CO2-mediated organocatalytic chlorine evolution under industrial conditions.

During the chlor-alkali process, in operation since the nineteenth century, electrolysis of sodium chloride solutions generates chlorine and sodium hydroxide that are both important for chemical manufacturing1-4. As the process is very energy intensive, with 4% of globally produced electricity (about 150 TWh) going to the chlor-alkali industry5-8, even modest efficiency improvements can deliver substantial cost and energy savings. A particular focus in this regard is the demanding chlorine evolution reaction, for which the state-of-the-art electrocatalyst is still the dimensionally stable anode developed decades ago9-11. New catalysts for the chlorine evolution reaction have been reported12,13, but they still mainly consist of noble metal14-18. Here we show that an organocatalyst with an amide functional group enables the chlorine evolution reaction; and that in the presence of CO2, it achieves a current density of 10 kA m-2 and a selectivity of 99.6% at an overpotential of only 89 mV and thus rivals the dimensionally stable anode. We find that reversible binding of CO2 to the amide nitrogen facilitates formation of a radical species that plays a critical role in Cl2 generation, and that might also prove useful in the context of Cl- batteries and organic synthesis19-21. Although organocatalysts are typically not considered promising for demanding electrochemical applications, this work demonstrates their broader potential and the opportunities they offer for developing industrially relevant new processes and exploring new electrochemical mechanisms.

Photoinduced Decarboxylative Thioacylation of N-Hydroxyphthalimide Esters with Tetraalkylthiuram Disulfides.

Dithiocarbamate is a key structural sequence in pharmaceuticals and agrochemicals, and its synthesis is crucial in organic chemistry. Although significant progress has been made in related synthesis research, developing a practical and universal synthesis method remains fascinating. Herein, we report a new visible-light-induced decarboxylation coupling reaction between N-hydroxyphthalimide esters and tetraalkylthiuram disulfides, which uses Ir(ppy)3 as a photocatalyst to promote the generation of corresponding decarboxylation thioacylation product-dithiocarbamates in high yields. This redox-neutral protocol uses inexpensive and readily available starting material under mild reaction conditions, exhibiting broad substrate scope and wide functional group compatibility. This method can be further used for post modification of complex natural products and bioactive drugs.

Visible light-driven photocatalytic sulfonative oxidation of benzyl secondary amines.

A method for the α-oxidation and sulfonation of benzyl secondary amines was developed utilizing Ir(III) or Eosin Y as the photocatalyst in the presence of O2 as a green oxidant. Using commercial substrates, 37 products from cyclic and acyclic benzylamines were achieved with good functional group compatibility in 48-87% yields. Furthermore, tetrahydroisoquinoline protected by an Ac or a Boc group was oxidized under standard conditions.

Single-Atom Manganese-Catalyzed Oxygen Evolution Drives the Electrochemical Oxidation of Silane to Silanol.

The oxygen evolution reaction (OER), characterized by a four-electron transfer kinetic process, represents a significant bottleneck in improving the efficiency of hydrogen production from water electrolysis. Consequently, extensive research efforts have been directed towards identifying single-atom electrocatalysts with exceptional OER performance. Despite the comprehensive understanding of the OER mechanism, its application to other valuable synthetic reactions has been limited. Herein, we leverage the MOOH intermediate, a key species in the Mn-N-C single-atom catalyst (Mn-SA@NC), which can be cyclically delivered in the OER. We exploit this intermediate' s capability to facilitate electrophilic transfer with silane, enabling efficient silane oxidation under electrochemical conditions. The SAC electrocatalytic system exhibits remarkable performance with catalyst loadings as low as 600 ppm and an exceptional turnover number of 9132. Furthermore, the catalytic method demonstrates stability under a 10 mmol flow chemistry setup. By serving as an OER electrocatalyst, the Mn-SA@NC drives the entire reaction, establishing a practical Mn SAC-catalyzed organic electrosynthesis system. This synthesis approach not only presents a promising avenue for the utilization of electrocatalytic OER but also highlights the potential of SACs as an attractive platform for organic electrosynthesis investigations.

Single-Atom Iron Catalyst as an Advanced Redox Mediator for Anodic Oxidation of Organic Electrosynthesis.

Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.

Three-Component Electrochemical Aminoselenation of 1,3-Dienes.

Azoles and organoselenium compounds are pharmacologically important scaffolds in medicinal chemistry and natural products. We developed an efficient regioselective electrochemical aminoselenation reaction of 1,3-dienes, azoles, and diselenide derivatives to access selenium-containing allylazoles skeletons. This protocol is more economical and environmentally friendly and features a broad substrate scope; pyrazole, triazole, and tetrazolium were all tolerated under the standard conditions, which could be applied to the expedient synthesis of bioactive molecules and in the pharmaceutical industry.

Electrocatalytic ring-opening dihydroalkoxylation of N-aryl maleimides with alcohols under metal- and oxidant-free conditions.

The electrocatalytic ring-opening dihydroalkoxylation of N-aryl maleimides with alcohols under metal- and oxidant-free conditions is described. This electrochemical process consists of anodic single-electron transfer oxidation, cathodic radical reduction, rearrangement-ring cleavage and nucleophilic addition cascade, which employs tetrabutylammonium bromide not only as a redox catalyst but also as an efficient supporting electrolyte, and offers a practical and environmentally friendly route to ring-opening difunctionalization products.

Synthesis of 2-Pyrazolines with a CF3- and Alkyne-Substituted Quaternary Carbon Center via [3 + 2] Cycloaddition of ß-CF3-1,3-enynes and Diazoacetates.

Given the importance of both the CF3 group and the alkyne moiety in synthetic/medicinal chemistry, we report here the first example of efficient synthesis of 2-pyrazolines with a CF3- and alkyne-substituted quaternary carbon center. This methodology has the advantages of high functional group compatibility, the avoidance of base and open-flask conditions, easily available and easy to handle reagent, and broad substrate scope. Notably, this protocol allows for the late-stage functionalization of biologically active molecules and the gram-scale synthesis.

A Single-Atom Cobalt Catalyst for the Fluorination of Acyl Chlorides at Parts-per-Million Catalyst Loading.

Improving the stability of sensitive catalytic systems is an emerging research topic in the catalysis field. However, the current design of heterogeneous catalysts mainly improves their catalytic performance. This paper presents a single-atom catalyst (SAC) strategy to improve the cobalt-catalysed fluorination of acyl chlorides. A stable Co-F intermediate can be formed through the oxidative fluorination of Co1 -N4 @NC SAC, which can replace the unstable high-valent cobalt catalytic system and avoid the use of phosphine ligands. In the SAC system, KF can be employed as a fluorinating reagent to replace the AgF, which can be applied to various substrates and scale-up conversion with high turnover numbers (TON=1.58×106 ). This work also shows that inorganic SACs have tremendous potential for organofluorine chemistry, and it provides a good reference for follow-up studies on the structure-activity relationship between catalyst design and chemical reaction mechanisms.

Electrochemically Enabled Selenium Catalytic Synthesis of 2,1-Benzoxazoles from o-Nitrophenylacetylenes.

The study reported an electrochemically mediated method for the preparation of 2,1-benzoxazoles from o-nitrophenylacetylenes. Different from the traditional electrochemical reduction of nitro to nitroso, the nitro group directly underwent a cyclization reaction with the alkyne activated by selenium cation generated by the anodic oxidation of diphenyl diselenide and finally produced the desired products.

Halogen-mediated electrochemical organic synthesis.

In general, halogenide anions are anodically oxidized into active species, which can be elemental halogen, halogen cations, or halogen radicals. These species subsequently react with substrates, such as olefins, ketones, or amines, to generate halogenated products. We review the mechanisms of these reactions.

Electrochemically enabled functionalization of indoles or anilines for the synthesis of hexafluoroisopropoxy indole and aniline derivatives.

An environmentally benign electrochemically enabled site-selective functionalization of indole or aniline derivatives with hexafluoroisopropanol in the presence of tetrabutyl ammonium hexafluorophosphate as the redox catalyst and electrolyte was demonstrated in this work. Under mild electro-oxidation conditions, a series of hexafluoroisopropoxy indole and aniline derivatives with pharmacological activity were obtained. This conversion does not need transition metals and oxidants, and has good functional group tolerance. The in vitro cytotoxicity of all compounds was evaluated by the MTT assay against four human cancer cell lines. The results revealed that hexafluoroisopropoxy indoles have good antitumor activity and compound 2i increased the intracellular levels of ROS and inhibited apoptosis in HeLa cells.

Palladium-catalyzed synthesis of 5-amino-1,2,4-oxadiazoles via isocyanide insertion.

A convenient and efficient palladium-catalyzed approach has been developed for the synthesis of 5-amino-1,2,4-oxadiazoles from amidoximes and isocyanides. Various 5-amino-1,2,4-oxadiazoles were obtained in moderate to high yields under mild conditions. The key to the success of this strategy involves new C-N bond and C-O bond formation via palladium-catalyzed isocyanide insertion.

Constructing Mononuclear Palladium Catalysts by Precoordination/Solvothermal Polymerization: Recyclable Catalyst for Regioselective Oxidative Heck Reactions.

Heterogeneous, metal, single-site catalysts often exhibit higher catalytic performance than other catalysts because of their maximized atom efficiency of 100 %. Reported herein is a precoordination/solvothermal polymerization strategy to fabricate a stable mononuclear Pd-metalized porous organic polymer catalyst (Pd@POP). Pd@POP was easy to use in regioselective organic reactions because the internal structure of this Pd@POP can be easily modified. The catalyst was used to solve the intractable regioselectivity problems of Heck reactions. Pd@POP-9 can efficiently activate the ends of olefins, thereby leading to high selectivity for substitution at the external position. To understand the reason underlying the high selectivity and activity of the catalyst, the systemic characterization of Pd@POP-9 and density-functional theory calculations were conducted. This Heck reaction is the first to be catalyzed by a recyclable mononuclear metal catalyst with unprecedented catalytic activity and regioselectivity.

TCR repertoire profiling of tumors, adjacent normal tissues, and peripheral blood predicts survival in nasopharyngeal carcinoma.

The T-cell immune responses in nasopharyngeal carcinoma patients have been extensively investigated recently for designing adoptive immunotherapy or immune checkpoint blockade therapy. However, the distribution characteristics of T cells associated with NPC pathogenesis are largely unknown. We performed deep sequencing for TCR repertoire profiling on matched tumor/adjacent normal tissue from 15 NPC patients and peripheral blood from 39 NPC patients, 39 patients with other nasopharyngeal diseases, and 33 healthy controls. We found that a lower diversity of TCR repertoire in tumors than paired tissues or a low similarity between the paired tissues was associated with a poor prognosis in NPC. A more diverse TCR repertoire was identified in the peripheral blood of NPC patients relative to the controls; this was related to a significant decrease in the proportion of high-frequency TCR clones in NPC. Higher diversity in peripheral blood of NPC patients was associated with a worse prognosis. Due to the peculiarity of the Vß gene usage patterns in the peripheral blood of NPC patients, 15 Vß genes were selected to distinguish NPC patients from controls by the least absolute shrinkage and selection operator analysis. We identified 11 clonotypes shared by tumors and peripheral blood samples from different NPC patients, defined as "NPC-associated" that might have value in adoptive immunotherapy. In conclusion, we here report the systematic and overall characteristics of the TCR repertoire in tumors, adjacent normal tissues, and peripheral blood of NPC patients. The data obtained may be relevant to future clinical studies in the setting of immunotherapy for NPC patients.

Circulating CD8+ T-cell repertoires reveal the biological characteristics of tumors and clinical responses to chemotherapy in breast cancer patients.

PURPOSE: CD8+ T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8+ T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy. EXPERIMENTAL DESIGN: We applied a high-throughput TCR ß-chain sequencing method to characterize the CD8+ T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8+ T-cell repertoire during chemotherapy were analyzed. RESULTS: We found that the HEC ratios of the CD8+ T-cell repertoires from HER2+ breast cancer patients were significantly higher than those of HER2- patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8+ T cells. Several Vß and CDR3 motifs preferentially used in HER2+ patients were identified. Besides, we found that the circulating CD8+ T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8+ T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response. CONCLUSIONS: Although functional studies of clonally expanded CD8+ T-cell populations are clearly required, our results suggest that the circulating CD8+ T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.

Praseodymium(III)-Catalyzed Regioselective Synthesis of C3-N-Substituted Coumarins with Coumarins and Azides.

A series of C3-N-substituted coumarins were synthesized in good yields directly from coumarins and azides in the presence of Pr(OTf)3 without any additives or ligands needed. The selected compounds 3a, 3c-e, 3g, 3i, 3q, 3u, and 3v exhibited good anticancer activities against MGC-803, A549, and NCI-H460 cell lines with IC50 in the range 8.75-38.54 µmol L-1.

Catalyst-Free Synthesis of Pyrrolo[1,2-a]quinolines via Dehydration/[3 + 2] Cycloaddition Directly from 2-Methylquinolines, Aldehydes, and Alkynoates.

A simple and efficient catalyst-free synthesis of pyrrolo[1,2-a]quinoline derivatives from 2-methylquinolines, aldehydes, and alkynoates via dehydration/[3 + 2] cycloaddition has been developed. The reaction conditions are tolerant to air, and H2O is the only byproduct of this transformation, thus offering an environmentally benign process with a wide range of potential applications in organic synthesis and medicinal chemistry.

Atom-Economic Synthesis of 4-Pyrones from Diynones and Water.

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

Palladium-Catalyzed Synthesis of 5-Iminopyrrolones through Isocyanide Double Insertion Reaction with Terminal Alkynes and Water.

With the combination of Pd(dppf)Cl2 and Cu(OAc)2, a variety of 5-iminopyrrolones were synthesized in moderate to good yields from terminal alkynes, isocyanide, and water via isocyanide double insertion and cycloaddition reaction. A plausible reaction mechanism for this process is depicted. Furthermore, selected compounds 3c, 3e, and 3h exhibited good activities against HepG2 (human liver cancer), NCI-H460 (human lung cancer), and SK-OV-3 (human ovarian cancer) cell lines with IC50 values in the range of 10.63-22.63 µmol L-1.