Angewandte Chemie最新文献

Original Article: Sumon Pratihar, Wenrui Zhong, Sheng Feng, Sayantan Chatterjee, Eric T. Kool, Angew. Chem. Int. Ed. 2025, 64, e202515681 (https://doi.org/10.1002/ange.202515681)

The illustrations of RNA in Figure 1a and the graphical abstract were missing a methylene group; they have been corrected.

Solar-driven selective synthesis of C₂ chemicals from CO₂ is a crucial pathway for carbon cycling, but it is limited by the high kinetic barrier of C─C coupling. This study proposes an epitaxial growth strategy for lattice-bonded asymmetric sites. By constructing a Bi₁─O─Bi₂ site at the Bi₃NbO₇ nano-dots/Bi₃O₄Br nanosheet (BNO/BOB) interface to promote C─C coupling for acetic acid production, the photocatalytic conversion rate of CO₂ to acetic acid can reach 192.3 µmol·g⁻¹·h⁻¹, with 91.4% selectivity. The apparent quantum efficiency at 380 and 400 nm reach 9.49% and 6.57%, respectively. The key mechanism originates from a cascade electron effect triggered by the interfacial Bi₁─O─Bi₂ sites: the interfacial charge redistribution induces a strong built-in electric field, where high-energy electrons selectively occupy the 2π antibonding orbitals of CO^* intermediates, significantly weakening the C─O bond in CO^* intermediate. Furthermore, the asymmetric charge redistribution effectively neutralizes the electrostatic repulsion between adjacent CO^* intermediates, synergistically stabilizing the OCCO^* transition state through d-π electron feedback from Bi sites. The dual effects synergistically lower the energy barriers for both the C─C coupling and hydrogenation steps, ultimately steering the reaction pathway towards long-lasting acetic acid formation.

Solar-driven selective synthesis of C₂ chemicals from CO₂ is a crucial pathway for carbon cycling, but it is limited by the high kinetic barrier of C─C coupling. This study proposes an epitaxial growth strategy for lattice-bonded asymmetric sites. By constructing a Bi₁─O─Bi₂ site at the Bi₃NbO₇ nano-dots/Bi₃O₄Br nanosheet (BNO/BOB) interface to promote C─C coupling for acetic acid production, the photocatalytic conversion rate of CO₂ to acetic acid can reach 192.3 µmol·g⁻¹·h⁻¹, with 91.4% selectivity. The apparent quantum efficiency at 380 and 400 nm reach 9.49% and 6.57%, respectively. The key mechanism originates from a cascade electron effect triggered by the interfacial Bi₁─O─Bi₂ sites: the interfacial charge redistribution induces a strong built-in electric field, where high-energy electrons selectively occupy the 2π antibonding orbitals of CO^* intermediates, significantly weakening the C─O bond in CO^* intermediate. Furthermore, the asymmetric charge redistribution effectively neutralizes the electrostatic repulsion between adjacent CO^* intermediates, synergistically stabilizing the OCCO^* transition state through d-π electron feedback from Bi sites. The dual effects synergistically lower the energy barriers for both the C─C coupling and hydrogenation steps, ultimately steering the reaction pathway towards long-lasting acetic acid formation.

Despite the high demands for azetidines as privileged motifs in medicinal chemistry, efficient synthesis platforms that enable the rapid preparation of diversely decorated azetidines remain limited. Although the bis-functionalization of highly strained 1-azabicyclobutane (ABB) has been one of the most viable, modular, and versatile methods for the synthesis of structurally diverse azetidines, the catalytic installation of aliphatic pendants to ABB remains underexplored. In this work, we report the multicomponent synthesis of the elusive all-carbon quaternary azetidines from ABBs through the radical addition of azetidines to various α,β-unsaturated esters, amides, ketones, a 1,3-enyne, and a vinylphosphonate ester. The reaction is facilitated by a bromide/nickel dual-catalyzed polar-radical relay strategy, enabling the radical difunctionalization of α,β-unsaturated carbonyl compounds via sequential ring-strain-release azetidinylation and Suzuki-type arylation or alkenylation. Variation in the individual components enabled the synthesis of >60 azetidine derivatives, including modifications of selected biorelevant molecules. The functional group interconversion of representative azetidine derivatives illustrates the method's potential to produce unprecedented spirocyclic azetidine hybrids, which may be useful for exploring uncharted areas of chemical space in drug design. Additionally, a diastereoselective synthesis using Evans’ oxazolidinone enabled the preparation of an enantiopure azetidine, potentially useful as a platform for library preparation of stereochemically diverse azetidines.

Phenylacetylide-copper (PACu), as an important photoactive intermediate in copper-catalyzed cross-couplings, suffers from limited visible-light absorption, rapid radiative recombination, and poor photostability, hindering its practical application. Herein, we report a conjugation engineering strategy to address these challenges by replacing phenylacetylene with extended π-system ligands, such as 2-ethynylnaphthalene (NA), 9-ethynylphenanthrene (FA), and 1-ethynylpyrene (BA), yielding a series of new alkynyl-copper photocatalysts (NACu, FACu, BACu). Experimental and theoretical studies reveal that enhanced π-conjugation narrows the band gap to 1.95 eV (BACu), extends absorption beyond 600 nm, promotes charge separation, and suppresses Cu^I oxidation during photocatalysis. The optimized BACu demonstrates exceptional photocatalytic activity and stability in [4 + 2] cycloaddition, Glaser coupling, and benzylamine oxidation, achieving >99% conversion and selectivity with excellent recyclability. This work provides fundamental insights into electronic structure modulation via conjugation engineering, offering a universal strategy for designing efficient and stable metal-alkynyl photocatalysts.

Site-specific antibody conjugation through glycoengineering offers a promising route to generate homogeneous glycosite-specific antibody‒drug conjugates (gsADCs) with improved therapeutic indices. Dozens of gsADCs are advancing from preclinical studies to clinical trials. However, current methods involve either multiple enzymes or lengthy preparation of substrates. Herein, we report a novel and synthetically streamlined platform utilizing LacNAc-derived 4,6-acetal glycosyl donors for glycosite-specific transglycosylation mediated by a single enzyme. These glycosyl donors can be synthesized in as few as two steps, representing a major advancement in synthetic accessibility compared to previously reported glycosyl donors, which often require more than 15 steps. Computational analysis showed that the acetal ring restricts conformation, directing donor 7 to a π–π-stabilized groove of the enzyme. Donor 7, along with a positive control, was evaluated in the context of gsADCs, consistently demonstrating potent and selective cytotoxicity toward HER2-positive cancer cells, while sparing HER2-negative cells. Furthermore, donor 7 was successfully adapted to generate glycosite-specific degrader-antibody conjugates (gsDACs), highlighting its broad utility. Additional studies revealed that donor 7 produces antibodies with markedly enhanced resistance to Endo S2 mediated hydrolysis. Together, these findings establish a practical and broadly applicable platform for glycosite-specific antibody conjugation, paving the way for next-generation antibody-based therapeutics.

Fluorinated four-membered rings represent valuable structural motifs in bioactive molecules and pharmaceuticals; however, the asymmetric synthesis of such fluorinated frameworks bearing chiral quaternary carbon centers has not yet been achieved. Herein, we report a Rh-catalyzed enantioselective defluoroarylation of gem-difluorinated cyclobutenes with aryl boronates, enabling the asymmetric construction of fluorinated cyclobutenes bearing chiral quaternary carbon centers with high enantioselectivity via an addition/β-fluoride elimination process. In situ treatment with an additional distinct aryl boronate enables one-pot bis-defluoroarylation to give unsymmetrical diarylated cyclobutenes.

Photoelectrochemical seawater electrolysis for the chloride oxidation reaction (ClOR) suffers from low selectivity against competing reactions and high onset potentials, which severely limits its efficiency for disinfectant production and marine-based chemical synthesis. Herein, we engineer an amorphous CoWO_x layer on BiVO₄ photoanodes that enables highly selective active chlorine (AC) production directly from natural seawater. The CoWO_x/BiVO₄ photoanode delivers a remarkable photocurrent density of 4.78 mA cm⁻² at 1.2 V_RHE under AM 1.5G illumination, with a record-low onset potential of 0.38 V_RHE. Notably, it maintains > 95% Faradaic efficiency and selectivity for AC production across a wide potential range of 0.9–1.8 V_RHE, and retains 86.9% selectivity at 0.6 V_RHE, overcoming the challenge of achieving efficient ClOR at low potentials. The incorporation of W suppresses the dissolution of Bi and V, while a dynamic Co²⁺/Co³⁺ equilibrium ensures operational stability over 150 h. In situ characterization and density functional theory (DFT) calculations reveal that CoWO_x accelerates Cl⁻ oxidation to •Cl intermediates and steers the reaction pathways toward selective AC formation by thermodynamically favoring key chlorine adsorption configurations. Scaled-up 25 cm² photoanodes achieves an AC production rate of 838 µmol h⁻¹. The resulting disinfectant exhibits broad-spectrum bactericidal efficacy, including 99.99% inactivation of E. coli and S. aureus within 24 h. This work establishes a scalable photoelectrode design for the direct, energy-efficient and selective production of valuable active chlorine from seawater.

Photosynthetische Mikroorganismen können zur lichtgetriebenen H₂-Entwicklung genutzt werden. Eine Einschränkung ist jedoch die damit verbundene Bildung von molekularem Sauerstoff als Nebenprodukt der Photosynthese, der die Aktivität des Biokatalysators für die H₂-Produktion, d. h. die Hydrogenase, inhibiert. Wir stellen eine elektrochemische Strategie vor, die eine effiziente Entfernung von O₂ aus immobilisierten mikrobiellen Zellen und deren Umgebung ermöglicht.

The asymmetric hydrogenation of all-carbon tetrasubstituted alkenes has long posed a significant challenge due to their pronounced steric hindrance. Conventional approaches typically rely on precious metal catalysts. Herein, we report the first nickel-catalyzed asymmetric hydrogenation of all-carbon tetrasubstituted electron-deficient alkenes. The developed catalytic system exhibits a broad substrate scope, delivering excellent reactivity and enantioselectivity across 37 examples (up to 99% yield, >99% ee, and TON up to 500). Combined experimental and computational studies reveal that van der Waals interactions play a pivotal role in governing enantioselectivity. This strategy further enables concise asymmetric syntheses of pharmaceutically relevant compounds, including Valerate and Esfenvalerate.