Lingchao Cai

Herein, we report a visible-light-enabled oxo-alkylation of styrenes utilizing aliphatic alcohol-derived N-alkoxyphthalimides (NAPIs) as alkyl radical precursors. Distinct from conventional deoxygenative approaches that retain the parent scaffold, this protocol proceeds via a deconstructive mechanism involving the β-fragmentation of alkoxy radicals. This strategy enables the synthesis of diverse α-alkyl ketones from a wide range of substrates, including primary, secondary, and tertiary alcohols, as well as various styrenes. Notably, the method facilitates the late-stage modification of complex natural scaffolds, such as sclareolide and β-pinene. Furthermore, the synthetic utility of this protocol is demonstrated through the one-carbon homologation of aliphatic alcohols.

Bicyclo[1.1.0]butanes (BCBs) have long served as versatile building blocks in organic synthesis, with their reactivity predominantly governed by radical-mediated or Lewis acid-catalyzed activation of the strained central C–C σ-bond. Herein, we report a metal- and base-free, phosphine-promoted strategy through n→σ* activation, enabling a strain-release Wittig-type olefination with diverse carbonyl compounds. This approach leverages the unique electronic properties of trivalent phosphines to induce ring opening of BCBs, generating zwitterionic phosphonium intermediates that evolve into ylides without requiring an external base, thereby enabling efficient C═C bond formation. The protocol exhibits broad substrate scope, accommodating both aromatic and aliphatic aldehydes and ketones. Mechanistic interrogation, supported by deuterium-labeling experiments and NMR spectroscopy, confirms the intermediacy of a phosphonium ylide and identifies the nucleophilic attack on the BCB σ-bond as the rate-determining step. Furthermore, the synthetic utility of this method is highlighted by gram-scale synthesis and diverse downstream transformations of the alkenylated products.

Alkene difunctionalization represents one of the most powerful and straightforward tools for the rapid assembly of structurally diverse organic molecules. This review provides a comprehensive overview of recent developments in the difunctionalization of alkenes enabled by photoinduced oxidative radical‐polar crossover (ORPC). By merging the advantages of radical reactivity and polar reaction pathways, this strategy enables the efficient construction of diverse 1,2‐difunctionalized skeletons under mild and controllable photochemical conditions. We systematically categorize these advances according to the type of radical species that add to the carbon–carbon double bond: carbon‐centered radicals (including alkyl, acyl, and allenyl radicals, etc.) and heteroatom‐centered radicals (focusing on nitrogen‐centered, sulfur‐centered radicals, and oxygen‐centered radicals). Mechanistic aspects involving radical generation, photoexcitation pathways, and various nucleophiles are discussed to underscore the distinctive role of photoredox catalysis in these transformations. Furthermore, we highlight the substrate scope, functional group tolerance, and synthetic utility of these reactions in complex molecule assembly and drug discovery.

Urea derivatives are privileged structural motifs in pharmaceuticals, organocatalysts, and functional materials due to their exceptional hydrogen-bonding capabilities. Classical synthetic strategies for ureas typically rely on the reaction of amines with phosgene or its derivatives─reagents that are highly toxic, moisture-sensitive, and require stringent handling conditions. Herein, we report a thiol-catalyzed, efficient, and scalable approach to access structurally diverse urea derivatives via bench-stable, nonvolatile, and isolable amidine building blocks. These key intermediates can be readily prepared from trichloroacetonitrile and amines under solvent-free conditions, offering operational simplicity and excellent functional group tolerance. This strategy not only avoids the use of safety-sensitive reagents but also enables broad substrate scope, including sterically hindered, chiral, and bioactive amines, thus providing a practical and sustainable platform for the synthesis of high-value urea-containing molecules.

Dicarbonyl architectures represent quintessential structural motifs, serving as versatile linchpins in organic synthesis and privileged scaffolds in pharmaceutical and natural product chemistry. Despite their ubiquity, a general, programmable strategy for the synthesis of diverse 1,n-dicarbonyls, particularly long-chain homologues, remains a formidable challenge, with existing methodologies often restricted to specific subtypes and suffering from operational constraints. Herein, we report a unified and innovative approach to address this long-standing synthetic bottleneck. By harnessing photoinduced alkoxy radicals derived from cycloalkanol precursors, employed as masked carbonyl synthons, we have developed a radical cascade manifold that seamlessly integrates β-fragmentation, Giese addition, and Kornblum oxidation. The strategic manipulation of the cycloalkanol ring size serves as a precise topological dial, enabling the programmable synthesis of 1,n-dicarbonyl compounds ranging from short- to long-chain variants.

Persistent endeavors have been dedicated to the synthesis of nitrogen-containing compounds, which hold paramount significance in biological processes and are indispensable in the realms of pharmaceuticals and advanced materials.

A mild and highly efficient photoinduced radical−radical coupling between N ‐alkoxyphthalimides (NAPI) and aryl thiolates is reported, which proceeds without the requirement of a photocatalyst and offers distinct advantages over traditional CS bond‐forming strategies. Mechanistic studies strongly support the formation of an electron donor–acceptor (EDA) complex based on thiolates. This method provides an alternative route for the preparation of aryl–alkyl thioethers and enriches the synthetic applications of N ‐alkoxyphthalimides as alkoxy radical precursors in the construction of a wide array of CX bonds.

Microdroplets enable selective, catalyst-free hydrogenation of biomass molecules via self-assembly and hydrogen bonding, paving the way for sustainable, tunable transformations.

Fluorine-containing organic compounds are vital in bioactive molecules and materials, with allylic gem-difluorides as key motifs in drugs. Herein, we report an efficient photocatalytic strategy for the synthesis of allylic gem-difluorides using bench-stable oxime esters as dual alkyl or aryl/iminyl radical precursors. The system exhibits a broad substrate scope with 39-87% yields and gram-scale scalability. Meanwhile, this methodology exhibits high regioselectivity and E selectivity. Additionally, the products can be further transformed into other functionalized products.