis of phenanthridines via a microwave-assisted [2+2+2] cyclotrimerization reaction has been developed.     

Silver-catalyzed 2-isocyanobiaryls insertion/cyclization with phosphine oxides: synthesis of 6-phosphorylated phenanthridines

A silver-catalyzed 2-isocyanobiaryls insertion/cyclization with phosphine oxides was described for the construction of the 6-phosphorylated phenanthridines through radical addition of in situ formed P-centered radical to 2-isocyanobiphenyls and homolytic aromatic substitution process. The reactions could proceed smoothly to give the desired 6-phosphorylated phenanthridines promoted by AgOAc (20 mol %) with PhI(OAc)₂ (3.0 equiv).     

Metal-Free Synthesis of Benzo[α]phenanthridines from Aromatic Aldehydes,Cyclohexanones,and Aromatic Amines

A three-component synthesis of benzo[α]phenanthridines from aromatic aldehydes,cyclohexanones,and aromatic amines has been developed,which is mediated by KI/DMS...     

The first stereocontrolled synthesis of 12-methyl-hexahydrobenzo[c]phenanthridine alkaloids

12-Methyl B/C hexahydrobenzo[c]phenanthridines have been synthesized stereoselectively starting from chiral nonracemic 2-aryl-4-pentenoic acids prepared by asymmetric allylation of (+)-(S,S)-pseudoephedrine-based arylacetamide enolates. Subsequent transformations (Friedel–Crafts acylation, stereocontrolled reductive amination, Pictet–Spengler cyclization and PPA catalyzed cationic cyclization) led to the synthesis of enantiomerically enriched hexahydrobenzo[c]phenanthridines in which the sequential formation of all the new stereogenic centres was controlled by the starting chiral acids.     

A versatile total synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition

A new versatile synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition was carried out. The coupling reaction between benzonitrile 6 with o-toluamides (8a-c) afforded 3-arylisoquinolines (9a-c) that were transformed to the protoberberines (11a-c) or benzo[c]phenanthridines (14a-c). These compounds were synthesized by ring closure of the two-carbon chain on either position 2 or 4 of the 3-arylisoquinolinone (9a-c). Several kinds of substituted benzo[c]phenanthridine alkaloids such as oxysanguinarine, oxyavicine, and oxynitidine as well as protoberberines such as 8-oxocoptisine, 8-oxopseudoberberine, and 8-oxopseudocoptisine were synthesized.     

Direct Photoexcitation of Benzothiazolines: Acyl Radical Generation and Application to Access Heterocycles

An acyl radical generation and functionalization strategy through direct photoexcitation of benzothiazolines has been developed. The formed acyl radical species can either be trapped by quinoxalin-2-ones to realize their C(3)-H functionalization or trigger a cascade radical cyclization with isonitriles to synthesise biologically important phenanthridines. The synthetic value of this protocol can be further illustrated by the modification of quinoxalin-2-ones, containing important natural products and drug-based complex molecules.     

Trifluoroacetic acid-mediated facile construction of 6-substituted phenanthridines

The trifluoroacetic acid-mediated reaction of 2-arylanilines with arylaldehydes has been developed to give a variety of 6-substituted phenanthridines. This is a very simple and convenient one-pot process for library construction.     

Toward safer methodologies for the synthesis of polyheterocyclic systems: intramolecular arylation of arenes under Mizoroki-Heck reaction conditions

[reaction: see text] A straightforward synthesis of ibudilast-related pyrazolo[1,5-f]phenanthridines is accomplished by a tandem amine-exchange/heterocyclization of arylenaminones followed by an intramolecular biaryl coupling of the so-formed diarylpyrazoles. The direct, environmentally convenient ring-closure of the latter pyrazole intermediates, which show a close resemblance to the antiinflammatory drug celecoxib, is efficiently performed under Mizoroki-Heck reaction conditions.     

Reagent‐Free C−H/N−H Cross‐Coupling: Regioselective Synthesis of N‐Heteroaromatics from Biaryl Aldehydes and NH3

An unprecedented synthesis of N‐heteroaromatics from biaryl aldehydes and NH₃ through reagent‐free C−H/N−H cross‐coupling has been developed. The electrosynthesis uses NH₃ as an inexpensive and atom‐economic nitrogen donor, requires no oxidizing agents, and allows efficient and regioselective access to a wide range of phenanthridines and structurally related polycyclic N‐heteroaromatic products.     

The directed metalation connection to aryl-aryl cross coupling.Regiospecific synthesis of phenanthridines,phenanthridinones and the biphenyl alkaloid ismine

Concise general routes to phenanthridines 4 and phenanthridinones 5 based on directed ortho metalation and cross coupling tactics are described; a short synthesis of the Amaryllidaceae alkaloid ismine (8b) is reported.     

Ru(TPP)CO]-Catalysed Intramolecular Benzylic CH Bond Amination, Affording Phenanthridine and Dihydrophenanthridine Derivatives

Shedding light on azides: [Ru(TPP)CO] (TPP=tetraphenyl porphyrin dianion), white light and O(2) were found to be a suitable catalyst combination to perform the annulation of several biaryl azides. The high chemoselectivity of the process allows the synthesis of phenanthridines and dihydrophenanthridines in good yield and purity.