Chemoselective reduction of isothiocyanates to thioformamides mediated by the Schwartz reagent.

Thioformamides are easily prepared - under full chemocontrol - through the partial reduction of isothiocyanates with the in situ generated Schwartz reagent. The high electrophilicity of the starting materials enables the straightforward addition of the hydride ion, thus constituting a reliable and high-yielding method for obtaining variously functionalized thioformamides. Sensitive chemical groups to the reduction conditions such as nitro, ester, alkene, azo, azide and keto groups do not interfere with the chemoselectivity of the process. Moreover, the stereochemical information embodied in the starting material is fully retained in the final products. The synthetic potential of the selected thioformamide template is also briefly discussed.

Radical Germylzincation of α-Heteroatom-Substituted Alkynes.

The regio- and stereoselective addition of germanium and zinc across the C-C triple bond of nitrogen-, sulfur-, oxygen-, and phosphorus-substituted terminal and internal alkynes is achieved by reaction with a combination of R3GeH and Et2Zn. Diagnostic experiments support a radical-chain mechanism and the ß-zincated vinylgermanes that show exceptional stability are characterized by NMR spectroscopy and X-ray crystallography. The unique feature of this new radical germylzincation reaction is that the C(sp2)-Zn bond formed remains available for subsequent in situ Cu(I)- or Pd(0)-mediated C-C or C-heteroatom bond formation with retention of the double bond geometry. These protocols offer modular access to elaborated tri- and tetrasubstituted vinylgermanes decorated with heteroatom substituents ß to germanium that are useful for the preparation of stereodefined alkenes.

Isocyanates and isothiocyanates as versatile platforms for accessing (thio)amide-type compounds.

The addition of carbon (Grignard and organolithium reagents) and hydride nucleophiles (Schwartz reagent) to isocyanates and isothiocyanates constitutes a versatile, direct and high yielding approach to the synthesis of functionalized (thio)amide derivatives including haloamides and formamides. The chemoselective delivery of a nucleophilic (eventually configurationally stable) organometallic species to a given iso(thio)cyanate is the crucial parameter for the success of the strategy. Thus, the influence of the factors governing classical methodologies (e.g. dehydrative condensation) such as steric hindrance and electronic properties of the reactants become practically negligible.

Investing in entropy: the strategy of cucurbit[n]urils to accelerate the intramolecular Diels-Alder cycloaddition reaction of tertiary furfuryl amines.

Cucurbit[n]urils, renowned for their host-guest chemistry, are becoming versatile biomimetic receptors. Herein, we report that cucurbit[7]uril (CB[7]) accelerates the intramolecular Diels-Alder (IMDA) reaction for previously elusive and unreactive tertiary N-methyl-N-(homo)allyl-2-furfurylamines by up to 4 orders of magnitude under mild conditions. Using 1H NMR titrations and ITC experiments, we characterize the dissimilar thermodynamic and kinetic properties of the complexes. We also determine the activation parameters (ΔG ≠, ΔH ≠ and ΔS ≠) leading to the transition state of the IMDA reactions, both in the bulk and included in CB[7], to shed light on the key role of the receptor on the acceleration observed. CB[7] acts as an "entropy trap" utilizing guest binding to primarily pay the entropy penalty for reorganizing the substrate in a high-energy reactive conformation that resembles the geometry of the highly ordered transition state required for the IMDA reaction. This study underscores the potential of cucurbit[n]urils as artificial active sites, emulating specific aspects of enzymatic catalysis.

Radical Germylzincation of Aryl- and Alkyl-Substituted Internal Alkynes.

The stereoselective germylzincation of internal alkynes delivering trisubstituted vinylgermanes is achieved via a radical chain process involving Ph3GeH and Et2Zn with AIBN as the initiator. Excellent levels of regiocontrol are observed for nonsymmetric (aryl, alkyl)-substituted alkynes and for propargylic alcohols with aryl-, alkyl-, or silyl-substituted alkynes. The germylzincation reaction can be combined in one pot with the Cu(I)-mediated electrophilic substitution of the C(sp2)-Zn bond to obtain synthetically challenging tetrasubstituted vinylgermanes.

Gold, Silver and Iron Oxide Nanoparticles: Synthesis and Bionanoconjugation Strategies Aimed at Electrochemical Applications.

Nanomaterials have revolutionized the sensing and biosensing fields, with the development of more sensitive and selective devices for multiple applications. Gold, silver and iron oxide nanoparticles have played a particularly major role in this development. In this review, we provide a general overview of the synthesis and characteristics of gold, silver and iron oxide nanoparticles, along with the main strategies for their surface functionalization with ligands and biomolecules. Finally, different architectures suitable for electrochemical applications are reviewed, as well as their main fabrication procedures. We conclude with some considerations from the authors' perspective regarding the promising use of these materials and the challenges to be faced in the near future.

Discerning the antioxidant mechanism of rapanone: A naturally occurring benzoquinone with iron complexing and radical scavenging activities.

Oxidative stress resulting from iron and reactive oxygen species (ROS) homeostasis breakdown has been implicated in several diseases. Therefore, molecules capable of binding iron and/or scavenging ROS may be reasonable strategies for protecting cells. Rapanone is a naturally occurring hydroxyl-benzoquinone with a privileged chelating structure. In this work, we addressed the antioxidant properties of rapanone concerning its iron-chelating and scavenging activities, and its protective potential against iron and tert-butyl hydroperoxide-induced damage to mitochondria. Experimental determinations revealed the formation of rapanone-Fe(II)/Fe(III) complexes. Additionally, the electrochemical assays indicated that rapanone oxidized Fe(II) and O2-, thus inhibiting Fenton-Haber-Weiss reactions. Furthermore, rapanone displayed an increased 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability in the presence of Fe(II). The above results explained the capacity of rapanone to provide near-full protection against iron and tert-butyl hydroperoxide induced mitochondrial lipid peroxidation in energized organelles, which fail under non-energized condition. We postulate that rapanone affords protection against iron and reactive oxygen species by means of both iron chelating and iron-stimulated free radical scavenging activity.

Chemoselective Schwartz Reagent Mediated Reduction of Isocyanates to Formamides.

Addition of the in situ generated Schwartz reagent to widely available isocyanates constitutes a chemoselective, high-yielding, and versatile approach to the synthesis of variously functionalized formamides. Steric and electronic factors or the presence of sensitive functionalities (esters, nitro groups, nitriles, alkenes) do not compromise the potential of the method. Full preservation of the stereochemical information contained in the starting materials is observed. The use of formamides in the nucleophilic addition of organometallic reagents (Chida-Sato allylation, Charette-Huang addition to imidoyl triflate activated amides, Matteson homologation of boronic esters) is briefly investigated.

The Use of the Comins-Meyers Amide in Synthetic Chemistry: an Overview.

Formylation reactions are fundamental operations in synthetic chemistry allowing the incorporation into a given structure formyl groups amenable to further deiivatization. Conceptually, the introduction of such groups through the reaction between an electrophilic donor and a nucleophilic acceptor (i.e. organometallic reagent) constitutes a reliable technique with widespread applications. In this Highlight, we summarize the effectiveness of the so called Comnins-Meyers amide - [2-(N-methyl-N-formylamino]pyridine - in such a chemistry with vistas to the synthesis of natural products and biologically active substrates.