Olefin Cyclopropanation by Radical Carbene Transfer Reactions Promoted by Cobalt(II)/Porphyrinates: Active‐Metal‐Template Synthesis of [2]Rotaxanes

A Co^II/porphyrinate‐based macrocycle in the presence of a 3,5‐diphenylpyridine axial ligand functions as an endotopic ligand to direct the assembly of [2]rotaxanes from diazo and styrene half‐threads, by radical‐carbene‐transfer reactions, in excellent 95 % yield. The method reported herein applies the active‐metal‐template strategy to include radical‐type activation of ligands by the metal‐template ion during the organometallic process which ultimately yields the mechanical bond. A careful quantitative analysis of the product distribution afforded from the rotaxane self‐assembly reaction shows that the Co^II/porphyrinate subunit is still active after formation of the mechanical bond and, upon coordination of an additional diazo half‐thread derivative, promotes a novel intercomponent C?H insertion reaction to yield a new rotaxane‐like species. This unexpected intercomponent C?H insertion illustrates the distinct reactivity brought to the Co^II/porphyrinate catalyst by the mechanical bond.     

Azidoimidazolinium Salts: Safe and Efficient Diazo‐transfer Reagents and Unique Azido‐donors

2‐Azido‐1,3‐dimethylimidazolinium chloride (ADMC) and its corresponding hexafluorophosphate (ADMP) were found to be efficient diazo‐transfer reagents to various organic compounds. ADMC was prepared by the reaction of 2‐chloro‐1,3‐dimethylimidazolinium chloride (DMC) and sodium azide. ADMP was isolated as a crystal having good thermal stability and low explosibility. ADMC and ADMP reacted with 1,3‐dicarbonyl compounds under mild basic conditions to give 2‐diazo‐1,3‐dicarbonyl compounds in high yields, which were easily isolated in virtue of the high water solubility of the by‐products. ADMP showed high diazo‐transfer ability to primary amines even in the absence of metal salt such as Cu(II). Using this diazotization approach, various alkyl/aryl azides were directly obtained from their corresponding primary amines in high yields. Furthermore, naphthols reacted with ADMC to give the corresponding diazonaphthoquinones in good to high yields. In addition, 2‐azido‐1,3‐dimethylimidazolinium salts were employed as azide‐transfer and migratory amidation reagents.     

Infrared laser ablation sample transfer for on‐line liquid chromatography electrospray ionization mass spectrometry

We have demonstrated an on‐line laser ablation sampling system and coupling of the system to liquid chromatography (LC) using an infrared (IR) laser to ablate and transfer materials into a flowing solvent stream. With this approach, samples are deposited on a microscope slide mounted on a translation stage and ablated in transmission geometry using a pulsed mid‐IR laser. The ablated material is captured in an exposed flowing solvent stream that carries the ablated material to the electrospray source. Post‐ablation separation is accomplished using a capillary column downstream of the capture zone. The performance of the system was assessed using peptide and protein mixtures ablated from the target and analyzed with and without LC separation. Copyright © 2012 John Wiley & Sons, Ltd.     

Continuous flow infrared matrix‐assisted laser desorption electrospray ionization mass spectrometry

Continuous flow infrared matrix‐assisted laser desorption electrospray ionization (CF IR MALDESI) mass spectrometry was demonstrated for the on‐line analysis of liquid samples. Samples in aqueous solution were flowed through a 50 µm i.d. fused‐silica capillary at a flow rate of 1–6 µL/min. As analyte aqueous solution flowed through the capillary, a liquid sample bead formed at the capillary tip. A pulsed infrared optical parametric oscillator (OPO) laser with wavelength of 2.94 µm and a 20 Hz repetition rate was focused onto the capillary tip for sample desorption and ablation. The plume of ejected sample was entrained in an electrospray to form ions by MALDESI. The resulting ions were sampled into an ion trap mass spectrometer for analysis. Using CF IR MALDESI, several chemical and biochemical reactions were monitored on‐line: the chelation of 1,10‐phenanthroline with iron(II), insulin denaturation with 1,4‐dithiothreitol, and tryptic digestion of cytochrome c. Copyright © 2010 John Wiley & Sons, Ltd.     

Investigation of a Lithium–Halogen Exchange Flow Process for the Preparation of Boronates by Using a Cryo‐Flow Reactor

Conducting low‐temperature organometallic reactions under continuous flow conditions offers the potential to more accurately control exotherms and thus provide more reproducible and scalable processes. Herein, progress towards this goal with regards to the lithium–halogen exchange/borylation reaction is reported. In addition to improving the scope of substrates available on a research scale, methods to improve reaction profiles and expedite purification of the products are also described. On moving to a continuous system, thermocouple measurements have been used to track exotherms and provide a level of safety for continuous processing of organometallic reagents. The use of an in‐line continuous liquid–liquid separation device to circumvent labour intensive downstream off‐line processing is also reported.     

Efficient Solid/Liquid Phase-Transfer Catalytic Diazo Transfer Synthesis

A simple and efficient solid/liquid phase-transfer catalytic diazo transfer reaction for the synthesis of diazocarbonyl, diazophosphonyl, and diazophosphinyl compounds is reported.     

Gas‐phase intramolecular hydroxyl‐amino exchange of protonated arginine and verified by the synthetic intermediate compound

A new fragmentation process was proposed to interpret the characteristic product ion at m/z 130 of protonated arginine. The α‐amino group was dissociated from protonated arginine and then combined with the (M + H‐NH₃) fragment to form an ion‐neutral complex which further generated a hydroxyl‐amino exchange intermediate compound through an ion‐molecule reaction. This intermediate compound was synthesized from argininamide through a diazo reaction, and then the reaction mixture was analyzed using liquid chromatography combined with mass spectrometry (LC‐MS). The collision‐induced dissociation experiments under the same conditions revealed that this intermediate compound produced the characteristic product ion at m/z 130 as well as protonated arginine, and in addition, density functional theory calculations were performed to confirm simultaneous loss of NH₃ and CO from this intermediate to give the m/z 130 ion.     

Ruthenium(II)/Chiral Brønsted Acid Co‐Catalyzed Enantioselective Four‐Component Reaction/Cascade Aza‐Michael Addition for Efficient Construction of 1,3,4‐Tetrasubstituted Tetrahydroisoquinolines

An elegant synergistic catalytic system comprising a ruthenium complex with a chiral Brønsted acid was developed for a four‐component Mannich/cascade aza‐Michael reaction. The ruthenium‐associated ammonium ylides successfully trapped with in situ generated imines indicates a stepwise process of proton transfer in the ruthenium‐catalyzed carbenoid N?H insertion reaction. The different decomposition abilities of various ruthenium complexes towards diazo compounds were well explained by the calculated thermodynamic data. The transformation features a mild, rapid, and efficient method for the synthesis of enantiomerically pure 1,3,4‐tetrasubstituted tetrahydroquinolines bearing a quaternary stereogenic carbon center from simple starting precursors in moderate yields with high diastereo‐ and enantioselectivity.     

Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow‐Generated Diazo Compounds and Propargylated Amines

We report herein the asymmetric coupling of flow‐generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10–20 minutes with high enantioselectivity (89–98 % de/ee), moderate yields and a wide functional group tolerance.     

芳基重氮盐及其18-冠醚-6络合物的低频红外光谱

本文合成了九种不同取代基的苯基四氟硼酸重氮盐及其与18-冠醚-6形成的分子络合物, 考察它们的低频红外光谱, 讨论这类络合物的成键状况。     

Comprehensive two‐dimensional monolithic liquid chromatography of polar compounds

Two‐dimensional liquid chromatography largely increases the number of separated compounds in a single run, theoretically up to the product of the peaks separated in each dimension on the columns with different selectivities. On‐line coupling of a reversed‐phase column with an aqueous normal‐phase (hydrophilic interaction liquid chromatography) column yields orthogonal systems with high peak capacities. Fast on‐line two‐dimensional liquid chromatography needs a capillary or micro‐bore column providing low‐volume effluent fractions transferred to a short efficient second‐dimension column for separation at a high mobile phase flow rate. We prepared polymethacrylate zwitterionic monolithic micro‐columns in fused silica capillaries with structurally different dimethacrylate cross‐linkers. The columns provide dual retention mechanism (hydrophilic interaction and reversed‐phase). Setting the mobile phase composition allows adjusting the separation selectivity for various polar substance classes. Coupling on‐line an organic polymer monolithic capillary column in the first dimension with a short silica‐based monolithic column in the second dimension provides two‐dimensional liquid chromatography systems with high peak capacities. The silica monolithic C₁₈ columns provide higher separation efficiency than the particle‐packed columns at the flow rates as high as 5 mL/min used in the second dimension. Decreasing the diameter of the silica monolithic columns allows using a higher flow rate at the maximum operation pressure and lower fraction volumes transferred from the first, hydrophilic interaction dimension, into the second, reversed‐phase mode, avoiding the mobile phase compatibility issues, improving the resolution, increasing the peak capacity, and the peak production rate.     

A Conjugate Addition Approach to Diazo‐Containing Scaffolds with β Quaternary Centers

Structurally complex diazo‐containing scaffolds are formed by conjugate addition to vinyl diazonium salts. The electrophile, a little studied α‐diazonium‐α,β‐unsaturated carbonyl compound, is formed at low temperature under mild conditions by treating β‐hydroxy‐α‐diazo carbonyls with Sc(OTf)₃. Conjugate addition occurs selectively at the 3‐position of indole to give α‐diazo‐β‐indole carbonyls, and enoxy silanes react to give 2‐diazo‐1,4‐dicarbonyl products. These reactions result in the formation of tertiary and quaternary centers, and give products that would be otherwise difficult to form. Importantly, the diazo functional group is retained within the molecule for future manipulation. Treating an α‐diazo ester indole addition product with Rh₂(OAc)₄ caused a rearrangement to occur to give a 2‐(1H‐indol‐3‐yl)‐2‐enoate. In the case of diazo ketone compounds, this shift occurred spontaneously on prolonged exposure to the Lewis acidic reaction conditions.     

Reactions of α‐diazoketones with indolinone imines: Synthesis of new 1,3,3‐triaryl‐1′‐methylspiro[azetidine‐2,3′‐indoline]‐2′,4‐diones

The paper describes the synthesis of new 1,3,3‐triary‐1′‐methylspiro[azetidine‐2,3′‐indoline]‐2′,4‐diones from reaction of the 2‐diazo‐1,2‐diarylethanones with 3‐arylimino‐1‐methyl‐2‐indolinones. The compounds have been characterized by satisfactory analytical and spectral (IR, ¹H NMR and ¹³C NMR) data. The diarylketenes, generated in situ from thermal decomposition of the 2‐diazo‐1,2‐diarylethanones, react with azomethine linkage in preference to carbonyl group leading to the formation of products.     

A New Reactivity Mode for the Diazo Group: Diastereoselective 1,3‐Aminoalkylation Reaction of β‐Amino‐α‐Diazoesters To Give Triazolines

A novel mode of reactivity for the diazo group, the 1,3‐addition of a nucleophile and an electrophile to the diazo group, has been realized in the intramolecular aminoalkylation of β‐amino‐α‐diazoesters to form tetrasubstituted 1,2,3‐triazolines. The reaction exhibited a broad scope, good functional group tolerance, and excellent diastereoselectivity. In addition, a new Au‐catalyzed intramolecular transannulation reaction of the obtained propargyl triazolines to give pyrroles has been discovered.     

Synthesis of α‐Nitro‐α‐diazocarbonyl Derivatives and Their Applications in the Cyclopropanation of Alkenes and in O?H Insertion Reactions

A facile and highly efficient method for the preparation of α‐nitro‐α‐diazocarbonyl derivatives by a diazo‐transfer reaction involving (trifluoromethyl)sulfonyl azide has been developed. These substrates undergo a rhodium‐catalyzed cyclopropanation reaction with a variety of alkenes. A systematic study of the reaction indicated that the diastereoselectivity of the cyclopropanation could be effectively controlled through the modification of the steric bulk of the diazo reagent. A novel O? H insertion reaction of the metal? carbene complex derived from the α‐nitro‐α‐diazocarbonyl reagent afforded the corresponding novel α‐nitro‐α‐alkoxy carbonyl derivatives.     

一类芳香族偶氮化合物的合成及表征

采用重氮偶合反应合成了一系列不同对位取代的4-[N，N-(二羟乙基)]氨基偶氮苯化合物，其结构用元素分析，IR，1HNMR，DSC，DSC等进行表征和确认。     

Membrane extraction for separation of copper cations from acid solution using polypropylene hollow fibre membrane

The membrane extraction of copper ions was carried out using hydrophobic poly(propylene) (PP) hollow fiber membrane modules and kerosene solutions containing organic extractant. The influences of different extractant on the extraction yield, mass transfer performance and mass transfer mechanism were studied. Compared with 2‐ethylhexyl phosphoric acid (2EHPA) and 2‐methyl‐5‐sulpho benzaldoxime (2M5SB), di‐(2‐ethylhexyl)phosphoric acid (D2EHPA) extractant system with high distribution coefficient exhibited higher extraction yield of 99.7%. The extraction equilibrium time, the final extraction yield and the total mass transfer coefficient were independent of the flow rates of two phases. The extraction equilibrium time and the final extraction yield at different flow rates of two phases were 80 min and near 99.5%, respectively. A mass transfer model of a complexation reaction describing the overall mass transfer resistance was controlled by interfacial reactions rather than the aqueous and organic boundary layer which could explain the effect of flow rate on the final extraction yield and the total mass transfer coefficient. This model showed that the mass transfer resistance and mass transfer coefficient were independent of Cu²⁺ when copper ion concentration was more than 0.06 g/L. However, when copper concentration was less than 0.06 g/l, the mass transfer resistance increased as Cu²⁺ concentration decreased, and the mass transfer coefficient decreased as Cu²⁺ concentration decreased. Extractant entrainment in the aqueous phase and membrane fouling were investigated primarily. It was found that the solvent entrainment could reduce to 10 ppm much lower than 200 ppm of the classic liquid–liquid extraction, and that the cleaning of contaminated membranes was not complete. However, it can be still concluded from this research that the membrane extraction in PP hollow fibre with D2EHPA extractant would be an effective and promising processing means for Cu²⁺ separation from aqueous solution. Copyright © 2005 John Wiley & Sons, Ltd.     

A Photoenzymatic Strategy for Radical-Mediated Stereoselective Hydroalkylation with Diazo Compounds

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, alternative functionalization of diazo compounds in enzymatic processes has been unexploited. Herein, we describe a photoenzymatic strategy for radical-mediated stereoselective hydroalkylation with diazo compounds. This method generates carbon-centered radicals through an ene reductase catalyzed photoinduced electron transfer process from diazo compounds, enabling the synthesis of γ-stereogenic carbonyl compounds in good yields and stereoselectivities. This study further expands the possible reaction patterns in photo-biocatalysis and offers a new approach to solving the selectivity challenges of radical-mediated reactions.     

偶氮苯取代乙炔功能化合物的合成与表征

采用偶氮偶联和金属钯催化偶联反应法,合成了一系列非线性光学基团直接取代乙炔化合物,其结构经^1HNMR,IR,DSC及元素分析等表征。     

Octakis(3‐azidopropyl)octasilsesquioxane: A Versatile Nanobuilding Block for the Efficient Preparation of Highly Functionalized Cube‐Octameric Polyhedral Oligosilsesquioxane Frameworks Through Click Assembly

A one‐step synthesis of octakis(3‐azidopropyl)octasilsesquioxane from commercially available octakis(3‐aminopropyl)octasilsesquioxane has been developed through a highly efficient diazo‐transfer reaction under very mild conditions. Nonaflyl azide is shown to be a safer, cheaper, and more efficient reagent for this transformation than the better known and generally used diazo‐transfer reagent triflyl azide. Octakis(3‐azidopropyl)octasilsesquioxane is an excellent nanobuilding block that can be readily octafunctionalized with a range of terminal alkynes by copper(I)‐catalyzed 1,3‐dipolar azide–alkyne cycloaddition to provide new functional nanocages, maintaining a perfect 3D cubic symmetry. The mildness, simplicity, and efficiency of this approach have been demonstrated in the preparation of a glyco‐polyhedral oligosilsesquioxane (POSS) conjugate and a BODIPY–POSS cluster (BODIPY=boron dipyrromethene).