Intramolecular N-arylation Research Articles

Regioselective Synthesis of 1,2- and 1,4-Dihydroquinolines by Palladium-Catalyzed Intramolecular N-Arylation

A series of 1,2- and 1,4-dihydroquinolines has been successfully prepared. The Pd-catalyzed intramolecular N-arylation of Z-enamines, formally prepared by the Horner–Wadsworth–Emmons olefination, proceeded efficiently to furnish the cyclized products. Depending on the cyclization conditions, substituted 1,4-dihydroquinolines and further isomerized 1,2-dihydroquinolines were independently obtained in high yields with an excellent control of isomerization of the double bond.

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations.

A series of functionalized benzimidazo[1,2-c]quinazoline derivatives was obtained in excellent yields under mild conditions through a CuI-catalyzed Ullmann N-arylation starting from easily available starting materials.

Atom-economical construction of tetracyclic [1,4]oxazepines involving intramolecular arylation of a 2-imidazoline moiety

Novel [1,4]oxazepines containing a fused imidazoline moiety were synthesized from 2-hydroxyphenyl imidazolines and bis-electrophilic aromatic substrates in a reaction involving sequential nucleophilic aromatic substitution steps and a Smiles rearrangement. A notable step was the remarkably facile, metal-free intramolecular N-arylation of the imidazoline moiety with a fluoro-, nitro- or chloroaromatic or heteroaromatic ring. The approach presented in this Letter not only details access to a new, medicinally relevant tetracyclic [1,4]oxazepine core but also extends the scope of imidazoline arylation chemistry.

One-Pot Synthesis of Quinolin-4(1H)-one Derivatives by a Sequential Michael Addition–Elimination/Palladium-Catalyzed Buchwald–Hartwig Amination Reaction

A convenient approach has been developed for the construction of quinolin-4(1<i>H</i>)-one frameworks, starting from (<i>Z</i>)-β-chlorovinyl aromatic ketones and amines. Intermolecular Michael addition of an amine to a (<i>Z</i>)-β-chlorovinyl ketone was followed by elimination of a chloride anion to give enamine intermediates, with full retention of the initial <i>Z</i>-configuration. The enamine intermediates were transformed into quinolin-4(1<i>H</i>)-one products by a palladium-catalyzed intramolecular N-arylation in a tandem one-pot manner, with good to excellent yields.

Mild one-pot Horner-Wadsworth-Emmons olefination and intramolecular N-arylation for the syntheses of indoles, all regio-isomeric azaindoles, and thienopyrroles.

The syntheses of various N-protected aromatic-ring fused pyrrole-2-carboxylate derivatives have been accomplished using mild one-pot Horner-Wadsworth-Emmons olefination and Cu-catalyzed intramolecular N-arylation reactions. The optimized mild one-pot reaction conditions of various 2-bromo arylcarboxaldehydes with commercially available N-protected phosphonoglycine trimethylesters gave the desired aromatic-ring fused pyrrole-2-carboxylates, such as substituted indole-, all regio-isomeric azaindole-, and thienopyrrole-2-carboxylates, in good to excellent yields. These conditions showed broad substrate compatibility, without the loss of the protecting group.

Application of nanoparticle mediated N-arylation of amines for the synthesis of pharmaceutical entities using vit-E analogues as amphiphiles in water

The first CuI-nanoparticle catalyzed inter and intramolecular N-arylation of amines using vitamin E analogues as amphiphiles was developed in water and is extended to azoles, substituted indoles, a bioactive natural product and intermediates of pharmaceutical entities.

Enantioselective construction of C2-symmetric spiro skeleton through intramolecular copper-catalyzed N-arylation

Enantioselective construction of a C2-symmetric spirobi(1,2,3,4-tetrahydroquinoline) fra mework has been achieved through an intramolecular Cu-catalyzed C‐N bond coupling of 1,3propanediamide substrates possessing bromophenyl substituents. The use of N,N’-dimethyl-1,2diphenylethylenediamine as the chiral ligand was fo und to be essential in this asymmetric catalysis. Optically pure compound was shortly obt ained by a single recrystallization of the enantioenriched product, which was successfully der ivatised to a new chiral diphosphine ligand.

ChemInform Abstract: Stereoselective Synthesis of Indoline, Tetrahydroquinoline, and Tetrahydrobenzazepine Derivatives from o‐Bromophenyl N‐tert‐Butylsulfinyl Aldimines.

The diastereoselective addition of an allylic indium intermediate to chiral o-bromophenyl sulfinyl imine 4 proceeded with good levels of diastereoselectivity. The resulting homoallylic amine derivatives were transformed into lactams 7 and 12, which upon copper-mediated intramolecular N-arylation led to the formation of benzo-fused 1-azabicyclo[j.k.0]alkanes 8 and 13. Benzo-fused 2-allyl-substituted heterocycles 14 could also be prepared by means of a palladium-catalyzed N-arylation of the corresponding free amines. The synthesis of the alkaloid (−)-angustureine was easily accomplished from (S)-2-allyltetrahydroquinoline (14b).

ChemInform Abstract: Transition‐Metal‐Free Synthesis of Benzimidazoles Mediated by KOH/DMSO.

Benzimidazoles are prepared by intramolecular N-arylations of amidines mediated by potassium hydroxide in DMSO at 120 °C. In this manner, diversely substituted products have been obtained in moderate to very good yields.

Modular Synthesis of Benzimidazole-Fused Phenanthridines from 2-Arylbenzimidazoles and o-Dibromoarenes by a Palladium-Catalyzed Cascade Process

An efficient palladium-catalyzed route for the synthesis of benzimidazole-fused phenanthridines from o-dibromoarenes and 2-arylbenzimidazoles is described. The sequentially accomplished reaction comprises intermolecular C-H arylation of 2-arylbenzimidazoles followed by an intramolecular N-arylation reaction promoted by the same Pd catalyst. This Pd-catalyzed double arylation provides a useful tool for the discovery of fluorescent materials.

Stereoselective Synthesis of Indoline, Tetrahydroquinoline, and Tetrahydrobenzazepine Derivatives from o-Bromophenyl N-tert-Butylsulfinyl Aldimines

The diastereoselective addition of an allylic indium intermediate to chiral o-bromophenyl sulfinyl imine 4 proceeded with good levels of diastereoselectivity. The resulting homoallylic amine derivatives were transformed into lactams 7 and 12, which upon copper-mediated intramolecular N-arylation led to the formation of benzo-fused 1-azabicyclo[j.k.0]alkanes 8 and 13. Benzo-fused 2-allyl-substituted heterocycles 14 could also be prepared by means of a palladium-catalyzed N-arylation of the corresponding free amines. The synthesis of the alkaloid (−)-angustureine was easily accomplished from (S)-2-allyltetrahydroquinoline (14b).

Transition-Metal-Free Synthesis of Benzimidazoles Mediated by KOH/DMSO

Benzimidazoles are prepared by intramolecular N-arylations of amidines mediated by potassium hydroxide in DMSO at 120 °C. In this manner, diversely substituted products have been obtained in moderate to very good yields.

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

An efficient and practical protocol has been developed to synthesize 5,6-dihydroindolo[1,2-a]quinoxaline derivatives by CuI-catalyzed intramolecular N-arylation under microwave irradiation. This method rapidly afforded the tetracyclic products with good to excellent yields (83–97%) in short reaction times (45–60 min).

Beneficial effect of carboxylic acid additives on the Pd-catalyzed intramolecular N-arylation of 2-amino-3-(2-chlorophenylsulfonyl)pyrroles

Carboxylic acid additives have been shown to significantly improve the yield of the Pd-catalyzed intramolecular N-arylation of 2-aminopyrroles containing a 2-chlorophenylsulfonyl group at the 3-position to give a novel tricyclic ring system. Pivalic and phenylacetic acid provided the best yield enhancement, while acetic acid showed moderate enhancement. Other acids showed limited to no enhancement or even a detrimental effect on the reaction.

Synthesis of (−)-Epi-Indolactam V by an Intramolecular Buchwald–Hartwig C–N Coupling Cyclization Reaction

The synthetic efforts toward the concise synthesis of (-)-indolactam V from simple and commercially available starting materials using palladium- and copper-catalyzed intramolecular N-arylation strategy for the elaboration of the requisite nine-membered lactam ring as the key step are described. The incorporation of a turn-inducing structural element along the linear precursor was fundamental to achieve the heterocyclization step as well as obtain the correct regio- and chemoselectivity. The stereoselective nature in the C-N coupling cyclization reaction is interpreted in terms of minimization of allylic strain at the transition state for the palladium-amido complex formation. Meanwhile, the synthesis of the (-)-epi-indolactam V and its enantiomer have been accomplished.

Copper-Catalyzed Enantioselective IntramolecularN-Arylation, an Efficient Method for Kinetic Resolutions

For the first time, copper-catalyzed intramolecular N-arylation was successfully applied to the kinetic resolution strategy. Under the catalysis of CuI-BINOL derived ligands, the kinetic resolution of rac-2-amino-3-(2-iodoaryl)propionates and rac-2-amino-4-(2-iodoaryl)butanoates afforded chiral intramolecular coupling products and recovered the starting materials in high enantioselectivity (s factors up to 245).

Palladium-catalyzed regio- and chemoselective ortho-benzylation of C–H bond using a functionalizable primary amide directing group: a concise synthesis of dibenzo[b,e]azepin-6-ones

A palladium-catalyzed regio- and chemoselective direct benzylation of primary benzamides with 2-bromobenzyl bromides under a mild basic condition has been developed affording various substituted diarylmethanes in good yields. Furthermore, the directing amide group (-CONH2) was subjected to intramolecular N-arylation with the aryl bromide moiety present in diarylmethanes leading to a concise synthesis of dibenzoazepinones.

Efficient copper-catalyzed intramolecular N-arylation for the synthesis of oxindoles

An efficient copper-catalyzed intramolecular N-arylation was performed by using substituted 2-(2-bromoaryl)acetamide with a small amount of Cu2O and benzene-1,2-diamine as catalytic system under aerobic conditions, which provided good to excellent yields of oxindoles with tolerance of a wide variety of substrates.

ChemInform Abstract: Designing a Sequential Ugi/Ullmann Type Reaction for the Synthesis of Indolo[1,2‐a]quinoxalinones Catalyzed by CuI/L‐Proline.

Abstract An efficient strategy for the one-pot syntheses of indolo[1,2-a]quinoxalinones catalyzed by CuI have been developed. The procedures combine the Ugi four-component reaction of aldehydes, 2-iodoaniline, 2-indole carboxylic acid, and isocyanides followed by the copper-catalyzed intramolecular N-arylation of the Ugi product in one-pot procedure, which afford the desired products in good to very good yields.

Synthesis of N-Alkoxyindol-2-ones by Copper-Catalyzed Intramolecular N-Arylation of Hydroxamates

The first example of copper-catalyzed intramolecular N-arylation of hydroxamic acid derivatives is presented. Based on this transformation a new method for the synthesis of N-alkoxyindol-2-ones from 2-(2-bromoaryl)acetylhydroxamates has been developed. The reaction conditions tolerate standard hydroxyl protecting groups on the hydroxylamine moiety and are also applicable for the synthesis of six-membered N-alkoxybenzolactams.