Gold-Catalyzed Regioselective Synthesis of Crowded Cyclopentadienes by Migratory Cycloisomerization of Vinylallenes.

We report the regioselective synthesis of silyl-substituted cyclopentadienyl esters through gold-catalyzed migratory cycloisomerization of silyl-substituted vinylallenes. This transformation is proposed to proceed through a perfectly orchestrated sequence of events including Nazarov-like cyclization and several silyl and hydrogen rearrangements. Furthermore, exploiting the multifaceted nature of the gold catalyst, we have also identified suitable conditions for the synthesis of these cyclopentadienes in a more straightforward manner through gold-catalyzed reaction of propargyl esters and alkynylsilanes.

Catalytic cyclopropanation reactions with α-silyl-, germanyl- and stannyl carbenes generated from cyclopropenes.

Silylcyclopropenes are employed as precursors of α-silyl vinyl carbenes and trapped with alkenes. Cyclopropylsilanes were obtained in good yields with ample scope and complete regio- and diastereoselectivity. Stereoretentive protodesilylations enabled access to -1,2-disubstituted cyclopropanes.

Gold-catalysed rearrangement of unconventional cyclopropane-tethered 1,5-enynes.

The synthesis of particular cyclopropane-tethered 1,5-enynes, namely 6-alkynyl-4-alkylidenebicyclo[3.1.0]hex-2-enes, enabled the discovery of unprecedented gold-catalyzed rearrangment to indenes.

Recent progress in the chemistry of 12-membered pyridine-containing tetraazamacrocycles: from synthesis to catalysis.

This article provides an overview (non-comprehensive) of the recent developments regarding pyridine-containing 12-membered tetraazamacrocycles with pyclen or Py2N2 backbones and their metal complexes from 2017 to the present. Firstly, the syntheses of newly described ligands and complexes with relevance to medicine are described. The second part deals with the reactivity of complexes bearing these ligands and their uses in catalysis.

Effect on Rheological Properties and 3D Printability of Biphasic Calcium Phosphate Microporous Particles in Hydrocolloid-Based Hydrogels.

The production of patient-specific bone substitutes with an exact fit through 3D printing is emerging as an alternative to autologous bone grafting. To the success of tissue regeneration, the material characteristics such as porosity, stiffness, and surface topography have a strong influence on the cell-material interaction and require significant attention. Printing a soft hydrocolloid-based hydrogel reinforced with irregularly-shaped microporous biphasic calcium phosphate (BCP) particles (150-500 µm) is an alternative strategy for the acquisition of a complex network with good mechanical properties that could fulfill the needs of cell proliferation and regeneration.

Cationic cyclization reactions with alkyne terminating groups: a useful tool in biomimetic synthesis.

Cyclization reactions through cationic intermediates have become a highly valuable tool in organic synthesis. The use of alkynes as the terminating group in this type of cationic process offers wide synthetic possibilities because this group can serve as a precursor of different functionalities. This article shows relevant examples of cationic cyclization reactions with alkynes as terminating groups with the intention of demonstrating the potential of this type of process, particularly in the context of biomimetic synthesis of natural products.

Gold-Catalyzed Reaction of Propargyl Esters and Alkynylsilanes: Synthesis of Vinylallene Derivatives through a Twofold 1,2-Rearrangement.

The reaction of propargyl esters with alkynylsilanes under gold catalysis provides vinylallene derivatives through consecutive [1,2]-acyloxy/[1,2]-silyl rearrangements. Good yields, full atom-economy, broad substrate scope, easy scale-up and low catalyst loadings are salient features of this novel transformation. Density Functional Theory (DFT) calculations suggest a reaction mechanism involving initial [1,2]-acyloxy rearrangement to generate a gold vinylcarbene intermediate which upon regioselective attack of the alkynylsilane affords a vinyl cation which undergoes a type II-dyotropic rearrangement involving the silyl group and the metal fragment.

Three-dimensional bioprinted cancer models: A powerful platform for investigating tunneling nanotube-like cell structures in complex microenvironments.

Bioprinting technology offers layer-by-layer positioning of cells within 3D space with complexity and a defined architecture. Cancer models based in this biofabrication technique are important tools to achieve representative and realistic in vivo conditions of the tumor microenvironment. Here, we show the development of a proof-of-concept three-dimensional bioprinted cancer model that successfully recapitulates the intercellular communication via the assembly of functional tunneling nanotube (TNT)-like cell projections.

Multicomponent and multicatalytic asymmetric synthesis of furo[2,3-]pyrrole derivatives: further insights into the mode of action of chiral phosphoric acid catalysts.

Multicomponent and multicatalytic reactions are those processes that try to imitate the way the enzymatic machinery transforms simple building blocks into complex products. The development of asymmetric versions of these reactions is a step forward in our dream of mirroring the exquisite selectivity of biological processes. In this context, the present work describes a new reaction for the asymmetric synthesis of furo[2,3-]pyrrole derivatives from simple 3-butynamines, glyoxylic acid and anilines in the presence of a dual catalytic system, formed from a gold complex and a chiral phosphoric acid.

Reactivity of Stabilized Vinyldiazo Compounds toward Alkenyl- and Alkynylsilanes under Gold Catalysis: Regio- and Stereoselective Synthesis of Skipped Dienes and Enynes.

We report the gold-catalyzed reaction of vinyldiazo compounds and alkenylsilanes to produce skipped dienes, which are common structural motifs in an array of bioactive compounds. This carbon-carbon bond-forming transformation proceeds with complete regio- and stereoselectivity with the silyl group serving as a regio- and stereocontrolling element. Likewise, the use of alkynylsilanes as reaction partners yielded skipped enynes resulting from a C(sp)-C(sp) coupling.

Generation of alkoxysulfonyl radicals from chlorosulfates and their intramolecular capture with alkynes to obtain sultones.

An unprecedented radical-mediated reaction of alkyne-containing chlorosulfates to synthesize sultones has been established. The reaction leads to the formation and subsequent capture of alkoxysulfonyl radicals, which are species known for a long time but not studied for synthetic purposes.

Gold(I)-Catalyzed One-Pot and Diastereoselective Synthesis of -2-Silyl-4,5-dihydrofurans from Propargylsilanes and Aldehydes.

A diastereoselective and high-yielding gold-catalyzed synthesis of -2-silyl-4,5-dihydrofurans is described. In addition to a sequential manner, this reaction could be performed in a one-pot procedure from propargylsilanes and aldehydes. A mechanistic proposal for the isomerization step is formulated.

3D printed gummies: Personalized drug dosage in a safe and appealing way.

Obtention of customized dosage forms is one of the main attractions of 3D printing in pharmaceuticals. In this sense, children are one of the groups within the population with a greater need for drug doses adapted to their requirements (age, weight, pathological state…), but most 3D printed oral dosages are solid forms and, therefore, not suitable for them. This work developed patient-tailored medicinal gummies, an alternative oral dosage form with eye-catching appearance and appropriate organoleptic characteristics.

Spiropiperidyl rifabutins: expanded in vitro testing against ESKAPE pathogens and select bacterial biofilms.

The expanded microbiological evaluation of a series of rifastures, novel spiropiperidyl rifamycin derivatives, against clinically relevant ESKAPE bacteria has identified several analogs with promising in vitro bioactivities against antibiotic-resistant strains of Enterococcus faecium and Staphylococcus aureus. Thirteen of the rifastures displayed minimum inhibitory concentrations (MICs) below 1 µg/ml against the methicillin- and vancomycin-resistant forms of S. aureus and E.

Synthesis of Spirocyclic Compounds by a Ring-Expansion/Cationic Cyclization Cascade Reaction of Chlorosulfate Derivatives.

A novel cascade reaction to prepare spirocarbocyclic compounds from chlorosulfate derivatives has been developed. The process involves an unusual thermal elimination of the chlorosulfate moiety, a ring-expansion reaction, and a subsequent cationic cyclization reaction. Despite the relatively complex skeletal rearrangement, the reaction described here is featured by its operational simplicity, being just a thermal process that does not require additional reagents, catalysts, or additives.

Cascade and multicomponent synthesis of structurally diverse 2-(pyrazol-3-yl)pyridines and polysubstituted pyrazoles.

The cascade reaction between N-tosylhydrazones and 2-alkynylpyridines leads to 2-(pyrazol-3-yl)pyridines, important structural motifs in ligands for transition metals and bioactive molecules. When the reaction is conducted with 2,6-diethynylpyridine, the important 2,6-bis(pyrazolyl)pyridines are obtained, featuring the arrangement of tridentate and also pentadentate ligands. A novel three-component version of the reaction has been designed, which involves the use of α-bromo-N-tosylhydrazones, alkynylpyridines and NH-azoles.

Half-sandwich ruthenium(ii) complexes with tethered arene-phosphinite ligands: synthesis, structure and application in catalytic cross dehydrogenative coupling reactions of silanes and alcohols.

The preparation of the tethered arene-ruthenium(ii) complexes [RuCl{η:κ(P)-CH(CH)OPR}] (R = Ph, n = 1 (9a), 2 (9b), 3 (9c); R = Pr, n = 1 (10a), 2 (10b), 3 (10c)) from the corresponding phosphinite ligands RPO(CH)Ph (R = Ph, n = 1 (1a), 2 (1b), 3 (1c); R = Pr, n = 1 (2a), 2 (2b), 3 (2c)) is presented. Thus, in a first step, the treatment at room temperature of tetrahydrofuran solutions of dimers [{RuCl(μ-Cl)(η-arene)}] (arene = p-cymene (3), benzene (4)) with 1-2a-c led to the clean formation of the corresponding mononuclear derivatives [RuCl(η-p-cymene){RPO(CH)Ph}] (5-6a-c) and [RuCl(η-benzene){RPO(CH)Ph}] (7-8a-c), which were isolated in 66-99% yield. The subsequent heating of 1,2-dichloroethane solutions of these compounds at 120 °C allowed the exchange of the coordinated arene.

Synthesis of Sultones from Chlorosulfates by a Complex Cascade Reaction Occurring under Mild Thermal Conditions.

Chlorosulfate derivatives are interesting reagents that have been traditionally used to get other sulfur-containing compounds by formal nucleophilic substitution of the chlorine atom. This work describes a different mode of reactivity of alkyne-containing chlorosulfates to get sultones, the sulfur analogues of lactones. The complex skeletal rearrangement observed in this transformation is comparable to those intricate processes promoted or catalyzed by organometallic compounds.

Oxyacylation of Iodoalkynes: Gold(I)-Catalyzed Expeditious Access to Benzofurans.

(Acetonitrile)[1,3-bis(2,6-diisopropylphenyl)-imidazole-2-ylidene] gold(I) catalyzes the cycloisomerization of 2-(iodoethynyl)aryl esters to give 3-iodo-2-acyl benzofurans. This catalytic transformation is the result of an unprecedented selective synthetic event, which comprises a [1,2]-iodine shift, a C-O ring-closure step, and a C-C bond-formation that installs the ketone functionality into the new ring. Experimental evidence supports the involvement of a β-iodo-substituted gold vinylidene as the intermediate species.

Propargylsilanes as Reagents for Synergistic Gold(I)-Catalyzed Propargylation of Carbonyl Compounds: Isolation and Characterization of σ-Gold(I) Allenyl Intermediates.

Reported herein is the isolation and characterization, for the first time, of a σ-gold allenyl complex as an intermediate in gold catalysis. This intermediate was captured during the study of a novel gold(I)-catalyzed propargylation of carbonyl compounds with propargylsilanes. Notably, the gold-catalyzed propargylation reaction, which proceeds with aldehydes and ketones, can be driven to the formation of either homopropargyl silyl ethers or the in situ synthesis of corresponding 2-silyl-4,5-dihydrofurans.

Regiodivergent Electrophilic Cyclizations of Alkynylcyclobutanes for the Synthesis of Cyclobutane-Fused O-Heterocycles.

Cyclobutane-fused dihydropyrans and methylenetetrahydrofurans are highly interesting cores found in numerous natural products. Both these cores are selectively prepared from a common alkynylcyclobutane precursor bearing an appended hydroxyl group herein. Thus, cyclobutane-fused dihydropyrans can be obtained by a selective 6-endo-dig iodocyclization, whereas gold-catalyzed 5-exo-dig cycloisomerization provides a bicyclic core containing a methylenetetrahydrofuran moiety as major product.

Divergent Multistep Continuous Synthetic Transformations of Allylic Alcohol Enabled by Catalysts Immobilized in Ionic Liquid Phases.

Two individual catalytic platforms (metal- and organo-catalyzed) based on the use of an ionic liquid phase were successfully integrated for the synthesis of α-cyano-amine and cyanohydrin trimethylsilyl ethers from allylic alcohol. The right combination of continuous flow processes enabled access to the divergent preparation of two alternative and interesting intermediate compounds from the same starting material.

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors.

The synthesis of 1,2-divinylcyclopropanes by the reaction of cyclopropenes with 1,3-dienes is reported. The process relies on the ability of ZnCl or [Rh(OAc)] to generate metal-vinyl carbene intermediates from cyclopropenes, which effect cyclopropanation of 1,3-dienes. Most of the reactions proceeded in reasonable yields while the diastereoselectivity strongly depends on the structure of the diene.

Unusual Reactivity of Isoquinolinones Generated by Silver-Catalyzed Cycloisomerizations of Imines Derived from ortho-Alkynylsalicylaldehydes.

8-Isoquinolinones derived from a silver-catalyzed cycloisomerization of in situ formed ortho-alkynylsalicylaldimines react with 1 equiv of acetylenedicarboxylate derivatives to give pyrano[2,3,4- ij]isoquinolines through a [4 + 2]-cycloaddition reaction. When 2 equiv of the alkyne are used, structurally complex benzo[ de]chromenes are obtained through an intricate cascade process comprising unusual formal [4 + 2]- and [2 + 2]-cycloadditions followed by several ring-opening and ring-closing processes.