Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

Preparation and Rearrangement of N-Vinyl Nitrones: Synthesis of Spiroisoxazolines and Fluorene-Tethered Isoxazoles

“…While studying the use of copper-mediated C–O bond forming coupling reactions for the preparation of N -enoxyphthalimides, we observed that N -vinyl nitrones can be prepared in a single step from fluorenone oxime and vinyl boronic acids under copper-mediated coupling conditions (Scheme ). , The reactivity of these fluorenone- N -vinyl nitrones is distinct from traditional nitrones because the electrophilic fluorenyl carbon does not participate in cycloaddition processes. This surprising characteristic can be exploited to afford spiroisoxazolines and fluorenone-tethered isoxazolesproducts normally inaccessible directly from nitronesthat exhibit privileged structural motifs present in bioactive pharmaceuticals, dyes, and organic materials. − Herein we describe the optimization and scope of the facile preparation of fluorenone- N -vinyl nitrones from fluorenone oxime and vinyl boronic acids as well as the unique synthetic utility of these new compounds.…”

Isothiazoles in the Design and Synthesis of Biologically Active Substances and Ligands for Metal Complexes

“…In the general context of the chemistry of heterocyclic compounds, data on the chemical properties of isothiazoles are presented in review articles, [28][29][30] whilst isothiazoles have been directly reviewed, [31][32][33][34] and covered in a monograph 35 devoted to biologically active isothiazoles. There are also reports summarizing data on isothiazole-ring-containing compounds in crop protection, 36 the involvement of the isothiazole core in cross-coupling reactions, 37 and [4+2] cycloadditions of isothiazole derivatives.…”

Harnessing the TEMPO-Catalyzed Aerobic Oxidation for Machetti–De Sarlo Reaction toward Sustainable Synthesis of Isoxazole Libraries

“…Designing practical and ecobenign synthetic methods from simple precursors with no formation of toxic byproducts is of substantial importance in sustainable chemistry. − In a similar vein, chemical transformations performed at aerobic conditions offer an added advantage from a green chemistry viewpoint. − On the other hand, chemical processes performed in water has an extensive advantage of both environmental compatibility as well as less expensiveness compared to organic solvents . Thus, there has been increasing recognition of water as an attractive medium for numerous organic transformations. − To this end, a plethora of heterocycles such as furans, pyridines, quinolines, indoles, triazines, acridines, pyrazines, and pyrimidines have been synthesized in aqueous media. − Likewise, isoxazoles are five-membered nitrogen/oxygen-containing heterocycles commonly found in a variety of pharmacologically active natural products, clinical drugs, and lead compounds (Figure , top panel). − With no confinement to biology, they also find extensive application as building blocks in synthetic chemistry , and as organic materials in optoelectronics. , Because of its unique physical properties, the construction of this heterocyclic nucleus has continued to attract the research community for decades. − The most frequently used strategy for isoxazole preparation involves [3 + 2] cycloaddition of alkynes with nitrile oxides or through the reaction between hydroxyl amine and a three-carbon component . Within these methods, the intermolecular cyclization between primary nitro compounds and alkynes have received wide attention, because it builds up an isoxazole core in a straightforward manner without requiring additional synthetic steps (Figure , bottom panel).…”