Organic Chemistry Frontiers最新文献

This study explores the application of modified cysteine in oligopeptides to overcome challenges in amino acid residue modification, with a focus on cysteine. Novel strategies for the functionalization of biomolecules are presented, with mechanistic investigations indicating the involvement of free radical processes, structural substitution, and nucleophilic displacement. Notably, the gram-scale synthesis of modified cysteine is achieved with high yields, highlighting its potential as a novel anti-fungus agent in biomedical and agrochemical research.

The chiral pyrrolo[1,2-a]indole skeleton represents a privileged structural motif in many natural products and pharmaceutical agents. Herein we developed an efficient [3 + 2] annulation of 2-nitrovinylindoles with azlactones via the cascade Michael addition and intramolecular acylation under the catalysis of a bifunctional tertiary amine in combination with DABCO, delivering a wide range of pyrrolo[1,2-a]indoles in good yields with high diastereo- and enantioselectivities. Alternatively, 7-nitrovinylindoles served as 4C synthons to perform enantioselective [4 + 2] annulation under identical conditions, smoothly affording pyrrolo[3,2,1-ij]quinoline skeletons with good to high stereoselectivities. Furthermore, a novel enantio-enriched indole-based tetracyclic skeleton was facilely derived from the obtained pyrrolo[1,2-a]indoles.

A novel method for electrochemical C(sp²)–H lactonization was developed. This strategy enabled the synthesis of various isocoumarins in moderate to excellent yields with good functional group tolerance. The gram-scale reaction and derivatizations of the product showed the applicability of this method. Relevant mechanism experiments supported the rare non-Kolbe process. Overall, this work provides a sustainable and cheaper approach for the synthesis of isocoumarins.

Here, we report a practical method to selectively access silylated pyrrolo[1,2-a]indoles using alkenyl indoles and readily available silanes through a radical cascade cyclization. The reaction proceeds through an unusual intermolecular polarity-mismatched addition of a nucleophilic silyl radical to e-rich alkene SOMOphiles via a coordination-assisted interaction. The scope and functional group compatibility of the protocol as well as a detailed mechanistic investigation are presented.

An interesting asymmetric organocatalytic cascade reaction of 3-hydroxyoxindoles with coumarins was accomplished using a chiral bisguanidinium hemisalt. A series of enantioenriched spirobenzofuran indolinones were afforded in high yields with high diastereo- and enantioselectivities. The reaction was found to involve several steps: an intermolecular Michael reaction, transesterification, a retro-Michael reaction, substitution and decarboxylation, and then an intramolecular Michael reaction to yield the product. The final step of this cascade is found to be the stereo-determining step. In addition, this reaction provides a facile route for the late-stage modification of several drug molecules via the installation of the spirobenzofuran indolinone scaffold.

The selective formation of ortho-fluoroanilines, representing versatile intermediates for the pharmaceutical and fine chemical industries, relies to date on, e.g., transition-metal-catalyzed fluorination of azobenzenes, which must be preformed from aniline derivatives. While few efficient methods for aniline synthesis were reported, sustainable, straightforward, and selective synthesis of fluoroanilines, and in particular ortho-fluoroanilines, remains challenging. Herein, we describe a domino approach that involves the simultaneous construction of a benzene ring and the installation of both amine and fluorine groups in a single operation under metal-free conditions, starting from readily available acyclic compounds. The developed atom- and cost-efficient, highly convenient, selective, and environmentally friendly four-step domino process allows the formation of a variety of functionalized ortho-fluoroanilines with yields of up to 80% and bypasses the selectivity issues of transition-metal-catalyzed aniline fluorination reactions. Furthermore, we show that the new domino products can efficiently be utilized to synthesize fluorinated azo dye and (tetrahydro)quinazoline derivatives in a bioactive form, i.e., possessing a first-time proven micromolar antiviral activity and high selectivity (EC₅₀ (HCMV) down to 1.9 ± 0.7 μM, CC₅₀ up to >100 μM), under conventional and/or visible-light mediated conditions.

A metal-free stereoselective intramolecular chlorocarbamoylation of alkynes/allenes driven by BCl₃ was described, which provides a general and practical method for constructing versatile and chlorinated methylene lactams or tetrahydroisoquinolinones with (Z) geometry at the double bond, featuring a stereochemically defined tetrasubstituted chloroethene.

Unlike artificial self-assemblies, many biological systems often rely on indirect input for their adaptive structures and function. To reduce the stark differences with their natural counterparts, artificial self-assemblies should also operate with the help of indirect inputs for adaptation. In this article we have demonstrated this using a new ring substituted peri-naphthoindigo (BuPNI) dye. The dye showed improved solubility in non-polar solvents and different aggregation behaviour than the parent PNI. The new dye underwent a self-assembly process in non-polar solvents (MCH, toluene), and the aggregation behaviour was tuned with the help of different guests like TFA, C60 fullerene and TfOH. By interacting with the donor–acceptor pairs of the dye, TFA was able to change the intermolecular arrangement. The rearrangement was found to be different when TfOH was used as a guest. Similarly, C60 fullerene interacted with the aggregated dye and produced a charge-transfer complex in the excited state. The guest-induced supramolecular rearrangement was also studied remotely by making changes in an adjacent solvent layer via a diffusion method. Placing an acid-induced rearranged aggregate in an organic solvent over an aqueous solution allowed the expulsion of the acid via diffusion, which in turn freed the chromophore and regenerated the original aggregate. The situation was reversed by the addition of acid to the aqueous layer. Contrary to the typical processes of acid-induced supramolecular rearrangements, which are spectroscopically reversible but not chemically reversible, our concept is fully reversible as it did not produce any unwanted waste (salt) in the reverse step.

Given the significance of organogermanium compounds in materials science, medicinal chemistry, and synthetic chemistry, transition-metal-catalyzed C–Ge coupling reactions have become a focal point in organic synthesis, driving innovation in organogermane chemistry. This review examines the development and recent advancements in transition-metal-catalyzed C–Ge coupling reactions, aiming to provide new insights and inspire further research and applications in this rapidly evolving field.

A series of 1,2,3-triarylazulenes was obtained using new synthetic methodology and subsequently subjected to Scholl-type oxidation aiming for conjugated azulene-embedded polycyclic aromatic hydrocarbons (PAHs). The oxidation yielded either unexpected azulen-1(8aH)-ones or desired purely hydrocarbon azulene-embedded PAHs, depending on the substitution pattern. Different reaction pathways were rationalized using DFT calculations, leading to the observation that 2-pyrenyl substituents facilitate formation of the desired conjugated molecules. The fully hydrocarbon azulene-embedded PAHs exhibit a relatively small electrochemical energy gap below 2 eV and optical absorption reaching the near-infrared (NIR) region. These properties are attributed to their non-alternant topology and retained azulene-like electronic structure.