Rhodium(III)‐Catalyzed N‐Nitroso‐Directed CH Addition to Ethyl 2‐Oxoacetate for Cycloaddition/Fragmentation Synthesis of Indazoles

Rh^III‐catalyzed N‐nitroso‐directed C?H addition to ethyl 2‐oxoacetate allows subsequent construction of indazoles, a privileged heterocycle scaffold in synthetic chemistry, through the exploitation of reactivity between the directing group and installed group. The formal [2+2] cycloaddition/fragmentation reaction pathway identified herein, a unique reactivity pattern hitherto elusive for the N‐nitroso group, emphasizes the importance of forward reactivity analysis in the development of useful C?H functionalization‐based synthetic tools. The synthetic utility of the protocol is demonstrated with the synthesis of a tricyclic‐fused ring system. The diversity of covalent linkages available for the nitroso group should enable the extension of the genre of reactivity reported herein to the synthesis of other types of heterocycles.     

Aliphatic Organoimido Derivatives of Polyoxometalates Containing a Bioactive Ligand

A series of aliphatic organoimido derivatives of hexamolybdate based on amantadine, namely (nBu₄N)₂[Mo₆O₁₈(?NC₁₀H₁₅)] ( 1 ), (nBu₄N)₂ {cis‐[Mo₆O₁₇(?NC₁₀H₁₅)₂]} ( 2 ), (nBu₄N)₂{trans‐[Mo₆O₁₇(?NC₁₀H₁₅)₂]} ( 3 ), and (nBu₄N)₂[Mo₆O₁₆(?NC₁₀H₁₅)₃] ( 4 ), was synthesized in reasonable yield by dehydration with N,N′‐dicyclohexylcarbodiimide (DCC). They were characterized by IR and UV/Vis spectroscopy, elemental analysis, ESI mass spectrometry, and single‐crystal X‐ray structure analysis. The spectral and structural similarities and differences between monosubstituted, cis‐disubstituted, and trans‐disubstituted organoimido derivatives were elucidated and may provide guidance for related work on organoimido‐functionalized Lindqvist‐type polyoxometalates. In addition, trans‐disubstituted and polysubstituted derivatives containing aliphatic organoimido ligands have not yet been reported, and the crystal structure of the trans isomer may lead us to a deeper understanding of disubstituted derivatives. Furthermore, proliferation and morphology of MCF‐7 cells were studied with compound 1 . The present results show that the DCC‐dehydrating protocol could be an efficient approach to covalently graft bioactive ligands such as amantadine onto POMs and enhance their application in clinical cancer treatment.     

Synthesis of Site‐Specifically Phosphate‐Caged siRNAs and Evaluation of Their RNAi Activity and Stability

A complete set of new photolabile nucleoside phosphoramidites were synthesized, then site‐specifically incorporated into sense or antisense strands of siRNA for phosphate caging. Single caging modification was made along siRNA strands and their photomodulation of gene silencing were examined by using the firefly luciferase reporter gene. Several key phosphate positions were then identified. Furthermore, multiple caging modifications at these key positions led to significantly enhanced photomodulation of gene silencing activity, suggesting a synergistic effect. The caging group on both the terminally phosphate‐caged siRNA and the single‐stranded caged RNA has comparatively high stability, whereas hydrolysis of the caged group from the internally caged siRNA was observed, irrespective of the presence of Mg²⁺. Molecular dynamic simulations demonstrated that enhanced hydrolysis of the caging group on internally phosphate‐caged siRNAs was due to easy fragmentation of the caging group upon formation of the pentavalent intermediate of the phosphotriester with attack by water. The caging group in the terminally phosphate‐caged siRNA or single‐stranded caged RNA prefers to form π–π stacks with nearby nucleobases. In addition to providing explanations for previous observations, this study sheds further light on the design of caged oligonucleotides and indicates the direction of future development of nucleic acid drugs with phosphate modifications.     

Cube‐in‐Cube Hollow Cu9S5 Nanostructures with Enhanced Photocatalytic Activities in Solar H2 Evolution

Hydrogen produced from water under solar energy is an ideal clean energy source, and the efficiency of hydrogen production usually depends on the catalytic systems based on new compounds and/or a unique nanostructure. Herein, well‐defined cube‐in‐cube hollow Cu₉S₅ nanostructures have been successfully prepared with Cu₂O nanocubes and CS₂ as precursors, and single‐shell hollow Cu₉S₅ nanocubes could be obtained by replacing CS₂ with Na₂S. The formation mechanism of cube‐in‐cube hollow nanostructures has been proposed based on the Kirkendell effect and an outward self‐assembly process. Further studies revealed that the cube‐in‐cube hollow Cu₉S₅ nanostructures exhibited better photocatalytic activity toward solar H₂ evolution and would be a promising photocatalyst in the solar hydrogen industry.     

Efficient Copper‐Catalyzed Direct Intramolecular Aminotrifluoromethylation of Unactivated Alkenes with Diverse Nitrogen‐Based Nucleophiles

A mild, convenient, and step‐economical intramolecular aminotrifluoromethylation of unactivated alkenes with a variety of electronically distinct, nitrogen‐based nucleophiles in the presence of a simple copper salt catalyst, in the absence of extra ligands, is described. Many different nitrogen‐based nucleophiles (e.g., basic primary aliphatic and aromatic amines, sulfonamides, carbamates, and ureas) can be employed in this new aminotrifluoromethylation reaction. The aminotrifluoromethylation process allows straightforward access to diversely substituted CF₃‐containing pyrrolidines or indolines, in good to excellent yields, through a direct difunctionalization strategy from the respective acyclic starting materials. Mechanistic studies were conducted and a plausible mechanism was proposed.     

Tailoring 3,3′‐Dihydroxyisorenieratene to Hydroxystilbene: Finding a Resveratrol Analogue with Increased Antiproliferation Activity and Cell Selectivity

Four novel compounds were designed by “tailoring” 3,3′‐dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2′,3′,6′‐hexamethyl‐4,4′‐dihydroxy‐trans‐stilbene) was concisely synthesized in a one‐pot Stille–Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI‐H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability. The observation should be helpful to rationally design resveratrol‐inspired antiproliferative agents.     

Highly Enantioselective Catalytic System for Asymmetric Copolymerization of Carbon Dioxide and Cyclohexene Oxide

A new ligand can be easily prepared, and its intramolecular dinuclear zinc complexes act as a high performance catalyst for the asymmetric alternating copolymerization of cyclohexene oxide and CO₂ under very mild conditions (1 atm CO₂, room temperature), affording completely alternating polycarbonates with up to 93.8 % enantiomeric excess (ee) and 98 % yield. A high M_n value of 28 600 and a relatively narrow polydispersity (M_w/M_n ratio) of 1.43 were also achieved.     

Well‐Defined Iron Complexes as Efficient Catalysts for “Green” Atom‐Transfer Radical Polymerization of Styrene,Methyl Methacrylate,and Butyl Acrylate with Low Catalyst Loadings and Catalyst Recycling

Environmentally friendly iron(II) catalysts for atom‐transfer radical polymerization (ATRP) were synthesized by careful selection of the nitrogen substituents of N,N,N‐trialkylated‐1,4,9‐triazacyclononane (R₃TACN) ligands. Two types of structures were confirmed by crystallography: “[(R₃TACN)FeX₂]” complexes with relatively small R groups have ionic and dinuclear structures including a [(R₃TACN)Fe(μ‐X)₃Fe(R₃TACN)]⁺ moiety, whereas those with more bulky R groups are neutral and mononuclear. The twelve [(R₃TACN)FeX₂]_n complexes that were synthesized were subjected to bulk ATRP of styrene, methyl methacrylate (MMA), and butyl acrylate (BA). Among the iron complexes examined, [{(cyclopentyl)₃TACN}FeBr₂] ( 4 b ) was the best catalyst for the well‐controlled ATRP of all three monomers. This species allowed easy catalyst separation and recycling, a lowering of the catalyst concentration needed for the reaction, and the absence of additional reducing reagents. The lowest catalyst loading was accomplished in the ATRP of MMA with 4 b (59 ppm of Fe based on the charged monomer). Catalyst recycling in ATRP with low catalyst loadings was also successful. The ATRP of styrene with 4 b (117 ppm Fe atom) was followed by precipitation from methanol to give polystyrene that contained residual iron below the calculated detection limit (0.28 ppm). Mechanisms that involve equilibria between the multinuclear and mononuclear species were also examined.     

Synthesis,characterization and properties of novel cellulose derivatives containing phosphorus: cellulose diphenyl phosphate and its mixed esters

Using ionic liquid 1-allyl-3-methylimidazolium chloride as reaction medium, a series of novel cellulose esters containing phosphorus including cellulose diphenyl phosphate (C-Dp) and cellulose acetate (CA)–diphenyl phosphate mixed esters was synthesized homogeneously. The degree of substitution was well controlled by altering reaction conditions, such as the molar ratio of the acylating reagents/anhydroglucose unit and reaction time. The structure and thermal properties of cellulose esters were characterized by FTIR, NMR, wide-angle X-ray powder diffraction and differential scanning calorimetry. All the products possessed excellent solubility in some common organic solvents, and transparent films of cellulose esters were obtained by solution casting. In contrast to C-Dp, CA–diphenyl phosphate mixed esters showed clear glass transitions. More interestingly, these cellulose mixed esters exhibited thermoplastic behavior and could be processed by traditional melt processing methods.