Variety Of Alkyl Research Articles

Rapid and Practical Synthesis of gem-Dibromoalkanes from Aldehydes by Tribromide Reagent.

gem-Dibromoalkanes are important synthetic building block in organic chemistry, but their preparation is still troublesome. Herein, we have developed a simple and practical protocol for the synthesis of gem-dibromoalkanes from aldehydes using tetrabutylammonium tribromide and triphenyl phosphite. A variety of alkyl and aromatic aldehydes can be transformed into the corresponding products within 10 minutes. This protocol is also applicable to alcohols, and the configuration of chiral alcohol is inverted during the process with excellent enantiopurity.

Ruthenium‐Catalyzed Selective B(4)‐H Amidation of o‐Carboranes with Dioxazolones

AbstractA ruthenium‐catalyzed selective B4 amidation of o‐carboranes with a variety of alkyl‐, aryl‐, and heteroaryl‐substituted dioxazolones is developed by carboxylic acid‐assisted B(4)‐H bond activation in o‐carborane acids, affording a multitude of (4)‐amidated o‐carboranes in good yields with the evolution of carbon dioxide. In addition, the two‐fold selective decarboxylative amidation reaction of the cage B(4)‐H bond in o‐carborane was accomplished.

Phenylimido complexes of rhenium: fluorine substituents provide protection, reactivity, and solubility.

Reactions of [Re(NPhF)Cl3(PPh3)2] ({NPhF}2- = p-fluorophenylimide) with a variety of alkyl and aryl isocyanides have been studied. Different reactivity patterns and products have been obtained depending on the steric and electronic properties of the individual ligands. This involves the formation of 1 : 1 and 1 : 2 exchange products of Re(V) with the general formulae mer-[Re(NPhF)Cl3(PPh3)(isocyanide)] and cis- or trans-[Re(NPhF)Cl3(isocyanide)2]. The stability of the obtained products is correlated with the substitution pattern of the isocyanide ligands. The products have been studied by single-crystal X-ray diffraction and spectroscopic methods, including IR and multinuclear NMR spectroscopy as well as mass spectrometry. The use of partially fluorinated starting materials and ligands allows the modulation of the solubilities of the starting materials and the products as well as the monitoring of the reactions by means of 19F NMR. The attachment of the CF3 or F substituent on the isocyanides gives control over the steric bulk and the electronic properties of the ligands and, thus, their reactivity.

Propylphosphonic anhydride (T3P®)-mediated synthesis of redox-active N-(acyloxy)phthalimides

Here, we report the novel synthesis of N-(acyloxy)phthalimides and their analogues as redox-active esters in the presence of propylphosphonic anhydride (T3P®) reagent using 2-methyltetrahydrofuran as a green solvent under mild reaction conditions. Our convenient technique provides a chromatography-free access to these remarkable synthetic intermediates with a wide substrate scope. By using our synthetic method, a variety of alkyl, aryl, arylalkyl and heteroaryl derivatives have been prepared.

Cross-Coupling Reactions of Monosubstituted Tetrazines.

A Ag-mediated Pd-catalyzed cross-coupling method for 3-bromo-1,2,4,5-tetrazine with boronic acids is presented. Electronic modification of the 1,1'-bis(diphenylphosphine)ferrocene (dppf) ligand was found to be crucial for good turnover. Using this fast method, a variety of alkyl-, heteroatom-, and halide-substituted aryl- and heteroaryl-tetrazines were prepared (29 examples, up to 87% yield).

One-pot three-component synthesis of a new series of tetrahydrobenzofuran-chromone conjugates

An efficient one-pot three-component protocol for the synthesis of novel tetrahydrobenzofuran-chromone conjugates using 3-formylchromones and 1,3-cyclohexandiones in the presence of a variety of alkyl or aryl isocyanides was developed. The reaction sequence consists of an initial Knoevenagel condensation of aromatic aldehydes with 1,3-cyclohexandione derivatives, followed by a [4 + 1] cycloaddition of with isocyanides, and then imine-enamine tautomerization to afford the products.

Palladium Catalyzed Aminocarbonylation of Benzylic Ammonium Triflates with Nitroarenes: Synthesis of Phenylacetamides

AbstractA palladium catalyzed reductive aminocarbonylation of benzylic ammonium triflates with nitroarenes for the synthesis of phenylacetamides was developed. Using Pd(acac)2/DPPF catalyst system, a range of different substituted phenylacetamides were prepared in moderate to good yields from benzylic ammonium triflates and nitroarenes through Csp3−N bond cleavage. A variety of alkyl, aryl, and halide substituents on both substrates can be used, and many useful functional groups can be tolerated.magnified image

Lighting the way coming and going

Catalysis Catalysts accelerate chemical reactions by breaking existing bonds and then forming new ones. Often, the factors that favor the first process can muddle the second one, constraining a catalyst's generality. Torres et al. found that visible light excitation of a palladium complex can facilitate both the breaking and making of carbon-halogen bonds (see the Perspective by Kathe and Fleischer). The reaction specifically forms acid chlorides by carbonylation of a wide variety of alkyl or aryl bromides and iodides. These products in turn can react further to form amides and esters. Science , this issue p. [318][1]; see also p. [242][2] [1]: /lookup/doi/10.1126/science.aba5901 [2]: /lookup/doi/10.1126/science.abb2104

New expanded-ring NHC platinum(0) complexes: Synthesis, structure and highly efficient diboration of terminal alkenes

The synthesis and structural characterization of a series of novel platinum(0) complexes were reported. A number of (NHC)Pt(dvtms) (dvtms = 1,3-divinyl-1,1,3,3-tetramethyldisiloxane) complexes were investigated in catalytic addition of B2Pin2 to terminal alkenes. The novel expanded ring N-heterocyclic carbene complex (7-Dipp)Pt(dvtms) showed highest performance, turnover numbers up to 3800 were achieved. The scope of the reaction was illustrated by 20 examples with a variety of alkyl, alkoxy, halogen, ester, ketone and acetal substituents.

Palladium/norbornene cooperative catalysis for ortho/ipso multifunctionalization of carbazoles

Palladium-catalyzed/norbornene-mediated direct functionalization of carbazoles is disclosed. The method offers an approach to a wide variety of alkyl- and alkenyl-substituted biologically interesting carbazole derivatives from carbazole halides, alkyl halides, and acrylates. Three new C–C bonds are formed at 2-, 3-, and 4-positions of carbazoles via two C–H activation reactions and a Heck-type functionalization in one pot.

Regioselective Single-Electron Tsuji-Trost Reaction of Allylic Alcohols: A Photoredox/Nickel Dual Catalytic Approach.

A radical-mediated functionalization of allyl alcohol derived partners with a variety of alkyl 1,4-dihydropyridines via photoredox/nickel dual catalysis is described. This transformation transpires with high linear and E-selectivity, avoiding the requirement of harsh conditions (e.g., strong base, elevated temperature). Additionally, using aryl sulfinate salts as radical precursors, allyl sulfones can also be obtained. Kinetic isotope effect experiments implicated oxidative addition of the nickel catalyst to the allylic electrophile as the turnover-limiting step, supporting previous computational studies.

Cyclization of RGD Peptides by Suzuki-Miyaura Cross-Coupling.

Halogenated l- or d-tryptophan obtained by biocatalytic halogenation was incorporated into RGD peptides together with a variety of alkyl or aryl boronic acids. Suzuki-Miyaura cross-coupling either in solution or on-resin results in side chain-to-tail-cyclized RGD peptides, for example, with biaryl moieties, providing a new dimension of structure-activity relationships. An array of RGD peptides differing in macrocycle size, the presence of d-amino acid, N-methylation, or connectivity between the indole moiety and the boronic acid showed that, in particular, connectivity exhibits a major impact on affinities toward integrins, for example, αVβ3. Structure-activity relationship studies yielded peptides with affinities toward αVβ3 in the low nanomolar range, good selectivity, and high plasma stability. Structural characteristics of representative molecules have been investigated by molecular dynamics simulations, which allowed understanding the observed activity differences.

Identification of Imidazo[1,2-b]pyridazine Derivatives as Potent, Selective, and Orally Active Tyk2 JH2 Inhibitors.

In sharp contrast to a previously reported series of 6-anilino imidazopyridazine based Tyk2 JH2 ligands, 6-((2-oxo-N1-substituted-1,2-dihydropyridin-3-yl)amino)imidazo[1,2-b]pyridazine analogs were found to display dramatically improved metabolic stability. The N1-substituent on 2-oxo-1,2-dihydropyridine ring can be a variety of alkyl, aryl, and heteroaryl groups, but among them, 2-pyridyl provided much enhanced Caco-2 permeability, attributed to its ability to form intramolecular hydrogen bonds. Further structure-activity relationship studies at the C3 position led to the identification of highly potent and selective Tyk2 JH2 inhibitor 6, which proved to be highly effective in inhibiting IFNγ production in a rat pharmacodynamics model and fully efficacious in a rat adjuvant arthritis model.

Photoinduced Nitrile Formation from O‐(Arylcarbonyl) oxime: Usage as a Photoremovable Protecting Group

AbstractEmploying a photoremovable protecting group is a useful technique to achieve precise conditional control over a biological function. This Communication reports the development of a photoremovable protecting group for the nitrile moiety. In the process, O‐(arylcarbonyl) oxime was photochemically converted into the corresponding nitrile in the presence of a carbazole photosensitizer by means of an electron transfer from the excited carbazole to the arylcarbonyl unit. A variety of alkyl and (hetero) aryl nitriles were generated from the corresponding O‐(arylcarbonyl) oximes. Moreover, a self‐contained variant, in which O‐(arylcarbonyl) oxime and carbazole units were covalently bonded, exhibited photochemical nitrile formation even in a highly diluted aqueous solution (0.1 mM), thus demonstrating that this molecular motif is potentially applicable in biological systems.

A novel dual-nano assisted synthesis of symmetrical disulfides from aryl/alkyl halides

Here, we have reported a novel approach towards dual-nano assisted synthesis of disulfides from coupling of alkyl/aryl halides and sulfur nanoparticles. The indium oxide nanoparticles as catalyst expedite the conversion and sulfur nanoparticle notably enhances the miscibility, providing a faster, high yielding and cost-effective process in ethanol-water system. The method has synthetic advantages in terms of mild reaction framework, catalyst regeneration, and absence of any sulfide or polysulfide linkage as by-product leading to a column free synthesis. A variety of alkyl, aryl and heteroaryl symmetrical disulfides are obtained in good to excellent yields up to exceeding 98%.

Manganese‐Catalyzed Cross‐Coupling of Aryl Halides and Grignard Reagents by a Radical Mechanism

The substrate scope and the mechanism have been investigated for the MnCl2‐catalyzed cross‐coupling reaction between aryl halides and Grignard reagents. The transformation proceeds rapidly and in good yield when the aryl halide component is an aryl chloride containing a cyano or an ester group in the para position or a cyano group in the ortho position. A range of other substituents gave no conversion of the aryl halide or led to the formation of side products. A broader scope was observed for the Grignard reagents, where a variety of alkyl‐ and arylmagnesium chlorides participated in the coupling. Two radical‐clock experiments were carried out, and in both cases an intermediate aryl radical was successfully trapped. The cross‐coupling reaction is therefore believed to proceed by an SRN1 mechanism, with a triorganomanganate complex serving as the most likely nucleophile and single‐electron donor. Other mechanistic scenarios were excluded based on the substrate scope of the aryl halide.

Chemo-, Regio-, and Stereoselective Copper(II)-Catalyzed Boron Addition to Acetylenic Esters and Amides in Aqueous Media.

Aqueous conditions were developed for conducting an open-to-air, copper(II)-catalyzed addition of pinBBdan to alkynoates and alkynamides. The simple and mild β-borylation protocol proceeds in a remarkably chemo-, regio-, and stereoselective fashion to afford 1,8-diaminonaphthalene protected (Z)-β-boryl enoates and primary, secondary, and tertiary enamides in good to excellent yields. These reactions demonstrate a high tolerance toward a variety of alkyl, aryl, and heteroatom functional groups and provide convenient access to a diverse range of vinylboronic acid derivatives.

Ullmann reactions of 1-amino-4-bromoanthraquinones bearing various 2-substituents furnishing novel dyes

Novel 1-amino-4-(ar)alkylaminoanthraquinone derivatives bearing different substituents (Br, CH2OH, CN, or CH3) at the 2-position of the anthraquinone scaffold were synthesized by copper-catalyzed Ullmann condensation. The 2-substituted 1-amino-4-bromoanthraquinone derivatives (bromaminic acid analogues) were reacted with a variety of alkyl-, aryl-, and aralkylamines. Different reaction conditions were applied depending on the physical state of the amine and the nature of the substituent at the 2-position of the anthraquinone scaffold. A solvent-free synthetic procedure was developed for reactions with liquid amines. Condensation with solid amines required the addition of a solvent, and reaction conditions had to be optimized for each of the anthraquinone derivatives. Our results emphasize that copper-catalyzed reactions are highly variable depending on the molecules and anions present in the medium, since different reaction mechanisms apply. The synthesized anthraquinone derivatives may be useful as new dyes, or may show biological activity and could be employed as tool compounds in experimental pharmacology.

Synthesis of 1,4,2-Oxathiazoles via Oxidative Cyclization of Thiohydroximic Acids.

An oxidative formation of 1,4,2-oxathiazoles from readily available thiohydroximic acids is reported. A variety of alkyl, aryl, and heteroaryl substituents are well tolerated for both the thiohydroximic acid and activating fragments, and the reaction has been demonstrated on gram-scale. This reaction represents the only method currently available to prepare a diverse set of oxathiazoles and expands the chemistry of C-H oxidation via appended N-OH functional groups. Finally, we also demonstrate the rapid preparation of a 1,4,2-oxathiazole analog of an anticancer lead molecule.

Enantiopure Trans-4,5-Disubstituted 2-Imidazolidinones via Copper(I)-Catalyzed Ring Opening of 1,1'-DiBoc-2,2'-Biaziridine with Grignard Reagents.

The copper-catalyzed ring opening of chiral-pool-derived 1,1'-diBoc-2,2'-biaziridine with Grignard reagents affords enantiopure 2-imidazolidinones in a desymmetrizing, cascade process involving the Boc protecting group. This divergent strategy provides reaction-ready, N-differentiated products and allows two C-C bond constructions concurrent to imidazolidinone formation. A variety of alkyl, cyclic, and aryl Grignard reagents are tolerated in reasonable to good yields.