Sergio Castillón

This study investigates the (3 + 2) cycloaddition of substituted cyclopropenones with elemental sulfur. Combined experimental and computational results highlight the involvement of reactive sulfur species, such as those generated from KF or sulfide impurities. Oxygen exerts minimal influence, whereas oxidants such as BQ or m-CPBA completely suppress the reaction. DFT calculations challenge conventional S₈-based mechanisms, pointing to an energetically costly process from inactivated S₈. Our results support that the cyclic S₈ molecules of elemental sulfur are inactive toward cyclopropenone reagents. The true reactive species are polysulfide anions, which can be present in different forms (FS_n^-, HS_n^-, or S_n^2-) depending on the additive type and purity of the sulfur source. These species undergo conjugate addition to the least substituted carbon of the cyclopropenone C═C bond, ultimately affording a five-membered heterocycle─1,2-dithiol-3-one─as a single regioisomer, through a ketenethialdehyde and thiet-2-one sequence.

Controlling the selectivity in palladium‐catalyzed telomerization of nonsymmetric dienes represents a challenge as several isomers can be obtained, although the four resulting from the attack of the nucleophile at the terminal carbon atom are the main products. Concerning telomerization of isoprene using amines as nucleophiles, the selectivity for three of these four isomers, tail‐to‐head, head‐to‐head, and tail‐to‐tail (1–3), were previously optimized as a result of solvent (pKa) and ligand control. However, the head‐to‐tail telomer (4) was always obtained in low selectivity. In this paper, we test different Pd catalytic systems with phosphine, phosphite, and phosphoramidite ligands under different solvents and pKa conditions to improve the selectivity for telomers 3 and 4. Results showed that, in the telomerization of isoprene with diethyl amine using non‐protic solvents and phosphite ligands with large cone angle afforded telomer 3 in high yield and selectivity (up to 90% yield and 90% selectivity for 3). Phosphite ligands with small cone angle provided telomer 4 with selectivity of 43% (80% yield), which was raised to 48% (23% yield) with ⁱPr₂NH as nucleophile. The significant effect of residual water on the solvent was quantitatively accessed, and greener solvents were tested as alternative for this reaction.

Stereoselective syntheses of 16 triazole-based 1-deoxysphingosine dual SphK inhibitors incorporating different systematic modifications highlight heptafluoropropyl and guanidinium motifs towards improving SphK2 inhibition.

A general methodology featuring a trifluoromethyl-directed 1,2-trans glycosylation reaction as a key step has been developed to give access to various 2-CF₃-glycoconjugates, including carbohydrate epitopes, amino acids, and lipids.

Ru and Rh nanoparticles catalyze the selective H/D exchange in phosphines using D₂ as the deuterium source. The position of the deuterium incorporation is determined by the structure of the P-based substrates, while activity depends on the nature of the metal, the properties of the stabilizing agents, and the type of the substituent on phosphorus. The appropriate catalyst can thus be selected either for the exclusive H/D exchange in aromatic rings or also for alkyl substituents. The selectivity observed in each case provides relevant information on the coordination mode of the ligand. Density functional theory calculations provide insights into the H/D exchange mechanism and reveal a strong influence of the phosphine structure on the selectivity. The isotope exchange proceeds via C-H bond activation at nanoparticle edges. Phosphines with strong coordination through the phosphorus atom such as PPh₃ or PPh₂Me show preferred deuteration at ortho positions of aromatic rings and at the methyl substituents. This selectivity is observed because the corresponding C-H moieties can interact with the nanoparticle surface while the phosphine is P-coordinated, and the C-H activation results in stable metallacyclic intermediates. For weakly coordinating phosphines such as P(o-tolyl)₃, the interaction with the nanoparticle can occur directly through phosphine substituents, and then, other deuteration patterns are observed.

A series of novel ONO ligands bearing an ionic pendant-armed (hereinafter indicated as ONONu, where Nu corresponds to an anionic nucleophile) were synthesized, characterized, and successfully coordinated to cobalt and manganese precursors. New air-stable cobalt (III) complexes (1–6) and manganese (II) complexes (7 and 8) were obtained and characterized. Single crystal X-ray diffraction analysis of the Co(III) compound 5 confirmed the presence of two quaternized ligands coordinated to the metal and iodide as counterion. These novel complexes were revealed to be active catalysts in the coupling reaction of carbon dioxide and propylene oxide (PO) in different degrees of success. Among these, the manganese complex 8 afforded the best results towards the formation of propylene carbonate (PC) with a productivity of 256 kg PC/(kg cat·h), achieving a TON of 4860.

The introduction of fluoroalkylthioether groups has attracted the attention of the drug-discovery community given the special physicochemical and pharmacokinetic features they confer to bioactive compounds, yet these are often limited to standard SCF₃ and SCF₂H moieties. Herein, two saccharin-based electrophilic reagents have been disclosed for the incorporation of uncommon SCF₂CF₂H and SCF₂CF₃ motifs. Their reactivity performance, multigram-scale preparation, and divergent derivatization have been thoroughly investigated with a variety of nucleophiles, including natural products and pharmaceuticals.

Methods that site‐selectively attach multivalent carbohydrate moieties to proteins can be used to generate homogeneous glycodendriproteins as synthetic functional mimics of glycoproteins. Here, we study aspects of the scope and limitations of some common bioconjugation techniques that can give access to well‐defined glycodendriproteins. A diverse reactive platform was designed via use of thiol‐Michael‐type additions, thiol‐ene reactions, and Cu(I)‐mediated azide‐alkyne cycloadditions from recombinant proteins containing the non‐canonical amino acids dehydroalanine, homoallylglycine, homopropargylglycine, and azidohomoalanine.