Beilstein Journal of Organic Chemistry最新文献

Azobenzene-based solar thermal fuels have undergone significant advancements over the past four decades, emerging as a promising technology for light-to-thermal energy conversion. While these materials exhibit considerable development potential, critical challenges remain that hinder their practical implementation. In this perspective, we systematically analyze four representative azobenzene-based solar thermal fuel systems including nanocarbon-hybrid, conjugated polymer, linear polymer, and small-molecule derivative formulations to trace their developmental trajectories and identify key limitations. Through this comparative analysis, we aim to clarify the current state of azobenzene-based solar thermal fuels, while mapping strategic pathways for future technological advancements in this rapidly evolving research field.

Switchable multicomponent reactions involving 3-substituted-5-amino-1,2,4-triazoles, pyruvic acid, and salicylaldehydes were studied under different conditions. Upon conventional heating, benzotriazolooxadiazocine-5-carboxylic acids were formed in the three-component reactions as single reaction products. Upon ultrasonic activation or mechanical stirring at room temperature, the multicomponent reaction of the same starting materials led to the formation of only tetrahydrotriazolopyrimidine derivatives.

A small library of bis- and tetraamides was synthesized by the Ugi reaction with α-ketoglutaric acid, tert-butyl isocyanide, aromatic aldehydes, and aromatic amines. When o-azidoanilines were used, azidated peptidomimetics were obtained, the post-cyclization of which by the aza-Wittig reaction yielded a series of substituted 3-(3-oxo-3,4-dihydroquinoxalin-2-yl)propanoic acids containing a pharmacophore quinoxalinone moiety. The tandem Ugi/aza-Wittig combination was also carried out in a one-pot procedure without isolation of the intermediate.

Photochemical denitrogenation reactions of bicyclic azoalkanes produce strained bicyclic compounds of interest to synthetic organic chemists. We report a computational study on the mechanism of diazabicyclo[2.2.1]heptenes to address long standing mechanistic questions. Indeed, the mechanism of these reactions has been disputed for over six decades. We employed non-adiabatic molecular dynamics (NAMD) simulations combined with state-of-the-art multireference quantum mechanical calculations to understand the photophysical properties and mechanisms of these diazabicyclo[2.2.1]heptenes. The energetically accessible lowest excitations are n _NN(σ_CN) → π* and range from 3.94-3.97 eV. From the >292 trajectories, the reaction proceeds through a dynamically concerted but asynchronous denitrogenation reaction. One σ_CN bond breaks along the S₁ surface; the other σ_CN breaks after hopping to the S₀. We identified two clusters of S₁/S₀ surface hopping points from these trajectories. In the first cluster, the methylene bridge is fully inverted relative to the reactant geometry. In the second cluster, the inversion is only partial, with one of the carbon atoms in the methylene bridge inverted relative to the reactant. We identified each cluster's corresponding minimum energy conical intersection (MECI), indicating at least two possible S₁/S₀-MECIs. Our dynamics simulations illustrate that inversion begins in the excited state immediately after the first σ_CN bond breaks. This inversion is driven by the atomic momenta acquired after the bond breaks. These dynamical effects promote the formation of the inverted housane, thereby explaining the observed selectivities. A minority of trajectories undergo thermal conversion in the ground state, producing the minor retained housane product from inverted housane/diradical.

Despite the rapid development of asymmetric synthesis, judging the remoteness of stereocontrol has remained an intuitive and empirical practice, particularly for reactions that create non-central chirality. We put forward a stereocontrol connectivity index to parameterize asymmetric reactions according to the bond connectivity relationships between the prochiral stereogenic elements, the reactive sites, and the stereochemical-defining substituents. The indices can be generated based on analysis of the chemical structures of the starting materials and products, without mechanistic insights of the transformation. Representative examples of reactions that establish point chirality, axial chirality, planar chirality, and "inherent chirality" are illustrated using the stereocontrol connectivity index produced following a unified 3-step process. Application of such stereochemical classification could facilitate the development of new synthetic methodologies and catalyst systems to construct diverse chiral molecules.

A novel copper-catalyzed arylation strategy for propargylsilanes utilizing diaryl-λ³-iodanes has been developed, enabling a cascade sequence involving 1,2-silyl migration and heterocyclization. The β-silicon effect facilitates the formation of stabilized allyl cation intermediates that undergo regioselective trapping by internal O- and N-nucleophiles furnishing functionalized heterocycles. This method provides access to tetrahydrofuran or pyrrolidine frameworks, each bearing a trifunctionalized (E)-configured vinyl side chain. The use of a shorter linker provides entry to 1,2,3,6-tetrahydropyridines. Additionally, in the absence of internal nucleophiles, this methodology yields aryl-substituted 1,3-dienes. This work introduces a palladium-free, single-step alternative to multistep heterocycle construction from propargylsilanes and highlights the synthetic potential of iodane-mediated carbofunctionalization under copper catalysis.

Light-mediated methodologies for the reduction of acylazolium species generated during N-heterocyclic carbene (NHC)-catalyzed reactions have been developed. Employing the simple amine, DIPEA, as the terminal reductant, products resulting from overall 2-electron or 4-electron-reduction processes could be obtained using either a photocatalytic approach under blue light irradiation or directly under UV-A light irradiation without an additional photocatalyst. Moreover, under the same photocatalyst-free conditions, UV-A-light-mediated reduction could be achieved using triethylsilane as the only reductant with subsequent desilylation and NHC elimination with fluoride delivering the corresponding aldehyde product.

Prostaglandin D₂ (PGD₂) is a key pathophysiological mediator in many human diseases and biological pathways. Tricyclic prostaglandin D₂ metabolite methyl ester (tricyclic-PGDM methyl ester), the major urinary metabolite of PGD₂, can be used as a clinical indicator for PGD₂ overproduction. However, the limited amount of tricyclic-PGDM methyl ester available has prevented its practical use, and synthesis methods for tricyclic-PGDM methyl ester are required. Based on the utilization of oxidative radical cyclization for the stereoselective construction of the cyclopentanol subunit with three consecutive stereocenters, we describe an asymmetric total synthesis of tricyclic-PGDM methyl ester in 9 steps and 8% overall yield.

Enantioselective desymmetrization is employed as a powerful tool for the creation of chiral centers. Within this scope, the enantioselective desymmetrization of prochiral 1,3-diols, which generates chiral centers by enantioselective functionalization of one hydroxy group, offers beneficial procedures for accessing diverse structural motifs. In this review, we highlight a curated compilation of publications, focusing on the applications of enantioselective desymmetrization of prochiral 1,3-diols in the synthesis of natural products and biologically active molecules. Based on the reaction types, three strategies are discussed: enzymatic acylation, transition-metal-catalyzed acylation, and local desymmetrization.

The value of small molecules that chemically modify proteins is increasingly being recognised and utilised in both chemical biology and drug discovery. The discovery of such chemical tools may be enabled by screening diverse sets of reactive probes. Most existing sets of reactive probes are armed with cysteine-directed warheads, a limitation that we sought to address. A connective synthesis was developed in which α-diazoamide substrates, armed with a S(VI) warhead, were reacted with diverse co-substrates. A high-throughput approach was used to identify promising substrate/co-substrate/catalyst combinations which were then prioritised for purification by mass-directed HPLC to yield a total of thirty reactive probes. The structural diversity of the probe set was increased by the multiplicity of reaction types between rhodium carbenoids and the many different co-substrate classes, and the catalyst-driven selectivity between these pathways. The probes were screened for activity against Trypanosma brucei, and four probes with promising anti-trypanosomal activity were identified. Remarkably, the synthetic approach was compatible with building blocks bearing three different S(VI) warheads, enabling the direct connective synthesis of diverse reactive probes armed with non-cysteine-directed warheads. Reactive probes that are synthetically accessible using our approach may be of value in the discovery of small molecule modifiers for investigating and engineering proteins.