Unexpected reactivity of Imidazo[2,1-b]thiazolines with organometallic reagents

[reaction: see text] The reaction of imidazo[2,1-b]thiazolines with various organometallic reagents is described. Nucleophilic attack of organolithium reagents on sulfur occurs with extrusion of ethylene to produce 2-thioalkyl- or 2-thioarylimidazoles. The outcome with Grignard reagents, however, is less predictable, with some reagents adding at sulfur and others reacting at C-2 or not at all.     

Uncatalysed coupling of an activated aryl chloride with aryllithium and aryl Grignard reagents

Substitution of the chloro group in 2-(2-chlorophenyl)-4,4-dimethyl-2-oxazoline to afford biaryls occurs upon reaction with either aryllithium reagents or aryl Grignard reagents. The reactions with Grignard reagents occur under similar conditions to a previously reported manganese-catalysed procedure. The reactions with lithium reagents, whilst not always affording greater yields of product than the Grignard reagents, involve much shorter reaction times and afford yields, which are comparable with those obtained from the corresponding fluoro derivative.     

Palladium(0)-catalyzed cis-selective alkylative and arylative cyclization of alkynyl enones with organoboron reagents

A palladium(0)-tricyclohexylphosphine catalyzes cis-selective alkylative and arylative cyclization of alkyne-containing electron-deficient alkenes with organoboron reagents to provide five- or six-membered rings with exo tri- or tetra-substituted alkenes. The opposite stereoselectivity to that for the alkyne-aldehyde cyclization using the same reagents would result from palladacycle-forming oxidative addition of the substrates to the Pd⁰ catalyst followed by transmetalation with the boron reagents, protonation, and reductive elimination. The functional group compatibility, availability, stability, and non-toxicity of the reagents, and the fact that no additives are needed make the process more practical than the Ni⁰-catalyzed cyclization with organozinc reagents.     

Reagents with a Crystalline Coat

Tetrakis(dimethoxyphenyl)adamantane (TDA) readily forms crystalline inclusion complexes with reactive, toxic, or malodorous reagents, such as benzoyl chloride, acetyl chloride, cyclohexyl isocyanide, phosphorus trichloride, and trimethylsilyl chloride. The crystals are stable and largely free of the problematic properties of the free reagents. When exposed to solvents such as DMSO or MeOH, the reagents react, and a large portion of the TDA precipitates. The TDA‐coated reagents may lead to a safer way of storing, handling, and delivering reagents, and ultimately to synthetic protocols that do not require fume hoods.     

Reaction of octafluorocyclopentene with various carbon nucleophiles

The treatment of octafluorocyclopentene with organolithium reagents gave the corresponding symmetrical disubstituted perfluorocyclopentenes in good to high yields. The reaction with Grignard reagents led to the monosubstituted perfluorocyclopentenes, which were subjected to the further nucleophilic substitution reaction using another Grignard or aryllithium reagents, unsymmetrical disubstituted perfluorocyclopentenes being obtained in high yields.     

Silver‐Catalyzed Benzylation and Allylation of Tertiary Alkyl Bromides with Organozinc Reagents

Silver salts catalyze the benzylation and allylation of tertiary alkyl bromides with organozinc reagents. The reactions create quaternary carbon centers efficiently. Treatment of gem‐dibromoalkanes with benzylic or allylic zinc reagents under silver catalysis leads to dibenzylation or diallylation. The functional‐group compatibility of the present reactions is wider than that of the previous reactions with Grignard reagents.     

Fluorinated stannanes : Part 1. The stereospecific synthesis of fluorinated stannanes via a novel transmetalation of fluorinated zinc and cadmium reagents

Fluorinated stannanes are versatile synthetic intermediates. Reaction of fluorinated vinyl, alkyl and aryl zinc or cadmium reagents with tri-n-butyltin chloride at room temperature yielded the corresponding tri-n-butyl stannanes in moderate to excellent yields. The zinc or cadmium reagents also reacted efficiently with other trialkyl and triaryl chlorostannanes. These zinc and cadmium reagents were prepared in excellent yields by stirring the fluorinated halides with activated zinc or cadmium metal.     

Single‐Electron‐Transfer‐Induced Coupling of Arylzinc Reagents with Aryl and Alkenyl Halides

Arylzinc reagents, prepared from aryl halides/zinc powder or aryl Grignard reagents/zinc chloride, were found to undergo coupling with aryl and alkenyl halides without the aid of transition‐metal catalysis to give biaryls and styrene derivatives, respectively. In this context, we have already reported the corresponding reaction using aryl Grignard reagents instead of arylzinc reagents. Compared with the Grignard cross‐coupling, the present reaction features high functional‐group tolerance, whereby electrophilic groups such as alkoxycarbonyl and cyano groups are compatible as substituents on both the arylzinc reagents and the aryl halides. Aryl halides receive a single electron and thereby become activated as the corresponding anion radicals, which react with arylzinc reagents, thus leading to the cross‐coupling products.     

Titrimetric determination of thiols: Tetrathionate, iron(III), cystine and hexacyanoferrate(III) as thiol reagents

Four analytical reagents, tetrathionate, iron(III), cystine and hexacyanoferrate(III) have been tested with respect to their specificity for oxidation of thiols to disulphides. Of a number of thiols studied, most have a strong tendency to oxidize beyond the disulphide stage with several of the commonly employed reagents. Tetrathionate, cystine and hexacyanoferrate(III) function in phosphate buffer of pH 7, but iron(III) does not require rigid control of pH, although the solution should be only feebly acidic. The reagents were used in excess and the thiosulphate or cysteine formed in the reaction of thiols with tetrathionate or cystine respectively was determined. The residual iron(III) was measured by adding ascorbic acid or mercaptoacetic acid and titrating with 2,6-dichlorophenolindophenol or iodine monochloride respectively; surplus hexacyanoferrate(III) was back-titrated with ascorbic acid. All four reagents react selectively with thiols even in the presence of several possible interfering substances and afford results that are accurate and precise.     

Synthetic application of water-soluble hypervalent iodine reagents in aqueous media

Along with the vigorous development of hypervalent iodine chemistry, water-soluble hypervalent iodine reagents have received considerable attentions in recent years. In order to obtain water-soluble hypervalent iodine reagents, two strategies have been employed including introduction of hydrophilic functional groups onto the phenyl ring and formation of complex of iodosylbenzene with crown ether. And, it is observed that four kinds of hypervalent iodine reagents exhibit more or less solubility in water including hypervalent iodine reagents containing hydrophilic ligands, diaryliodonium salts, oligomeric iodosylbenzene sulfate, and iodylbenzene and its derivatives. In this review, we summarize these water-soluble hypervalent iodine reagents and their broad synthetic applications in aqueous media.     

Synthesis, characterization and primary evaluation of the synthetic efficiency of supported vinyltins and allyltins

Supported vinyltins and allyltins grafted to an insoluble cross-linked polystyrene matrix were prepared using methods usually employed in solution, like hydrostannylation of alkynes, transmetallation of a tin halide with organomagnesium or organozinc reagents, and substitution of an allyl halide by a supported stannylanion or S_N2′ substitution of a supported β-stannylacrolein acetal by cyanocopper reagents in the presence of boron trifluoride etherate. The insoluble grafted organotin reagents were analysed by HRMAS NMR, allowing an unambiguous assignment of their isomeric distribution or the identification of side products. When involved in Stille cross-coupling reactions (vinyltins) or in addition on aldehydes (allyltins), these supported reagents exhibit similar reactivity and similar stereoselectivity when compared to the tributyltin analogues, with the advantage to prevent problems due to the contamination by tin residues.     

Preparation and addition--elimination reactions of benzyl alpha,beta,beta-trifluoroacrylate. A new stereoselective approach to (Z)-beta-substituted alpha,beta-difluoroacrylates

Benzyl alpha,beta,beta-trifluoroacrylate (1) was prepared in good yield via the reductive Br-F elimination of benzyl 2-bromo-2,3,3,3-tetrafluoropropanoate or the palladium-catalyzed cross-coupling reaction of 1,2,2-trifluorovinylstannane with benzyl chloroformate. On treating 1 with various Grignard reagents or dialkylzinc reagents in the presence of copper(I) salt, the corresponding beta-substituted alpha,beta-difluoroacrylates were obtained in high yields with high Z-selectivity. Additionally, trialkylaluminum reagents were also found to be good nucleophiles, the corresponding addition-elimination products being afforded in good yields but with low stereoselectivity.     

Benzil and Benzoin: General Spray Reagents for the Visualization of Organic Compounds on Thin Layer Chromatograms

Benzil and Benzoin spray reagents have been adopted to detect some organic compounds on thin layer chromatograms (TLC). These reagents were found to visualize sugars, amino acids, dicarboxylic acids and some natural products on thin layer plates. Colors produced with these reagents were shades of the spectrum and characteristic of individual or class of the organic and natural products.     

Direct Arylation/Alkylation/Magnesiation of Benzyl Alcohols in the Presence of Grignard Reagents via Ni-, Fe-, or Co-Catalyzed sp(3) C-O Bond Activation

Direct application of benzyl alcohols (or their magnesium salts) as electrophiles in various reactions with Grignard reagents has been developed via transition metal-catalyzed sp(3) C-O bond activation. Ni complex was found to be an efficient catalyst for the first direct cross coupling of benzyl alcohols with aryl/alkyl Grignard reagents, while Fe, Co, or Ni catalysts could promote the unprecedented conversion of benzyl alcohols to benzyl Grignard reagents in the presence of (n)hexylMgCl. These methods offer straightforward pathways to transform benzyl alcohols into a variety of functionalities.     

Determination of water samples and ene-diols or thiols in samples inaccessible for direct K.Fischer titration

Novel reagents and the rapid technique were developed for the simultaneous determination of water and ene-diols or thiols in chemical products, drugs and other materials which are inaccessible for direct K.Fischer titration. The reagents consist of iodine, tetramethylammonium iodide or potassium iodide, base (diethanolamine, triethanolamine, sodium acetate and/or urea) in methanol mixed with N,N-dimethylformamide, or with formamide, or with dimethyl sulfoxide and N,N-dimethylformamide mixture as a solvent. The use of the reagents is based on the consecutive titration first of an ene-diol or thiol by the novel reagents and then of water by a conventional K.Fischer reagent in the same cell in a titration system protected from water vapour and oxygen, with a double burette and electrometric location of the end point in both titrations. The time for both titrations is 8-15 min.     

Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells

Current approaches to introduce terminal alkynes for bioorthogonal reactions into biomolecules still present limitations in terms of either reactivity, selectivity, or adduct stability. We present a method for the ethynylation of cysteine residues based on the use of ethynylbenziodoxolone (EBX) reagents. The acetylene group is directly introduced onto the thiol group of cysteine and can be used for copper‐catalyzed alkyne‐azide cycloaddition (CuAAC) without further processing. Labeling proceeded with reaction rates comparable to or higher than the most often used iodoacetamide on peptides or maleimide on the antibody trastuzumab, and high cysteine selectivity was observed. The reagents were also used in living cells for cysteine proteomic profiling and displayed improved coverage of the cysteinome compared to previously reported iodoacetamide or hypervalent iodine reagents. Fine‐tuning of the EBX reagents allows optimization of their reactivity and physical properties.     

Structural modification of bacterial cellulose

The microfibrillar nature of bacterial cellulose produced by Acetobacter was modified by various chemical reagents in a culture medium. The chemical reagents included antibiotics to inhibit cell division or certain protein synthesis, and reducing reagents that induce reductive cleavage of disulfide bonds in proteins. Among the reagents tested, nalidixic acid and chloramphenicol induced elongation of bacteria, resulting in the formation of wider cellulose ribbons or aggregates of ribbons. The Young's modulus of the sheets made from such cellulose increased, while dithiothreitol, which produced ribbons having only 45% of the width of the control, produced sheets with undiminished Young's modulus. Although further study is necessary to clarify the effect of such modifications, nalidixic acid and chloramphenicol produced a bacterial cellulose with superior mechanical properties.     

Preparation of allyltin reagents grafted on solid support: clean and easily recyclable reagents for allylation of aldehydes

The preparation of polymer-supported allyltin reagents was shown to be possible for both unfunctionalized and functionalized allyl units. These reagents were treated with aldehydes in the presence of cerium(III) or indium(III) salts to afford high yields of homoallylic alcohols, practically uncontaminated with organotin residues (less than 5 ppm). Some mechanism aspects are briefly discussed and the potential for regeneration and reuse of these supported reagents is pointed out.     

Cerium Salt Promoted Homocoupling Reaction of Dialkylanilines in Water

Highly regioselective homocoupling of N,N-dialkylanilines can be achieved in water with cerium reagents, in which various N,N,N′,N′-tetraalkylbenzidines are obtained from N,N-dialkylanilines either by direct oxidation by cerium（Ⅳ）reagents or by cerium（Ⅲ） reagents in the presence of hydroperoxide.     

New polyfunctional magnesium reagents for organic synthesis

The iodine-magnesium exchange reaction allows the preparation of polyfunctional aryl, heteroaryl, or alkenyl magnesium reagents at low temperature. These reagents display the typical reactivity of Grignard compounds and undergo various copper-catalyzed reactions such as allylation or 1,4-addition. Using this halogen-metal exchange reaction, it was possible to generate polyfunctional magnesium reagents on the solid phase.