A divergent visible light-induced photocycloaddition (PCA) of benzene derivatives with allenes is described, enabled by efficient sensitization of simple arene moieties using an iridium triplet sensitizer. The reactions, governed by the tethered allene chain, proceed selectively through two distinct pathways: para- and ortho-cycloaddition. The para-cycloaddition pathway, influenced by substituent effect, can further deliver a range of formal meta-type products following a subsequent di-π-methane rearrangement. In comparison, the ortho-cycloaddition pathway produces linear tricyclic cyclobutenes via cascade electrocyclic reactions. Modulated by the substituent on the allene moiety, a sequential di-π-methane rearrangement furnishes different formal meta-type products. Control experiments, together with density functional theory (DFT) calculations, provide a comprehensive understanding of the underlying reaction pathways.

Herein, we report a palladium-catalyzed cross-coupling reaction of sulfonylhydrazones with aryl or alkenyl halides, affording a diverse array of substituted dibenzo[a,e]cyclooctatetraenes featuring planar chirality. Substituents can be efficiently installed onto both aryl and alkene moieties. Preliminary asymmetric investigations have also been conducted, presenting a promising strategy for the enantioselective synthesis of cyclooctatetraene, an underexplored chiral diene ligand.

Herein, we report the first enantioselective functionalization of methylene cycloalkenes─an underexplored class of reactive 1,3-dienes. The process involves a palladium-catalyzed enantioselective hydroamination of methylene cycloalkenes using pyrazole derivatives, affording a variety of chiral tertiary amines. A machine-learning model based on universal descriptors from quasi-transition-state (UD-qTS) strategy, combined with a physicochemically grounded data-augmentation protocol, has been employed to accelerate the optimization process. Deuterium-labeling experiments and density functional theory (DFT) calculations revealed that the reaction proceeded through a ligand-to-ligand hydrogen transfer (LLHT) pathway, which is both the rate-determining and enantio-determination step. Subsequent inner-sphere nucleophilic attack by the pyrazole anion enables regioselective C3 (referring to 1,3-diene)-N1 (referring to pyrazole) bond formation. Furthermore, the resulting products can be transformed into acyclic alkenes, which are equivalent to the hydroamination products of acyclic 1,3-dienes.

The synthesis of cyclobutane-fused heterocycles via photocycloaddition (PCA) of heteroarenes has been widely explored. However, achieving high enantioselectivity remains challenging. Represented herein is a report on an efficient and enantioselective intermolecular [2+2] cycloaddition of indoles with various alkenes and aryl allenes under visible light irradiation. A chiral oxazaborolidinium ion (COBI) was used to engage indole substrates via efficient BCOBI-Osub coordination. Upon photoexcitation, the resulting adduct undergoes radical addition to alkenes, the enantio-determining step, followed by radical recombination to afford cyclobutane products. This strategy significantly expands substrate compatibility and functional group tolerance, providing an efficient and versatile route to enantioenriched cyclobutane-fused heterocycles.

The stereoselective reduction of strained molecules and subsequent synthetic transformations provide an efficient strategy to access multi-substituted carbocycles. These carbocycles are important structural skeletons in natural products and bioactive molecules. We report here a Luche-type enantioselective reduction of cyclobutenones and strained-ring fused cyclic imides. This process utilizes the catalysis of Sc-N,N'-dioxide ligand complex and NaBH4 as reductant. Moreover, the developed methodology is applicable to the strained olefins, which are not tolerated under metal hydride conditions.

The transition-metal catalyzed enantioselective 1,4-addition and subsequent functionalization strategy provides a powerful approach to construct 2,3-disubstituted cycloalkanones, which are further utilized as important intermediates in the total synthesis of natural products. This concept article highlights recent advances in the methodology development and related synthetic applications.

The palladium-catalyzed enantioselective redox-neutral coupling of alkenes with organoboronic reagents remains an unfulfilled challenge. Herein, we report a divergent palladium-catalyzed enantioselective hydroarylation of cyclobutenes with arylboronic acids, affording both 1,2- and 1,3-hydroarylation products. The regioselectivity was tuned by judicious choice of chiral ligands. The palladium-hydride species was generated from a palladium catalyst and arylboronic acid or in situ generated HOAc, as supported by deuterated experiments and density functional theory (DFT) calculations. We anticipate that this redox-neutral coupling with organoboronic reagents could stimulate interest in other unsaturated alkene systems.

2-Azabicyclo[2.1.1]hexanes (aza-BCHs) are constrained pyrrolidine analogues with improved physicochemical characteristics in drug design. Here, we report a direct visible light-mediated photocycloaddition of 4-aza-coumarins with mono- or disubstituted bicyclo[1.1.0]butanes for synthesizing aza-BCHs without an external catalyst. The introduction of the ester group on 4-azacoumarin is critical for direct imine excitation and versatile synthetic utility. Preliminary mechanistic studies indicated that the reaction took place primarily at the triplet hypersurface. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Although three different modes of photocycloaddition between arenes and alkenes are well-known, the control of reaction selectivity remains a long-standing challenge. In this study, we present the first tunable photocycloaddition of 1-naphthol derivatives under visible light irradiation, affording ortho, meta, and para cycloadducts, respectively. The success of the reaction hinges on a rational design of naphthalene substrates and the judicious selection of solvents and sensitizer. The reaction mechanism is further elucidated through a combination of control experiments and density functional theory (DFT) calculations.

We developed here a Pd/C-catalyzed diastereoselective cis-hydrogenation of benzocyclobutene derivatives under mild conditions to deliver an array of bicyclo[4.2.0]octane scaffolds with up to five stereocenters. The pi-bond localization enabled hydrogenation of the arene moiety to occur even at room temperature under 1 atm of a H-2 atmosphere.

Aliphatic strained rings have been increasingly applied in medicinal chemistry due to their beneficial physicochemical and pharmacokinetic properties. However, the divergent synthesis of enantioenriched cyclobutane derivatives with various structural patterns continues to be a significant challenge. Here, we disclose a palladium-catalyzed enantioselective desymmetrization of cyclobutenes, resulting in a series of hydroarylation and 1,2- and 1,3-diarylation products via the interceptions of a common Heck intermediate. Mechanistic investigations provide valuable insights into understanding the catalytic mode of the palladium catalysts and the observed variations in the deuterium-responsive behavior during reactions. Furthermore, the synthetic utility is demonstrated in the syntheses of deuterated drug candidate belaperidone skeletons and pseudosymmetrical truxinic acid-type derivatives.

Aspirin, also named acetylsalicylate, can directly acetylate the side-chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic-labeling aspirin-d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+-dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity. Interestingly, the lysine 408 of SIRT1 can be acetylated by CBP acetyltransferase in cells without aspirin supplement. Aspirin can inhibit SIRT1 to increase the levels of acetylated p53 and promote p53-dependent apoptosis. Moreover, the knock-in mice of the acetylation-mimic mutant of SIRT1 show the decreased production of pro-inflammatory cytokines and maintain intestinal immune homeostasis. The study indicates the importance of the acetylated internal functional site of SIRT1 in maintaining intestinal immune homeostasis.

Cyclobutanes with a gem -dimethyl group are common motifs in natural products. However, strategies for constructing enantioenriched gem -dimethyl cyclobutanes are still underdeveloped. Herein, we report an enantioselective approach to synthesize a broad group of chiral 2,3-disubstituted cyclobutanones through sequential 1,4-conjugate addition/trapping/cross-coupling of readily available cyclobutenones. The intermediate 2-bromocyclobutanone provides a valuable synthetic handle for further coupling transformations. In addition, this strategy was successfully utilized to synthesize gem -dimethyl cyclobutane-containing natural products, including (+)-β-caryophyllene, (−)-raikovenal, (−)-1β,9α H -5-linoleoyloxy-4,5-secocaryophyllen-4-one, and (−)-rumphellanones A−C.

2-Acetonaphthones, which bear an alkenyl group tethered to its C1 carbon atom via an oxygen atom, were found to undergo an enantioselective intramolecular ortho photocycloaddition reaction. A chiral oxazaborolidine Lewis acid leads to a bathochromic absorption shift of the substrate and enables an efficient enantioface differentiation. Visible light irradiation (λ=450 nm) triggers the reaction which is tolerant of various groups at almost any position except carbon atom C8 (16 examples, 53–99 % yield, 80–97 % ee ). Consecutive reactions were explored including a sensitized rearrangement to tetrahydrobiphenylenes, which occurred with full retention of configuration. Evidence was collected that the catalytic photocycloaddition occurs via triplet intermediates, and the binding mode of the acetonaphthone to the chiral Lewis acid was elucidated by DFT calculations.

The incorporation of aromatic difluoromethyl motifs has proven to be a fruitful strategy for enhancing the therapeutic profiles of modern pharmaceutical candidates. While the defluorofunctionalization of trifluoromethylarenes offers a promising pathway towards diverse aromatic difluoromethyl compounds, current methods are predominantly limited to two-component reactions. Multicomponent cascade reactions (MCRs) involving a transient aromatic difluoromethyl radical are still uncommon and highly sought after owing to their capacity to rapidly generate challenging molecular structures. In this study, we present a photocatalytic manifold that combines commercially available trifluoromethylarenes, feedstock dienes and various nucleophiles to achieve a modular defluorinative MCR. This method features mild reaction conditions and a broad substrate scope with excellent functional group compatibility. Furthermore, this protocol enables a previously unreported process of formal defluorinative editing for the resulting MCR aromatic difluoromethyl adducts. Preliminary mechanistic studies support the proposed photoinduced palladium catalytic cycle.

2-Azabicyclo[2.1.1]hexanes (aza-BCHs) are constrained pyrrolidine analogues with improved physicochemical characteristics in drug design. Here, we report a direct visible light-mediated photocycloaddition of 4-aza-coumarins with mono- or disubstituted bicyclo[1.1.0]butanes for synthesizing aza-BCHs without an external catalyst. The introduction of the ester group on 4-azacoumarin is critical for direct imine excitation and versatile synthetic utility. Preliminary mechanistic studies indicated that the reaction took place primarily at the triplet hypersurface.

Conjugate addition and allylic substitution are two essential chemical transformations,and they could be competitive for substrates with multiple reactive sites.Herein,we report the diversified enantioselective synthesis of cyclobutenes via the functionalization of cyclobutenones.The conjugate addition of cyclobutenones with arylzinc halides provided enantioenriched cyclobutenes with all-carbon quaternary centers.On the other hand,when cyclobutenones with gem-dichloro groups were employed,a chemo-and en-antioselective allylic substitution occurred.Further synthetic utility was demonstrated for synthesizing versatile cyclobutane deriva-tives,together with ring-opening and expansion products.

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic synthesis. We report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available dichlorocyclobutanones. The substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic conditions. Further transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

Cu-based liquid-like thermoelectric materials have garnered tremendous attention due to their inherent ultralow lattice thermal conductivity. However, their practical application is hampered by stability issues under a large current or temperature gradient. It has been reported that introduction of copper vacancies can enhance the chemical stability, whereas the micromechanism behind this macroscopic improvement still remains unknown. Here, we have established a quasi in situ TEM method to examine and compare the structural evolution of Cu2-xS0.2Se0.8 (x = 0, 0.05) under external electric fields. It is then found that the preset Cu vacancies could favor the electric-induced formation of a more stable intermediate phase, i.e., the hexagonal CuSe-type structure in the form of either lamellar defects (majorly) or long-range order (minorly), in which ordering of S and Se also occurred. Thereby, copper and chalcogen atoms could largely be solidified into the matrix, and the elemental deposition and evaporation process is mitigated under an electric field.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.