Tandem Four-Component Reaction to Access Fused Polycycles Exhibiting Aggregation-Enhanced Through-Space Charge Transfer Emission.

Rapid construction of new fluorescence emitters is essential in advancing synthetic luminescent materials. This study illustrated a piperidine-promoted reaction of chiral dialdehyde with benzoylacetonitrile and malonitrile, leading to the formation of the 6/6/7 fused cyclic product in good yield. The proposed reaction mechanism involves a dual condensation/cyclization process, achieving the formation of up to six bonds for fused polycycles. The single crystal structure analysis revealed that the fused cyclic skeleton contains face-to-face naphthyl and cyanoalkenyl motifs, which act as the electronic donor and acceptor, respectively, potentially resulting in through-space charge transfer (TSCT) emission. While the TSCT emissions were weak in solution, a notable increase in luminescence intensity was observed upon aggregation, indicating bright fluorescent light. A series of theoretical analyses further supported the possibility of spatial electronic communication based on frontier molecular orbitals, the distance of charge transfer, and reduced density gradient analysis. This work not only provides guidance for the one-step synthesis of complex polycycles, but also offers valuable insights into the design of aggregation-enhanced TSCT emission materials.

Reduction-Specified Coupling Reactions of Nitroarenes by Heterogeneous Cobalt Catalysis.

The in-depth study on reduction-specified coupling reactions of the nitroarenes by heterogeneous cobalt catalysis opens a door for diversified syntheses of functional N-containing molecules. Guided by the structure-function relationship of heterogeneous materials, rational design of nano-catalysts can effectively regulate the routes of organic reactions. Precise transformation of the intermediates generated during the nitroarene reduction with a suitable nano-catalyst is a promising way to develop new tandem reactions, and to synthesize structurally novel compounds that are of difficult access with the conventional approaches.

Stacked Covalent Organic Ribbons Perpendicular to Graphene Oxide Sheets; a 1D-p-2D Design for Photocatalytic Tandem Reactions.

Development of one dimensional covalent organic frameworks (1D-COFs) with potential in light absorption and catalysis is still challenging, due to their rapid interpenetration to form 2D and 3D porous structures. Here we report a successful synthesis of imine-linked 1D covalent organic ribbons (COR), using two simple linear building blocks 1,4-Benzenediamine (Bda) and [2,2'-Bipyridine]-5,5'-dicarbaldehyde (Bpy). The obtained 1D structure with nanorod morphology could keep its physicochemical characteristic properties when it is perpendicular to the surface of graphene oxide (GO) sheets (1D-p-2D structure). Due to an AB π- π stacking and efficient charge transfer between perpendicular 1D COR and GO sheets, the obtained nanocomposite showed strong visible light absorbance (400-700 nm) with coefficient of 4.400 M-1 cm-1 and decreased recombination rate of photogenerated reactive species by 92 %. The strategy of 1D-p-2D light driven system greatly enhanced the photocatalytic activity in practical applications such as both oxidation and hydrogenation tandem reactions to a rate constant of higher than 0.02 min-1 . This study presents the first case of 1D covalent organic polymers grown perpendicularly on a carbon-based layer for boosting electron mobility through the junction between the two components.

Enantioselective formal total synthesis of dihydrospirotryprostatin B.

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

Rhodium-Catalyzed Tandem Asymmetric Allylic Decarboxylative Addition and Cyclization of Vinylethylene Carbonates with N-Nosylimines.

A enantioselective tandem transformation, concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs), in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, providing highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

Microwave-Mediated, Catalyst-Free Synthesis of 1,2,4-Triazolo[1,5-a]pyridines from Enaminonitriles.

A catalyst-free, additive-free, and eco-friendly method for synthesizing 1,2,4-triazolo[1,5-a]pyridines under microwave conditions has been established. This tandem reaction involves the use of enaminonitriles and benzohydrazides, a transamidation mechanism followed by nucleophilic addition with nitrile, and subsequent condensation to yield the target compound in a short reaction time. The methodology demonstrates a broad substrate scope and good functional group tolerance, resulting in the formation of products in good-to-excellent yields. Furthermore, the scale-up reaction and late-stage functionalization of triazolo pyridine further demonstrate its synthetic utility. A plausible reaction pathway, based on our findings, has been proposed.

Constructing Tandem Fenton-like Reaction Systems Based on Structure Adaption to Boost Water Contaminant Mineralization Efficiency.

Mineralization of emerging contaminants by using advanced oxidation processes (AOPs) is a desirable option to ensure water safety, but still challenged by the excessive chemical and/or energy input. Here, we conceptually proposed the tandem reaction system (TRS) of different reactive oxygen species (ROS) based on structure adaption of target contaminants. To construct a model TRS, we first realized highly selective generation of three classical ROS (1O2, HO• and SO4•-) by peroxymonosulfate activation in an electrochemical Fenton-like system, where three replaceable Fe-centered cathodes were rationally designed as electronic mediator. The 1O2+SO4•--TRS exhibited nearly 100% mineralization of sulfamethoxazole (SMX), whereas only 34.2%, 56.2% and 60.8% for each of the single 1O2/HO•/SO4•--AOP systems. Mechanism exploration of SMX degradation in TRS evidenced that the initial reaction with 1O2 selectively destructed the sulfonamide bridge of SMX to form p-aminobenzenesulfonic acid, which will be vulnerable to sequent SO4•- attack to facilitate mineralization. Successful extendibility of 1O2+SO4•--TRS to other sulfonamide antibiotics and 1O2+HO•-TRS to phenolic and arylcarboxylic compounds, as well as the demonstration of 1O2+SO4•--TRS in treatment of three actual pharmaceutical wastewaters strongly support that TRS is a powerful and sustainable strategy to enhance the mineralization of emerging contaminants in water.

Boundary-Rich Carbon-Based Electrocatalysts with Manganese(II)-Coordinated Active Environment for Selective Synthesis of Hydrogen Peroxide.

Coordinated manganese (Mn) electrocatalysts owing to their electronic structure flexibility, non-toxic and earth abundant features are promising for electrocatalytic reactions. However, achieving selective hydrogen peroxide (H2 O2 ) production through two electron oxygen reduction (2e-ORR) is a challenge on Mn-centered catalysts. Targeting this goal, we report on the creation of a secondary Mn(II)-coordinated active environment with reactant enrichment effect on boundary-rich porous carbon-based electrocatalysts, which facilitates the selective and rapid synthesis of H2 O2 through 2e-ORR. The catalysts exhibit nearly 100 % Faradaic efficiency and H2 O2 productivity up to 15.1 mol gcat -1 h-1 at 0.1 V versus reversible hydrogen electrode, representing the record high activity for Mn-based electrocatalyst in H2 O2 electrosynthesis. Mechanistic studies reveal that the epoxide and hydroxyl groups surrounding Mn(II) centers improve spin state by modifying electronic properties and charge transfer, thus tailoring the adsorption strength of *OOH intermediate. Multiscale simulations reveal that the high-curvature boundaries facilitate oxygen (O2 ) adsorption and result in local O2 enrichment due to the enhanced interaction between carbon surface and O2 . These merits together ensure the efficient formation of H2 O2 with high local concentration, which can directly boost the tandem reaction of hydrolysis of benzonitrile to benzamide with nearly 100 % conversion rate and exclusive benzamide selectivity.

Studies on the Biomimetic Synthesis of Marine Ladder Polyethers via Endo-Selective Epoxide-to-Epoxonium Ring-Opening Cascades.

Marine ladder polyethers have attracted the attention of chemists and biologists because of their potent biological activities. Synthetic chemists have attempted to construct their polyether frameworks by epoxide ring-opening cascades, as Nakanishi hypothesis describes. However, Baldwin's rules of ring closure state that exo-selective intramolecular cyclization of epoxy alcohols is preferred over endo-selective cyclization. Herein, we investigated epoxide ring-opening cascades of polyepoxy alcohols in [EMIM]BF4/PFTB (1-ethyl-3-methylimidazolium tetrafluoroborate /perfluoro-tert-butyl alcohol) and found that all-endo products were formed via epoxide-to-epoxonium ring-opening cyclizations (not restricted by Baldwin's rules, which only apply to intramolecular hydroxyl-to-epoxide cyclizations). We determined that the key factor enabling polyepoxy alcohols to undergo a high proportion of all-endo-selective cyclization was inhibition of exo-selective hydroxyl-to-epoxide cyclization starting from the terminal hydroxyl group of a polyepoxy alcohol. By introducing a slow-release protecting group to the terminal hydroxyl group, we could markedly increase the cyclization yields of polyether fragments with hydrogen atoms at the ring junctions. For the first time, we constructed consecutively fused six-membered-ring and fused seven-, eight-, and nine-membered-ring polyether fragments by epoxide-to-epoxonium ring-opening cyclizations through the addition of a suitable Lewis acid. We also suggest that the biosynthesis of marine ladder polyethers may proceed via epoxide-to-epoxonium ring-opening cyclization of polyepoxide.

The Tandem Nitrate and CO2 Reduction for Urea Electrosynthesis: Role of Surface N-Intermediates in CO2 Capture and Activation.

Electrochemical reduction of CO2 and nitrate offers a promising avenue to produce valuable chemicals through the using of greenhouse gas and nitrogen-containing wastewater. However, the generally proposed reaction pathway of concurrent CO2 and nitrate reduction for urea synthesis requires the catalysts to be both efficient in both CO2 and nitrate reduction, thus narrowing the selection range of suitable catalysts. Herein, we demonstrate a distinct mechanism in urea synthesis, a tandem NO3 - and CO2 reduction, in which the surface amino species generated by nitrate reduction play the role to capture free CO2 and subsequent initiate its activation. When using the TiO2 electrocatalyst derived from MIL-125-NH2, it intrinsically exhibits low activity in aqueous CO2 reduction, however, in the presence of both nitrate and CO2, this catalyst achieves an excellent urea yield rate of 43.37 mmol ⋅ g-1 ⋅ h-1 and a Faradaic efficiency of 48.88 % at -0.9 V vs. RHE in a flow cell. Even at a low CO2 level of 15 %, the Faradaic efficiency of urea synthesis remains robust at 42.33 %. The tandem reduction procedure was further confirmed by in situ spectroscopies and theoretical calculations. This research provides new insights into the selection and design of electrocatalysts for urea synthesis.

One-Pot Tandem Coupling Method for the Short-Step Formal Synthesis of Riccardin C.

One-pot reactions reduce reagent amounts and circumvent process treatments, such as work-up and purifications in multi-step reactions. In this study, we achieved the formal total synthesis of riccardin C through a one-pot reaction by simultaneously linking four units through two Sonogashira coupling reactions and one Suzuki coupling reaction, followed by reduction and deprotection. Thus, this one-pot method comprised five steps and did not require the purification of intermediate reaction mixtures, which saves resources, such as reagents and solvents, and expedites the work process.

Fullerene C70 as Photoredox Catalyst for the Synthesis of Pyrrolo[2,1-a]isoquinolines by 1,3-Dipolar Cycloaddition-Aromatization Sequence.

Herein, fullerene (C70 ) is introduced as an effective photoredox catalyst for the construction of a highly functionalised pyrrolo[2,1-a]isoquinoline framework by 1,3-dipolar cycloaddition-aromatisation reaction sequence. The ability of C70 to efficiently harvest visible light, its long-triplet state lifetime, good photostability, and strong singlet oxygen generation potential (Φ▵ ≈1), make it an efficient photoredox catalyst. Upon photoirradiation, C70 promotes the formation of singlet oxygen and superoxide radical by energy transfer (EnT) and single electron transfer (SET) mechanism. The superoxide radical acts as a potential oxidant in the formation of azomethine ylide through the oxidation-deprotonation tandem process. Azomethine ylide further participates in [3+2]-cycloaddition reaction protocol with alkene/alkyne to give the corresponding pyrrolo[2,1-a]isoquinolines. Interestingly, this protocol allows the activation of a wide range of substrates giving access to a diverse library of 48 well-decorated pyrrolo[2,1-a]isoquinolines with good functional group tolerance.

Progress Toward the Asymmetric de Novo Synthesis of Lanostanes: A Counter Biomimetic Cucurbitane-to-Lanostane Type Transformation.

An oxidative rearrangement has been established that enables a cucurbitane-to-lanostane type rearrangement that is counter to known biomimetic transformations that proceed in an opposite direction by way of a lanostane-to-cucurbitane transformation. Here, an oxidative dearomatization/Wagner-Meerwein rearrangement with a substrate bearing the characteristic cucurbitane triad of quaternary centers at C9, C13 and C14, and possessing an alkene at C11-C12, proceeds in a manner that selectively shifts the methyl group at C9 to C10 in concert with the establishment of a sterically hindered allylic cation. The major product isolated from this transformation is formed by trapping of the allylic cation by addition of acetate to C12, rather than termination of the cascade by loss of a proton at C8. While proceeding by way of a unique sequence of bond-forming reactions that begins by oxidative dearomatization, this process achieves what we believe is an unprecedented cucurbitane-to-lanostane transformation, generating a product that contains the characteristic lantostane triad of quaternary centers at C10, C13 and C14 while also delivering a functionalized C-ring.

Synthesis of 5,6-Dihydropyrazolo[5,1-a]isoquinolines through Tandem Reaction of C,N-Cyclic Azomethine Imines with α,ß-Unsaturated Ketones.

An innovative and efficient approach has been developed for the synthesis of 5,6-dihydropyrazolo[5,1-a]isoquinolines. This one-pot tandem reaction involves the reaction of C,N-cyclic azomethine imines with α,ß-unsaturated ketones, using K2CO3 as the base and DDQ as the oxidant. The process results in functionalized 5,6-dihydropyrazolo[5,1-a]isoquinolines with good yields. This convenient one-step method encompasses a tandem [3 + 2]-cycloaddition, detosylation, and oxidative aromatization.

A Photosensitizing Metal-Organic Framework as a Tandem Reaction Catalyst for Primary Alcohols from Terminal Alkenes and Alkynes.

Owing to the wide and growing demand for primary alcohols, the development of efficient catalysts with high regioselectivity remains a worthwhile pursuit. However, according to Markovnikov's rule, it is a challenge to obtain primary alcohols with high yields and regioselectivity from terminal alkenes or alkynes. Herein, we report the synthesis of a photosensitizing two-dimensional (2D) metal-organic framework (MOF) from cyclic trinuclear copper(I) units (Cu-CTUs) and a boron dipyrro-methene (Bodipy) ligand. The MOF features broadband light absorption, excellent photoinduced charge separation efficiency, and photochemical properties. By integrating the copper-catalyzed hydroboration and photocatalyzed aerobic oxidation, it can catalyze terminal alkenes and alkynes to produce primary alcohols via a one-pot tandem reaction with excellent regioselectivity, good overall yields in two-step reactions (up to 85 %), broad substrate compatibility (32 examples) and good reusability under mild conditions.

Enolates ambushed - asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles.

Metal enolates are useful intermediates and building blocks indispensable in many organic synthetic transformations. Chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents are structurally complex intermediates that can be employed in many transformations. In this review, we describe this burgeoning field that is reaching maturity after more than 25 years of development. The effort of our group to broaden possibilities to engage metal enolates in reactions with new electrophiles is described. The material is divided according to the organometallic reagent employed in the conjugate addition step, and thus to the particular metal enolate formed. Short information on applications in total synthesis is also given.

Synthesis of functionalized pyrrole derivatives via diverse cyclization of azomethine ylide and olefins.

The azomethine ylides are generally used in 1,3-dipolar cycloadditions with various dipolarophiles. In this work, a new and diverse route has been developed for the azomethine ylides, for synthesis of novel pyrrole derivatives. The azomethine ylide, produced via C-H activation of unreactive C(sp3)-H bond of 2-methylquinoline, by molecular iodine, in the presence of pyridine. Herein, we represent novel pyrrole derivatives, synthesized from the reaction of pyridinium ylide with olefins, which formed via a reaction of isatin, dialkyl acetylenedicarboxylate derivatives and pyridine as a base in moderate to excellent yields. Various features of this cyclization, discussed.

New Bicyclic Azalide Macrolides Obtained by Tandem Palladium Catalyzed Allylic Alkylation/Conjugated Addition Reaction.

Unprecedented tandem allylic alkylation/intermolecular Michael addition was used in the preparation of novel bicyclic azalides. NMR spectroscopy was used not only to unambiguously determine and characterize the structures of these unexpected products of chemical reaction but also to investigate the effect the rigid bicyclic modification has on the conformation of the whole molecule. Thus, some of the macrolides prepared showed antibacterial activity in the range of well-known antibiotic drug azithromycin.

Palladium-Catalyzed Tandem Cycloisomerization/Cross-Coupling of Carbonyl- and Imine-Tethered Alkylidenecyclopropanes.

Pd0 catalysts featuring phosphorus-based monodentate ligands can detour the reactivity of carbonyl-tethered alkylidenecyclopropanes (ACPs) from standard (3+2) cycloadditions towards tandem cycloisomerization/cross-coupling processes. This new reactivity lies on the formation of key π-allyl oxapalladacyclic intermediates, which are subsequently trapped with external nucleophilic partners, instead of undergoing canonical C-O reductive eliminations. Importantly, the use of imine-tethered ACP's is also feasible. Therefore, the method provides a straightforward and stereoselective entry to a wide variety of highly functionalized cyclic alcohols and amines.

Aryne 1,4-Disubstitution and Remote Diastereoselective 1,2,4-Trisubstitution via a Nucleophilic Annulation-[5,5]-Sigmatropic Rearrangement Process.

Both aryne 1,4-disubstitution and 1,2,4-trifunctionalization were accomplished from tertiary amines bearing a penta-2,4-dien-1-yl moiety. These transformations could directly incorporate a C-N and a C-C bond para to each other on an aryne intermediate via a sequential nucleophilic addition and [5,5]-sigmatropic rearrangement. When arynes bearing 3-tethered electrophiles were employed, a cascade regioselective nucleophilic addition, intramolecular cyclization, and remote diastereoselective [5,5]-sigmatropic rearrangement process was observed. Our density functional theory (DFT) calculations revealed that hydrogen-bonding interactions between two C-H hydrogens on the penta-2,4-dien-1-yl chain and the oxygen anion generated upon N-nucleophilic annulation reaction in the [5,5]-sigmatropic rearrangement step is responsible for the remote diastereoselective control in this reaction system.