Pd-catalyzed sequential reaction for the synthesis of fused tricyclic compounds containing a dihydrofuran or isobenzofuranone unit

A novel Pd-catalyzed sequential reaction for the synthesis of fused tricyclic compounds with a dihydrofuran or isobenzofuranone unit was developed.

Synthesis of novel chiral phosphine-triazine ligand derived fromα-phenylethylamine for Pd-catalyzed asymmetric allylic alkylation

A novel chiral phosphine-triazine ligand was synthesized from chiral α-phenylethylamine through a three-step procedure. In a model reaction of Pd-catalyzed allylic alkylation of rac-1,3-diphenylprop-2-en-1-y1 pivalate with dimethyl malonate, good enantioselectivity （90% e.e.） was obtained by using this ligand.

THE SPIN DELOCALIZATION SUBSTITUENT PARAMETER σ 10. SYNTHESIS OF SUBSTITUTED α, β, β-TRIFLUOROSTYRENES BY THE Pd-CATALYZED CROSS-COUPLING OF TRIFLUOROVINYLZINC BROMIDE WITH ARYL HALIDES

Palladium-catalyzed coupling of trifluorovinylzinc reagent with substituted aryl halides Y-C_6H_4-X (Y=p-NO_2, p-and m-COOMe, p-COOH, p-CONH_2, p- and m-CN; X=Br, I, Cl) provides a synthetic method for α, β, β-trifluorostyrenes(Y-TFS's). A series of previously unavailable Y-TFS's were thus obtained.

Recent Advances in Pd-Catalyzed Reactions Involving the “On-Water” Mechanism

As the chemical industry grapples with the need for more eco-friendly practices,the use of water as a reaction medium is gaining attraction in organic transformations.This mini-review delves into Pd-catalyzed reactions that utilize the "on-water" mechanism,spanning from 2019 to late 2023.These reactions are neatly categorized into several types: (A) Catalytic C—H activations,(B) Mizoroki- Heck-type reactions,(C) Suzuki-Miyaura reactions,and (D) Cyclization reactions.By showcasing the potential of water as a sustainable reaction medium for organic transformations,these reactions leave no doubt about the importance of embracing eco-friendly practices in the chemical industry.Key Scientists In 1980,a seminal work by Breslow et al.showed an acceleration of reaction rate in the Diels-Alder reaction.Sharpless and co-workers noted a significant increase in the rate of the [2σ+2σ+2π] cycloaddition of quadricyclane and dimethyl azodicarboxylate (DMAD) when the reaction was conducted in water,as opposed to when it was carried out in organic solvents.The term "on-water" was then coined to describe this phenomenon.This strategy was further expanded to transition-metal catalyzed transformations by Ackermann in 2011.Later,Varma and Leazer disclosed a Pd-catalyzed Mizoroki-Heck type arylation of alkenes with diaryliodonium salts “on-water”.The enantioselective version of "on-water" process was not realized until 2014 by the Zhou group.Later on,the Schaub group described a Pd-catalyzed Suzuki–Miyaura coupling reaction of electron-poor aryl chlorides with water,using only 50 ppm of catalyst loading.Very recently,Liu and Lin extended the "on-water" strategy to Pd-catalyzed double Mizoroki-Heck reactions.This mini-review has focused on Pd-catalyzed reactions involving the “on-water” mechanism.

Unlocking Biomolecular Activity through Pd-Catalyzed Azides Reduction

Comprehensive Summary Pd-mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules,precise regulation of protein function,and cellular engineering.However,the availability of cleavable"caging"groups is quite limited,and their application in nucleic acid modification has seldom been reported.Herein,we introduce a method based on Pd-catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules.We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function,followed by the release of biological activity through Pd-catalyzed NaBH4 reduction amination reaction.This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes,prodrugs,and to regulate the biological function of RNA,including reverse transcription extension,binding to ligands,and cleavage activity of the CRISPR-Cas system.All results confirm that this strategy provides an efficient and controllable"OFF to ON"biological switch,capable of achieving significant regulatory effects substoichiometrically,and is expected to be extended to other biological applications.

Pd-catalyzed asymmetric carbonyl alkynylation:Synthesis of axial chiral ynones

Ynones are important skeletons in bioactive molecules and valuable building blocks for organic synthesis,thus great efforts have been devoted to their preparation.While,introducing prochiral substrates to construct ynones bearing a chiral framework is unrealized to date.Herein,we reported the first example of Pd/SOP-catalyzed asymmetric carbonylative alkynylation via a non-classical carbonylative Sonogashiratype approach(acyl-Pd(Ⅱ)species generated from nucleophiles).By using cyclic diaryliodonium salts as prochiral substrates,various axial chiral ynones with good functional group tolerance(39 examples),satisfied yields(71%-96%)and excellent enantioselectivities(generally 94%-99%ee)were produced.Synthesis of bioactive compounds,scale-up experiment and useful transformations were also conducted to demonstrate the utility of this process.

Pd-Catalyzed Ortho-Directed C-H Glycosylation of Arenes Using N-linked Bidentate Auxiliaries

Main observation and conclusion A set of Pd-catalyzed ortho-directed C-H glycosylation reactions with glycosyl chloride donors using various N-linked bidentate auxil-iaries has been developed for synthesis of C-aryglycosides.A broad range of pyranose and furanose moieties can be installed on the ortho position of arylamine,carbazole,indole and benzylamine type substrates in high yield and with high regio-and diastereoselec-tivity.These auxiliaries can be readily installed and removed under relatively mild conditions.

The Pd-catalyzed synthesis of difluoroethyl and difluorovinyl compounds with a chlorodifluoroethyl iodonium salt(CDFI)

Herein, we report a simple and efficient method for the direct installation of chlorodifluoroethyl group onto aromatic molecules of various aromatic amides with a new 2-chloro,2,2-difluoroethyl(mesityl)iodonium salt(CDFI). Moreover, the chlorodifluoroethyl compounds could be smoothly converted into difluorovinyl compounds in a one-pot or discrete procedure and regarded as a steady source of difluorovinyl compounds with “HCl-mask”.

Synthesis of 1,3,5-Trisubstituted [4-tert-Butyl 2-（5,5-difluoro- 2,2-dimethyl-6-vinyl-l,3-dioxan-4-yl）acetate]pyrazoles via a Pd-Catalyzed C--H Activation

The gem-difluoromethylenated acetonide 2 was efficiently synthesized as new precursor of HMG-CoA reduc- tase inhibitor. Straightforward olefination via Pd-catalyzed C4-H activation of 1,3,5-trisubstituted pyrazoles 1 was proceeded smoothly in the presence of Pd（OAc）2 and AgCO3. This protocol has merits in terms of the improved atomic economy and prevention from the generation of by-products.

Mechanistic insight into the synergistic Cu/Pd-catalyzed carbonylation of aryl iodides using alcohols and dioxygen as the carbonyl source

Pd-catalyzed carbonylation,as an efficient synthetic approach to the installation of carbonyl groups in organic compounds,has been one of the most important research fields in the past decade.Although elegant reactions that allow highly selective carbonylations have been developed,straightforward routes with improved reaction activity and broader substrate scope remain long-term challenges for new practical applications.Here,we show a new type of synergistic Cu/Pd-catalyzed carbonylation reaction using alcohols and dioxgen as the carbonyl sources.A broad range of aryl iodides and alcohols are compatible with this protocol.The reaction is concise and practical due to the ready availability of the starting materials and the scalability of the reaction.In addition,the reaction affords lactones and lactams in an intermolecular fashion.Moreover,DFT calculations have been performed to study the detailed mechanisms.

Synthesis and Potential Application of Novel C_(2)-Symmetrical Bis(ferrocenyl)P2N Ligand

A novel chiral bis(ferrocenyl) P2N ligand 1 with C2-symmetry was synthesized through a four-step procedure from (R)-N,N-dimethyl-1-ferrocenylethylamine. In a model reaction of Pd-catalyzed allylic alkylation of 1,3-diphenylprop-2-enyl acetate 6 with dimethyl malonate, good enantioselectivity (86% e.e.) was obtained.

Palladium-Catalyzed[4+4]Cycloaddition of Homo-TMM All-Carbon 1,4-Dipole Precursors for Construction of Benzofuro[3,2-b]azocines and Furo[3,2-b]azocines

We developed a novel Pd-catalyzed[4+4]cycloaddition of(benzo)furan-derived azadienes with homo-TMM all-carbon 1,4-dipoles in situ generated fromα-allyl malonate derivatives,affording an array of benzofuro[3,2-b]azocines and furo[3,2-b]azocines with good to excellent yields(up to 96%)and exclusive regioselectivities.This methodology featured mild reaction conditions and good functional group tolerance.The synthetic utility was demonstrated by a gram-scale reaction.Furthermore,the catalytic asymmetric[4+4]cycloaddition version has also been explored.

[3+2]Cycloaddition of Vinyl Cyclopropane and Hydroxylamines via Isocynate Intermediate toγ-Lactams

Comprehensive Summary A general and efficient strategy for the synthesis ofγ-lactams has been reported.The hydroxylamines form Lossen rearrangement products of electron-deficient group migration with base and then undergo[3+2]cycloaddition reaction with vinyl cyclopropane,which could be performed with broad substrate scope,excellent functional group tolerance and high efficiency to produce the desired products.It also allowed further modification to other derivatives of theseγ-lactams.

Palladium-Catalyzed Addition of Carbon Monoxide and Carbon Tetrachloride to 1-Octene in Supercritical Carbon Dioxide

The Pd-catalyzed addition of carbon monoxide and carbon tetrachloride to 1-octene gave coadduct [alkyl 2-(2,2,2-trichloroethyl)octanoate] as the major product in supercritical carbon dioxide by using pyridine as the base. It was found that the selectivity and the yield of coadduct were greatly affected by the pressure of carbon dioxide,the reaction temperature and the amounts of alcohol and base used.

An efficient synthesis of substituted 1,4-diazepines by a Pd catalyzed amination and sequential hydrogenation condensation

An efficient synthesis of substituted 1,4-diazepines is developed.The accessible intermediates have been obtained via Pd-catalyzed amination.The subsequent hydrogenation and intramolecular condensation sequences could be conducted successively in one pot without special operation.The mild and general strategy enables the synthesis of various substituted 1,4-diazepines in high yields.

Asymmetric synthesis of ABC tricyclic systems in Daphniphyllum alkaloid

Efficient synthetic routs for the direct and rapid construction of[5-6-6]ABC tricyclic systems of daphmanidin A-type and calyciphylline A-type alkaloids have been successfully developed.For the daphmanidin A-type,the synthesis of[5-6-6]tricyclic framework utilize a HCl-mediated intramolecular Aldol reaction to construct the bicyclo[2.2.2]octane core and a thermal condensation to afford the ABC ring system.In addition,for the calyciphylline A-type,an improved synthesis of ABC[5-6-6]tricyclic system was developed,featuring an introduction of methyl ester group at C2 before the Pd-catalyzed intramolecular oxidative alkylation to construct the desired bowl-shape tricyclic core with stereochemical control.

Palladium-Catalyzed Oxidation of Dihydromyrcene to Citronellal in Supercritical Carbon Dioxide

Citronellal was the major product of catalytic oxidation of dihydromyrcene with oxygen using the catalyst comprised of (MeCN)2PdClNO2 and CuCl2 in a tertiary alcohol in supercritical carbon dioxide. It was found that the chemoselectivity of the reaction and the yield of citronellal were greatly affected by the pressure of carbon dioxide, the reaction temperature and the molar ratio of Pd/Cu.

Synthesis of Substituted Benzoxacycles via a Pd（ll）-Catalyzed Intramolecular Arylation Reaction of Allylic Alcohols

ein a Pd-catalyzed intramolecular allylation reaction of unprotected allylic alcohols was developed,and the reaction proceeded through a Pd（Ⅱ）-mediated allylic carbocation species formation,followed by a Friedel-Crafts type annulation to afford functionalized chromanes.

Palladium-catalyzed R_2(O)P-directed C(sp^2)–H activation

In recent years,transition-metal-catalyzed inert C–H bond activation has developed rapidly and is a powerful protocol for the construction of new C–C or C–X bonds and the introduction of new functional groups.Our group has also developed a series of R2(O)P-directed Pd-catalyzed C–H functionalizations involving olefination,hydroxylation,acetoxylation,arylation,and acylation through an uncommon seven-membered cyclo-palladium pretransition state.Unlike previously used directing groups,the R2(O)P group acts as a directing group and is also involved in the construction of P,-hetero-ligands.

Palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines with amines

A concise and efficient approach was developed for the synthesis of mono-substituted and di-substituted pyrimidines products via palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines and amines. This synthetic methodology can produce various di-substituted pyrimidines in high yields with good functional group tolerance, and provide a complementary tool for the syntheses of important intermediates of nucleosides and purines with bioactivities.