Intramolecular O-arylation Research Articles

Copper(II)-catalyzed Synthesis of Benzoxazoles from Inactive 2-chloroanilides.

Benzoxazoles are of great importance in natural products, pharmaceutical agents as well as synthetic intermediates. Although many works on the construction of benzoxazoles by Cu-catalyzed intramolecular O-arylation of ortho-haloanilides have been reported, only a few reports about transition metal-catalyzed synthesis of benzoxazoles from inactive 2-chloroanilides so far. This work aimed to explore a green and cheap protocol for intramolecular O-arylation of inactive 2-chloroanilides to prepare 2-arylbenzoxazoles. We found that Cu(acac)2/1,10-Phen complex was beneficial to intramolecular O-arylation of 2-chloroanilides using K2CO3 as a base in EtOH at 90 °C to prepare benzoxazoles. An efficient and green method was developed for Cu(II)-catalyzed intramolecular Oarylation of inactive 2-chloroanilides. In this way, many 2-arylbenzoxazoles were prepared in good yields.

Cu(II)/Vasicine Promoted Intramolecular C-O Formation: Synthesis of Benzoxazoles in EtOH.

Benzoxazoles are valuable bicyclic aromatic compounds; the construction of benzoxazoles via C-O cross-coupling reactions has attracted more and more attention. The best condition of C-O bond formation from o-haloanilides was carried out, taking Cu(OTf)2 (5 mol%) and vasicine (10 mol%) as the catalysts in EtOH in the presence of K2CO3 (2 eq.) for 12 h at 90°C. A series of 2-substituted benzoxazoles have been prepared in high yields from 2-bromoanilides and 2- iodioanilides under mild conditions. We have developed an efficient Cu-vasicine catalytic system for intramolecular C-O bond formation. This strategy is applicable to the synthesis of a wide variety of 2-substituted benzoxazoles by intramolecular O-arylation of o-haloanilides.

Efficient Cu-catalyzed intramolecular O-arylation for synthesis of benzoxazoles in water.

An efficient method was developed for synthesis of benzoxazoles by Cu-catalyzed intramolecular O-arylation of o-halobenzanilides in water. This strategy provides several advantages, such as high yields, water as a green solvent and functional groups tolerance.

Copper-catalyzed synthesis of 2-aminopyridylbenzoxazoles via domino reactions of intermolecular N-arylation and intramolecular O-arylation.

A simple and general approach to nitrogen-containing heterocycles via copper-catalyzed domino reaction has been developed, and the corresponding 2-aminopyridylbenzoxazole derivatives were obtained in good to excellent yields using the readily available starting materials. This method possesses unique step economy features, and is of high tolerance towards various functional groups in the substrates.

One-Pot Synthesis of 2-(Het)aryl/alkyl-3-cyanobenzofurans from 2-(2-Bromoaryl)-3-(het)aryl-3-(methylthio)acrylonitriles and Benzyl Carbamate.

A one-pot synthesis of 2-(het)aryl/alkyl-3-cyanobenzofurans has been reported. The overall sequence involves base-induced reaction of 2-(2-bromoaryl)-3-(het)aryl-3-(methylthio)acrylonitriles with benzyl carbamate, generating α-(het)aroyl-α-(2-bromoaryl)acetonitriles, which are in situ subjected to copper-catalyzed intramolecular O-arylation, furnishing the 2-(het)aryl/alkyl-3-cyanobenzofurans in high yields. A probable mechanism for the base-induced cleavage of 2-(2-bromoaryl)-3-(het)aryl-3-(methylthio)acrylonitriles to α-(het)aroyl-α-(2-bromoaryl)acetonitriles in the presence of benzyl carbamate has been proposed.

Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B.

(+)-Psiguadial B is a diformyl phloroglucinol meroterpenoid that exhibits antiproliferative activity against the HepG2 human hepatoma cancer cell line. This full account details the evolution of a strategy that culminated in the first enantioselective total synthesis of (+)-psiguadial B. A key feature of the synthesis is the construction of the trans-cyclobutane motif by a Wolff rearrangement with in situ catalytic, asymmetric trapping of the ketene. An investigation of the substrate scope of this method to prepare enantioenriched 8-aminoquinolinamides is disclosed. Three routes toward (+)-psiguadial B were evaluated that featured the following key steps: (1) an ortho-quinone methide hetero-Diels-Alder cycloaddition to prepare the chroman framework, (2) a Prins cyclization to form the bridging bicyclo[4.3.1]decane system, and (3) a modified Norrish-Yang cyclization to generate the chroman. Ultimately, the successful strategy employed a ring-closing metathesis to form the seven-membered ring and an intramolecular O-arylation reaction to complete the polycyclic framework of the natural product.

Access to 8-Azachromones via Activation of C-H in N-Oxides.

A concise and practical synthetic method has been developed for 8-azachromones, including 8-azaflavones, which have emerged as a promising class of compounds. Using commercially available nicotinates as the starting material, 8-azachromones were obtained in only three steps. The key intramolecular O-arylation reaction was achieved by nucleophilic attack of enolates to C2 of N-oxides under PyBrop or Ac2O activation conditions. These studies provide the basis for the access to 8-azachromones, enabling future work including the discovery and development of novel chromonoid drugs or other functional materials.

The base-promoted synthesis of multisubstituted benzo[b][1,4]oxazepines.

A novel protocol to synthesize multisubstituted benzo[b][1,4]oxazepines from N-(2-haloaryl)enaminones has been developed. In this procedure, only 2 equiv. of Cs2CO3 was required. A variety of polysubstituted benzo[b][1,4]oxazepine derivatives were provided in up to 95% yield for 27 examples.

Copper-Catalysed One-Pot Synthesis of 2,3,4,9-Tetrahydro-1H-Xanthen-1-Ones from 2-Halobenzylbromides and Cyclic-1,3-Diketones in Water

A simple, environmentally friendly, tandem C-benzylation and intramolecular O-arylation for the sequential one-pot synthesis of functionalised 4H-chromenes is reported. The reactions between 2-halobenzylbromides and cyclic-1,3-diketones were catalysed by CuO/oxalohydrazide/hexane-2,5-dione in water to produce 2,3,4,9-tetrahydro-1H-xanthen-1-ones in moderate to high yields. A simple, environmental friendly, tandem C-benzylation and intramolecular O-arylation for the sequential one-pot synthesis of 2,3,4,9-tetrahydro-1H-xanthen-1-ones in water is described.

ChemInform Abstract: A General Route for Synthesis of N‐Aryl Phenoxazines via Copper(I)‐Catalyzed N‐,N‐, and O‐Arylations of 2‐Aminophenols.

A novel copper(I)-catalyzed tandem reaction of N- and O-arylations of 2-[N-(2-chlorophenyl)amino]phenols was developed, by which a series of structurally novel N-aryl phenoxazines were synthesized efficiently. This success owes much to the discovery of highly efficient homogeneous copper(I)-catalyzed intramolecular O-arylation of chlorobenzenes under ligand-free-like conditions. Since 2-[N-(2-chlorophenyl)amino]phenols were prepared also by copper(I)-catalyzed N-arylation of 2-aminophenols, thus a general route for efficient synthesis of N-aryl phenoxazines was established via copper(I)-catalyzed N-, N-, and O-arylations of 2-aminophenols in two steps.

Recent advances in dibenzo[b,f][1,4]oxazepine synthesis

Abstract Dibenzo[b,f][1,4]oxazepine (DBO) derivatives possess an array of pharmacological activities, and are of growing pharmaceutical interest. Twelve recent synthetic protocols to construct DBO and DBO derivatives have been described in this review. The reported methods include cyclocondensation with two precursors exemplified by substituted 2-aminophenols and substituted 2-halobenzaldehydes, substituted 2-nitro-1-bromobenzene and substituted 2-triazolylphenols, substituted 2-nitro-1-bromobenzene and substituted 2-hydrazonamidophenol, substituted 2-nitro-1-bromobenzene and substituted 2-(aminomethyl)phenol, and 2-aminobenzonitrile and 1,4-dichloro-2-nitrobenzene. Other methods include copper catalysis, 1,3-dipolar cycloaddition, domino elimination-rearrangement-addition sequence, and an Ugi four-component reaction followed by an intramolecular O-arylation. These methods will serve as a guide to chemists in developing DBO derivatives of pharmacological interest.

ChemInform Abstract: Pd‐Catalyzed Desymmetric Intramolecular O‐Arylation Reaction: Enantioselective Synthesis of (3,4‐Dihydro‐2H‐chromen‐3‐yl)methanols.

An enantioselective intramolecular O-arylation was achieved through desymmetrization with Pd-catalyzed coupling reactions. The intramolecular asymmetric aryl C–O coupling reactions of 2-(2-haloaryl)propane-1,3-diols led to the enantioselective formation of chiral (3,4-dihydro-2H-chromen-3-yl)methanols in good yields and high enantiomeric selectivity.

Copper-catalysed intramolecular O-arylation: a simple and efficient method for benzoxazole synthesis.

A wide range of 2-substituted benzoxazoles can be efficiently synthesized from N-(2-iodo-/bromo-phenyl)benzamides, and even the less reactive N-(2-chlorophenyl)benzamides, via Cu-catalysed intramolecular coupling cyclization reactions using methyl 2-methoxybenzoate as the ligand under mild reaction conditions. In addition, the benzoxazoles can be easily prepared from the primary amides coupling with o-dihalobenzenes in a single step.

Pd-Catalyzed Desymmetric IntramolecularO-Arylation Reaction: Enantioselective Synthesis of (3,4-Dihydro-2H-chromen-3-yl)methanols

An enantioselective intramolecular O-arylation was achieved through desymmetrization with Pd-catalyzed coupling reactions. The intramolecular asymmetric aryl C-O coupling reactions of 2-(2-haloaryl)propane-1,3-diols led to the enantioselective formation of chiral (3,4-dihydro-2H-chromen-3-yl)methanols in good yields and high enantiomeric selectivity.

ChemInform Abstract: Intramolecular O‐Arylation Route to 2‐Substituted Benzoxazoles Mediated by Ferrocene Tethered Polymer Supported Ionic Liquid Phase Catalyst.

Abstract A novel ferrocene tethered polymer supported ionic liquid phase catalyst has been synthesized and successfully applied for intramolecular O-arylation of o-iodoanilides to corresponding benzoxazoles. The catalyst was easily recovered by simple filtration that greatly simplified the purification step and resulted in quantitative yields, without ionic liquid impurities in the products.

Expeditive Access to 2-Substituted 4H-Pyrido[1,3]oxazin-4-ones via an Intramolecular O-Arylation

Unreported 2-substituted 4H-pyrido[e][1,3]oxazin-4-ones are synthesized via an unprecedented intramolecular O-arylation of N-aroyl- and N-heteroaroyl-(iso)nicotinamides under microwave irradiations, in good to excellent yields. The broad applicability was demonstrated by 24 examples with a variety of substituents at the 2-position of the final compounds and 3 possible positions for the nitrogen atom of the pyridine ring. In addition, transformation of one of these compounds into 2-hydroxypyridyl-substituted 1,2,4-triazole and 1,2,4-oxazinone was realized. This approach opens a rapid access to a new bicyclic heteroaromatic chemical series with high potential in medicinal chemistry.

ChemInform Abstract: Iron‐Catalyzed Synthesis of 2‐Arylbenzo[b]furans

Abstractby Sonogashira cross‐coupling and intramolecular o‐arylation of o‐iodophenols and aryl acetylenes or silylacetylenes

Intramolecular O-arylation route to 2-substituted benzoxazoles mediated by ferrocene tethered polymer supported ionic liquid phase catalyst

A novel ferrocene tethered polymer supported ionic liquid phase catalyst has been synthesized and successfully applied for intramolecular O-arylation of o-iodoanilides to corresponding benzoxazoles. The catalyst was easily recovered by simple filtration that greatly simplified the purification step and resulted in quantitative yields, without ionic liquid impurities in the products.

Iron-Catalyzed Synthesis of 2-Arylbenzo[b]furans

An iron-catalyzed procedure was employed to achieve both the Sonogashira cross-coupling and intramolecular o-arylation of o-iodophenols and aryl acetylenes/1-substituted-2-trimethylsilyl acetylenes. A variety of 2-arylbenzo[b]furans were synthesized in moderate to good yields under the catalysis of 5% FeCl3 and 10% 1,10-phenanthroline.

Copper(I)-Catalyzed Intramolecular O-Arylation for the Synthesis of 2,3,4,9-Tetrahydro-1H-xanthen-1-ones with Low Loads of CuCl

As little as 0.5 mol % CuCl is sufficient to catalyze the intramolecular O-arylation of easily accessible 2-(2-bromobenzyl)cyclohexane-1,3-diones to provide the corresponding 2,3,4,9-tetrahydro-1H-xanthen-1-ones with yields ranging from 83% to 99%.