Synthesis of Nitrogen-Containing Heterocyclic Scaffolds through Sequential Reactions of Aminoalkynes with Carbonyls

Sequential reactions of aminoalkynes represent a powerful tool to easily assembly biologically important polyfunctionalized nitrogen heterocyclic scaffolds. Metal catalysis often plays a key role in terms of selectivity, efficiency, atom economy, and green chemistry of these sequential approaches. This review examines the existing literature on the applications of reactions of aminoalkynes with carbonyls, which are emerging for their synthetic potential. Aspects concerning the features of the starting reagents, the catalytic systems, alternative reaction conditions, pathways and possible intermediates are provided

Electrocatalytic Hydrogen Evolution Reaction Enabling Cyanation of Electron-poor Carbons with Acetone Cyanohydrin

The Pt-cathode hydrogen evolution reaction (Pt-HER) of acetone cyanohydrin provides an alternative method for introducing the cyano group onto electrophilic carbons of imines and chalcones. The synthesis of α-aminonitriles and β-cyano ketones has been achieved smoothly with a small excess of cyanating agent (2 equivalent), catalytic amount of supporting electrolyte and low electricity consumption (0.02 F/mol). Besides demonstrating a general atom economy, the high Faradaic efficiency, allows for a scale-up with low-demanding electrochemical design and short electrolysis times

On Route to Diverse Nitrogen-Bridged Polyhetero-cycles with an N(acyl), N(aryl)-acetal Core

An expeditious assembling of fused poly-heterocyclic structures having a N(Acyl), N(aryl)-Acetal core has been accomplished by cascade reaction of ortho-functionalized anilines with 2-formylbenzonitrile and subsequent intramolecular N-amidic cyclization on different electrophilic carbons. The syntheses have been finalized using both cathodically-initiated and conventional base-catalyzed methods and comparing the two approaches in terms of substrate/product scope, efficiency, energy-saving and sustainability in general

Friedländer-Type Reaction of 4-Cholesten-3-one with 2′-Aminoacetophenone: Angular versus Linear Quinoline-Fused Steroids

To optimize the experimental conditions used for the Friedländer-type condensation, an angular fused 4-substituted quinoline steroid has been obtained in very high yield and regioselectivity using readily available 4-cholesten-3-one and 2′-aminoacetophenone. Moreover, by varying the reaction conditions and the catalyst, the corresponding linear regioisomer was also achieved with an acceptable isolated yield and high chemoselectivity. Both structures have been definitively elucidated via 2D-NMR and fully characterized

Unrevealing the Nitrogen Elusive Chirality of 3-Sulfanyl and 3-Sulfinyl N-Tosyl Isoindolinones by ECD Spectra: an Experimental and Theoretical Investigation

The nitrogen–hybridization/pyramidalization of two solvated N-tosylisoindolinone derivatives having chiral residues in adjacent (I) or adjacent and distal (II) position has been investigated by a theoretical-computational procedure based on Molecular Dynamics simulations and Quantum–Chemical calculations. After validation of our methodology in providing a reliable repertory of conformations by modeling the electronic circular dichroism (EDC) spectra, the electronic features associated with N-pyramidalization were further characterized through Natural Bond Order (NBO) analysis. Comparing against the N-geometry observed in crystal structures as a reference, our findings reveal that the presence of neighbouring chiral centers induces a more pronounced N-pyramidalization in solution than in the solid state, both in I and II. Furthermore, NBO analysis confirms that the N-lactam mostly retains the sp2 character but exhibits slight configurational distortion (ξI=13°; ξII=21°), which significantly influences the chiroptical activities observed in ECD spectra of I and II. This substantiates the N-lactams as configurationally stable chiral centers

Electrochemical-Induced Cascade Reaction of 2-Formyl Benzonitrile with Anilines: Synthesis of N-Aryl Isoindolinones

An electrochemical initiated tandem reaction of anilines with 2-formyl benzonitrile has been developed. Thus, unprecedented 3-N-aryl substituted isoindolinones have been conveniently achieved by constant current electrolysis in a divided cell using catalytic amount of electricity and supporting electrolyte and a Pt-cathode as working electrode. The origin of the electrochemical activation as well as the mechanism of the subsequent chemical cascade reactions have been investigated by DFT calculations

Gold Salts as Alternative Catalysts in Promoting Cascade Condensation of 2-Aminobenzaldehydes with Alcohols and Amines

The distinctive features of gold self-relay catalysts were alternatively utilized in the intriguing cascade condensation of 2-aminobenzaldehydes with alcohols and amines. Using NaAuCl4·2H2O as a catalyst, a range of 13-alkyloxy-7,11b-dihydro-6H,13H-6,12-[1,2]benzenoquinazolino[3,4-a]quinazoline derivatives was produced in good to high yields through A3B condensation of various 2-aminobenzaldehydes with alcohols. By carefully choosing the reaction conditions, gold catalysis also proved effective for A2B condensation with primary aryl- and benzylamines, facilitating the synthesis of challenging McGeachin bisaminals, including a chiral nonracemic derivative of 2-(S)-methylbenzylamine. The mild conditions of this gold-catalyzed approach may lead to new advancements in the field

Regional specific gas volume as an early marker of chronic lung allograft dysfunction (CLAD)

After lung transplantation, CLAD develops in its distinct subtypes of bronchiolitis obliterans syndrome (BOS) and resctictive allograft syndrome (RAS). Our aim was to investigate if quantitative analysis of specific gas volume, SVg, obtained from multivolume CT scans of transplanted lung allografts, can be helpful fon an ealry detection of BOS and RAS

eEtherification: An Electrochemical Strategy toward the Synthesis of Sterically Hindered Dialkyl Ethers from Activated Alcohols

Traditional etherification methods, although staples in synthetic chemistry, often fall short in the efficient construction of sterically hindered dialkyl ethers, especially under mild and practical conditions. Recent advances have attempted to address these limitations, typically relying on transition metal catalysts, external reductants, or harsh reaction conditions. In this work, we disclose a novel electrochemical approach that enables the synthesis of sterically hindered ethers from economically relevant and readily accessible alcohols without the need for sacrificial oxidants. Our protocol exploits mild conditions to generate reactive carbocations, which are subsequently captured by alcohol nucleophiles to yield the desired ethers. This method is cost-effective, practical, and broad in scope, providing a valuable addition to chemists’ synthetic toolkit for ether synthesis