Synlett

Over decades, Cope rearrangements have attracted significant research interest in the field of synthetic organic chemistry relying on their ability to undergo stereoselective structural reorganization. Despite substantial progress, the development of this field remained confined to the use of parent 1,5-hexadienes. Against the backdrop of classical Cope reaction, we report the utilization of unconventional 1,6-heptadienes to develop the arylative Cope rearrangement by harnessing the interplay between the π-activation and cross-coupling reactivity mode of gold complexes. Several mechanistic investigations such as 31P NMR study, HRMS analysis, cross-over experiment, control experiments were performed to support the proposed cyclization-induced [3,3]-rearrangement mechanism in arylative Cope reaction.1 Gold-Catalyzed Cope Rearrangements2 Gold-Catalyzed Arylative Cope Rearrangement3 Conclusion

We describe a simple and efficient method for the synthesis of various benzoselenazoles and benzothiazoles by the Ullman coupling reaction of dihalobenzenes with acyl iso(seleno/thio)cyanate–malononitrile adducts in the presence of a copper catalyst with K2CO3 as a base at room temperature, without the help of additional ligands. Notable features of this protocol include the use of mild copper-catalyzed reaction conditions, simple and readily available raw materials, easy purification with the help of a solvent, and the synthesis of 17 new benzoselenazole and benzothiazole compounds.

Due to an inherent polarity mismatch of the corresponding retrosynthetic synthons, 1,4-dicarbonyl synthesis through polar pathways requires a retrosynthetic rethink. While umpolung-based approaches exist, efficient control of both the absolute and relative configuration of newly formed stereogenic centres within this motif has long proven particularly challenging. In this Synpact article, we highlight our work on the stereodivergent synthesis of 1,4-dicarbonyl compounds through an unusual transformation that relies on vinyl sulfoxides and ynamides as reactants. This method allows stereoselective access to each and every one out of the four possible stereoisomers of a generic 1,4-dicarbonyl target in a process where enantio- and diastereoselectivity are ‘dialled into’ the vinyl sulfoxide partner. Recent studies show that the thus formed 1,4-dicarbonyls serve as excellent linchpins for structural diversification into highly substituted heterocycles, including those found in natural products.1 Introduction2 [3,3]-Sigmatropic Rearrangement of Ynamides and Vinyl Sulfoxides under Acid Catalysis3 Cyclisation towards γ-Lactones and γ-Lactams4 Application in Total Synthesis5 Conclusion

Allylic ethers are a common occurrence in natural products, and are often used as intermediates in target-oriented synthesis. Their synthesis often relies on the use of transition-metal catalysts. Here, we report an organocatalytic method for the allylation of O-centered nucleophiles, the Lewis base catalyzed allylation of silyl ethers with allylic fluorides. The method relies on the concept of latent pronucleophiles in Lewis base catalysis to overcome common limitations in substrate scope, even permitting the allylation of sterically congested O-pronucleophiles. When chiral Lewis base catalysts are used, the allyl ethers are produced in an enantioenriched form through kinetic resolution of fluorides, where the stereoselectivity is determined by the chiral catalyst.

Spirocyclobutanes have gained significant attention in medicinal chemistry discovery programs due to their broad spectrum of biological activities and clinical applications. Utilizing ring strain in small molecules to drive organic transformations is one of the most powerful tools in chemical synthesis. Our research group has focused on developing new synthetic strategies enabled by ring strain to construct complex molecules selectively and efficiently. This account summarizes our recent efforts toward the synthesis of a library of functionalized spirocyclobutanes by harnessing the ring strain of bicyclo[1.1.0]butanes. Three spicrocyclization cascades have been developed to incorporate a diverse range of radical precursors into spirocycobutanes.1 Introduction2 Synthesis of Spirocyclobutyl Lactones and -Lactams using Bifunctional Reagents3 Dual Photoredox/Nickel Catalysis for the Synthesis of Spirocyclobutyl Lactams4 Synthesis of Spirocyclobutyl Oxindoles under Photoredox Catalysis5 DFT Studies6 Conclusion

Mild biphasic conditions enable dibutylviologen salts to act as both phase-transfer catalysts and electrocatalysts for the electroreduction of vicinal dibromides. Optimized experimental reaction conditions permit the production of the corresponding alkenes in competitive yields for a wide range of activated and nonactivated substrates, demonstrating good functional-group tolerance.

Mechanochemistry, a solvent-free approach that harnesses mechanical energy, is emerging as a transformative technique in modern chemistry. It has emerged from a niche technique to a versatile tool with broad applications. By inducing physical and chemical transformations, it enables the synthesis of complex molecules and nanostructured materials. Recent advancements have extended its applications beyond simple physical transformations to encompass catalytic processes, unlocking new possibilities for selective synthesis and product design. This account delves into the fundamentals of mechanochemistry and its applications in organic synthesis, also beyond traditional synthetic routes. Mechanochemistry offers new avenues for molecular and materials discovery, expanding the scope of accessible chemical space.1 Introduction2 Organic Synthesis in Ball Mills3 Combination with Different Energy Sources4 Advantages of Mechanochemistry5 Future of Mechanochemistry6 Conclusion

A green and sustainable electrochemical approach is developed for the regioselective C3–H trifluoro/difluoromethylation of 2H-indazoles at room temperature. Relatively less expensive C-soft (+)/Ni-foam (–) electrodes are utilized to selectively functionalize the 2H-indazoles effectively by avoiding the use of any external oxidant and transition-metal salt. Moreover, along with the C3–H trifluoromethylation, for the very first time, direct C3–H difluoromethylation of 2-phenyl-2H-indazoles is accomplished. Diverse C3–H trifluoro/difluoromethylated 2H-indazoles having an array of functionalities are successfully synthesized in moderate to very good yields. As an application, a precursor of both an estrogen receptor ligand and an acetyl Co-A carboxylase inhibitor is synthesized. A plausible reaction mechanism is proposed based on control experiments and cyclic voltammetry studies.

Epoxidation of α,β-unsaturated ketones under visible-light irradiation constitutes a significant chemical transformation with potential applications in the synthesis of epoxypropane derivatives. An organophotoredox catalytic system is herein reported to facilitate efficient aerobic epoxidation. This protocol enables the conversion of α,β-unsaturated ketones into their corresponding epoxy products with moderate to high yields under benign reaction conditions. The methodology demonstrates broad functional-group compatibility, providing a reliable and direct route to a variety of functionalized epoxypropane compounds. Additionally, the absence of heavy metals in this strategy renders it particularly suitable for the pharmaceutical industry, offering a new avenue for the synthesis of epichlorohydrin drugs.

A simple strategy for the synthesis of a variety of tetrahydropyridines in good to excellent yields via a Cu(OTf)2 catalyzed quaternary ammonium salt mediated ring-opening of activated azetidines followed by cyclization with alkynes in a domino ring-opening cyclization (DROC) is described. The formation of the products has been explained by an SN2-type ring-opening of azetidines with alkynes.