ABSTRACT The abrupt reorganization of the electronic configuration of spin‐crossover (SCO) compounds upon the transition from the low‐spin (LS) to the high‐spin (HS) state leads to significant changes in their structural, optical, and magnetic properties. As spin‐transitions can be triggered by a variety of external stimuli such as variations in temperature, pressure, or through light irradiation, these systems have attracted considerable attention for the design of multifunctional and stimuli‐responsive molecular materials. In this context, the synergistic coupling of SCO and luminescent properties holds great promise for the development of molecular spintronic devices capable of correlating the luminescence with an external perturbation, or of probing the magnetic state of the metal center through variations in emission intensity. This contribution provides a comprehensive overview of the field of luminescent SCO materials, with particular emphasis on systems that exhibit a genuine interplay between the two properties, both in materials and at the molecular level.

ABSTRACT The strategic generation of α‐fluoro radicals underpins powerful routes to fluorine‐rich architectures of high value in molecular design. Here, we disclose an operationally simple, catalyst‐free method for the photochemical activation of α‐halo fluorinated precursors using visible light and two inexpensive additives, sodium iodide and 2,6‐lutidine. This mild protocol enables in‐situ halide exchange and subsequent homolytic C–I bond scission to generate α‐fluoro radicals under ambient conditions. The generality of the platform is demonstrated across esters, sulphones, and nitriles, facilitating intermolecular coupling with alkenes, heteroarenes, and propellanes to access diverse fluorinated scaffolds. Mechanistic studies support the formation of a weak electron donor–acceptor complex that mediates bond activation, while the benign conditions permit merger with energy transfer catalysis for stereodivergent product formation.

ABSTRACT To celebrate the 125th anniversary of the Swiss Chemical Society, we present a review and perspective to highlight the recent research in breath analysis that has been conducted in Switzerland, with a particular focus on secondary electrospray ionization mass spectrometry (SESI‐HR‐MS). We focus on breath analysis research from 2019, the publication year of the last major review. We highlight where improvements are needed in experimental and clinical protocols and outline the current gaps in the field, to support the implementation of breath analysis into the clinical domain.

ABSTRACT C─H bond functionalization has appeared as one of the most efficient tools for building complex molecular scaffolds. Despite growing interest in remote C─H bond functionalization, achieving the distal site selectivity is highly challenging. Traditional “end‐on template” based methods usually require additional steps for installing and removing long directing templates, and often rely on expensive transition metals, which makes the process less sustainable. In this essay, an alternative concept known as “complementary catalysis” is discussed to achieve remote C─H arylation without the use of large templates. This approach requires a small directing group to control regioselectivity under mild conditions without any externally added ligands or activators. Most importantly, it paves a more sustainable route by improving the atom and step economy.

ABSTRACT This perspective highlights a distinctive class of symmetric molecular architectures, methylene‐bridged calixarene polyhedral, that, despite long‐standing theoretical interest, have not yet been synthesized. It consolidates all previously proposed members of this family, introduces a new representative, and assesses their synthetic feasibility through computational strain analyses. Five polyhedra were examined: methanospherophane, Cram's prototype carcerand, two augmented prismatic dimers, and the newly postulated calix[5]arene‐based icosidodecahedron. Homodesmotic hydrogenolysis reactions were employed to estimate strain energies, complemented by angular deviation analysis from ideal collinearity (180°). Among all candidates, the methanospherophane emerged as the only nearly strain‐free structure, while Cram's carcerand and the icosidodecahedron exhibited significant strain. The prismatic dimers showed intermediate stability. Methanospherophane thus emerges as the leading candidate for the first successful synthesis, potentially opening the door to this fascinating class of methylene‐bridged calixarene polyhedra.

ABSTRACT The directing group free alkenylation of indoles is underdeveloped and a highly desirable transformation in the field of π‐excessive heterocycle chemistry. In this study to access C2‐alkenylindoles, 3‐chloroindoles were utilized as C2‐indolyl electrophiles toward allyl boronic acid nucleophiles. This approach provides access to NH‐free C2‐alkenylindoles bearing no substitution at their C3‐position. The reversed‐allylated products underwent in situ isomerization under the influence of Lewis acidic allyl boronic acid, eventually delivering the desired 2‐alkenyl indoles. A range of electronically different indoles took part in this reaction, providing products in good yields, and diastereoselectivities vary depending on the steric nature of allyl moieties. Synthesis of carbazole‐based alkaloids hyellazole and 6‐chlorohyellazole demonstrated the synthetic utility of this one‐pot cascade protocol.

ABSTRACT ( S )‐Pyrrolidin‐3‐ol and ( R )‐3‐fluoropyrrolidine are key intermediates in Roche's drug candidates, Vicasinabin and Mosperafenib. Sourcing these compounds proved challenging, particularly for ( R )‐3‐fluoropyrrolidine, for which a quality of ≥ 99.8% purity and ≥ 99.95% chiral purity along with stringent impurity control was required. To address these challenges, a scalable process for the manufacturing of ( R )‐3‐fluoropyrrolidine hydrochloride salt using a stereoselective S N 2 reaction was developed based on prior work on ( S )‐pyrrolidin‐3‐ol synthesis. The process was successfully scaled up in the pilot plant, enabling the production of a total of 798 kg of high‐purity ( R )‐3‐fluoropyrrolidine hydrochloride salt to support the clinical development of Mosperafenib. Key steps included “pump‐hydrogenation” to improve the yield of ( S )‐pyrrolidin‐3‐ol from the cost‐effective starting material ( S )‐4‐chloro‐3‐hydroxybutyronitrile. This was followed by in situ Boc‐protection, and a two‐step stereospecific fluorination involving mesylation and nucleophilic substitution with potassium fluoride. Finally, Boc‐deprotection using HCl followed by recrystallization from n ‐BuOH and water, ensured efficient removal of impurities including the undesired enantiomer. This streamlined approach addressed supply challenges, ensured consistent quality, and established an efficient, robust manufacturing process for ( R )‐3‐fluoropyrrolidine hydrochloride.

ABSTRACT Reactions of the Lewis acidic, cationic bismuth compound [BiMe 2 (SbF 6 )] ( 1 ) with the spin trap α‐phenyl‐ N ‐ tert butyl‐nitrone (PBN) yield simple Lewis acid/base adducts [BiMe 2 (PBN)(SbF 6 )] ( 2 ) and [BiMe 2 (PBN) 2 ][SbF 6 ] ( 3 ). Such adducts have, for the first time, been fully characterized for the frequently used spin trap PBN. The ability of 2 and 3 to release PBN‐trapped methyl radicals under thermal conditions is investigated. This is compared to the ability of a small series of simple neutral organobismuth compounds BiR 3 (R = Me, n Bu, i Pr, t Bu, CF 3 ) and one mixed aryl/alkyl‐substituted bismuth complex to transfer carbon‐based radicals to PBN. Applied analytical techniques include NMR spectroscopy, elemental analysis, mass spectrometry, single‐crystal X‐ray diffraction analysis, and EPR spectroscopy.

ABSTRACT The C(sp 3 )─H allylation reaction using allyl phenyl sulfone was affected by persulfate anion (PS) under microwave (MW) irradiation. The MW/PS protocol has been found to be applicable to a wide variety of C(sp 3 )─H bonds of ethers, alkanes, aldehydes, and ketones, leading to the C(sp 3 )─H allylated compounds. The origin of the site‐selectivity in the allylation of cyclohexanone is discussed in terms of the polarity‐governed transition states for the radical cascades involving hydrogen atom transfer (HAT), radical addition, and β‐elimination.