Lanthanide SMMs Based on Belt Macrocycles: Recent Advances and General Trends

Enhancement of axial magnetic anisotropy is the central objective to push forward the performance of Single-Molecule Magnet (SMM) complexes. In the case of mononuclear lanthanide complexes, the chemical environment around the paramagnetic ion must be tuned to place strongly interacting ligands along either the axial positions or the equatorial plane, depending on the oblate or prolate preference of the selected lanthanide. One classical strategy to achieve a precise chemical environment for a metal centre is using highly structured, chelating ligands. A natural approach for axial-equatorial control is the employment of macrocycles acting in a belt conformation, providing the equatorial coordination environment, and leaving room for axial ligands. In this review, we present a survey of SMMs based on the macrocycle belt motif. Literature systems are divided in three families (crown ether, Schiff-base and metallacrown) and their general properties in terms of structural stability and SMM performance are briefly discussed.     

Versatile Near-Infrared Super-Resolution Imaging of Amyloid Fibrils with the Fluorogenic Probe CRANAD-2

CRANAD-2 is a fluorogenic curcumin derivative used for near-infrared detection and imaging in vivo of amyloid aggregates, which are involved in neurodegenerative diseases. We explore the performance of CRANAD-2 in two super-resolution imaging techniques, namely stimulated emission depletion (STED) and single-molecule localization microscopy (SMLM), with markedly different fluorophore requirements. By conveniently adapting the concentration of CRANAD-2, which transiently binds to amyloid fibrils, we show that it performs well in both techniques, achieving a resolution in the range of 45–55 nm. Correlation of SMLM with atomic force microscopy (AFM) validates the resolution of fine features in the reconstructed super-resolved image. The good performance and versatility of CRANAD-2 provides a powerful tool for near-infrared nanoscopic imaging of amyloids in vitro and in vivo.     

Synthesis of Highly Substituted γ‐Butyrolactones by a Gold‐Catalyzed Cascade Reaction of Benzyl Esters

Easily accessible benzylic esters of 3‐butynoic acids in a gold‐catalyzed cyclization/rearrangement cascade reaction provided 3‐propargyl γ‐butyrolactones with the alkene and the carbonyl group not being conjugated. Crossover experiments showed that the formation of the new C?C bond is an intermolecular process. Initially propargylic–benzylic esters were used, but alkyl‐substituted benzylic esters worked equally well. In the case of the propargylic–benzylic products, a simple treatment of the products with aluminum oxide initiated a twofold tautomerization to the allenyl‐substituted γ‐butyrolactones with conjugation of the carbonyl group, the olefin, and the allene. The synthetic sequence can be conducted stepwise or as a one‐pot cascade reaction with similar yields. Even in the presence of the gold catalyst the new allene remains intact.     

Influence of Polarity and Activation Energy in Microwave–Assisted Organic Synthesis (MAOS)

The aim of this work was to determine the parameters that have decisive roles in microwave-assisted reactions and to develop a model, using computational chemistry, to predict a priori the type of reactions that can be improved under microwaves. For this purpose, a computational study was carried out on a variety of reactions, which have been reported to be improved under microwave irradiation. This comprises six types of reactions. The outcomes obtained in this study indicate that the most influential parameters are activation energy, enthalpy, and the polarity of all the species that participate. In addition to this, in most cases, slower reacting systems observe a much greater improvement under microwave irradiation. Furthermore, for these reactions, the presence of a polar component in the reaction (solvent, reagent, susceptor, etc.) is necessary for strong coupling with the electromagnetic radiation. We also quantified that an activation energy of 20–30 kcal mol⁻¹ and a polarity (μ) between 7–20 D of the species involved in the process is required to obtain significant improvements under microwave irradiation.     

Pd0‐Catalyzed Intramolecular α‐Arylation of Sulfones: Domino Reactions in the Synthesis of Functionalized Tetrahydroisoquinolines

A new strategy for the synthesis of tetrahydroisoquinolines based on the Pd⁰‐catalyzed intramolecular α‐arylation of sulfones is reported. The combination of this Pd‐catalyzed reaction with intermolecular Michael and aza‐Michael reactions allows the development of two‐ and three‐step domino processes to synthesize diversely functionalized scaffolds from readily available starting materials.     

Experimental and Theoretical Studies on the Rearrangement of 2‐Oxoazepane α,α‐Amino Acids into 2′‐Oxopiperidine β2,3,3‐Amino Acids: An Example of Intramolecular Catalysis

Enantiopure β‐amino acids represent interesting scaffolds for peptidomimetics, foldamers and bioactive compounds. However, the synthesis of highly substituted analogues is still a major challenge. Herein, we describe the spontaneous rearrangement of 4‐carboxy‐2‐oxoazepane α,α‐amino acids to lead to 2′‐oxopiperidine‐containing β^2,3,3‐amino acids, upon basic or acid hydrolysis of the 2‐oxoazepane α,α‐amino acid ester. Under acidic conditions, a totally stereoselective synthetic route has been developed. The reordering process involved the spontaneous breakdown of an amide bond, which typically requires strong conditions, and the formation of a new bond leading to the six‐membered heterocycle. A quantum mechanical study was carried out to obtain insight into the remarkable ease of this rearrangement, which occurs at room temperature, either in solution or upon storage of the 4‐carboxylic acid substituted 2‐oxoazepane derivatives. This theoretical study suggests that the rearrangement process occurs through a concerted mechanism, in which the energy of the transition states can be lowered by the participation of a catalytic water molecule. Interestingly, it also suggested a role for the carboxylic acid at position 4 of the 2‐oxoazepane ring, which facilitates this rearrangement, participating directly in the intramolecular catalysis.