Single-Pd-Site Catalyst Induced by Different Dimensional Nitrogen of N-Doping Carbon for Efficient Hydroaminocarbonylation of Alkynes.

The unsaturated amides are traditionally synthesized by acylation of carboxylic acids or hydration of nitrile compounds but are rarely investigated by hydroaminocarbonylation of alkynes using heterogeneous single-metal-site catalysts (HSMSCs). Herein, single-Pd-site catalysts supported on N-doping carbon (NC) with different nitrogen dimensions inherited from corresponding metal-organic-framework precursors are successfully synthesized. 2D NC-supported single-Pd-site (Pd1/NC-2D) exhibited the best performance with near 100% selectivity and 76% yield of acrylamide for acetylene hydroaminocarbonylation with better stability, superior to those of Pd1/NC-3D, single-metal-site/nanoparticle coexisting catalyst, and nanoparticle catalyst. The coordination environment and molecular evolution of the single-Pd-site during the process of acetylene hydroaminocarbonylation on Pd1/NC-2D are detailly illuminated by various characterizations and density functional theoretical calculations (DFT). DFT also showed the energy barrier of rate-determining step on Pd1/NC-2D is lower than that of Pd1/NC-3D. Furthermore, Pd1/NC-2D catalyst illustrated the general applicability of the hydroaminocarbonylation for various alkynes.

Synthesis of Multisubstituted 2,3-Allenamides via Palladium-Catalyzed Carbonylation of Propargylic Esters.

2,3-Allenamides are an important class of unsaturated group-substituted carbonyl compounds. A palladium-catalyzed aminocarbonylation of propargyl acetates with amines for the synthesized tri-/tetrasubstituted 2,3-allenamides has been developed. A broad range of tri-/tetrasubstituted 2,3-allenamides have been prepared from propargyl acetates in good to excellent yields. The reaction featured mild reaction conditions and good functional group tolerance. The applicability of this methodology was further highlighted by the late-stage modification of several natural products and pharmaceuticals.

Mechanistic Insights into the Palladium-Catalyzed Perfluoroalkylative Carbonylation of Unactivated Alkenes to ß-Perfluoroalkyl Esters: A DFT Study.

Transition metal-catalyzed multicomponent carbonylation is an efficient synthetic strategy to access multifunctional esters in high yields with broad functional group tolerance and good chemoselectivity. Considering the development of highly efficient synthetic methods for esters, it remains significant to grasp the mechanism of constructing multifunctional esters. Herein, density functional theoretical calculations were carried out to acquire mechanistic insight into the synthesis of ß-perfluoroalkyl esters from a specific palladium-catalyzed perfluoroalkylative carbonylation of unactivated alkenes using carbon monoxide. A detailed mechanistic understanding of this reaction route includes (1) multistep radical reaction process, (2) C-C coupling and CO insertion, (3) ligand exchange, and (4) Pd-based intermediate oxidation and reductive elimination. The multistep radical process was fundamentally rationalized, including Rf· formation and radicals A and E from unactivated alkene and CO oxidation, respectively. The potential energy calculation indicated that the CO insertion into the perfluorinated alkyl radicals preceded Pd-catalyzed oxidation in the competitively multistep free radical reaction process. In addition, the I-/PhO- exchange step was predicted to be spontaneous to products. The IGMH analysis further attested to the reductive elimination process involved in the rate-determining step. Thus, a simple and valid density functional theory (DFT) approach was developed to reveal the multistep radical mechanism for the Pd-catalyzed perfluoroalkylative carbonylation of unactivated alkenes to access functional ß-perfluoroalkyl esters.

The regulatory mechanism of rapid lignification for timely anther dehiscence.

Anther dehiscence is a crucial event in plant reproduction, tightly regulated and dependent on the lignification of the anther endothecium. In this study, we investigated the rapid lignification process that ensures timely anther dehiscence in Arabidopsis. Our findings reveal that endothecium lignification can be divided into two distinct phases. During Phase I, lignin precursors are synthesized without polymerization, while Phase II involves simultaneous synthesis of lignin precursors and polymerization. The transcription factors MYB26, NST1/2, and ARF17 specifically regulate the pathway responsible for the synthesis and polymerization of lignin monomers in Phase II. MYB26-NST1/2 is the key regulatory pathway responsible for endothecium lignification, while ARF17 facilitates this process by interacting with MYB26. Interestingly, our results demonstrate that the lignification of the endothecium, which occurs within approximately 26 h, is much faster than that of the vascular tissue. These findings provide valuable insights into the regulation mechanism of rapid lignification in the endothecium, which enables timely anther dehiscence and successful pollen release during plant reproduction.

Palladium-Catalyzed Carbonylative Multicomponent Fluoroalkylation of 1,3-Enynes: Concise Construction of Diverse Cyclic Compounds.

Multicomponent reactions, particularly those entailing four or more reagents, have presented a longstanding challenge due to the inherent complexities associated with balancing reactivity, selectivity, and compatibility. In this study, we describe a palladium-catalyzed multi-component fluoroalkylative carbonylation of 1,3-enynes. A series of products featuring three active functional groups-allene, fluoroalkyl, and carboxyl, were efficiently and selectively integrated in a single chemical operation. Furthermore, more intricate fluoroalkyl-substituted pyrimidinones can be constructed by simply altering the 1,3-bisnucleophilic reagent. This approach also provides a valuable strategy for the late-stage modification of naturally occurring molecules and concise construction of diverse cyclic compounds.

Carbonylative synthesis and functionalization of indoles.

Carbonylation processes have become widely recognized as a versatile, convenient, and low-cost method for the synthesis of high-value compounds. Given the great importance of heterocyclic compounds, the carbonylative approach has become increasingly important for their synthesis. In this mini-review, as a class of benzo-fused nitrogen-containing heterocyclic compounds, we summarized and discussed the recent achievements on the synthesis and functionalization of indole derivatives via carbonylative approaches.

Transition-Metal-Catalyzed Carbonylative Multifunctionalization of Alkynes.

Currently, the construction of new carbon-carbon bonds and value-added structures in an atom- and step economical manner has become a continuous pursuit in the synthetic chemistry community. Since the first transition-metal-catalyzed hydroformylation of ethylene was reported by Otto Roelen in the 1930s, impressive progress has been achieved in the carbonylative functionalization of unsaturated C-C bonds. In contrast to alkenes, the carbonylative functionalization of alkynes offers tremendous potential for the construction of multisubstituted carbonyl-containing derivatives because of their two independently addressable π-systems. This review provides a timely and necessary investigation of transition-metal-catalyzed carbonylative mutifunctionalization of alkynes with the exclusion of carbonylative hydrofunctionalizations. Different transition metals including palladium, rhodium, iridium, ruthenium, iron, copper, etc. were applied to the development of novel carbonylative transformation. Various C-C, C-N, C-O, C-S, C-B, C-Si, and carbon-halogen bonds were formed efficiently and give the corresponding tri- or tetrasubstituted α,ß-unsaturated ketones, diesters, and heterocycles.

Cobalt-Catalyzed Direct Alkoxylation of Indoles.

Cobalt(II) salt as a non-noble metal catalyst has been widely used in direct C-H bond functionalization in recent years. In this work, we developed a cobalt-catalyzed C-H cleavage and alkoxylation of indoles with alcohols for the rapid construction of 2-alkoxylindole scaffolds. In the presence of Co(acac)2 as the catalyst, the reaction proceeds well to give a variety of 2-alkoxylindole derivatives in moderate to high yields. Control experiments suggest that a radical process might be involved in the reaction and the Co(III) species is the active catalyst.

Palladium-catalyzed Heck/aminocarbonylation of alkene-tethered carbamoyl chlorides with nitro compounds for the synthesis of carbamoyl-substituted oxindoles.

A straightforward and efficient approach for the synthesis of carbamoyl-substituted oxindoles has been developed via a palladium-catalyzed Heck cyclization and reductive aminocarbonylation reaction of alkene-tethered carbamoyl chlorides with nitro compounds. The reaction showed good compatibility toward versatile functional groups, and both nitroarenes and nitroalkanes were well tolerated. Using Mo(CO)6 as a solid CO source, without external reductants, a broad range of carbamoyl-substituted oxindoles were obtained in moderate to high yields.

Radical selenylative cyclization of trifluoromethyl propargyl imines for the synthesis of trifluoromethyl- and seleno-azaspiro[4,5]-tetraenones and quinolines.

A radical selenylative cyclization of trifluoromethyl propargyl imines with diselenides for the regiodivergent construction of diversely functionalized azaspiro[4,5]-tetraenones and quinolines has been developed, which enables dual incorporation of CF3 and Se groups into heterocycles in a one-pot reaction. When using Oxone as a green oxidant, the reaction proceeds through oxidative dearomative ipso-annulation or intramolecular ortho-annulation exhibiting good regioselectivity. The synthetic utility of this method is demonstrated by a scale-up reaction and further modification of the obtained products.

[Common diseases and drug use of Pseudostellaria heterophylla].

Pseudostellaria heterophylla in large-scale cultivation needs to apply pesticides to control diseases, and non-standard use of pesticide may cause excessive pesticide residues in medicinal materials, increasing the risk of clinical medication. To accurately monitor the residual pesticides, this paper investigated the drug use during the process of P. heterophylla disease prevention in 25 P. he-terophylla planting enterprises or individual households in Guizhou province. It was found that there were 8 common diseases in P. he-terophylla planting, including leaf spot, downy mildew, virus disease, root rot, dropping disease, purple feather disease, white silk disease, and damping-off disease. Twenty-three kinds of pesticides were used in disease control, mainly chemical synthetic pesticides, accounting for 78.3%, followed by biological pesticides and mineral pesticides, accounting for 13.0% and 8.7%, respectively. The disease prevention and control drugs were all low-toxic pesticides, and there were no varieties banned in the Chinese Pharmacopoeia(2020 edition). However, the pesticides used have not been registered on P. heterophylla, and the excessive use of drugs was serious. The present monitoring of pesticide residues in P. heterophylla is mainly based on traditional pesticides such as organochlorine, organophosphorus, and carbamate, which does not effectively cover the production of drugs and had certain safety risks. It is suggested to speed up the research and registration of drug use in the production of P. heterophylla, increase the use of biological pesticides, and further improve the monitoring indicators of pesticide residues in combination with the actual production of drugs, so as to promote the high-quality development of P. heterophylla industry.

Palladium-Catalyzed Direct Carbonylation of Bromoacetonitrile to Synthesize 2-Cyano-N-acetamide and 2-Cyanoacetate Compounds.

Nitrile compounds containing ester and amide groups are important functionalized chemicals in synthetic and medicinal chemistry. In this article, an efficient and convenient palladium-catalyzed carbonylative procedure toward 2-cyano-N-acetamide and 2-cyanoacetate compounds has been developed. The reaction proceeds under mild conditions via radical intermediate which is suitable for late-stage functionalization. Gram-scale experiment was performed successfully under low catalyst loading and gave the target product in excellent yield. Additionally, this transformation can be performed under atmospheric pressure and provide alternative routes to 7 drug precursors.

Regioselective and Enantioselective Copper-Catalyzed Hydroaminocarbonylation of Unactivated Alkenes and Alkynes.

Given the prevalence of amide backbones in marketed pharmaceuticals and their ubiquity as critical binding units in natural peptides and proteins, it remains important to develop novel methods to construct amide bonds. We report here a general method for the anti-Markovnikov hydroaminocarbonylation of unactivated alkenes under mild conditions, using copper catalysis in combination with hydroxylamine electrophile reagents and poly(methylhydrosiloxane) (PMHS) as a cheap and environmentally friendly hydride source. The reaction tolerates a variety of functional groups and efficiently converts unactivated terminal alkenes, 1,1-disubstituted alkenes, and cyclic alkenes to the corresponding amides with exclusive anti-Markovnikov selectivity (and high enantioselectivities/diastereoselectivities). Additionally, with minimal modification of the reaction conditions, alkynes can also undergo tandem hydrogenation-hydroaminocarbonylation to alkyl amides.

Enantioselective Double Carbonylation Enabled by High-Valent Palladium Catalysis.

Palladium-catalyzed carbonylation reactions are efficient methods for synthesizing valuable molecules. However, realizing a carbonylation with excellent yield and chemo-, regio-, and enantioselectivities by classical low-valent palladium catalysis is highly challenging. Herein, we describe an enantioselective carbonylation reaction using a high-valent palladium catalysis strategy and employing a chiral sulfoxide phosphine (SOP) ligand. This double aminocarbonylation reaction begins with the formation of a carbamoylpalladium(II) species, which undergoes enantioselective oxidative addition with a cyclic diaryliodonium salt to generate a palladium(IV) intermediate, followed by a second CO insertion and reductive elimination. The mechanism has been illustrated with experimental and computational studies.

Improving the imaging diagnostic strategy for pulmonary artery masses based on 18F-FDG PET/CT integrated with CTPA.

OBJECTIVE: To evaluate the diagnostic accuracy of computed tomography pulmonary angiography (CTPA) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for pulmonary artery (PA) masses. METHODS: Of 2889 patients with PA filling defects of PA on CTPA, 79 consecutive patients suspicious for PA malignancy who subsequently underwent 18F-FDG PET/CT were enrolled. All masses were diagnosed on the basis of pathological findings or clinical imaging follow-up. For each mass, morphological CT signs, standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG PET/CT were used as diagnostic markers. RESULTS: Expansive growth, irregular margin, invasion, CT contrast uptake, and wall eclipse sign were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of no more than 4 CT signs did not accurately discriminate between the natures of masses. Mean SUVmax, SUVmean, MTV, and TLG values were significantly higher in malignant masses compared to those in benign masses. The diagnostic accuracy of 18F-FDG PET/CT parameters (SUV, MTV, and TLG) was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, SUVmax > 3.4 significantly increased the identification of malignancies. CONCLUSIONS: CTPA is a useful imaging modality for diagnosing PA masses, especially when at least 5 abnormal CT signs are identified. Similarly, 18F-FDG PET/CT accurately identified malignant masses and provided additional valuable information on diagnostic uncertainties after CTPA.

TFBen (Benzene-1,3,5-triyl triformate): A Powerful and Versatile CO Surrogate.

Carbonylative reactions by the using of CO surrogates constitute a facile avenue for the assembly of valuable carbonyl-containing compounds due to the colorless, toxic, flammable, and not easy-handing character of carbon monoxide gas. Recent advances in the carbonylative transformations with TFBen (benzene-1,3,5-triyl triformate) as a safe and convenient CO precursor are systematically summarized and discussed, which can be divided into three parts based on the patterns of the obtained products. This Review focuses on the discussion of the application of TFBen in carbonylative synthesis of various carbonyl-containing compounds.

Cobalt-Catalyzed Four-Component Carbonylation of Methylarenes with Ethylene and Alcohols.

Direct conversion of raw materials to fine chemicals is greatly economically influential. We developed a non-expensive cobalt-catalyzed multicomponent carbonylative reaction for the synthesis of γ-aryl carboxylic acid esters from readily available methylarene, ethylene, and CO, which are widely found in multiple FDA-approved drugs.

Additive-Controlled Divergent Synthesis of Indole and 4H-Benzo[d][1,3]oxazine Derivatives: Palladium-Catalyzed Carbonylative Cyclization of 2-Alkynylanilines and Benzyl Chlorides.

A palladium-catalyzed divergent carbonylative synthesis of indoles and 4H-benzo[d][1,3]oxazines from 2-alkynylanilines and benzyl chlorides with benzene-1,3,5-triyl triformate (TFBen) as the CO source has been developed. The reaction using AlCl3 as the additive produced various indoles in high yields, while a series of 4H-benzo[d][1,3]oxazines was achieved in moderate yields with AcOH as the additive.

Visible-light-induced defluorinative carbonylative coupling of alkyl iodides with α-trifluoromethyl substituted styrenes.

A visible-light-mediated defluorinative carbonylative cross-coupling of alkyl iodides with α-trifluoromethyl styrenes has been developed. The reaction occurs at room temperature under blue light irradiation, and various gem-difluoroalkenes were obtained in moderate to good yields. Synthetic transformations of the obtained product were performed as well.

Palladium-catalyzed cascade Heck-type cyclization and reductive aminocarbonylation for the synthesis of functionalized amides.

A palladium-catalyzed Heck/carbonylative cyclization process has been explored for the synthesis of functionalized amides. By using nitroarenes as readily accessible nitrogen sources, a variety of amide products were obtained in moderate to excellent yields with good functional group compatibility. Furthermore, a late-stage modification of a natural molecule is also achieved by this protocol.