Beilstein Journal of Organic Chemistry最新文献

Axial chirality is present in a variety of naturally occurring compounds, and is becoming increasingly relevant also in medicine. Many axially chiral compounds are important as catalysts in asymmetric catalysis or have chiroptical properties. This review overviews recent progress in the synthesis of axially chiral compounds via asymmetric organocatalysis. Atroposelective organocatalytic reactions are discussed according to the dominant catalyst activation mode. For covalent organocatalysis, the typical enamine and iminium modes are presented, followed by N-heterocyclic carbene-catalyzed reactions. The bulk of the review is devoted to non-covalent activation, where chiral Brønsted acids feature as the most prolific catalytic structure. The last part of the article discusses hydrogen-bond-donating catalysts and other catalyst motifs such as phase-transfer catalysts.

Polysarcosine emerges as a promising alternative to polyethylene glycol (PEG) in biomedical applications, boasting advantages in biocompatibility and degradability. While the self-assembly behavior of block copolymers containing polysarcosine-containing polymers has been reported, their potential for shape transformation remains largely untapped, limiting their versatility across various applications. In this study, we present a comprehensive methodology for synthesizing, self-assembling, and transforming polysarcosine-poly(benzyl glutamate) block copolymers, resulting in the formation of bowl-shaped vesicles, disks, and stomatocytes. Under ambient conditions, the shape transformation is restricted to bowl-shaped vesicles due to the membrane's flexibility and permeability. However, dehydration of the polysarcosine broadens the possibilities for shape transformation. These novel structures exhibit asymmetry and possess the capability to encapsulate smaller structures, thereby broadening their potential applications in drug delivery and nanotechnology. Our findings shed light on the unique capabilities of polysarcosine-based polymers, paving the way for further exploration and harnessing of their distinctive properties in biomedical research.

Phenethylamines and phenylisopropylamines of scientific relevance can be prepared with a NaBH₄/CuCl₂ system in 10 to 30 minutes via reduction of substituted β-nitrostyrenes. This one-pot procedure allows the quick isolation of substituted β-nitrostyrene scaffolds with 62-83% yield under mild conditions, without the need for special precautions, inert atmosphere, and time-consuming purification techniques.

The discovery of the optimal conditions for chemical reactions is a labor-intensive, time-consuming task that requires exploring a high-dimensional parametric space. Historically, the optimization of chemical reactions has been performed by manual experimentation guided by human intuition and through the design of experiments where reaction variables are modified one at a time to find the optimal conditions for a specific reaction outcome. Recently, a paradigm change in chemical reaction optimization has been enabled by advances in lab automation and the introduction of machine learning algorithms. Therein, multiple reaction variables can be synchronously optimized to obtain the optimal reaction conditions, requiring a shorter experimentation time and minimal human intervention. Herein, we review the currently used state-of-the-art high-throughput automated chemical reaction platforms and machine learning algorithms that drive the optimization of chemical reactions, highlighting the limitations and future opportunities of this new field of research.

The polycyclic skeleton of tris(4,5-dehydro-2,3:6,7-dibenzotropone) is a key structural fragment in carbon schwarzites, a theoretical form of negatively curved carbon allotrope. This report presents a new synthesis of this compound using a Ni-mediated Yamamoto coupling reaction and structural analysis of it with X-ray crystallography. Interestingly, it is observed that tris(4,5-dehydro-2,3:6,7-dibenzotropone) crystallized from its solution in hexane resulting in colorless and yellow crystal polymorphs, where it adopts conformations of approximate C _s and C ₂ symmetry, respectively. Furthermore, expanding its π-skeleton through the Barton-Kellogg and Scholl reactions led to the successful synthesis of a curved polycyclic arene containing three heptagons and two pentagons.

Acenaphthylene-fused heteroarenes with a variety of five- and six-membered heterocycles such as thiophene, furan, benzofuran, pyrazole, pyridine and pyrimidine were synthesized via an efficient Pd-catalyzed reaction cascade in good to high yields (45-90%). This cascade involves an initial Suzuki-Miyaura cross-coupling reaction between 1,8-dihalonaphthalenes and heteroarylboronic acids or esters, followed by an intramolecular C-H arylation under the same conditions to yield the final heterocyclic fluoranthene analogues. The method was further employed to access polyoxygenated benzo[j]fluoranthenes, which are all structurally relevant to benzo[j]fluoranthene-based fungal natural products. The effectiveness of our strategy was demonstrated via a concise, four-step synthesis of the tetramethoxybenzo[j]fluoranthene derivative 18, which represents a formal total synthesis of the fungal natural product bulgarein.

The reactivity of our recently disclosed hypervalent iodine reagents (HIRs) bearing a benzylamine with in situ-generated sulfenate salts was investigated. Under the studied conditions sulfonamides have been obtained in up to 52% yield. This reaction has been extended to a variety of HIRs and sulfenate salts to explore the different reactivity of these new reagents. A plausible mechanism is proposed, suggesting a possible radical pathway.

The rising popularity of bioconjugate therapeutics has led to growing interest in late-stage functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available building blocks like organohalides can be converted into alkyl radicals by means of photoinduced silane-mediated halogen-atom transfer (XAT) to offer a mild and straightforward methodology of alkylation. In this research, we present a metal-free strategy for the photochemical alkylation of dehydroalanine derivatives. Upon abstraction of a hydride from tris(trimethylsilyl)silane (TTMS) by an excited benzophenone derivative, the formed silane radical can undergo a XAT with an alkyl bromide to generate an alkyl radical. Consequently, the alkyl radical undergoes a Giese-type reaction with the Dha derivative, forming a new C(sp³)-C(sp³) bond. The reaction can be performed in a phosphate-buffered saline (PBS) solution and shows post-functionalization prospects through pathways involving classical peptide chemistry.

The high potential of non-covalent arene-fluoroarene intermolecular interactions in the design of liquid crystals lies in their ability to strongly promote self-assembly, improve the order and stability of the supramolecular mesophases, and enable tuneability of the optical and electronic properties, which can potentially be exploited for advanced applications in display technologies, photonic devices, sensors, and organic electronics. We recently successfully reported the straightforward synthesis of several mesogens containing four lateral aliphatic chains and derived from the classical triphenylene core self-assembling in columnar mesophases based on this paradigm. These mesogenic compounds were simply obtained in good yields by the nucleophilic substitution (S_NFAr) of various types of commercially available fluoroarenes with the electrophilic organolithium derivatives 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl (2Li-BP n). In a continuation of this study, aiming at testing the limits of the reaction and providing a large diversity of structures, a structurally related series of compounds is reported here, namely 1,2,4-trifluoro-6,7,10,11-tetraalkoxy-3-(perfluorophenyl)triphenylenes (F n). They were obtained by reacting the above mentioned 2,2'-dilithiobiphenyl derivatives with decafluorobiphenyl, C₆F₅-C₆F₅. These compounds differ from the previously reported series, 1,2,4-trifluoro-6,7,10,11-tetraalkoxy-3-aryltriphenylenes (PH n), solely by the substitution of the terminal phenyl ring with a pentafluorophenyl ring. Thus, as expected, they display a Col_hex mesophase over large temperature ranges, with only small differences in the mesophase stability and transition temperatures. Furthermore, the presence of the terminal fluorophenyl group enables a subsequent second annulation, yielding a new series of extended polyaromatic mesomorphic compounds, i.e., 1,1',3,3',4,4'-hexafluoro-6,6',7,7',10,10',11,11'-octaalkoxy-2,2'-bitriphenylene (G nm) which were found to display a Col_rec mesophase. The specific nucleophilic substitution patterns of the F n derivatives and the antiparallel stacking mode into columnar structures stabilized by arene-perfluoroarene intermolecular interactions were confirmed by the single-crystal structure of the alkoxy-free side chain analog, i.e., 1,2,4-trifluoro-3-(perfluorophenyl)triphenylene (F). UV-vis absorption and fluorescence emission spectroscopies reveal green photoluminescence with fluorescence quantum yields of up to 33% for the F n derivatives. The J-aggregation for the inner fluorine-substituted dimers G nm is energetically and stereoelectronically more favorable and G66 exhibits thin-film fluorescence with a large red-shift of the emission peak.