Gu Zhan

A visible‐light‐driven, synergistic photoredox/selenium dual catalytic system has been developed for the synthesis of 2‐acyl‐3‐arylnaphthofurans. Utilizing readily accessible propargylic aryl ethers, this transformation proceeds via a [3,3]‐rearrangement/cyclization cascade under mild conditions. This protocol exhibits a broad substrate scope and excellent functional group tolerance, efficiently affording the target 2‐acyl‐3‐arylnaphtho‐ or benzofurans in moderate to good yields. The synthetic utility of the method is further highlighted by diverse downstream transformations of the products. Based on mechanistic investigations, a plausible pathway is proposed to elucidate the reaction process. This strategy provides a practical and sustainable alternative to traditional approaches for accessing biologically relevant naphthofuran, benzofuran, and naphthothiophene scaffolds.

This work unveils a metal- and base-free, N -iodosuccinimide-mediated, light-promoted intramolecular cascade reaction for synthesizing diverse benzo[4,5]indolo[3,2- c ]isoquinolines, which serve as efficient organic photocatalysts.

Axially chiral arylpyrroles are a promising class of compounds with broad applications in catalysis, medicinal chemistry, and materials science. Herein, we report a copper-catalysed dynamic kinetic asymmetric (4 + 1) cyclization for the atroposelective synthesis of arylpyrroles bearing a single stereogenic axis or 1,2-diaxes from 1,3-enynes and amines. This dynamic kinetic asymmetric transformation employs a chiral Cu/Pybox complex, with air as the oxidant and DABCO serving as both a base and a proton shuttle. A key feature is the reversibility of the aza-Michael addition, which enables the dynamic formation/cleavage of distal C-N bonds. The 5-endo-dig cyclization serves as both the rate-determining and stereodetermining step, ensuring precise stereocontrol of the proximal stereocenters by the catalyst. This strategy overcomes long-standing challenges in the stereocontrol of distal C-N bond formation and enables the synthesis of atropisomeric DMAP catalysts with two stereogenic axes. DFT calculations provide insights into the mechanism of stereocontrol.

Mechanotransduction, converting physical forces into biochemical signals, has emerged as a key regulatory mechanism in cancer. The Piezo family (Piezo1 and Piezo2) is critical mechanically activated ion channels that transduce mechanical stimuli into intracellular calcium flux, influencing proliferation, migration, and differentiation. Emerging evidence strongly implicates their dysregulation in shaping cancer phenotypes and remodeling of the tumor microenvironment. Altered Piezo expression occurs in multiple malignancies (e.g., breast, lung, and colorectal cancer), correlating with progression, metastasis, and clinical outcomes. Piezo channels also intersect with immune and angiogenic pathways, extending the mechanical influence to the tumor ecosystem. Thus, Piezos act as central integrators of tumor physiology by integrating mechanical stress with biochemical and immune signaling. However, translating Piezo-targeted interventions into clinical practice remains challenging. This perspective summarizes current understanding of Piezos’ structure and gating, their roles in cancer, and the opportunities and obstacles for Piezo-based therapy, aiming to delineate future translational pathways.

A metal- and base-free, N -iodosuccinimide-mediated, light-promoted intramolecular cascade reaction has been developed for the rapid construction of benzo[4,5]indolo[3,2- c ]isoquinolines. This transformation proceeds through two sequential intramolecular C–N bond-forming events under mild conditions, affording densely fused nitrogen-rich polycycles with broad substrate scope and good functional-group tolerance. The resulting π-extended scaffolds exhibit intrinsic photophysical properties and function as organic photocatalysts for redox-neutral difunctionalization of acrylamides.

Water-promoted, catalyst-free single-carbon deletion enables sustainable deconstructive amination of dienes to fully substituted pyrroles.

Dynamic kinetic resolution enables the first catalytic asymmetric transformation of sulfilimidoyl fluorides to chiral sulfinimidate esters, giving idebenone-derived sulfilimine 3bg with improved metabolic stability and anti-inflammatory activity.

The rational design of bioactive molecules increasingly utilizes sulfur-containing groups such as sulfoximines and sulfilimines. While sulfonimidoyl fluorides have enabled efficient asymmetric synthesis of sulfoximines as versatile chiral S(VI) electrophiles, their S(IV) counterparts, sulfilimidoyl fluorides, have not been successfully applied to asymmetric sulfilimine synthesis due to instability and rapid racemization at sulfur. Here, we report the catalytic asymmetric transformation of sulfilimidoyl fluorides, granting direct access to enantioenriched sulfinimidate esters via dynamic kinetic resolution. Central to this process is a bifunctional tertiary amine–hydrogen bond donor catalyst that induces stereocontrol through secondary interactions, stabilizing the transition state during esterification. The method demonstrates broad substrate scope with both sulfenamides and alcohols. Mechanistic studies show that stereoselectivity is established during esterification, distinguishing this strategy from previous methods. This work addresses a key challenge in sulfilimidoyl fluoride chemistry and broadens access to S-stereogenic scaffolds for drug discovery.

Catalytic C-H alkylation of pyridines with unactivated internal alkenes containing heteroatom functional groups is, in principle, an ideal means for the synthesis of functionalized alkylpyridines, which are important heterocyclic structural motifs in many pharmaceuticals, agrochemicals, and biologically active compounds. However, such a transformation has remained undeveloped to date, probably due to the lack of suitable catalysts. Here we report a rare-earth-catalyzed C-H alkylation of pyridines with unactivated internal alkenes that leverages a wide array of native heteroatom functional groups, including ethers, thioethers, and tertiary amines, to serve as an efficient promoter for the regioselective hydropyridylation and hydropyridylmethylation of internal alkenes. This protocol provides an atom-efficient and straightforward approach for the selective synthesis of a new family of C2-alkylated pyridines with diverse ether, thioether, and tertiary amine functional groups, featuring 100% atom efficiency, broad substrate scope, high yield, and excellent regioselectivity. Experimental and computational studies reveal that the coordination of the heteroatom (O, S, or N) in internal alkenes to the catalyst metal center is crucial for achieving the unprecedented activity and regioselectivity.