Palladium‐Catalyzed Carbonylation of Diols to Cyclic Carbonates

The catalytic alkoxycarbonylation of 1,2‐diols by (neocuproine)palladium(II) acetate (neocuproine=2,9‐dimethyl‐1,10‐phenanthroline) or palladium(II) acetate/(−)‐sparteine using N‐chlorosuccinimide as the oxidant affords cyclic carbonates. The oxidative carbonylation of diols proceeds under mild conditions, requiring only 1 atm of carbon monoxide, and produces cyclic carbonates in moderate to good yields. Both 1,2‐ and 1,3‐diols can be carbonylated using (neocuproine)Pd(OAc)₂ and sodium dichloroisocyanuric acid, which serves as a competent oxidant and base for this system, to yield 5‐ and 6‐membered cyclic carbonates.     

New Synthesis of Aryl and Heteroaryl N‐Acylureas via Microwave‐Assisted Palladium‐Catalysed Carbonylation

A new, practical synthesis of aryl and heteroaryl N‐acylureas has been developed via palladium‐catalysed carbonylation of aryl or heteroaryl halides in the presence of urea nucleophiles. A range of reactions illustrating the wide scope of this reaction was carried out under microwave irradiation, using either carbon monoxide gas in a vessel equipped with a gas inlet adapter, or molybdenum hexacarbonyl as the carbon monoxide source in standard microwave vials. The reactions proceeded in good to excellent yields. To illustrate the usefulness of this method a one‐step synthesis of the important insecticide diflubenzuron is reported.     

Double Carbonylation Reactions of Enynols and Thiols to Form Thioester Substituted 6‐Membered Ring Lactones

The double carbonylation reaction of enynols with thiols affords functionalized 6‐membered ring lactones. Two kinds of 6‐membered ring lactones were obtained by the use of different palladium complexes with added phosphine ligands.     

Alkoxycarbonylation of 3,3,3‐Trifluoropropyne: an Intriguing Reaction to Prepare Trifluoromethyl‐Substituted Unsaturated Acid Derivatives

The addition of CO and methanol to 3,3,3‐trifluoropropyne is catalysed by Pd(OAc)₂ in the presence of (6‐methylpyrid‐2‐yl)diphenylphosphine and CH₃SO₃H. The main products of the reaction are the methyl esters of 2‐(trifluoromethyl)propenoic acid 1 and of 3‐(trifluoromethyl)propenoic acid 2 (4,4,4‐trifluorobut‐2‐enoic acid). The regioselectivity of the reaction can be controlled to a great extent by a suitable choice of the composition of the catalytic system and the reaction conditions. Thus, 1 can be obtained in 93% yield by using P(CO)=20 atm and high ligand/Pd and acid/Pd ratios. On the other hand, selectivity up to 85% in 2 can be achieved using P(CO)=80 atm and a low ligand/Pd ratio together with a high acid/Pd ratio. The reaction mechanism is also discussed.     

Optically Active 2,3‐Allenoates via Palladium‐Catalyzed Carbonylation of Enantioenriched Propargylic Mesylates

Under mild conditions, optically active 2,3‐allenoates were synthesized from enantioenriched propargylic mesylates with moderate to excellent yields and high efficiency of chirality transfer by using palladium(0) bis(dibenzylideneacetone) (3 mol%) with (S)‐(−)‐5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole [(S)‐SEGPHOS] (3 mol%) as the catalyst and diammonium hydrogen phosphate (1.1 equiv .) as the base.     

A Palladium‐Catalyzed Carbonylative–Deacetylative Sequence to 1,3‐Keto Amides

An efficient three‐component reaction involving carbon monoxide with a range of aryl bromides and N‐substituted acetoacetamides is reported for the synthesis of β‐keto amides. This transformation is promoted by Pd‐catalysis followed by an acid‐mediated deacetylation upon work‐up, enabling a large number of β‐keto amides to be isolated. Finally, d₂‐¹³C‐dyclonine could be synthesized in three steps utilizing the developed catalytic system as the key step.

     

A Microfluidic Approach to the Rapid Screening of Palladium‐Catalysed Aminocarbonylation Reactions

The evaluation and selection of the most appropriate catalyst for a chemical transformation is an important process in many areas of synthetic chemistry. Conventional catalyst screening involving batch reactor systems can be both time‐consuming and expensive, resulting in a large number of individual chemical reactions. Continuous flow microfluidic reactors are increasingly viewed as a powerful alternative format for reacting and processing larger numbers of small‐scale reactions in a rapid, more controlled and safer fashion. In this study we demonstrate the use of a planar glass microfluidic reactor for performing the three‐component palladium‐catalysed aminocarbonylation reaction of iodobenzene, benzylamine and carbon monoxide to form N‐benzylbenzamide, and screen a series of palladium catalysts over a range of temperatures. N‐Benzylbenzamide product yields for this reaction were found to be highly dependent on the nature of the catalyst and reaction temperature. The majority of catalysts gave good to high yields under typical flow conditions at high temperatures (150 °C), however the palladium(II) chloride‐Xantphos complex [PdCl₂(Xantphos)] proved to be far superior as a catalyst at lower temperatures (75–120 °C). The utilised method was found to be an efficent and reliable way for screening a large number of palladium‐catalysed carbonylation reactions and may prove useful in screening other gas/liquid phase reactions.     

2‐Arylacetamides as Versatile Precursors for 3‐Aminoisocoumarin and Homophthalimide Derivatives: Palladium‐Catalyzed Cascade Double Carbonylation Reactions

The synthesis of biologically relevant homophthalimide and 3‐aminoisocoumarin nuclei via palladium‐catalyzed carbonylation of 2‐(2‐iodoaryl)acetamides has been developed. The degree of N‐substitution on the starting amide substrate dictates whether C−N or C−O coupling takes place in the final step of the catalytic cycle giving rise to each type of heterocycle. The introduction of a second C−halogen bond in the starting acetamides allows a catalytic cascade double carbonylation involving a C−H activation step to give fused heterocyclic structures.

     

Anaerobic Palladium‐Catalyzed Chemoselective Oxidation of Allylic and Benzylic Alcohols with α‐Bromo Sulfoxide as a Co‐oxidant

A chemoselective palladium‐catalyzed anaerobic oxidation of allylic and benzylic alcohols using an α‐bromo sulfoxide as a co‐oxidant is described for the first time. The catalyst system is simple and has a long life because of the allowance of phosphane ligands under the non‐aerobic conditions. The advantages of the described method include no overoxidation of primary alcohols to carboxylic acids because of the mild conditions applied, the tolerance of oxygen‐sensitive functionalities such as a carbon‐carbon double bond, an organothio group, or a diorganoamino group and the effective preparation of α,β‐unsaturated aldehydes and ketones, resulting from the oxidation of primary and secondary allylic alcohols, since a competitive Heck reaction with the co‐oxidant does not occur.     

Palladium‐Catalyzed Synthesis of Functional Tetralins via Benzylic Activation

2‐Monosubstituted, 2,2‐ and 2,3‐disubstituted tetralin derivatives have been synthesized from α,α′‐dihalo‐o‐xylenes and activated olefins using a palladium catalyst under basic conditions. The effects of temperature, base, palladium precursor and solvent have been fully explored, and this new catalytic reaction has been extended to a variety of substrates.     

Synthesis of Fused Cyclopentenones through Palladium‐Catalyzed Cyclization of 2‐Iodoaryl Allenols

A versatile strategy for the synthesis of fused cyclopentenones, key structural motifs in biologically relevant compounds such as indenones and indole alkaloids, has been established successfully through regioselective palladium‐catalyzed cyclization of 2‐iodoaryl allenols.

     

Progress in the Palladium‐Catalyzed α‐Arylation of Ketones with Chloroarenes

Non‐ and deactivated chloroarenes can be coupled with a wide range of ketones to yield the corresponding arylmethyl ketones in good to excellent yields using a palladium(II) acetate/n‐BuPAd₂ catalyst system. Depending on the ketone, the chloroarene/ketone ratio and the base, mono or diarylation can be effected selectively.     

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.     

Palladium‐Catalyzed Oxidative Carbonylation of Aromatic C−H Bonds with Alcohols using Molybdenum Hexacarbonyl as the Carbon Monoxide Source

With molybdenum hexacarbonyl as the carbon monoxide source, a general palladium‐catalyzed carbonylative transformation of the C−H bond on aromatic rings to produce esters has been developed. Good yields of the corresponding products have been obtained with wide functional group tolerance and excellent regioselectivity. A variety of aliphatic alcohols are suitable reactants here.

     

Palladium‐Catalyzed Cyclization Reactions of Acetylene‐Containing Amino Acids

Enantiomerically pure acetylene‐containing α‐amino acids were used as versatile starting materials for the synthesis of a variety of heterocycles via Pd‐mediated cyclization reactions. Depending on the protecting group strategy, both the carboxylate and the amine function of the amino acids could participate in the cyclizations, thus giving rise to oxygen heterocycles (α‐aminolactones) and nitrogen heterocycles (cyclic α‐amino acid derivatives), respectively. Beside the straightforward cyclization, cyclization/cross‐coupling reactions were also successfully carried out to provide the corresponding substituted cyclic amino acid derivatives.     

Easy,Green and Safe Carbonylation Reactions through Zeolite‐Catalyzed Carbon Monoxide Production from Formic Acid

Zeolites with the right shape and acid site density and strength, such as certain ZSM‐5 forms, were able to cleanly decompose formic acid to carbon monoxide (CO), and the latter could be directly used in palladium‐catalyzed carbonylation reactions. A simple two‐reactor system was designed to produce CO conveniently and then further react this gas in a safe way. The two‐reactor system is particularly cheap, easy to set up and use. In addition, the carbonylation conditions without pressure allowed for very efficient CO incorporation, with only 1% of palladium(II) chloride (PdCl₂) and Xantphos.

     

Palladium‐Catalyzed Intramolecular Coupling of Aryl Halides and Ketone Enolates: Synthesis of Hexahydro‐2,6‐methano‐1‐2

The palladium‐catalyzed intramolecular coupling of 2‐haloanilines and ketone enolates is a useful methodology for the synthesis of hexahydro‐2,6‐methano‐1‐2 derivatives. A study about the reaction conditions of the process is reported.     

Palladium‐Catalyzed Three‐Component Synthesis of Functionalized Allylamines by Intermolecular Tandem Carbopalladation–Amination

Highly regio‐ and stereoselective formation of allylamines has been achieved through a three‐component reaction between iodobenzene, an allene, and an amine in acetonitrile, catalyzed by in situ formed and by isolated palladium‐diphosphine catalysts.     

Remarkable Ligand Effects in Regioselective Palladium‐Catalysed Allylic Substitution Reactions

The use of tricyclohexylphosphine (and related phosphines) in palladium‐catalysed allylic substitution reactions enables the selective conversion of branched allylic acetates into the branched substitution products (up to 120:1 regioselectivity). Linear allylic acetates do not show the same selectivity for the branched substitution products, thereby demonstrating a memory effect.