Palladium(II)‐Catalyzed Oxidation of Alcohols with Air as Reoxidant

Oxidation of primary and secondary aliphatic and secondary benzylic alcohols into their corresponding aldehydes and ketones was achieved in good yields with palladium catalysts using air as the reoxidant of palladium. The use of palladacycle 1 resulted in higher yields and a faster reaction than the use of Pd(OAc)₂ as the palladium source.     

On the Palladium(II)‐Catalysed Oxidative Rearrangement of Propargylic Acetates

The catalytic transformation of propargylic acetates into the corresponding α‐acetoxyenones in the presence of palladium(II) chloride is described. Water is a necessary component in this unusual oxidative rearrangement.     

Microwave‐Assisted Synthesis of Pyrazino[2,1‐b]quinazolines and 3‐Indolyl‐2(1H)‐pyrazinones Employing a Chemoselective Silver(I)‐ and Gold(I)‐Catalyzed Reaction

Novel microwave‐assisted syntheses of pyrazino[2,1‐b]quinazolines and 3‐indolyl‐2(1H)‐pyrazinones employing silver(I)‐ or gold(I)‐catalyzed protocols have been elaborated. The scope and limitations of these processes have been investigated.     

Assisted Tandem Palladium(II)/Palladium(0)‐Catalyzed C‐ and N‐Arylations of Quinoxalin‐2(1 H)‐ones in Water

A straightforward assisted tandem palladium(II)‐ and palladium(0)‐catalyzed direct C‐3 and N‐4 arylation of quinoxalin‐2(1 H)‐ones with boronic acids and aryl halides in water as safe and cheap solvent is reported. This environmentally friendly catalytic protocol is compatible with a wide range of functional groups and allows construction of various biologically important quinoxalin‐2(1 H)‐one backbones.

     

Palladium(II)‐Catalyzed Aerobic Intermolecular Cyclization of Acrylic Acid with Alkenes to α‐Methylene‐γ‐butyrolactones

The methodology in this article is a palladium(II)/copper(II)‐ or palladium(II)‐catalyzed intermolecular cyclization of acrylic acid with alkenes to produce α‐methylene‐γ‐butyrolactone derivatives using molecular oxygen as an environmentally benign oxidant. In this system, the carboxylato, especially trifluoroacetato, or trimethylacetato ligand, plays a quite important role to afford a high catalytic activity by suppressing the deposition of palladium(0) black.     

Palladium(II)‐Catalyzed Hydration of Alkynylphosphonates to β‐Ketophosphonates

A highly efficient palladium(II)‐catalyzed hydration of a wide range of alkynylphosphonates to the corresponding β‐ketophosphonates has been developed to give high yields at 80 °C in 1, 4‐dioxane, with no acidic or alkaline cocatalysts required. The described catalytic system should provide an efficient alternative to highly toxic mercury‐catalyzed methodologies and be useful in synthetic programs.     

Solvent‐Free Aerobic Oxidation of Alcohols Catalyzed by an Efficient and Recyclable Palladium Heterogeneous Catalyst

A simple alumina‐supported palladium catalyst prepared by an adsorption method is highly efficient and recyclable in the solvent‐free oxidation of alcohols with molecular oxygen. The adsorption method results in high dispersion of palladium probably as mononuclear or oligonuclear species on alumina surface. These palladium species are transformed to small Pd nanoparticles (ca. 5 nm), which are probably the true active species, during the course of alcohol oxidation.     

Mercury(II)‐Catalyzed Synthesis of Spiro[4.5]decatrienediones from Allenyl Ketones and Comparison with Silver(I)‐, Palladium(II)‐ and Brønsted Acid‐Catalyzed Reactions

The allenyl p‐methoxybenzyl ketone 3a and allenyl p‐siloxybenzyl ketones 6b selectively delivered three different products with three different transition metal‐catalysts. With Hg(II)‐catalysts a spiro[4.5]decene 9 , with Ag(I)‐catalysts a 2‐substituted furan ( 10/11 ) and with Pd(II)‐catalysts a 2,4‐disubstituted furan ( 8/12 ) was formed. Only with perchloric acid the intermolecular addition of water to the allene, leading to 1,3‐dicarbonyl compounds 7 , was observed. While with the corresponding allenyl o‐methoxybenzyl ketone 3b the Ag(I)‐ and Pd(II)‐catalysts provided the expected products, the mercury‐catalyst led to a new and interesting side‐product rac‐ 17 which combined both the furan moiety and the spiro[4.5]decene moiety. Efforts to prepare allenyl hydroxybenzyl ketones failed, in one case a small amount of a 5H‐benzo[b]oxepin‐4‐one 21 was isolated. It also was not possible to extend the spirocyclization to allenyl p‐siloxyphenyl ketone 6a or allenyl 2‐(p‐siloxyphenyl)ethyl ketone 6c .     

Chlorinative Cyclization of 1,6‐Enynes by Enantioselective Palladium(II)/Palladium(IV) Catalysis

A novel asymmetric catalysis via a palladium(II)/palladium(IV) cycle has been developed by utilizing a chiral spiro bis(isoxazoline) ligand (SPRIX). Intramolecular chlorinative cyclization of 1,6‐enynes catalyzed by a palladium‐SPRIX complex proceeded enantioselectively to afford α‐methylene‐γ‐lactone derivatives.     

Regioselective Synthesis of Naphtho‐fused Heterocycles via Palladium(0)‐Catalyzed Tandem Reaction of N‐Tosylhydrazones

We have developed a palladium(0)‐catalyzed tandem process which involves the cross‐coupling reaction of N‐tosylhydrazones with dibromide compounds followed by a sequence of intramolecular 5‐exo‐trig, 3‐exo‐trig cyclization, ring opening, and β‐hydride elimination to produce 6‐endo‐trig cyclized products. The strategy was successfully applied for the regioselective synthesis of substituted benzo[b]naphtho[2,1‐d]thiophenes, naphtho[1,2‐b]benzofurans, and benzo[a]carbazoles in moderate to excellent yields.

     

Facile Palladium‐Catalyzed Synthesis of 3‐Arylpyrazolo[1,5‐a]pyrimidines

An efficient palladium‐catalyzed synthesis of 3‐arylpyrazolo[1,5‐a]pyrimidines has been investigated. The key step in the synthesis is a Suzuki biaryl coupling of 3‐bromo‐2,5‐dimethyl‐7‐aminopyrazolo[1,5‐a]pyrimidines with arylboronic acids to provide 3‐arylpyrazolo[1,5‐a]pyrimidines in moderate to good yield. The synthetic utility of this methodology has been demonstrated by a concise and convergent synthesis of R121920, a potent CRHR₁ antagonist recently undergoing clinical evaluations.     

Synthesis of 1H‐Indole‐3‐carboxamidines through a Palladium‐Catalyzed Three‐Component Reaction Involving Isocyanide Insertion as a Key Step

A three‐component reaction involving isocyanides, o‐alkynyltrifluoroacetanilides, and amines for the efficient synthesis of 2‐substituted 1H‐indole‐3‐carboxamidines has been developed. The reaction proceeds through intramolecular aminopalladation of alkynes activated by isocyanide‐ligated palladium(II) species. Dioxygen acts as the sole oxidant to regenerate the active palladium(II) species.

     

Generation of 4‐Cyanoisoquinolines and 4‐Amidylisoquinolines via a Palladium‐Catalyzed Cyanative Reaction of 2‐Alkynylbenzaldimines with Isocyanides

An efficient route to 4‐cyanoquinolines via a palladium‐catalyzed cyanative reaction of 2‐alkynylbenzaldimines with isocyanides has been developed. The transformation proceeds through 6‐endo cyclization, isocyanide insertion, and cyanation. 4‐Amidylisoquinolines can be generated as well if water is involved in the reaction.

     

Highly Diastereoselective Synthesis of 2,6‐Di[1‐(2‐alkylaziridin‐1‐yl)alkyl]pyridines,Useful Ligands in Palladium‐Catalyzed Asymmetric Allylic Alkylation

C₂‐Symmetrical, enantiopure 2,6‐di[1‐(1‐aziridinyl)alkyl]pyridines (DIAZAPs) were prepared by a high‐yielding, three‐step sequence starting from 2,6‐pyridinedicarbaldehyde and (S)‐valinol or (S)‐phenylglycinol. The new compounds were tested as ligands in palladium‐catalyzed allylation of carbanions in different solvents. Almost quantitative yield and up to 99 % enantiomeric excess were obtained in the reactions of the enolates derived from malonate, phenyl‐ and benzylmalonate dimethyl esters with 1,3‐diphenyl‐2‐propenyl ethyl carbonate.     

An Efficient Route to 3‐Amidylindoles via a Palladium‐ Catalyzed Tandem Reaction of 2‐Alkynylanilines with Isocyanides

A palladium‐catalyzed reaction of 2‐alkynylaniline, isocyanides, and silver acetate is described, leading to 3‐amidylindoles in moderate to good yields. During the process, five new bonds are formed with high reaction efficiency in one‐pot procedure.     

Selective Intramolecular Palladium(II)‐Catalyzed Aminooxygenation vs. Diamination of Alkenylureas: Efficient Microwave‐Assisted Reactions to Bicyclic Piperazinones

Alkenylureas arising from glycine allylamides were proven to be suitable substrates for the synthesis of bicyclic five‐membered ring‐fused piperazinones. The reported intramolecular domino processes, performed under oxidative conditions with bis(acetonitrile)palladium dichloride as catalyst and copper(II) chloride in a stoichiometric amount by microwave activation, were completely selective, involving either diamination or aminooxygenation. While the latter process is determined by the direct intervention of the urea oxygen on the σ‐alkylpalladium intermediate, the diamination reaction can in principle derive from a direct attack of the second nitrogen atom on the palladium complex or on the first formed chloromethylpiperazinone. Indeed, this latter species was isolated and proved to be capable of conversion solely into the imidazopiperazinone.     

Copper‐Catalyzed N‐Aryl‐β‐enaminonitrile Synthesis Utilizing Isocyanides as the Nitrogen Source

A novel synthetic protocol for N‐aryl‐β‐enaminonitriles, which are useful building blocks for heterocycle synthesis, was developed using isocyanides as the nitrogen source. Using copper‐catalyzed one‐step reactions between isocyanides and benzyl cyanides under mild conditions, diverse N‐aryl‐β‐enaminonitriles could be synthesized in excellent yields and with high atom‐efficiency. N‐Alkyl‐β‐enaminonitriles were also synthesized in good yields. A mechanism involving an imidoyl‐copper intermediate was proposed based on mechanistic studies and previous reports. In addition, we demonstrated that a synthesized N‐aryl‐β‐enaminonitrile could be utilized for the synthesis of a β‐keto nitrile compound and 3‐aminopyrazole.

     

Microwave‐Assisted Synthesis of N‐Heterocyclic Carbene‐ Palladium(II) Complexes

The microwave‐assisted synthesis of two different types of N‐heterocyclic carbene‐palladium(II) complexes, (NHC)Pd(acac)Cl (NHC=N‐heterocyclic carbene; acac=acetylacetonate) and (NHC)PdCl₂(3‐chloropyridine), has been carried out. A drastic reduction in reaction times (20 to 88 times faster, depending on the complex) was observed when compared to the previously described, conventionally‐heated synthesis of these complexes. The protocol also allowed for the synthesis of (IPr)Pd(acac)Cl [IPr=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene] on a 5‐mmol scale in 30 min, with the reactants loaded in air.     

Palladium‐Catalyzed Methoxycarbonylation of 1,3‐Butadiene: Catalysis and Mechanistic Studies

The palladium‐catalyzed methoxycarbonylation of 1,3‐butadiene to methyl 3‐pentenoate has been studied. Intermediates of the proposed catalytic cycle were synthesized and the elementary steps of the reaction have been investigated in detail. It is shown that the first step of the catalytic cycle, the formation of crotylpalladium complexes from 1,3‐butadiene, proceeds even at room temperature. Examination of the influence of different reaction parameters on product yield and selectivity demonstrate the importance of chelating phosphine ligands and benzoic acids as additive in order to get good results.     

Cyclopropyl Building Blocks for Organic Synthesis, 131. Palladium‐Catalyzed Bicyclization with Carbonyl Insertion of Alkenyl‐Tethered Propargyl Carbonates Towards a Scalable Synthesis of Various 2‐(Bicyclo[3.1.0]hex‐1‐yl)acrylates

The Pd‐catalyzed 5‐exo‐trig‐3‐exo‐trig cascade cyclization of 1,6‐enynes with a propargyl carbonate terminus offers the shortest synthetic route to variously substituted 2‐(bicyclo[3.1.0]hex‐1‐yl)acrylates, a novel class of prospective monomers for low‐shrinkage polymers. To apply this reaction to large‐scale preparations of the said bicyclic acrylates, a flexible Pd catalyst system with tunable reactivity has been developed. The dependence of the product and diastereomer distribution on both the reaction conditions, including the type of palladium catalyst used, and on the nature of the substrate has been investigated. A variety of methyl 2‐(bicyclo[3.1.0]hex‐1‐yl)acrylates and parent carboxylic acids as well as some of their derivatives of potential interest towards a technical application were prepared on a multigram scale. A general large‐scale synthesis of the cyclization precursors bearing one or two carbonyl groups in the tether is also disclosed.