Convenient Reagent Research Articles

A Convenient One-Pot Process for Converting Thiols into Sulfonyl Fluorides Using H2O2 as an Oxidant

AbstractA novel protocol for synthesizing sulfonyl fluorides from thiols in one pot is reported. Utilizing SOCl2 and H2O2 as low-cost and convenient reagents allows the direct oxidative chlorination of readily available thiol derivatives to give the corresponding sulfonyl chlorides, with subsequent fluoride–chloride exchange mediated by KHF2 giving access to the desired sulfonyl fluorides. This transformation features mild conditions, operational simplicity and high efficiency, and utilizes a broad substrate scope, including a variety of aryl, alkyl, benzyl and heteroaryl thiols.

Trihaloisocyanuric Acids: Useful Reagents for Halogenation Reactions and Heterocyclic Scaffold Construction

Abstract: Trihaloisocyanuric acids [1,3,5-trihalo-1,3,5-triazine-2,4,6-(1H,3H,5H)-triones] are commercially available or easily prepared solids. They are highly reactive, stable, easily handled, and have an excellent atom economy, transferring up to three halogen atoms to organic substrates. In these regards, the present review summarizes their synthetic applications as safe and convenient reagents. Therefore, electrophilic halogenation reactions of alkenes, alkynes, arenes, heteroarenes, carbonyl compounds, and heteroatoms, as well as radical halogenation involving saturated substrates and in situ halogenated intermediates for Appel-type reactions are presented and discussed. Remarkably, applications of trihaloisocyanuric acids in processes for the construction of heteroarene scaffolds based on electrophilic halo- and oxidative cyclization, multicomponent reactions, and telescopic reactions are also given.

Carbon-Based Weakly Coordinating Anions: Molecular Design, Synthesis and Applications.

Although carbanions, which are usually regarded as reactive species and powerful metalation reagents, can be stabilized through choice of the substitution pattern, they have rarely been considered for the design of weakly coordinating anions (WCA). Here, we report on an evaluation of the potential of a series of differently substituted carbanions to serve as WCA by computational methods. This led us to the synthesis of the water- and air-stable allyl anion 1 with triflyl and 3,5-bis(trifluoromethyl)phenyl (ArF) moieties, which can be isolated in high yields even on a gram-scale. Single crystal X-ray crystallography and NMR studies confirmed the weak coordination ability of the anion by showing negligible or only weak interactions with different cations. This property enabled the application of 1 in the stabilization of reactive group 14 and 15 cations. In addition to the crystallization of a phosphenium cation, the first all-carbon salt with a non-aromatic carbanion is reported, which revealed to be a convenient reagent for hydride abstraction such as from silanes. Overall, this work demonstrates the so far untapped potential of carbanions as WCA, that are accessible with a variety of different cations for various applications.

Generation of New Synthons for Synthesis Through Activation of Nitromethane.

Nitromethane is used as a common solvent, stabilizer, and fuel additive. Nitromethane has also been used as a sustainable building block and convenient reagent in chemical synthesis. In this Minireview, we summarize the recent advances in activation of nitromethane, using nitromethane as the source of cyano group, nitrogen, methylamine, formyl group, C1, nitroso, and oxime.

HTIB as an Efficient and Convenient Reagent for Oxidative Cleavage of C=N in Pyrimidinyl Hydrazones

This study is aimed to explore the efficiency of [hydroxy(tosyloxy)iodo]benzene (HTIB) in the oxidative cleavage of some pyrimidinyl hydrazones. The protocol involves stirring the hydrazone derivatives with HTIB in dichloromethane at room temperature. The oxidative cleavage of C = N in pyrimidinyl hydrazones regenerated parent ketones in high yields. The methodology has advantage of preventing over oxidation of carbonyl functionality.. KEYWORDS :[Hydroxy(tosyloxy)iodo]benzene, Hydrazone, Hypervalent iodine reagent, Oxidative cleavage, Pyrimidine.

Glycerol‐1,2‐carbonate: A mild reagent for the N‐glycerylation of pyrazolecarboxylates

AbstractIn this study, glycerol‐1,2‐carbonate was employed as a convenient reagent for the synthesis of more complex pyrazole‐containing heterocyclic systems. 3‐O‐Tosylated glycerol‐1,2‐carbonate (TGC) was used for alkylation of NH‐pyrazolecarboxylates. The obtained N‐glycerylated pyrazoles were further treated with diverse nucleophiles for 2‐oxo‐1,3‐dioxolane ring cleavage. The synthesized 1‐(2,3‐dihydroxypropyl)‐1H‐pyrazole‐5‐carboxylates were subsequently hydrolyzed and treated with p‐toluenesulfonic acid, yielding a series of 6‐(hydroxymethyl)‐6,7‐dihydro‐4H‐pyrazolo[5,1‐c][1,4]ox‐azin‐4‐ones.

Chemistry of new polyfluorinated oxiranyl anions and epoxy silanes

The reaction of partially fluorinated epoxides with strong, hindered bases in the presence of electrophiles resulted in functionalization of the epoxy ring. For example, the reaction of hexafluoroisobutene epoxide with LDA and trimethyl- or triethychlorosilanes at low temperature led to the formation of the corresponding epoxy silanes. In the case of the E- and Z-epoxides of 1,1,1,3,3,3-hexafluorobutene-2, the deprotonation step can be successfully carried out using i-PrMgCl.LiCl (Turbo Grignard reagent), and the reaction with chlorosilanes can be carried out at ambient temperature, which significantly simplifies the synthetic protocol. The process was found to be stereospecific, proceeding with complete retention of configuration of the epoxide ring and giving access to pure E- or Z-isomers of the corresponding epoxy silanes. Using this protocol, the corresponding epoxy silanes were also prepared from the epoxides of E-3,3,3,1-tetrafluoropropene-1 and 3,3,3-trifluoropropene-1.The new silanes were demonstrated to be convenient reagents for the transfer of a fluorinated epoxy moiety to carbonyl compounds under fluoride anion catalysis. This process was shown to proceed with complete retention of the geometry of the epoxy ring.

Umfassende Studie der Gesteigerten Reaktivität von Turbo‐Grignard‐Reagenzien**

AbstractSeit ihrer Einführung im Jahr 2004 revolutionierten Knochel's sogenannte Turbo‐Grignard‐Reagenzien die Anwendung der Grignard‐Reagenzien. Durch die einfache Zugabe von LiCl zu einem Magnesium‐Alkyl kann eine außerorderliche Steigerung der Reaktivität beobachtet werden. Die genaue Zusammensetzung der reaktiven Spezies blieb jedoch lange Zeit ein Rätsel, obwohl das reaktive Gemisch nicht nur in der Synthese breite Anwendung fand, sondern auch in anderen Bereichen wie der Materialwissenschaft Einzug hielt. Um dieses Rätsel zu lösen, kombinierten wir Einkristall‐Röntgendiffraktometrie mit NMR‐Spektroskopie in Lösung und vollendeten unsere Untersuchungen mit quantenchemischen Berechnungen. Durch die breite Vielfalt unserer Methoden, gelang uns ein Einblick in und eine erstmalige Erklärung für die außergewöhnliche Reaktivität dieses äußerst praktikablen Reagenzes, indem wir die Struktur der ersten bimetallischen Spezies [t‐Bu2Mg ⋅ LiCl ⋅ 4 THF] mit zwei tert‐Butylanionen am Magnesium‐zentrum und eingebautem Lithiumchlorid aufklärten.

Comprehensive Study of the Enhanced Reactivity of Turbo-Grignard Reagents.

Since its introduction in 2004, Knochel's so called Turbo-Grignard reagents revolutionized the usage of Grignard reagents. Through the simple addition of LiCl to a magnesium alkyl an outstanding increase in reactivity can be achieved. Though the exact composition of the reactive species remained mysterious, the reactive mixture itself is readily used not only in synthesis but also found its way into more distant fields like material science. To unravel this mystery, we combined single-crystal X-ray diffraction with in-solution NMR-spectroscopy and closed our investigations with quantum chemical calculations. Using such a variety of methods, we have gained insight into and an explanation for the extraordinary reactivity of this extremely convenient reagent by determining the structure of the first bimetallic reactive species [t-Bu2 Mg ⋅ LiCl ⋅ 4 thf] with two tert-butyl anions at the magnesium center and incorporated lithium chloride.

N-Trifluoromethoxyphthalimide: A Shelf-Stable Reagent for Nucleophilic Trifluoromethoxylation

Due to the unique properties of the OCF3 group, trifluoromethyl ether compounds play an important role in pharmaceuticals and agrochemicals. Recently, considerable attention has been focused on the development of practical and convenient reagents for the direct incorporation of the OCF3 group into organic compounds. Herein, we reported a new trifluoromethoxylating reagent N-trifluoromethoxyphthalimide (Phth-OCF3). The reagent was a stable solid and released an OCF3 anion under mild reaction conditions. We demonstrated the application of Phth-OCF3 for the nucleophilic trifluoromethoxylation of various alkyl electrophiles.

Radical Arylaminoformylation of Activated Alkenes to Amides Containing All‐Carbon Quaternary Stereocenters

AbstractHerein we report an Ag+/S2O82− inducted measure for functionalized succinyl diamides bearing an all‐carbon quaternary stereocenter via a radical aminoformylation/aryl‐migration/desulfonylation cascade. The improved process is developed employing readily available and inexpensive oxalic monoamide as a carbamoyl radical precursor through radical Smiles rearrangement. Additionally, the tolerance to oxygen and water, operational simplicity, convenient reagents, as well as scalability, enhance the practical value of the proposed synthesis strategy.

Synthesis and properties of [NR4]3[SbS4] (R = Me, Et, n-Pr, n-Bu) and the crystal structures of [N(n-Bu)4]3[SbS4]⋅6H2O and [N(n-Bu)4]3[Sb(S2O3)3]·2THF

The tetra-alkylammonium tetrathioantimonate(V) salts, [NR4]3[SbS4] (R = Me, Et, n-Pr, n-Bu), have been prepared in basic solution from aqueous [NR4]OH, sulfur and Sb2S3, and characterised by microanalysis, IR, Raman, 1H and 121Sb NMR spectroscopy. The crystal structure of [N(n-Bu)4]3[SbS4]·6H2O shows the presence of the tetrahedral [SbS4]3− anion (disordered over two sites), and also connected through an H-bonding network with the lattice water molecules. The alkylammonium salts are soluble in water and, with the exception of [NMe4]3[SbS4], are also soluble in weakly polar organic solvents, including halocarbons and MeCN. Solubility increases with the R group Me < Et < n-Pr < n-Bu, making the [N(n-Bu)4)3[SbS4] a convenient reagent to explore coordination chemistry or materials applications for which water as the solvent is not suitable. [N(n-Bu)4]3[Sb(S2O3)3]·2THF, the first thiosulfate complex of a p-block element, was produced by slow decomposition of [N(n-Bu)4]3[SbS4] in THF solution in the presence of the [NH(n-Bu)3]Cl (as a source of H+), confirming the instability of the [SbS4]3− anion in acidic media, and the crystal structure of [N(n-Bu)4]3[Sb(S2O3)3]·2THF shows a trigonal antiprismatic coordination geometry with a S3O3 donor set at the antimony(III) centre in the anion.

Organo-cyanamides: convenient reagents for catalytic amidation of carboxylic acids.

An unprecedented DMAP-catalysed amidation of aryl and alkyl carboxylic acids with organo-cyanamides has been developed. Unlike the use of N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as an electrophilic cyanating reagent, an unusual desulfonylation/decyanation reaction model has been disclosed for the first time. Remarkable features of this reaction include readily available substrates, simple operation and broad scope, enabling the efficient synthesis of structurally diverse amides. The synthetic utility of this protocol was demonstrated by the late-stage amidation of bioactive carboxylic acids and a scale-up reaction.

Synthesis of Trifluoromethylated γ-Lactams through Radical Cascades of N-Cyano Alkenes with CF3SO2Na.

We report herein a facile strategy to synthesize trifluoromethylated γ-lactams through trifluoromethylcarbonylation of N-cyano alkenes using readily available CF3SO2Na as the CF3 radical source. A range of trifluoromethyl-containing γ-lactams was obtained in good yields. This transition-metal-free protocol is demonstrated with mild conditions, broad substrate scope, good functional group tolerance, convenient reagents, and an easy-to-handle operating system.

Applications of N-Halo Reagents in Multicomponent Reactions: A Still Underrated Approach for the Construction of Heterocyclic Scaffolds

Abstract:Heterocyclic scaffolds are important from both academic and industrial points of view. Due to their biological and pharmacological activities, they are useful intermediates in organic synthesis and have great interest in medicinal and natural products chemistry. N-halo compounds bearing an electron-withdrawing group on nitrogen (e.g., carbonyl, sulfonyl) present the unique chemical properties of the N-X bond that give them broad synthetic utility for diverse organic transformation. In the past years, significant progress has been achieved in the synthesis of heterocyclic compounds with the intermediacy of N-halo compounds. Numerous strategies (e.g., electrophilic cyclizations, asymmetric halocyclizations, oxidative cyclizations, radical processes) were implemented featuring high atom- and step-economy, and more efficient procedures are continually being developed. An interesting approach consists of using Nhalo compounds to promote multicomponent reactions (MCRs), which rapidly became an emerging field in heterocyclic construction. MCRs are recognized for their mild conditions, high convergence, and efficiency. Thus, the present review will focus attention on the main topics and utilization of N-halo compounds (N-halosuccinimides, trihaloisocyanuric acids, N-halosulfonamides, etc.) as green and convenient reagents in heterocyclic construction via MCRs. Examples of the preparation of azoles, pyridines, 1,4-dihydropyridines, chromenes, and xanthenes, among other scaffolds are presented and discussed.

N‐Alkoxyphtalimides as Versatile Alkoxy Radical Precursors in Modern Organic Synthesis

AbstractO‐substituted derivatives of N‐hydroxyphthalimide (NHPI) have attracted much attention recently as synthetically available, stable, and convenient reagents for the generation of free radicals under mild conditions. The single‐electron reduction by a photoredox catalyst or another reagent results in the N−O bond cleavage of an NHPI derivative with the release of free radicals that undergo selective synthetic transformations. Whereas N‐acyloxyphtalimides (NHPI esters) are well known as a convenient C‐radical source due to the facile one‐electron reduction followed by the decarboxylation, N‐alkoxyphtalimides are much less studied as radical precursors. The present review shows that N‐alkoxyphtalimides are effective reagents for free‐radical transformations starting from the generation of alkoxy free radicals. Visible light induced reactions are discussed first, these processes are classified according to the way how intermediate alkoxy radicals transformed to C‐centered radicals: via hydrogen atom transfer to oxygen atom (HAT, including 1,5‐HAT, 1,2‐HAT, and intermolecular HAT) or via β‐scission. Other photochemical radical reactions of alkoxyphthalimides and non‐photochemical tin‐mediated processes are discussed separately.

Synthesis of Dihydro‐5H‐Benzo[c]‐Fluorenes, Dihydroindeno[c]‐Chromenes and Thiochromenes via Intramolecular Cyclization and their Effect on Human Leukemia Cells

AbstractIn this work, we describe the construction of a series of 6,7‐dihydro‐5H‐benzo[c]fluorenes. Their synthesis is based on an intramolecular‐cyclization of tricyclic substrates, which has an alcohol functional group in acidic conditions at ambient temperature. Certain reaction optimization conditions reveal that triflic acid was the most convenient reagent for this transformation, affording a broad range of fluorene derivatives in a 37 to 93% yield. We illustrate the robustness of this methodology through a gram‐scale synthesis, and the preparation of dihydroindeno[c]‐chromenes thiochromenes, and azulenes derivatives.magnified image

Decarbonylative cascade cyclization of ortho-cyanoarylacrylamides with pivaldehyde: Access to tert-butyl containing quinolone-2,4(1H,3H)-diones

A TBPB initiated decarbonylative cascade cyclization of ortho-cyanoarylacrylamides with pivaldehyde leads to tert-butyl containing quinolone-2,4(1H,3H)-diones by formation of both C(sp3)–C(sp3) and C(sp3)–C(sp2) bonds. The reaction features simple reaction conditions and convenient reagents. Two radical additions are involved in the transformation.

Oxime‐Derived Iminyl Radicals in Selective Processes of Hydrogen Atom Transfer and Addition to Carbon‐Carbon π‐Bonds

AbstractOximes represent one of the fundamental organic compound classes with a wide range of synthetic applications. In the last decade O‐substituted oximes were recognized as the synthetically available and versatile precursors of iminyl radicals via one‐electron oxidation or one‐electron reduction employing visible light photoredox catalysts, salts of abundant metals (such as Cu or Fe), or other convenient reagents. Iminyl radicals are powerful synthons for various processes of cyclization, ring‐opening, CH‐functionalization, and coupling. The present review is focused on the synthetic methods based on oxime‐derived iminyl radicals developed in the last few years excluding ring opening reactions of cyclic iminyl radicals that were summarized in recent publications. The review consists of two main parts: (1) reactions of iminyl radicals involving 1,n‐hydrogen atom transfer (n=5 in most cases) and (2) reactions involving the addition of iminyl radical to the carbon‐carbon π‐bond.magnified image

The Role of Changing Loop Conformations in Streptavidin Versions Engineered for High-affinity Binding of the Strep-tag II Peptide

The affinity system based on the artificial peptide ligand Strep-tag® II and engineered tetrameric streptavidin, known as Strep-Tactin®, offers attractive applications for the study of recombinant proteins, from detection and purification to functional immobilization. To further improve binding of the Strep-tag II to streptavidin we have subjected two protruding loops that shape its ligand pocket for the peptide – instead of D-biotin recognized by the natural protein – to iterative random mutagenesis. Sequence analyses of hits from functional screening assays revealed several unexpected structural motifs, such as a disulfide bridge at the base of one loop, replacement of the crucial residue Trp120 by Gly and a two-residue deletion in the second loop. The mutant m1-9 (dubbed Strep-Tactin XT) showed strongly enhanced affinity towards the Strep-tag II, which was further boosted in case of the bivalent Twin-Strep-tag®. Four representative streptavidin mutants were crystallized in complex with the Strep-tag II peptide and their X-ray structures were solved at high resolutions. In addition, the crystal structure of the complex between Strep-Tactin XT and the Twin-Strep-tag was elucidated, indicating a bivalent mode of binding and explaining the experimentally observed avidity effect. Our study illustrates the structural plasticity of streptavidin as a scaffold for ligand binding and reveals interaction modes that would have been difficult to predict. As result, Strep-Tactin XT offers a convenient reagent for the kinetically stable immobilization of recombinant proteins fused with the Twin-Strep-tag. The possibility of reversibly dissociating such complexes simply with D-biotin as a competing ligand enables functional studies in protein science as well as cell biology.