Transition-Metal-Free Approach for Z-Vinyl Fluorides by Hydrofluorination of Alkynes bearing SF4 and SF5 Groups.

The synthesis of vinyl fluorides plays a crucial role in various scientific disciplines, including pharmaceutical and materials sciences. Herein, we present a direct and stereoselective hydrofluorination method for the synthesis of Z isomers of vinyl fluorides from alkynes containing unexplored SF5 and SF4 groups. Our strategy employed tetrabutylammonium fluoride (TBAF) as a fluorine source. It demonstrates high compatibility with aryls, biaryls, heteroaryls, and tert-alkyl groups, allowing facile incorporation of SF5 and SF4 groups across the triple bond without any transition-metal catalysts. This approach avoids the potential decomposition of the SF5 or SF4 units via coordination with transition metals or acidic protic sources. Remarkably, this transformation proceeded at room temperature without any additional additives, providing the Z isomer of vinyl fluorides in excellent yield and high selectivity. The presence of a water molecule as a hydrate in TBAF is essential for efficient conversion. This methodology opens new avenues for the synthesis of enchanting SF5 - and SF4 -containing fluorinated vinylic scaffolds, thereby providing advanced opportunities for novel drug discovery and fluorinated polymers.

Pyranthiones/Pyrones: "Click and Release" Donors for Subcellular Hydrogen Sulfide Delivery and Labeling.

Hydrogen sulfide (H2 S), one of the most important gasotransmitters, plays a critical role in endogenous signaling pathways of many diseases. However, developing H2 S donors with both tunable release kinetics and high release efficiency for subcellular delivery has been challenging. Here, we describe a click and release reaction between pyrone/pyranthiones and bicyclononyne (BCN). This reaction features a release of CO2 /COS with second-order rate constants comparable to Strain-Promoted Azide-Alkyne Cycloaddition reactions (SPAACs). Interestingly, pyranthiones showed enhanced reaction rates compared to their pyrone counterparts. We investigated pyrone biorthogonality and demonstrated their utility in protein labeling applications. Moreover, we synthesized substituted pyranthiones with H2 S release kinetics that can address the range of physiologically relevant H2 S dynamics in cells and achieved quantitative H2 S release efficiency in vitro. Finally, we explored the potential of pyranthiones as H2 S/COS donors for mitochondrial-targeted H2 S delivery in living cells.

An Atom-Economic Method for 1,2,3-Triazole Derivatives via Oxidative [3 + 2] Cycloaddition Harnessing the Power of Electrochemical Oxidation and Click Chemistry.

An electrochemical method was developed to accomplish the reagentless synthesis of 4,5-disubstituted triazole derivatives employing secondary propargyl alcohol as C-3 synthon and sodium azide as cycloaddition counterpart. The reaction was conducted at room temperature in an undivided cell with a constant current using a pencil graphite (C) anode and stainless-steel cathode in a MeCN solvent system. The proposed reaction mechanism was convincingly established by carrying out a series of control experiments and further supported by electrochemical and density functional theory (DFT) studies.

Tunable Supramolecular Ag+-Host Interactions in Pillar[n]arene[m]quinones and Ensuing Specific Binding to 1-Alkynes.

We developed an improved, robust synthesis of a series of pillar[6]arenes with a varying number (0-3) of quinone moieties in the ring. This easy-to-control variation yielded a gradually less electron-rich cavity in going from zero to three quinone units, as shown from the strength of host-guest interactions with silver ions. Such macrocycle-Ag2 complexes themselves were shown to display an unprecedented, sharp distinction between terminal alkynes, which strongly bound to such complexes, and internal alkynes, internal alkenes and terminal alkenes, which do hardly bind.

Cascade Detrifluoroacetylation, C-S Bond Cleavage, and SN2' Reaction of α,α-Difluorinated Gem-Diols with MBH Esters.

A new SN2' reaction type of Morita-Baylis-Hillman (MBH) ester with sulfonyl anion, generated in situ via detrifluoroacetylation as a nucleophile is developed. Experimental results and DFT calculations disclose that the reaction proceeds via C-C bond cleavage to generate a PhSO2CF2 anion, C-S bond cleavage to generate a sulfonyl anion with the release of CF2 carbene, and an SN2' reaction with the MBH ester. The reaction features operational simplicity, wide substrate scope, high yields, and excellent stereoselectivity, which represents a new reaction mode of fluorinated gem-diols and also provides an efficient way to obtain ß,γ-unsaturated sulfones.

Anti-Markovnikov Intermolecular Hydroamination of Alkenes and Alkynes: A Mechanistic View.

Hydroamination, the addition of an N-H bond across a C-C multiple bond, is a reaction with a great synthetic potential. Important advances have been made in the last decades concerning catalysis of these reactions. However, controlling the regioselectivity in the amine addition toward the formation of anti-Markovnikov products (addition to the less substituted carbon) still remains a challenge, particularly in intermolecular hydroaminations of alkenes and alkynes. The goal of this review is to collect the systems in which intermolecular hydroamination of terminal alkynes and alkenes with anti-Markovnikov regioselectivity has been achieved. The focus will be placed on the mechanistic aspects of such reactions, to discern the step at which regioselectivity is decided and to unravel the factors that favor the anti-Markovnikov regioselectivity. In addition to the processes entailing direct addition of the amine to the C-C multiple bond, alternative pathways, involving several reactions to accomplish anti-Markovnikov regioselectivity (formal hydroamination processes), will also be discussed in this review. The catalysts gathered embrace most of the metal groups of the Periodic Table. Finally, a section discussing radical-mediated and metal-free approaches, as well as heterogeneous catalyzed processes, is also included.

A Cu-promoted reaction of ß-keto trifluoromethyl amines enabling stereoselective synthesis of trifluoromethylated aziridines.

An efficient Cu(I) complex-promoted intramolecular cyclization reaction of ß-keto trifluoromethyl amines has been developed, providing access to a series of unprotected trifluoromethylated aziridines with good chemical yields and excellent stereoselectivity (trans : cis > 99 : 1). The reaction can be carried out under mild conditions and tolerates a wide range of substrates with diverse functional groups, representing a straightforward method for the preparation of trifluoromethylated aziridines from readily available starting materials.

Regio- and Z-Selective Alkyne Hydroamination and Hydrophenoxylation using Tetrafluoro-λ6 -Sulfanyl Alkynes under Superbasic, Naked Anion Conditions.

Alkyne hydroamination is an effective approach for the production of enamines and enamine-containing N-heterocycles. However, stereoselectivity control is a considerable challenge in this reaction because of the electronic repulsion between an incoming nitrogen lone pair and the alkyne π-system. Herein, we propose a methodology involving ß-regio- and Z-selective alkyne hydroamination by using tetrafluoro-λ6 -sulfanyl (SF4 ) alkynes under superbasic, naked anion conditions. The reaction is compatible with a wide variety of N-heterocycles, including indoles, carbazoles, pyrazoles, and imidazoles, and selectively furnishes SF4 -linked Z-vinyl enamines with ß-regioselectively. Moreover, the method can be extended to the ß- and Z-controlled, base-mediated alkyne hydrophenoxylation with phenols to provide SF4 -linked Z-vinyl ethers in high yields. As the SF4 unit has attracted attention as a bioisostere for alkynes, p-benzenes, bicyclo[1.1.1]pentyl (BCP) groups, and cubanes in medicinal chemistry, this chemistry represents an effective approach to creating novel drug candidates incorporating SF4 -containing molecules.

High Rates of Quinone-Alkyne Cycloaddition Reactions are Dictated by Entropic Factors.

Reaction rates of strained cycloalkynes and cycloalkenes with 1,2-quinone were quantified by stopped flow UV-Vis spectroscopy and computational analysis. We found that the strained alkyne BCN-OH 3 (k2 1824 M-1 s-1 ) reacts >150 times faster than the strained alkene TCO-OH 5 (k2 11.56 M-1 s-1 ), and that derivatization with a carbamate can lead to a reduction of the rate constant with almost half. Also, the 8-membered strained alkyne BCN-OH 3 reacts 16 times faster than the more strained 7-membered THS 2 (k2 110.6 M-1 s-1 ). Using the linearized Eyring equation we determined the thermodynamic activation parameters of these two strained alkynes, revealing that the SPOCQ reaction of quinone 1 with THS 2 is associated with ΔH≠ of 0.80 kcal/mol, ΔS≠ =-46.8 cal/K⋅mol, and ΔG≠ =14.8 kcal/mol (at 25 °C), whereas the same reaction with BCN-OH 3 is associated with, ΔH≠ =2.25 kcal/mol, ΔS≠ =-36.3 cal/K⋅mol, and ΔG≠ =13.1 kcal/mol (at 25 °C). Computational analysis supported the values obtained by the stopped-flow measurements, with calculated ΔG≠ of 15.6 kcal/mol (in H2 O) for the SPOCQ reaction with THS 2, and with ΔG≠ of 14.7 kcal/mol (in H2 O) for the SPOCQ reaction with BCN-OH 3. With these empirically determined thermodynamic parameters, we set an important step towards a more fundamental understanding of this set of rapid click reactions.

Fluorinated Imines in Tandem and Cycloaddition Reactions.

The chemistry of fluorinated compounds has experienced extraordinary growth in recent decades due to the many and varied properties which many of the compounds that contain fluorinated groups possess. Among all of them, fluorinated chiral imines, in particular the Ellman's imines, are of great importance since they are some of the most interesting building blocks for the synthesis of a large number of enantioenriched carbocycles and heterocycles with extraordinary biological and synthetic properties. This personal account covers the most significant results obtained in our research group in the last two decades concerning asymmetric tandem reactions, paying special attention to the intramolecular aza-Michael reaction (IMAMR), diversity oriented synthesis (DOS), asymmetric tandem reactions involving a p-tolylsulfinyl group as chiral inducer and cycloaddition processes, in particular, the Pauson-Khand reaction, [2+2+2]-cycloadditions and metathesis reactions, starting mainly from enyne compounds and through the use of fluorinated chiral N-sulfinyl imines and their derivatives as starting materials.

Hydrogen Production from Methanol-Water Solution and Pure Water Electrolysis Using Nanocomposite Perfluorinated Sulfocationic Membranes Modified by Polyaniline.

In this work, we report the preparation of Nafion membranes containing two different nanocomposite MF-4SC membranes, modified with polyaniline (PANI) by the casting method through two different polyaniline infiltration procedures. These membranes were evaluated as a polymer electrolyte membrane for water electrolysis. Operating conditions were optimized in terms of current density, stability, and methanol concentration. A study was made on the effects on the cell performance of various parameters, such as methanol concentration, water, and cell voltage. The energy required for pure water electrolysis was analyzed at different temperatures for the different membranes. Our experiments showed that PEM electrolyzers provide hydrogen production of 30 mL/min, working at 160 mA/cm2. Our composite PANI membranes showed an improved behavior over pristine perfluorinated sulfocationic membranes (around 20% reduction in specific energy). Methanol-water electrolysis required considerably less (around 65%) electrical power than water electrolysis. The results provided the main characteristics of aqueous methanol electrolysis, in which the power consumption is 2.34 kW h/kg of hydrogen at current densities higher than 0.5 A/cm2. This value is ~20-fold times lower than the electrical energy required to produce 1 kg of hydrogen by water electrolysis.

Computational Study on the Co-Mediated Intramolecular Pauson-Khand Reaction of Fluorinated and Chiral N-Tethered 1,7-Enynes.

The Co2(CO)8-mediated intramolecular Pauson-Khand reaction is an elegant approach to obtain cyclopentenone derivatives containing asymmetric centers. In this work, we employed density functional theory calculations at the M11/6-311+G(d,p) level of theory to investigate the mechanism and reactivity for the Pauson-Khand reaction of fluorinated and asymmetric N-tethered 1,7-enynes. The rate-determining step was found to be the intramolecular alkene insertion into the carbon-cobalt bond. The stereoselectivity of the alkene insertion step was rationalized by the different transition states showing the coordination of the alkene through the Re- and Si-face. The effects of different fluorine groups and steric effects on both the alkenyl and alkynyl moieties were also theoretically investigated.

Electric Conductivity Study of Porous Polyvinyl Alcohol/Graphene/Clay Aerogels: Effect of Compression.

In this work, poly(vinyl alcohol) (PVOH)/graphene (GN) oxide/clay aerogels were prepared using montmorillonite (MMT) and kaolinite (KLT) as fillers. This work paves the way for the development of aerogels filled with MMT or KLT with high conductivity. The mechanical properties of the polymer/clay aerogels are enhanced by incorporating GN into these systems. These composite materials have an enhanced thermal stability, and the combination of PVOH and GN leads to interconnected channels which favored the conductivity when a clay (MMT or KLT) is added to the mixed PVOH/GN matrix. However, after compressing the samples, the conductivities drastically decreased. These results show that the design of solid MMT/GN and KLT/GN composites as aerogels allows maximizing the space utilization of the electrode volume to achieve unhindered ion transport, which seems contrary to the general design principle of electrode materials where a suitable porous structure is desired, such as in our uncompressed samples. These findings also demonstrate the potential of these materials in electrodes, sensors, batteries, pressure-sensing applications, and supercapacitors.

Computational insights into the inverse electron-demand Diels-Alder reaction of norbornenes with 1,2,4,5-tetrazines: norbornene substituents' effects on the reaction rate.

The study of the reaction rates and mechanism of click chemistry reactions still remains an interesting challenge in organic chemistry. In this regard, the inverse electron demand Diels-Alder (IEDDA) reaction represents a promising metal-free alternative with enhanced reaction rates compared to other reactions of the click chemistry toolbox. Among the different types of dienophiles used in the IEDDA reactions, norbornenes have been widely used given their high stability and fast reaction rates. The inverse electron-demand Diels Alder reaction of 3,6-dipyridin-2-yl-1,2,4,5-tetrazine with a series of norbornene derivatives was studied with quantum mechanical calculations at the M06-2X/6-311+G(d,p) level of theory. The theoretical predictions were confirmed with the experimental data and analyzed with the use of the distortion/interaction model. The obtained results will help in obtaining a better understanding of the factors that affect the relative cycloaddition rates of norbornenes with tetrazines, which are crucial for selectively tuning their efficacy.

Asymmetric Michael Addition in Synthesis of ß-Substituted GABA Derivatives.

γ-Aminobutyric acid (GABA) represents one of the most prolific structural units widely used in the design of modern pharmaceuticals. For example, ß-substituted GABA derivatives are found in numerous neurological drugs, such as baclofen, phenibut, tolibut, pregabalin, phenylpiracetam, brivaracetam, and rolipram, to mention just a few. In this review, we critically discuss the literature data reported on the preparation of substituted GABA derivatives using the Michael addition reaction as a key synthetic transformation. Special attention is paid to asymmetric methods featuring synthetically useful stereochemical outcomes and operational simplicity.

Intramolecular rhodium-catalysed [2 + 2 + 2] cycloaddition of linear chiral N-bridged triynes: straightforward access to fused tetrahydroisoquinoline core.

A route for the preparation of merged symmetrical tetrahydroisoquinolines with central chirality through a rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition involving enantiopure triynes as substrates is described. The results show that linear triynes lacking a 3-atom tether can undergo efficient cyclisation. The N-tethered 1,7,13-triynes used in our approach were easily prepared from readily accessible chiral homopropargyl amides, the basic building blocks in our approach, which were efficiently obtained by diastereoselective addition of propargyl magnesium bromide to Ellman imines. Additional substitution at the benzene rings could be attained when substituted triynes at the terminal triple bonds were employed, giving access to more complex tetrahydroisoquinolines after the rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition. Among the different transition-metal catalysts, the Wilkinson complex (RhCl(PPh3)3) afforded higher yields in the cyclisation of linear triynes; however, triynes bearing a Br substituent at the terminal positions underwent the cyclisation more efficiently in the presence of [RhCl(CO)2]2.

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes.

Incorporation of fluorine into organic molecules is a well-established strategy in the design of advanced materials, agrochemicals, and pharmaceuticals. Among numerous modern synthetic approaches, functionalization of unsaturated bonds with simultaneous addition of trifluoromethyl group along with other substituents is currently one of the most attractive methods undergoing wide-ranging development. In this review article, we discuss the most significant contributions made in this area during the last decade (2012-2021). The reactions reviewed in this work include chloro-, bromo-, iodo-, fluoro- and cyano-trifluoromethylation of alkenes and alkynes.

On the Stability and Formation of Pillar[n]arenes: a DFT Study.

The increased use of both pillar[5]arenes and pillar[6]arenes, stimulated by increasingly efficient syntheses of both, has brought forward the question as to what drives the intermediates in this Friedel-Crafts ring formation to form a pillar[5]arene, a pillar[6]arene, or any other sized macrocycle. This study sets out to answer this question by studying both the thermodynamics and kinetics involved in the absence and presence of templating solvents using high-end wB97XD/6-311G(2p,2d) DFT calculations.

Proton Exchange Membrane Fuel Cells (PEMFCs): Advances and Challenges.

The study of the electrochemical catalyst conversion of renewable electricity and carbon oxides into chemical fuels attracts a great deal of attention by different researchers. The main role of this process is in mitigating the worldwide energy crisis through a closed technological carbon cycle, where chemical fuels, such as hydrogen, are stored and reconverted to electricity via electrochemical reaction processes in fuel cells. The scientific community focuses its efforts on the development of high-performance polymeric membranes together with nanomaterials with high catalytic activity and stability in order to reduce the platinum group metal applied as a cathode to build stacks of proton exchange membrane fuel cells (PEMFCs) to work at low and moderate temperatures. The design of new conductive membranes and nanoparticles (NPs) whose morphology directly affects their catalytic properties is of utmost importance. Nanoparticle morphologies, like cubes, octahedrons, icosahedrons, bipyramids, plates, and polyhedrons, among others, are widely studied for catalysis applications. The recent progress around the high catalytic activity has focused on the stabilizing agents and their potential impact on nanomaterial synthesis to induce changes in the morphology of NPs.

Unveiling anion-induced folding in tripodal imidazolium receptors by ion-mobility mass spectrometry.

The anion-induced folding of tripodal imidazolium receptors has been investigated by NMR spectroscopy, electrospray ionization ion mobility mass spectrometry and DFT calculations. Such folding can be switched by anion release upon collision induced dissociation.