Parallel synthesis of a library of benzoxazoles and benzothiazoles using ligand-accelerated copper-catalyzed cyclizations of ortho-halobenzanilides

A general method for the formation of benzoxazoles via a copper-catalyzed cyclization of ortho-haloanilides is reported. This approach complements the more commonly used strategies for benzoxazole formation which require 2-aminophenols as substrates. The reaction involves an intramolecular C-O cross-coupling of the ortho-haloanilides and is believed to proceed via an oxidative insertion/reductive elimination pathway through a Cu(I)/Cu(III) manifold. The reaction is also applicable to the formation of benzothiazoles. A variety of ligands including 1,10-phenanthroline and N,N'-dimethylethylenediamine were shown to provide ligand acceleration/stabilization in the reaction. Optimal conditions for cyclization used a catalyst combination of CuI and 1,10-phenanthroline (10 mol %). The method was amenable to a parallel-synthesis approach, as demonstrated by the synthesis of a library of benzoxazoles and benzothiazoles substituted at various positions in the ring. Most examples utilized the cyclization of ortho-bromoanilides, but ortho-iodoanilides and ortho-chloroanilides also undergo a reaction under these conditions. The rate of reaction of the ortho-haloanilides follows the order I > Br > Cl, consistent with oxidative addition being the rate-determining step.     

Oxidative Cyclization Reaction of 2‐Aryl‐Substituted Cinnamates To Form Phenanthrene Carboxylates by Using MoCl5

The oxidative cyclization reaction of 2‐aryl cinnamates and derivatives thereof can be easily performed with MoCl₅ as the oxidant. This powerful reagent allows oxidative coupling reactions for which other reagents fail. The best results are obtained when the 2‐phenyl substituent of the cinnamate is equipped with two methoxy groups. Even iodo moieties in the bay region of phenanthrene are tolerated under the reaction conditions. If naphthalene moieties are involved, a rearrangement of the skeleton occurs, providing an elegant route to highly functionalized angular arenes. The cyclization is demonstrated for 15 example substrates with isolated yields of up to 99 % for the phenanthrene derivative. The broad scope of the reaction underlines the usefulness of MoCl₅ and MoCl₅/TiCl₄ in the oxidative coupling reaction.     

Synthesis of Substituted 2‐Amino‐1,3‐oxazoles via Copper‐Catalyzed Oxidative Cyclization of Enamines and N,N‐Dialkyl Formamides

A facile synthesis of 2‐amino‐1,3‐oxazoles via Cu^I‐catalyzed oxidative cyclization of enamines and N ,N ‐dialkyl formamides has been developed. The reaction proceeds through an oxidative C−N bond formation, followed by an intramolecular C(sp²)−H bond functionalization/C−O cyclization in one pot. This protocol provides direct access to useful 2‐amino‐1,3‐oxazoles and features protecting‐group‐free nitrogen sources, readily available starting materials, a broad substrate scope and mild reaction conditions.     

Highly efficient construction of benzene ring in carbazoles by palladium-catalyzed endo-mode oxidative cyclization of 3-(3'-alkenyl)indoles

[reaction: see text] A highly efficient construction of the benzene ring in carbazoles by palladium-catalyzed endo-mode oxidative cyclization of 3-(3'-alkenyl)indoles was developed. The reaction utilizes benzoquinone as the stoichiometric oxidant and is conducted under mild conditions.     

Carbon-carbon bond formation in palladium(II)-catalyzed allylic oxidation: a novel oxidative carbocyclization of allene-substituted olefins

A new efficient palladium(II)-catalyzed oxidative carbocyclization has been developed. It was found that allene-substituted olefins 1 cyclized in the presence of 1 mol % Pd(O2CCF3)2 and p-benzoquinone (2 equiv) to give bicyclic ring systems 2 in good to excellent yields. The cyclization constitutes a new type of carbon-carbon bond forming reaction between an allene and an olefin under oxidative conditions.     

Research in the chemistry of heterocyclic quinoneimines. 3. Oxidative cyclization of 2,5-diarylamino-substituted 1,4-benzoquinone-4-phenylimines — Simple method for the preparation of 2-arylamino-5-aryl-3-phenazinones

2,5-Diarylamino-1,4-benzoquinone-4-phenylimines, which are formed in the reaction of 1,4-benzoquinone-4-phenylimine with aromatic amines, are converted under oxidative conditions to products of intramolecular oxidative cyclization, viz., 2-arylamino-5-aryl-3-phenazinones.See [4] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 330–333, March, 1984.     

Base-mediated synthesis of quinolines: an unexpected cyclization reaction between 2-aminobenzylalcohol and ketones

Quinolines are prepared in an oxidative cyclization reaction between 2-aminobenzylalcohol and ketones. This reaction, that involves a hydrogen transfer, is mediated solely by a base without the need for a transition metal catalyst.     

Low-molecular-weight polybenzimidazoles from aromatic dinitriles and aromatic diamines

Three oligomeric benzimidazoles have been prepared by the oxidative cyclization of the corresponding polyamidines. These materials are high melting and are soluble in solvents like dimethylformamide. They exhibit inherent viscosities of 0.20–0.25 in DMF at 0.5g/100 ml. Several model compounds have also been prepared to show the feasibility and scope of the oxidative cyclization reaction.     

Electrochemical Tri- and Difluoromethylation-Triggered Cyclization Accompanied by the Oxidative Cleavage of Indole Derivatives

Considering their unique roles in organic synthesis, and pharmaceutical and agrochemical applications, the development of fluoroalkylation, cyclization, and indole oxidative cleavage are important topics. Herein, an unprecedented electrochemical tri- and difluoromethylation/cyclization/indole oxidative cleavage process occurring in an undivided cell is presented. The protocol employs a readily prepared Langlois reagent as the fluoroalkyl source, affording a series of tri- or difluoromethylated 2-(2-acetylphenyl)isoquinoline-1,3-diones in good yields with excellent stereoselectivity. It is worth noting that this new methodology merges the fluoroalkylation/cyclization of N-substituted acrylamide alkenes with the oxidative cleavage of an indole C(2)=C(3) bond under external oxidant-free conditions.     

Pyrrolidine and piperidine formation via copper(II) carboxylate-promoted intramolecular carboamination of unactivated olefins: diastereoselectivity and mechanism

An expanded substrate scope and in-depth analysis of the reaction mechanism of the copper(II) carboxylate-promoted intramolecular carboamination of unactivated alkenes is described. This method provides access to N-functionalized pyrrolidines and piperidines. Both aromatic and aliphatic gamma- and delta-alkenyl N-arylsulfonamides undergo the oxidative cyclization reaction efficiently. N-Benzoyl-2-allylaniline also underwent the oxidative cyclization. The terminal olefin substrates examined were more reactive than those with internal olefins, and the latter terminated in elimination rather than carbon-carbon bond formation. The efficiency of the reaction was enhanced by the use of more organic soluble copper(II) carboxylate salts, copper(II) neodecanoate in particular. The reaction times were reduced by the use of microwave heating. High levels of diastereoselectivity were observed in the synthesis of 2,5-disubstituted pyrrolidines, wherein the cis substitution pattern predominates. The mechanism of the reaction is discussed in the context of the observed reactivity and in comparison to analogous reactions promoted by other reagents and conditions. Our evidence supports a mechanism wherein the N-C bond is formed via intramolecular syn aminocupration and the C-C bond is formed via intramolecular addition of a primary carbon radical to an aromatic ring.     

Pd(II)-catalyzed oxidative cyclization reaction for the preparation of 2-substituted 1,2,3,4-tetrahydroquinolines with halide functionality

The first Pd(II)-catalyzed oxidative cyclization reaction was developed for preparation of 2-substituted 1,2,3,4-tetrahydroquinolines from olefinic tosylamides. Under the optimized conditions, up to 86% yield was obtained. This reaction provides direct and easy access to 2-substituted 1,2,3,4-tetrahydroquinolines with halide functionality.     

Preparation of isoindolinones via a palladium-catalyzed diamination

A Pd(II)-catalyzed cyclization using oxidative olefin diamination was developed for the preparation of isoindolinones from ortho-olefinic N-methoxybenzamides. Using the optimized reaction conditions, the desired products were obtained in up to 90% yield using NFSI as the oxidant. This reaction provides an efficient and direct access to isoindolinones with amine functionality, an important drug skeleton.     

Palladium-catalyzed aerobic oxidative cyclization of N-aryl imines: indole synthesis from anilines and ketones

We report here an operationally simple, palladium-catalyzed cyclization reaction of N-aryl imines, affording indoles via the oxidative linkage of two C-H bonds under mild conditions using molecular oxygen as the sole oxidant. The process allows quick and atom-economical assembly of indole rings from inexpensive and readily available anilines and ketones and tolerates a broad range of functional groups.     

Oxidative cyclization of amidoximes and thiohydroximic acids: A facile and efficient strategy for accessing 3,5-disubstituted 1,2,4-oxadiazoles and 1,4,2-oxathiazoles

A facile and practical protocol has been developed for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles and 1,4,2-oxathiazoles through oxidative cyclization of amidoximes and thiohydroximic acids, respectively at room temperature. Use of mild reaction conditions, inexpensive reagents, broad substrate scope and good to excellent yield of the products are the salient features of this protocol.     

Facile Oxidative Rearrangements Using Hypervalent Iodine Reagents

Aromatic substituents migrate in a novel oxidative cyclization mediated by iodine(III) reagents. 4-Arylbut-3-enoic acids are cyclized and rearranged to 4-arylfuran-2(5H)-ones by hypervalent iodine compounds in good to excellent yields under mild reaction conditions. Other ring sizes are also accessible. The mechanism of the reaction is described in detail, and calculations highlight the cationic nature of the intermediates in the rearrangement. The fast access to heavily substituted furanones is used for the synthesis of biologically active derivatives.     

Oxidative cyclization of some aldehyde semicarbazones induced by metallic salts

The oxidative cyclization of some aldehyde semicarbazones 10 with four different oxidizing agents has been effected. The structure of the semicarbazones and the nature of cyclizing agent affected the rate and yield of cyclization but they did not show any influence on the regiochemistry of reaction. In fact, 1,2,4-triazoline 20 was the only heterocyclic ring obtained by the cyclization reaction.     

Mechanistic study of nickel-catalyzed ynal reductive cyclizations through kinetic analysis

The mechanism of nickel-catalyzed, silane-mediated reductive cyclization of ynals has been evaluated. The cyclizations are first-order in [Ni] and [ynal] and zeroth-order in [silane]. These results, in combination with the lack of rapid silane consumption upon reaction initiation, are inconsistent with mechanisms involving reaction initiation by oxidative addition of Ni(0) to the silane. Silane consumption occurs only when both the alkyne and aldehyde are present. Mechanisms involving rate-determining oxidative cyclization to a metallacycle followed by rapid reaction with the silane are consistent with the data obtained.     

Metal-free visible-light-induced oxidative cyclization reaction of 1,6-enynes and arylsulfinic acids leading to sulfonylated benzofurans

A new and convenient visible-light-induced method has been developed for the synthesis of sulfonylated benzofurans via oxidative cyclization reaction of 1,6-enynes and arylsulfinic acids.This reaction was carried out under metal-free and mild conditions,in which the C-S,C-C and C=O bonds could be sequentially formed in one pot operation.     

Radical oxidative cyclization of spiroacetals to bis-spiroacetals: an overview

The use of iodobenzene diacetate and iodine under photolytic conditions provides and efficient method for the oxidative cyclization of spiroacetals bearing an hydroxyalkyl side chain to bis-spiroacetals. An overview is provided of the use of this reaction for the synthesis of several bis-spiroacetal containing natural products such as the polyether antibiotics salinomycin and CP44,161 and the shellfish toxins, the spirolides.     

TBHP/AIBN-Mediated Synthesis of 2-Amino-thioazoles from Active Methylene Ketones and Thiourea under Metal-free Conditions

A new oxidative system of tert-butyl hydroperoxide (TBHP)/azodiisobutyronitrile (AIBN) has been used for the first time for a convenient, metal-free synthesis of substituted 2-aminothioazoles from active methylene ketone derivatives and thiourea. The reaction is postulated to proceed via an oxidative cyclization initiated by a radical process and followed by a condensation reaction.