Accelerated Discovery of Energy Transfer-Catalyzed Dearomative Cycloadditions through a Data-Driven Three-Layer Screening Strategy.

Visible-light-mediated energy transfer (EnT) photocatalysis has emerged as a highly appealing strategy for converting planar (hetero)arenes into complex, medicinally relevant, three-dimensional (3D) architectures. Current methodologies for intermolecular dearomative photocycloadditions, however, are restricted to bicyclic (hetero)aromatic systems, while the more abundant monocyclic (hetero)arenes remain vastly underexplored. Accessing the triplet state of the ubiquitous monocyclic (hetero)arenes poses a formidable challenge due to their high triplet energy barriers.

Photochemical Dearomative Vicinal Aminooximation of Heteroarenes with -Nitrosamines.

A photochemical dearomative vicinal aminooximation of heteroarenes with -nitrosamines as bifunctional reagents is reported, enabling the synthesis of heterocyclic scaffolds with amino and oxime functionalities under mild catalyst-free conditions. A wide range of heteroarenes, including indoles and benzofurans, engaged in the reaction, and the bifunctionalized dearomatized products can further undergo diverse transformations to yield a variety of compounds.

Cycloparaazine, a full-azine carbon nanoring.

Cycloparaphenylenes (CPPs) and related carbon nanorings (CNRs) represent iconic molecular entities in molecular nanocarbon science. While theoretical studies predict that the introduction of nitrogen atoms (N-doping) onto CPP frameworks would add a number of fascinating properties, only a handful of partially N-doped carbon nanorings have been synthesized. We herein report the synthesis of a long-awaited cycloparaazine (CPA), where every para-connected aromatic moiety consists of a N-heterocycle, and two other highly N-doped CNRs.

Radical Addition to 2-Allenylaryl Isocyanides for the Preparation of 2,3-Difunctionalized Quinolines.

2-Allenylaryl isocyanides are presented as a novel platform to construct quinolines carrying various substituents in positions 2 and 3 via radical addition cyclization cascades. Carbon-, sulfur-, and tin-centered radicals add to the isonitrile functionality to generate the corresponding imidoyl radicals, which undergo 6--cyclization onto the -allenyl moiety. The newly generated benzylic radicals are either reduced or cyanated.

C-to-N atom swapping and skeletal editing in indoles and benzofurans.

Skeletal editing comprises the structural reorganization of compounds. Such editing can be achieved through atom swapping, atom insertion, atom deletion or reorganization of the compound's backbone structure. Conducted at a late stage in drug development campaigns, skeletal editing enables diversification of an existing pharmacophore, enhancing the efficiency of drug development.

closo-Carboranyl Analogs of β-Arylethylamines: Direct Synthesis from Alkenes via EnT-Catalysis.

closo-Carboranes are icosahedral carbon-boron clusters with unique properties and broad applicability. They particularly stand out in the context of drug development as privileged structural motifs for boron neutron capture therapy (BNCT) and as highly hydrophobic bioisosteres for the rotational volume of phenyl rings. Herein, we unveil the synthesis of N-protected carboranyl analogs of β-arylethylamines-widely found structural motifs in biologically active molecules-via a one-step alkene difunctionalization approach.

Cyclic Bifunctional Reagents Enabling a Strain-Release-Driven Formal [3 + 2] Cycloaddition of 2-Azirines by Cascade Energy Transfer.

The energy transfer (EnT)-catalyzed ring opening and further decarboxylation of isoxazole-5(4)-ones enables the in situ generation of strained 2-azirines. Subsequent selective C(sp)-C(sp) bond cleavage of the azirine intermediate allows a formal [3 + 2] cycloaddition with a wide range of electrophiles, unlocking access to valuable pyrroline-type moieties. Mechanistic experiments in combination with density functional theory (DFT) calculations revealed the unique nature of the EnT-cascade process for the generation and ring opening of the three-membered aza-cycle while providing insight into the regio- and diastereoselectivity of the annulation.

Phenothiazine Sulfoxides as Active Photocatalysts for the Synthesis of γ-Lactones.

-substituted phenothiazines are prominent and highly effective organic photoredox catalysts, particularly known for their strong reducing capabilities. Despite their wide utility, the closely related phenothiazine sulfoxides, which easily form upon oxidation, have been largely overlooked and have not been explored in the context of photocatalysis. Herein, we describe the discovery and application of -phenylphenothiazine sulfoxide as a photocatalyst for the reductive activation of cyclic malonyl peroxides, giving access to complex γ-lactones starting from simple olefins.

Diastereoselective 1,3-nitrooxygenation of bicyclo[1.1.0]butanes.

Cyclobutanes are strained carbocycles found in many drugs and natural products. Herein, we report a diastereoselective 1,3-nitrooxygenation of bicyclo[1.1.

8-Ethynyl-2'-deoxyisoguanosine with two tautomeric forms in the unit cell: crystal structure, packing and Hirshfeld surface analysis.

Isoguanine nucleosides constructed by different heterocyclic skeletons play a significant role in the context of genetic code expansion, as well as for purine-purine base pairing. However, with respect to structure analysis, only limited information is available on this class of nucleosides. In this study, the single-crystal X-ray structure of 8-ethynyl-2'-deoxyisoguanosine, CHNO·CHNO·2HO (1), has been investigated.

Deconjugative Photoisomerization of Cyclic Enones.

The deconjugative isomerization of α,β-unsaturated carbonyl compounds enables regioisomeric products to be forged with simultaneous of alkene reactivity. Although highly enabling, the endergonic nature of the net process coupled with governing regioselectivity outcomes, renders it challenging. Innovations in the positional isomerization of linear species, often by light-triggered activation, have re-energized this area.

Size-Controlled Self-Assembly for Bimodal In Vivo Imaging.

Contrast agents (CAs) are essential in biomedical imaging to aid in the diagnosis and therapy monitoring of disease. However, they are typically restricted to one imaging modality and have fixed properties such as size, shape, toxicity profile, or photophysical characteristics, which hampers a comprehensive view of biological processes. Herein, rationally designed dye assemblies are introduced as a unique CA platform for simultaneous multimodal and multiscale biomedical imaging.

Mechanistic insights into the regiodivergent insertion of bicyclo[1.1.0]butanes towards carbocycle-tethered N-heteroarenes.

Ring scaffolds constitute important sub-structures in nature and across the chemical industries. However, their straight-forward introduction into a target molecule or cross-linkage between cyclic motifs of choice comprise major challenges for methodology development. Herein, the interconnection of two prominent representatives of the 2D and 3D cyclic chemical space-namely N-heteroarenes and unsaturated carbocycles-in the form of hybrid cyclobutane-tethered N-heteroarenes is targeted.

Enantioselective Synthesis of Tetrahydro-1-1,3-methanocarbazoles by Formal (3 + 3)-Cycloaddition Using Bicyclo[1.1.0]butanes.

Asymmetric synthesis presents many challenges, with the selective formation of chiral bridged polyheterocycles being a notable example. Cycloadditions using bicyclo[1.1.

Pyrazinyl-Substituted Aminoazoles as Covalent Inhibitors of Thrombin: Synthesis, Structure, and Anticoagulant Properties.

This study presents a novel series of -acylated 1,2,4-triazol-5-amines and 1-pyrazol-5-amines, featuring a pyrazin-2-yl moiety, developed as covalent inhibitors of thrombin. These compounds demonstrated potent inhibitory activity, with derivatives and achieving IC values as low as 0.7 and 0.

Lewis acid-catalyzed [2π+2σ] cycloaddition of dihydropyridines with bicyclobutanes.

Herein we report a simple BF-catalyzed cycloaddition of dihydropyridines with bicyclobutanes for the expedient synthesis of novel three-dimensional azacycle-fused bicyclo[2.1.1]hexane scaffolds.

A General Three-Component Nozaki-Hiyama-Kishi-Type Reaction Enabled by Delayed Radical-Polar Crossover.

Nozaki-Hiyama-Kishi (NHK) reactions offer a mild approach for the formation of alcohol motifs through radical-polar crossover-based pathways from various radical precursors. However, the application of multicomponent NHK-type reactions, which allow the formation of multiple bonds in a single step, has been largely restricted to bulky alkyl radical precursors, thus limiting their expanded utilization. Herein, we disclose a general three-component NHK-type reaction enabled by delayed radical-polar crossover, which efficiently tolerates a plethora of radical precursors that were previously unavailable.

Solvent-Dependent Divergent Cyclization of Bicyclo[1.1.0]butanes.

Bicyclo[1.1.0]butanes (BCBs) have recently garnered significant research interest as versatile precursors for synthesizing potential [n.

Energy Transfer (EnT) Catalysis of Non-Symmetrical Borylated Dienes: Origin of Reaction Selectivity in Competing EnT Processes.

Energy transfer catalysis (EnT) has had a profound impact on contemporary organic synthesis enabling the construction of higher in energy, complex molecules, via efficient access to the triplet excited state. Despite this, intermolecular reactivity, and the unique possibility to access several reaction pathways via a central triplet diradical has rendered control over reaction outcomes, an intractable challenge. Extended chromophores such as non-symmetrical dienes have the potential to undergo [2+2] cycloaddition, [4+2] cycloaddition or geometric isomerisation, which, in combination with other mechanistic considerations (site- and regioselectivity), results in chemical reactions that are challenging to regulate.

Anomeric Amide-Enabled Alkene-Arene and Alkene-Alkene Aminative Coupling.

Despite the prominence of C-N bond forming cross-coupling reactions as a strategy to assemble molecular fragments, aminative coupling approaches, in which two fragments are assembled directly at the heteroatom, represents a rarely exploited retrosynthetic strategy. Herein, we report the design, synthesis, and implementation of an anomeric amide reagent capable of promoting highly regioselective aminative alkene-arene and alkene-alkene coupling reactions. This transformation follows a sequence of catalyst-free chloroamination, N-deprotection, and formal nitrene functionalization, all in one-pot.

Ring expansion of indene by photoredox-enabled functionalized carbon-atom insertion.

Skeletal editing has received unprecedented attention as an emerging technology for the late-stage manipulation of molecular scaffolds. The direct achievement of functionalized carbon-atom insertion in aromatic rings is challenging. Despite ring-expanding carbon-atom insertion reactions, such as the Ciamician-Dennstedt re-arrangement, being performed for more than 140 years, only a few relevant examples of such transformations have been reported, with these limited to the installation of halogen, ester and phenyl groups.

Formal [2σ + 2σ]-Cycloaddition of Aziridines with Bicyclo[1.1.0]butanes: Access to Enantiopure 2-Azabicyclo[3.1.1]heptane Derivatives.

Saturated nitrogen heterocycles are among the most significant structural components in small-molecule pharmaceuticals. Herein, a protocol for the construction of enantiopure 2-azabicyclo[3.1.

Nitrogen-to-functionalized carbon atom transmutation of pyridine.

The targeted and selective replacement of a single atom in an aromatic system represents a powerful strategy for the rapid interconversion of molecular scaffolds. Herein, we report a pyridine-to-benzene transformation nitrogen-to-carbon skeletal editing. This approach proceeds a sequence of pyridine ring-opening, imine hydrolysis, olefination, electrocyclization, and aromatization to achieve the desired transmutation.

Manipulating the Substituent Sphere of a Bicyclic Silicon(I) Ring Compound Results in Anionic Cubane-Type Clusters and a Tetrahedral Silanide.

The reaction of the bicyclic silicon(I) ring compound Si{N(SiMe)Mes} 1 with strong zwitterionic character and moderate sterical demand of the amido substituents with two equivalents of KC was investigated. This resulted in the unexpected abstraction of two amido substituents from 1 and additionally in dimerization to a dianionic Si cluster compound 2 with four unsubstituted silicon atoms and two [K([18]crown-6)] counter cations. Performing this reaction in the absence of [18]crown-6 results in release of only one amido substituent from 1 and dimerization to a dianionic Si cluster 3 with only two unsubstituted silicon atoms.