A catalytic strategy for insitu generation of substituted pi-allyl palladium dipoles from neutral eta(3) -propargyl palladium complexes has been disclosed, enabling the construction of enantiomerically enriched aza-bicyclo[3.2.1]octane frameworks through cascade cyclization reactions based on neutral zwitterionic pi-propargyl palladium species derived from vinylidenecyclopropane-diesters (VDCP-diesters) and their analogues. This protocol demonstrates remarkable synthetic efficiency under mild reaction conditions, achieving moderate to good yields (42 examples) with excellent stereochemical control (>90% ee in most cases). This asymmetric catalytic reaction can be applied in a series of semigram-scale manipulations, and the obtained cycloadducts can be transformed into diverse functionalized products while retaining excellent enantioselectivities. On the basis of mechanistic investigations and DFT calculations, the critical palladacyclobutenization-protonolysis sequence has been elucidated as the pivotal chirality-determining step in the whole plausible reaction pathway.

Harziane diterpenoids possess a highly caged 6/5/7/4 core framework and four contiguous stereocenters, including two quaternary ones, and present significant challenges to chemical synthesis. Herein, we report an efficient strategy to rapidly access harziane diterpenoids by merging local desymmetrization and radical retrosynthesis. The strained bicyclo[5.2.0]nonene motif was installed using a local desymmetrizing intramolecular aldol reaction with high diastereotopic group selectivity, while the bridged [3.2.1] ring system and three contiguous stereocenters were rapidly forged by means of three strategic radical fragment couplings, i.e., Baran reductive olefin coupling, photocatalytic deoxygenative alkylation, and acyl radical cyclization.

Despite significant progress in the stereoselective synthesis of polysubstituted cyclopropanes, the catalytic diastereodivergent synthesis of polysubstituted cyclopropanes from cyclopropenes remains challenging. Here, we report a copper-catalyzed diastereodivergent hydro-gem-difluoroallylation of 1,3-disubstituted cyclopropenes with 3,3-difluoroallyl sulfonium salt. By fine-tuning the steric effect of the N-heterocyclic carbene (NHC) ligand, the reaction can selectively produce two diastereoisomers from the same starting materials, thereby providing a convenient route to gem-difluoroallylated cyclopropanes. The synthetic utility of this approach is further demonstrated by diverse transformations of the resulting products, making it an attractive approach for obtaining various fluorinated cyclopropanes of medicinal interest. Density functional theory calculations reveal that both the steric effect of the NHC ligands and the coordination interactions between the copper center and the chelating group on the cyclopropenes are key factors in controlling the diastereoselectivity.

A catalyst-free intermolecular dearomatization reaction of indoles with hypervalent-iodine-based nitrooxylating reagent is reported. Various alkoxyated 3,3-disubstituted oxindoles bearing a quaternary carbon stereogenic center are obtained in good to excellent yields (up to 92%) under mild conditions. Meanwhile, the obtained products can undergo a variety of transformations smoothly, including Sonogashira coupling reaction, Suzuki coupling reaction, and demethylation reaction mediated by BBr3. In addition, natural product (+/-)-convolutamydine A is synthesized by employing this method as the key step, showcasing the synthetic potential of the current method.

This study aims to develop a sensitive and precise method for determining chiral thiols using an efficient multicomponent reaction. This innovative approach leverages the coupling of 19F-labeled chiral amines, o-phthalaldehyde, and targeted thiol analytes to rapidly generate diastereoisomeric isoindole derivatives. These derivatives exhibit distinctive 19F NMR signals, providing valuable insights for chiral discrimination. The introduction of chiral amines bearing dual 19F labels enables dual-site detection, significantly enhancing the system's resolving capabilities. The superior resolving power of this methodology is demonstrated through the simultaneous chiral discrimination of eight chiral thiols, showcasing its potential for analyzing complex samples in biological studies and pharmaceutical development.

Subcellular lipid composition and transport substantially influence the physiological and pathological functions of both cells and organelles. However, lipid transport and turnover between organelles remain poorly understood due to a lack of methods for selectively labelling lipids in organelles. Here we develop a subcellular photocatalytic labelling strategy that enables organelle-selective lipid analysis by mass spectrometry and the quantitative profiling of lipid transport between organelles. We use this approach to quantitatively characterize fatty-acyl-dependent transport of phosphatidylethanolamine and phosphatidylserine lipids between the endoplasmic reticulum and mitochondria, the nucleus or lysosomes. Further experiments revealed the relative contributions of various biosynthesis pathways to the phosphatidylethanolamine and phosphatidylserine lipid compositions in the mitochondria, nucleus and lysosomes. Lysosome-specific photocatalytic labelling revealed the impact of the mTOR kinase pathway on lysosomal lipid metabolism. Together, this subcellularly localized photocatalytic labelling of lipids quantitatively deciphers the subcellular lipid composition and transport, enhancing our understanding of lipid metabolism in living organisms.

While copper-catalyzed asymmetric propargylic substitution has emerged as a versatile tool for constructing chiral propargylic frameworks, its application in forging cyclic chiral quaternary carbon centers remains a significant synthetic challenge. This work demonstrates a dinuclear copper-catalyzed asymmetric [3 + 2] annulation strategy between tertiary propargyl carbonates and diverse C,O-bisnucleophiles under mild conditions. The protocol enables efficient synthesis of chiral dihydrofurans featuring cyclic quaternary stereocenters with broad substrate compatibility. The stereochemical control may arise from the unique coordination geometry of dinuclear copper-allenylidene intermediates, which spatially aligns the electrophilic site within the chiral ligand environment. This spatial arrangement overcomes inherent steric challenges in the stereoselective formation of quaternary carbons bearing dual alkyl substituents, offering mechanistic insights into cooperative dinuclear catalysis for asymmetric transformations.