Xianxiu Xu

The de novo synthesis of structurally novel 4-chalcogenylated pyrrolo[2,3- c ]quinolines via a three-component biheterocyclization–chalcogenation of two distinct isocyanides with various chalcogen nucleophiles was developed.

A hexafluoroisopropanol (HFIP)-promoted Ugi three-component reaction of electron rich aryl, alkenyl or heteroaryl group-tethered isocyanides, aldehydes and amines was developed for the rapid and general synthesis of a wide range of isoquino-line/quinoline/carboline-substituted methylamine and α-amino acid derivatives. In this reaction, the in situ formed nitrilium was intramolecularly trapped by the nucleophiles tethered at isocyanides to form the corresponding heterocyclic framework, wherein an obviously gem-disubstituent (Thorpe-Ingold) effect was observed.

Herein, we present a mechanistically distinct approach to the multicomponent difunctionalisation of styrenes with alkyl halides and oxygen by integrating α-aminoalkyl radical-mediated halogen-atom transfer (XAT) with copper catalysis under air-equilibrated conditions. This strategy eliminates the need for external peroxides or photoredox conditions, offering a streamlined and efficient alternative. Mechanism studies uncover a unique role for the copper catalyst: instead of directly activating alkyl halides, inexpensive CuCl₂ oxidizes a tertiary amine to generate an α-aminoalkyl radical, which then drives XAT to release alkyl radicals. These radicals subsequently add to alkenes, facilitating efficient difunctionalisation. This method accommodates a broad range of alkyl radical precursors, including fluoroalkyl- and alkyl halides, and demonstrates compatibility with diverse styrenes, enabling the modular synthesis of β-(fluoro)alkylated ketones with excellent functional group tolerance under mild conditions. Notably, the strategy's practical utility is exemplified through the late-stage functionalisation of biologically active molecules and pharmaceuticals, showcasing its potential for rapid, efficient access to structurally complex molecules.

A general protocol for the synthesis of a variety of functionalized quinazolinones has been developed through a sequential Pd-catalyzed coupling/1,5-alkyloxy/thio/azole shift/6π electrocyclization reaction of isocyanides and 2-carbonylaryl azides. When 3-(2-isocyanoethyl)indoles were utilized, an unusual competitive reaction between [1,5]-shift and indole-spirocyclization was observed, which renders a modular synthesis of quinazolinones and spiroindolenine-3,3'-pyrrolo[2,1-b]quinazolinones in a highly chemoselective manner.

Despite both fluoroalkylsulfonyl groups and benzofurans are important bioactive moieties, the construction of fluoroalkanesulfonylated benzofurans that incorporate these two fragments remains underdeveloped. Here, we report a tandem cyclization protocol to construct a wide range of 3-fluoroalkylsulfonyl benzofurans using readily accessible o-hydroxyphenyl propargyl alcohols and sodium fluoroalkanesulfinates. Furthermore, this synthetic strategy can also be adapted to prepare 3-thio benzofurans by changing the S-nucleophiles to thiols or thiophenols.

Herein, we disclose a photoinduced radical cascade cyclization of alkynes with sulfinates via a novel EDA complex for the synthesis of various 3-sulfonylindoles and vinyl sulfone oxindoles, which are crucial motifs in medicinal and biological chemistry. The reaction proceeds under mild, photocatalyst- and transition-metal-free conditions, featuring operational simplicity, broad substrate scope, and easy scalability. Mechanistic studies reveal that the reaction is initiated with a photoinduced intermolecular charge transfer from sulfinates to N-sulfonamides, generating a sulfonyl radical followed by an N-centered radical, thus enabling the cascade cyclization process.

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation.