Bismuth Tri‐ and Tetraarylcarboxylates: Crystal Structures,In Situ X‐ray Diffraction,Intermediates and Luminescence

A systematic investigation of the systems Bi³⁺/carboxylic acid/HNO₃ for the tri‐ and tetracarboxylic acids pyromellitic acid (H₄Pyr), trimellitic acid (H₃Tri) and trimesic acid (H₃BTC) acid led to the discovery of five new bismuth carboxylates. Structural characterisation allowed the influence of the linker geometry and the Bi³⁺:linker molar ratio in the starting solution on the crystal structure to be determined. The crystallisation of three selected compounds was investigated by in situ energy‐dispersive X‐ray diffraction. Three new crystalline intermediates were observed within minutes, and two of them could be isolated by quenching of the reaction mixture. Their crystal structures were determined from laboratory and synchrotron X‐ray powder diffraction data and allowed a possible reaction pathway to be established. In depth characterisation of the luminescence properties of the three bismuth pyromellate compounds was carried out. Fluorescence and phosphorescence could be assigned to (mainly) ligand‐ and metal‐based transitions. The polymorphs of Bi(HPyr) exhibit different luminescence properties, although their structures are very similar. Surprisingly, doping of the three host structures with Eu³⁺ and Tb³⁺ ions was only successful for one of the polymorphs.     

Bioorthogonal Cycloadditions with Sub‐Millisecond Intermediates

Tetrazine‐ and sydnone‐based click reactions have emerged as important bioconjugation strategies with fast kinetics and N₂ or CO₂ as the only byproduct. Mechanistic studies of these reactions have focused on the initial rate‐determining cycloaddition steps. The subsequent N₂ or CO₂ release from the bicyclic intermediates has been approached mainly through computational studies, which have predicted lifetimes of femtoseconds. In the present study, bioorthogonal cycloadditions involving N₂ or CO₂ extrusion have been examined experimentally at the single‐molecule level by using a protein nanoreactor. At the resolution of this approach, the reactions appeared to occur in a single step, which places an upper limit on the lifetimes of the intermediates of about 80 μs, which is consistent with the computational work.     

Study of the Natural Product Intermediates of Steviolbioside,Steviol, and Isosteviol; O‐ and N‐Acylated Forms of Benzotriazoyl Esters

Glycosides, steviolside, and rubaudioside A, which are extracted from the leaves of Stevia rebaudiana, can be used as sweetener for food additive. Intermediates of steviolbioside, steviol, and isosteviol are very stable compounds obtained from benzotriazol‐1‐yloxtri(pyrrolidinol)phosphonium hexafluorophosphate. They are suitable to be used in amide and amide dimer synthesis. These nature product intermediates possess special characteristics. The spectra data showed two tautomeric groups: an ester form and an amide form. Their nuclear magnetic resonance, mass and chromatographic/mass/mass spectra were examined.     

Synthesis and Morphology Control of AM‐6 Nanofibers with Tailored ‐V‐O‐V‐ Intermediates

Microporous vanadosilicates with octahedral VO₆ and tetrahedral SiO₄ units, better known as AM‐6, have been hydrothermally synthesized with different morphologies by controlling the Na/K molar ratio of the initial gel mixtures. The morphology of the AM‐6 materials changed from bulky cube to nanofiber aggregates as the Na/K molar ratio decreased from 1.9 to 0.2. Raman spectroscopy revealed that the VO₃^? intermediate species plays an important role in the formation of the nanofiber morphology. The orientation of ‐V‐O‐V‐ chains in nanofiber aggregates was examined by confocal polarized micro‐Raman spectroscopy. It was found that these aggregates are assemblies of short ‐V‐O‐V‐ chains perpendicular to the axis of nanofibers. The obtained AM‐6 nanofibers greatly increase the exposed proportion of V? O terminals, and thus improve the catalytic performance.     

Nylon Intermediates from Bio‐Based Levulinic Acid

Use of ZrO₂/SiO₂ as a solid acid catalyst in the ring‐opening of biobased γ‐valerolactone with methanol in the gas phase leads to mixtures of methyl 2‐, 3‐, and 4‐pentenoate (MP) in over 95 % selectivity, containing a surprising 81 % of M4P. This process allows the application of a selective hydroformylation to this mixture to convert M4P into methyl 5‐formyl‐valerate (M5FV) with 90 % selectivity. The other isomers remain unreacted. Reductive amination of M5FV and ring‐closure to ?‐caprolactam in excellent yield had been reported before. The remaining mixture of 2‐ and 3‐MP was subjected to an isomerising methoxycarbonylation to dimethyl adipate in 91 % yield.     

Breslow Intermediates from Aromatic N‐Heterocyclic Carbenes (Benzimidazolin‐2‐ylidenes,Thiazolin‐2‐ylidenes)

We report the first generation and characterization of elusive Breslow intermediates derived from aromatic N‐heterocyclic carbenes (NHCs), namely benzimidazolin‐2‐ylidenes (NMR, X‐ray analysis) and thiazolin‐2‐ylidenes (NMR). In the former case, the diamino enols were generated by reaction of the free N,N‐bis(2,6‐diisopropylphenyl)‐ and N,N‐bis(mesityl)‐substituted benzimidazolin‐2‐ylidenes with aldehydes while the dimer of 3,4,5‐trimethylthiazolin‐2‐ylidene served as the starting material in the latter case. The unambiguous NMR identification of the first thiazolin‐2‐ylidene‐based Breslow intermediate rests on double ¹³C labeling of both the NHC and the aldehyde component. The acyl anion reactivity was confirmed by benzoin formation with excess aldehyde.     

1,3‐Difunctionalization of Aminocyclopropanes via Dielectrophilic Intermediates

We report an oxidative ring‐opening strategy to transform acyl, sulfonyl or carbamate protected aminocyclopropanes into 1,3‐dielectrophilic carbon intermediates bearing a halide atom (Br, I) and a N,O‐acetal. Replacing the alkoxy group of the N,O‐acetal can be achieved under acidic conditions through an elimination–addition pathway, while substitution of the halides by nucleophiles can be done under basic conditions through a S_N2 pathway, generating a wide range of 1,3‐difunctionalized propylamines. A proof of concept for asymmetric induction was realized using a chiral phosphoric acid (CPA) as catalyst, highlighting the potential of the method in enantioselective synthesis of important building blocks.     

Direct and Single‐Molecule Visualization of the Solution‐State Structures of G‐Hairpin and G‐Triplex Intermediates

We present the direct and single‐molecule visualization of the in‐pathway intermediates of the G‐quadruplex folding that have been inaccessible by any experimental method employed to date. Using DNA origami as a novel tool for the structural control and high‐speed atomic force microscopy (HS‐AFM) for direct visualization, we captured images of the unprecedented solution‐state structures of a tetramolecular antiparallel and (3+1)‐type G‐quadruplex intermediates, such as G‐hairpin and G‐triplex, with nanometer precision. No such structural information was reported previously with any direct or indirect technique, solution or solid‐state, single‐molecule or bulk studies, and at any resolution. Based on our results, we proposed a folding mechanism of these G‐quadruplexes.     

Single‐Molecule Observation of Intermediates in Bioorthogonal 2‐Cyanobenzothiazole Chemistry

We report a single‐molecule mechanistic investigation into 2‐cyanobenzothiazole (CBT) chemistry within a protein nanoreactor. When simple thiols reacted reversibly with CBT, the thioimidate monoadduct was approximately 80‐fold longer‐lived than the tetrahedral bisadduct, with important implications for the design of molecular walkers. Irreversible condensation between CBT derivatives and N‐terminal cysteine residues has been established as a biocompatible reaction for site‐selective biomolecular labeling and imaging. During the reaction between CBT and aminothiols, we resolved two transient intermediates, the thioimidate and the cyclic precursor of the thiazoline product, and determined the rate constants associated with the stepwise condensation, thereby providing critical information for a variety of applications, including the covalent inhibition of protein targets and dynamic combinatorial chemistry.     

De Novo Synthesis of Mono‐ and Oligosaccharides via Dihydropyran Intermediates

The importance of carbohydrates is evident by their essential role in all living systems. Their syntheses have attracted attention from chemists for over a century. Most chemical syntheses in this area focus on the preparation of carbohydrates from naturally occurring monosaccharides. De novo chemical synthesis of carbohydrates from feedstock starting materials has emerged as a complementary method for the preparation of diverse mono‐ and oligosaccharides. In this review, the history of de novo carbohydrate synthesis is briefly discussed and particular attention is given to methods that address the formation of glycosidic bonds for potential de novo synthesis of oligosaccharides. Almost all methods of this kind involve the formation of dihydropyran intermediates. Recent progress in forming dihydropyrans by Achmatowicz rearrangement, hetero‐Diels–Alder cycloaddition, ring‐closing metathesis, and other methods is also elaborated.     

Helicene‐Grafted Silica Nanoparticles Capture Hetero‐Double‐Helix Intermediates during Self‐Assembly Gelation

A mixture of a pseudoenantiomeric ethynylhelicene (M)‐tetramer and a (P)‐pentamer forms a hetero‐double‐helix in a solution, which self‐assembles and gelates solvents. When gelation was conducted in the presence of chiral silica (P)‐nanoparticles grafted with (P)‐helicene, the resulting hetero‐double‐helix intermediate was adsorbed on the (P)‐nanoparticles, and was removed from the solution by aggregation and precipitation. The resulting precipitates contained only the hetero‐double‐helix, not random coil or clusters of the hetero‐double‐helix. (P)‐Nanoparticles did not extract the hetero‐double‐helix from the self‐assembly gels. The hetero‐double‐helix was then isolated by liberating it from the precipitates in 2‐bromopropionic acid, and was crystallized from the solution. The crystalline hetero‐double‐helices were isolated for several other combinations of pseudoenantiomeric ethynylhelicene oligomers.     

Zwitterionic Phosphoranides as Intermediates in the Reaction of Phosphorus Tribromide with N,N‐Dimethyl‐N′‐arylformamidines

Cyclic zwitterionic phosphoranides 2a,b were found to be intermediate products in the reaction of N,N‐dimethyl‐N′‐(aryl)formamidines with PBr₃. The structure of phosphoranide 2a was determined by means of the X‐ray and quantum chemistry investigations. Mechanism of its formation was proposed based on Density functional theory (DFT) calculations. Reactions of 2 with amines and selenium yielded either C‐phosphorylated formamidines or benzazaphospholes. The first example of intramolecular heterocyclization of a pentavalent phosphorus derivative 15b into 3Н‐1,3‐benzazaphosphole has been demonstrated.     

Sigmatropic Rearrangements of Hypervalent‐Iodine‐Tethered Intermediates for the Synthesis of Biaryls

Metal‐free dehydrogenative couplings of aryliodanes with phenols to afford 2‐hydroxy‐2′‐iodobiaryls have been developed. This reaction proceeds through ligand exchange on the hypervalent iodine atom followed by a [3,3] sigmatropic rearrangement and with complete regioselectivity. This coupling, in combination with in situ oxidation by mCPBA, enables the convenient conversion of iodoarenes into desirable biaryls. The obtained biaryls have convertible iodo and hydroxy groups in close proximity, and are thus synthetically useful, as exemplified by the controlled syntheses of π‐extended furans and a substituted [5]helicene. DFT calculations clearly revealed that the rearrangement is sigmatropic, with C?C bond formation and I?O bond cleavage proceeding in a concerted manner. Acetic acid, which was found to be the best solvent for this protocol, renders the iodine atom more cationic and thus accelerates the sigmatropic rearrangement.