Copper- and palladium-catalyzed intramolecular C-S bond formation: a convenient synthesis of 2-aminobenzothiazoles

Copper- and palladium-catalyzed intramolecular C-S bond formation by cross-coupling between an aryl halide and thiourea functionality is demonstrated for the synthesis of 2-aminobenzothiazoles, wherein the Cu-catalyzed protocol is generally superior and more cost effective than the Pd-catalyzed protocol; the Cu-catalyzed reaction also further expands recent studies exploring the utility of Cu salts as replacements for Pd in carbon-heteroatom bond-forming reactions. A one-pot variant combining the synthesis of the thiourea and the cyclization was also demonstrated.     

Thiophenol-mediated intramolecular radical cyclization: an efficient method for the synthesis of benzoxocine derivatives

A new, efficient, high yielding method for the synthesis of benzoxocine derivatives has been developed via a thiophenol-mediated intramolecular 8-endo radical cyclization. This method allowed the synthesis of the backbone of several sesquiterpenes.     

A one-pot method for the synthesis of 2-aminobenzimidazoles and related heterocycles

A rapid and efficient one-pot method for the synthesis of 2-aminobenzimidazoles and related heterocycles is described. The reaction is mediated by a polymer-supported carbodiimide, which simplifies product isolation. The scope and limitations of this method are described.     

An efficient method for the preparation of tertiary esters by palladium-catalyzed alkoxycarbonylation of aryl bromides

The palladium-catalyzed alkoxycarbonylation of aryl bromides is described for the efficient preparation of tertiary esters. The protocol proved compatible with a wide variety of functionalized (hetero)aromatic bromides, as well as several different sterically hindered tertiary alcohols, affording the alkoxycarbonylated products in high yields. Finally, the formation of aromatic trityl esters is discussed.     

Mild and efficient palladium-catalyzed intramolecular direct arylation reactions

The influence of ligand, stoichiometric base, and additive has been evaluated in the context of intramolecular direct arylation reactions. Under the optimal conditions, arylation of simple arenes can be performed under very mild conditions, with heating to 50 °C. The role of the pivalic acid additive is rationalized by invoking a concerted palladation-deprotonation pathway where the pivalate is behaving as either an intramolecular base from the palladium metal or through an intermolecular deprotonation in a similar manner as that previously described by Echavarren and Maseras.     

An inexpensive cyclodiphosphazane as an efficient ligand for the palladium-catalyzed amination of aryl bromides and chlorides

An economic and novel ligand, cyclodiphosphazane [ClPN(t-Bu)]₂ (1), was introduced in the palladium-catalyzed amination of unactivated aryl halides. The catalyst allows for the amination of aryl chlorides and bromides with secondary cyclic amines and anilines in good yields.     

An efficient assembly of heterobenzazepine ring systems utilizing an intramolecular palladium-catalyzed cycloamination

Azaheterocyclic compounds are interesting and medicinally relevant targets. Herein we disclose an improved synthesis into the oxazepine and thiazepine ring systems. The key step in the synthesis exploits recent advancements in the palladium-catalyzed amination reaction, which was utilized to form the seven-membered rings. General conditions for this reaction were Pd2dba3, P(t-Bu)3, NaO-t-Bu alone or with K2CO3, in toluene. The scope of the reaction was investigated, and has been shown to be effective on a variety of substrates as illustrated.     

An efficient palladium-catalyzed synthesis of cinnamaldehydes from acrolein diethyl acetal and aryl iodides and bromides

The reaction of aryl iodides and bromides with acrolein diethyl acetal in the presence of Pd(OAc)(2), (n)()Bu(4)NOAc, K(2)CO(3), KCl, and DMF, at 90 degrees C until the disappearance of the acetal followed by the addition of 2 N HCl to the crude reaction mixture, affords cinnamaldehydes in good to high yields. A variety of functional groups are tolerated in the aryl halides, including ether, aldehyde, ketone, ester, dialkylamino, nitrile, and nitro groups. The presence of substituents close to the oxidative addition site does not hamper the reaction.     

An improved method for the palladium-catalyzed amination of aryl iodides

Aryl iodides are coupled with amines to give the corresponding arylamines in high yield in the presence of palladium, a suitable ligand, and NaOt-Bu. Functionalized aryl iodides give good yields of the corresponding arylamines when Cs(2)CO(3) is substituted as the base.     

Phosphonium-mediated cyclization of N-(2-aminophenyl)thioureas: efficient synthesis of 2-aminobenzimidazoles

BOP efficiently promoted the phosphonium-mediated cyclization of thioureas, leading to a convenient synthesis of 2-aminobenzimidazoles. Compared to conventional methods, the reactions were complete at room temperature with times ranging from a few minutes to 1 h in near quantitative yields. This method is also applicable to the synthesis of more challenging structures such as 2-akylaminobenzimidazoles and 2-(N-acyl)-aminobenzimidazoles. The methodology described herein represents a mild and efficient route to a variety of 2-aminobenzimidazoles.     

Highly efficient and functional-group-tolerant catalysts for the palladium-catalyzed coupling of aryl chlorides with thiols

The cross-coupling reaction of aryl chlorides with aliphatic and aromatic thiols catalyzed by palladium complexes of the strongly binding bisphosphine CyPF-tBu ligand (1) is reported. Most of the reactions catalyzed by complexes of ligand 1 occur with turnover numbers that exceed those of previous catalysts by two orders of magnitude. The reactions occur with excellent yields, broad scope and high tolerance of functional groups. Coupling of aryl halides with thiols in the presence of low loadings of catalysts derived from other Josiphos type ligands, as well as ligands of other structural types, are also described.     

The development of efficient catalysts for palladium-catalyzed coupling reactions of aryl halides

In the mid 1990s, we started a program on the development of more efficient palladium catalysts for the C-C and C-N coupling reactions of aryl halides, especially aryl chlorides. In this contribution, our investigations on new catalyst systems and their application in organic synthesis are summarized.     

Highly efficient CuOx/OMS-2 catalyst for synthesis of phenoxathiin derivatives via intramolecular arylations of phenols with aryl halides

Phenoxathiin and its derivatives have attracted a great deal of interest due to their unique chemical and physical properties and their applications in fluorescent materials, antifungal activities and selective inhibitors. In the presence of copper supported on manganese oxide-based octahedral molecular sieves OMS-2 (CuO_x/OMS-2), the heterogeneously catalytic synthesis of phenoxathiinan derivatives via intramolecular arylations of phenols with aryl bromide or aryl chloride has been achieved. TEM and XRD have confirmed the CuO_x/OMS-2 catalyst has been successfully reused 8 times without a significant decrease in the yield, with simple filtration and washing as a means of separation.     

A general and efficient palladium-catalyzed intramolecular cyclization reaction of beta-brominated porphyrins

A general and efficient synthesis of fused five-membered porphyrins from the readily available beta-brominated porphyrins via palladium-catalyzed intramolecular cyclization has been developed, which can be applied for various metal complexes of beta-brominated porphyrins or free base ones and generally results in good yields of the fused five-membered porphyrins.     

An efficient palladium-catalyzed synthesis of benzils from aryl bromides: vinylene carbonate as a synthetic equivalent of glyoxal

An expedient synthetic procedure of benzil derivatives from aryl bromides was developed using vinylene carbonate as a glyoxal equivalent in a palladium-catalyzed reaction. The reaction involved a sequential diarylation of vinylene carbonate to form 4,5-diaryl-1,3-dioxol-2-one, ring-opening to benzoin derivative, and an oxidation process.     

Addition of grignard reagents to aryl acid chlorides: an efficient synthesis of aryl ketones

[chemical reaction: see text]. Direct addition of Grignard reagents to acid chlorides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether proceeds selectively to provide aryl ketones in high yields. A possible tridentate interaction between Grignard reagents and bis[2-(N,N-dimethylamino)ethyl] ether moderates the reactivity of Grignard reagents, preventing the newly formed ketones from nucleophilic addition by Grignard reagents.     

Design and synthesis of thioether-imidazolium chlorides as efficient ligands for palladium-catalyzed Suzuki-Miyaura coupling of aryl bromides with arylboronic acids

The catalyst composed of 0.25-0.025 mol % of [Pd(allyl)Cl]₂ and 0.5-0.05 mol % of the thioether-imidazolium chloride 3c was proven to be efficient in the Suzuki-Miyaura cross-coupling reactions of aryl bromides with arylboronic acids.     

An efficient palladium-catalyzed Heck coupling of aryl chlorides with alkenes

Catalyst system PdCl₂(PCy₃)₂/Cs₂CO₃ in dioxane was found to be the efficient catalyst system for Heck cross-coupling reactions of deactivated, neutral, and activated aryl chlorides with a variety of alkenes under mild conditions to afford selectively E-arylated alkenes in good to excellent yields.