Organic & Biomolecular Chemistry最新文献

Metal-catalyzed electrochemical C-H activation has emerged as a promising strategy for cost-effective and sustainable molecular assembly. Herein, we describe a palladaelectro-catalyzed ortho-C-H activation/arylation of arenes, using arenediazonium salts as aryl sources. The arylation of 2-phenylpyridine derivatives with ortho-selectivity was achieved under electrochemical conditions, avoiding stoichiometric chemical oxidants and employing exceedingly mild conditions. This versatile arylation reaction also features a broad substrate scope, accommodating both electron-withdrawing and electron-donating groups on the aryl and pyridine moieties, with moderate yields. Detailed mechanistic studies using cyclic voltammetry, reactions in the presence of TEMPO, and experiments in a divided cell strongly support electrochemical palladium catalyst recycling and the formation of aryl radicals through cathodic reduction of arenediazonium salts.

The synthesis of axially chiral benzimidazoles with a peri-substituted naphthalene and a dimethylamino group at positions 1 and 2, respectively, was developed. We evaluated these compounds in the desymmetrization reaction of cis-tetrahydrophthalic anhydride with benzyl alcohol, as the nucleophilic sp² imidazole nitrogen atom is able to catalyze the acyl-transfer reaction. The prepared benzimidazoles demonstrated catalytic activity and showed that their axial chirality impacts stereoselectivity.

Integrating fluorine into heterocyclic structures via cyclization reactions under metal-free conditions is attractive for organic synthesis. Herein, we describe solvent dependent fluorinative cyclizations of o-hydroxyarylenaminones, which were promoted by H₂O and NFSI under metal-free conditions, to furnish 2,3-substituted chromanones. Di- and monofluorinated 2-hydroxyl chromanones could be achieved selectively in a THF-H₂O or EtOH-H₂O system at ambient temperature under an air atmosphere.

An imine derived from 4-(N,N-dimethylamino)benzaldehyde and a primary amine undergoes very rapid hydrolysis in weak acid, however, it can be encapsulated within cucurbit[7]uril (CB7) to give a host/guest complex that completely protects the labile imine bond.

In recent years, significant achievements have been made in the field of electroorganic chemistry regarding the difunctionalization of alkenes. Researchers have developed innovative strategies utilizing the unique reactivity of electrochemical processes to synthesize complex molecules with high regioselectivity and stereoselectivity. This technology is widely applied in the total synthesis of natural products and in the pharmaceutical industry. This article reviews the research progress in the electrochemical difunctionalization of alkenes through three different radical-mediated pathways over the past five years. It includes discussions on 1,2-stereoselective and non-diastereoselective difunctionalization reactions, rearrangements, intramolecular migrations, and cyclization processes. The summary emphasizes innovative electrode designs, reaction mechanisms, and the integration with other emerging technologies, highlighting the potential of this method in modern organic chemistry. Additionally, it aims to address current challenges and propose possible solutions, providing a promising direction for electrochemically mediated difunctionalization reactions of alkenes.

Heterocyclic molecules containing organochalcogens are important scaffolds that have attracted scientific interest due to their remarkable pharmacological properties. As a consequence, in recent years several protocols have been developed for the synthesis of this class of compounds. More specifically, cyclization reactions have become a powerful tool in the synthesis of heterocycles containing two or more chalcogen atoms. This review summarizes the recent advances in the synthesis of heterocycles containing two or more chalcogens (S, Se, and Te), through a wide diversity of cyclization reactions with different substrates, with emphasis on cyclization reactions of chalcogenoalkynes and alkenes in chalcogenocyclization reactions, highlighting their scope, main advantages, synthetic differences, and limitations.

The excessive hydrophilicity of carbohydrates hampers their application in drug discovery. Deoxyfluorination is one of the strategies to increase sugar lipophilicity. However, lipophilicities of dideoxy-difluorinated monosaccharides are still well below the desired range for oral drug candidates. Here we investigate the power of deoxychlorination to increase sugar lipophilicities. A series of dideoxygenated chloro-fluorosugars was synthesized and for these substrates it was shown that deoxychlorination increased the log P by an average of 1.37 log P units, compared to 0.83 log P units for analogous deoxyfluorination. This shows the potential of deoxychlorination of carbohydrates to increase lipophilicity while limiting the number of potentially important hydrogen bond donating groups to be sacrificed, and will be of interest for glycomimetic development.

An efficient strategy for constructing di/trifluoromethyl bis(1,2,4-triazoline)spiranes and 1,2,4-triazoles via 1,3-dipolar cycloaddition reaction of nitrilimines and carbodiimides was developed. Various N-aryl di/trifluoromethyl acetohydrazonoyl bromides are well tolerated in the reaction, providing the target products in good regioselectivity and yields. This method features simple operation, high efficiency and mild reaction conditions for the rapid synthesis of complex fluoroalkylated nitrogen-rich spirocyclic compounds.

The naphthalene ring is a moiety featured by many bioactive agents. Dihydroxynaphthalenes are readily available substances but their use for the synthesis of a series of compounds results in limited chemical diversity due to the similar reactivity of the phenolic hydroxyl groups. Herein, we describe the use of regioselective lipases in acylation and hydrolysis reactions to synthesize 5 different regioisomeric acetoxyhydroxynaphthalenes on a 91-122 mg scale with moderate to good yields (50-78%) from 1,3-, 1,6- and 1,7-dihydroxynaphthalenes and their corresponding diacetates. Reactions were optimised through medium engineering, thus providing information on the impact of different organic solvents on conversion and selectivity. Additionally, computational studies using molecular dynamic simulations were performed and suggested a correlation between the regiopreference displayed by lipase CAL-B in hydrolytic reactions and a distance ≤3.2 Å between the most reactive carbonyl group and the Ser-105 residue on the catalytic site. The herein described enzymatic methods may allow for introducing two different moieties at the naphthalene ring through a protection-deprotection strategy, thus allowing for better exploitation of the chemical space.

We present a practical synthesis of 2'-hydroxy-3',4',5',6'-tetramethoxyacetophenone, a multi-substituted benzene derivative, via CuCl-catalyzed Ullmann-type coupling reaction with MeONa. 2'-Hydroxy-3',4',5',6'-tetramethoxyacetophenone is the key intermediate for the total synthesis of various polymethoxyflavones. Subsequently, nobiletin, tangeretin, and gardenin A-D, are synthesized from this intermediate.