Isotopic Labeling Experiments Research Articles

A large-scale LC-MS dataset of murine liver proteome from time course of heavy water metabolic labeling

Metabolic stable isotope labeling with heavy water followed by liquid chromatography coupled with mass spectrometry (LC-MS) is a powerful tool for in vivo protein turnover studies. Several algorithms and tools have been developed to determine the turnover rates of peptides and proteins from time-course stable isotope labeling experiments. The availability of benchmark mass spectrometry data is crucial to compare and validate the effectiveness of newly developed techniques and algorithms. In this work, we report a heavy water-labeled LC-MS dataset from the murine liver for protein turnover rate analysis. The dataset contains eighteen mass spectral data with their corresponding database search results from nine different labeling durations and quantification outputs from d2ome+ software. The dataset also contains eight mass spectral data from two-dimensional fractionation experiments on unlabeled samples.

Organo‐Mediator Enabled Electrochemical Deuteration of Styrenes

AbstractDespite widespread use of the deuterium isotope effect, selective deuterium labeling of chemical molecules remains a major challenge. Herein, a facile and general electrochemically driven, organic mediator enabled deuteration of styrenes with deuterium oxide (D2O) as the economical deuterium source was reported. Importantly, this transformation could be suitable for various electron rich styrenes mediated by triphenylphosphine (TPP). The reaction proceeded under mild conditions without transition‐metal catalysts, affording the desired products in good yields with excellent D‐incorporation (D‐inc, up to >99 %). Mechanistic investigations by means of isotope labeling experiments and cyclic voltammetry tests provided sufficient support for this transformation. Notably, this method proved to be a powerful tool for late‐stage deuteration of biorelevant compounds.

Organo-Mediator Enabled Electrochemical Deuteration of Styrenes.

Despite widespread use of the deuterium isotope effect, selective deuterium labeling of chemical molecules remains a major challenge. Herein, a facile and general electrochemically driven, organic mediator enabled deuteration of styrenes with deuterium oxide (D2O) as the economical deuterium source was reported. Importantly, this transformation could be suitable for various electron rich styrenes mediated by triphenylphosphine (TPP). The reaction proceeded under mild conditions without transition-metal catalysts, affording the desired products in good yields with excellent D-incorporation (D-inc, up to > 99%). Mechanistic investigations by means of isotope labeling experiment and cyclic voltammetry tests provided sufficient support for this transformation. Notably, this method proved to be a powerful tool for late-stage deuteration of biorelevant compounds.

Mechanistic insight into the hydrogen transfer pathway for selective upcycling of PET to arenes

Selective upcycling of waste plastics into value-added chemicals is of great significance for achieving the resource utilization. In the present study, the selective transformation of polyethylene terephthalate (PET) into arenes (benzene, toluene and p-xylene, labeled as BTX) via one-pot reaction in methanol without external hydrogen supply was put forward, which included methanol reforming, PET methanolysis and following in-situ hydrodeoxygenation. Mechanistic insight into the hydrogen transfer pathway in methanol-mediated PET upcycling into BTX over Pt/TiO2 was systematically elucidated. Remarkably, isotope labeling experiments revealed that hydrogen atoms from methanol could be transferred to the aromatic rings, owing to the formation of electron-deficient sites during conjugation. Density functional theory (DFT) calculations further confirmed that the cleavage of C–O bond in PET methanolysis derivatives took precedence over direct saturation of CO bond, followed by in-situ hydrodeoxygenation transformation for the production of BTX. Using Pt/TiO2 as catalyst for H-transfer upcycling of PET in methanol, desirable BTX yield of 77.96% could be achieved after 3 h reaction. The present research will supply a novel perspective for the high-value utilization of waste oxygen-rich plastics via hydrogen transfer manner.

Analysis of Rhizonin Biosynthesis Reveals Origin of Pharmacophoric Furylalanine Moieties in Diverse Cyclopeptides

AbstractRhizonin A and B are hepatotoxic cyclopeptides produced by bacterial endosymbionts (Mycetohabitans endofungorum) of the fungus Rhizopus microsporus. Their toxicity critically depends on the presence of 3‐furylalanine (Fua) residues, which also occur in pharmaceutically relevant cyclopeptides of the endolide and bingchamide families. The biosynthesis and incorporation of Fua by non‐ribosomal peptide synthetases (NRPS), however, has remained elusive. By genome sequencing and gene inactivation we elucidated the gene cluster responsible for rhizonin biosynthesis. A suite of isotope labeling experiments identified tyrosine and l‐DOPA as Fua precursors and provided the first mechanistic insight. Bioinformatics, mutational analysis and heterologous reconstitution identified dioxygenase RhzB as necessary and sufficient for Fua formation. RhzB is a novel type of heme‐dependent aromatic oxygenases (HDAO) that enabled the discovery of the bingchamide biosynthesis gene cluster through genome mining.

Analysis of Rhizonin Biosynthesis Reveals Origin of Pharmacophoric Furylalanine Moieties in Diverse Cyclopeptides.

Rhizonin A and B are hepatotoxic cyclopeptides produced by bacterial endosymbionts (Mycetohabitans endofungorum) of the fungus Rhizopus microsporus. Their toxicity critically depends on the presence of 3-furylalanine (Fua) residues, which also occur in pharmaceutically relevant cyclopeptides of the endolide and bingchamide families. The biosynthesis and incorporation of Fua by non-ribosomal peptide synthetases (NRPS), however, has remained elusive. By genome sequencing and gene inactivation we elucidated the gene cluster responsible for rhizonin biosynthesis. A suite of isotope labeling experiments identified tyrosine and l-DOPA as Fua precursors and provided the first mechanistic insight. Bioinformatics, mutational analysis and heterologous reconstitution identified dioxygenase RhzB as necessary and sufficient for Fua formation. RhzB is a novel type of heme-dependent aromatic oxygenases (HDAO) that enabled the discovery of the bingchamide biosynthesis gene cluster through genome mining.

Catalytic Asymmetric Synthesis of Zinc Metallacycles.

Transition-metal-catalyzed reductive coupling reactions of alkynes and imines are attractive methods for the synthesis of chiral allylic amines. Mechanistically, these reactions involve oxidative cyclization of the alkyne and the imine to generate a metallacyclic intermediate, which then reacts with H2 or a H2 surrogate to form the product. As an alternative to this hydrogenolysis pathway, here we show that transmetalation to zinc can occur, forming a zinc metallacycle product. This organozinc product serves as a versatile nucleophile for carbon-carbon and carbon-heteroatom coupling reactions. Mechanistic studies based on isotopic labeling experiments and DFT calculations suggest that the key transmetalation step occurs between a Co(II) species and ZnCl2.

Highly selective synthesis of surface FeIV=O with nanoscale zero-valent iron and chlorite for efficient oxygen transfer reactions

High-valent iron-oxo species (FeIV=O) has been a long-sought-after oxygen transfer reagent in biological and catalytic chemistry but suffers from a giant challenge in its gentle and selective synthesis. Herein, we propose a new strategy to synthesize surface FeIV=O (≡FeIV=O) on nanoscale zero-valent iron (nZVI) using chlorite (ClO2-) as the oxidant, which possesses an impressive ≡FeIV=O selectivity of 99%. ≡FeIV=O can be energetically formed from the ferrous (FeII) sites on nZVI through heterolytic Cl-O bond dissociation of ClO2- via a synergistic effect between electron-donating surface ≡FeII and proximal electron-withdrawing H2O, where H2O serves as a hydrogen-bond donor to the terminal O atom of the adsorbed ClO2- thereby prompting the polarization and cleavage of Cl-O bond for the oxidation of ≡FeII toward the final formation of ≡FeIV=O. With methyl phenyl sulfoxide (PMS16O) as the probe molecule, the isotopic labeling experiment manifests an exclusive 18O transfer from Cl18O2- to PMS16O18O mediated by ≡FeIV=18O. We then showcase the versatility of ≡FeIV=O as the oxygen transfer reagent in activating the C-H bond of methane for methanol production and facilitating selective triphenylphosphine oxide synthesis with triphenylphosphine. We believe that this new ≡FeIV=O synthesis strategy possesses great potential to drive oxygen transfer for efficient high-value-added chemical synthesis.

Visible-Light-Mediated Three-Component Decarboxylative Coupling Reactions to Synthesize 1,4-Diol Monoethers.

An efficient approach for 1,2-difunctionalization of aromatic olefins and the synthesis of functionalized 1,4-diols monoethers has been established via a photoinduced three-component reaction of an α-alkoxycarboxylic acid, an aromatic olefin, and an aldehyde. The reaction proceeds by photoinduced oxidative decarboxylation of the carboxylic acid followed by the addition of the α-alkoxyalkyl radical to the olefin, one-electron reduction of the addition radical, and the nucleophilic attack of the resulting carbanion to the aldehyde. Besides the convenient one-pot protocol of the three-component reaction, this method offers several other advantages, including good functional group tolerance for the three substrates, gentle reaction conditions, and ease of scaling up. The reaction mechanism has been investigated through free radical trapping experiment and isotope labeling experiments.

Trichloromethylative Olefin Lactonization by Photoredox Catalysis

AbstractA trichloromethylative olefin lactonization reaction using an iridium photoredox catalyst was developed. The reactions proceeded at room temperature for olefins with various substituents and substitution patterns, and a variety of lactones with a tetrasubstituted carbon and trichloromethyl group were obtained regio‐ and stereoselectively. The reaction mechanism was elucidated through isotope labeling experiments. The chemical properties of the lactones containing the trichloromethyl groups were investigated, and synthetic transformations of the product were realized.

Surface hydrophobic modification of MXene to promote the electrochemical conversion of N2 to NH3

Hydrophobic treatment of the catalyst surfaces can suppress the competitive hydrogen evolution reaction (HER) during the nitrogen reduction reaction (NRR). In this work, the surface of Ti3C2Tix MXene is modified by cetyltrimethylammonium bromide (CTAB) and trimethoxy (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) silane (FOTS) to increase the hydrophobicity of MXenes. The ammonia (NH3) production rate and faradaic efficiency (FE) are improved from 37.62 to 54.01 μg h−1 mg−1cat. and 5.5% to 18.1% at −0.7 V vs. RHE, respectively after surface modification. 15N isotopic labeling experiment confirms that nitrogen in produced ammonia originates from N2 in the electrolyte. The excellent NRR activity of surface hydrophobic MXenes is mainly due to surfactant molecules, which inhibit the entry of water molecules and the competitive HER, which have been verified by in situ FT-IR, DFT and molecular dynamics calculations. This strategy provides an ingenious method to design more active NRR electrocatalysts.

Effect of Cations on Electrocatalytic CO2-to-Methanol Conversion by Heterogenized Molecular Catalyst

Catalytic benefit and role of electrolyte cations for electrochemical CO2 reduction reaction have recently received significant research attention. It has been experimentally and theoretically demonstrated that cations can stabilize the key intermediate species, for example, *CO2 –, through mid- or short-range electrostatic interactions, facilitating the CO2 activation step.1-2 However, to date, these discussions are mostly limited to CO2-to-CO conversion (a two electron/proton transfer reaction) and electrostatic stabilization of reaction intermediate species.In present work, we show that cations play a crucial role in further reducing CO2 to methanol. We found that cations engage as a promoter in the rate determining step of the CO2-to-methanol conversion, which involves a proton-coupled electron transfer, beyond the first CO2 activation step. For this study, heterogenized molecular catalyst with a cobalt single site (Co-N4) was employed, achieving ~25% methanol selectivity at –0.78 V vs. RHE. Through an isotope labeling experiment (13CO2 reduction reaction), we validated that methanol is produced by the CO2 reduction reaction. Furthermore, electrolytes with different cation species and concentrations were tested in a systematic manner to investigate the promoting effect of cations on methanol production. In addition, using deuterated electrolytes, we studied kinetic isotope effect, proposing a reaction pathway for CO2-to-methanol conversion on the cobalt single site. Our findings offer new insights into the beneficial effect of cations on electrochemical CO2 reduction reaction kinetics besides their widely acknowledged stabilizing effect. Our discovery also opens up new research directions where non-covalent interactions between electrolyte species and reaction intermediates are utilized to enhance electrocatalytic production of a desired product in CO2 reduction reaction beyond two-electron transfer products.In this talk, I will discuss the promoting effect of cations on the electrochemical reduction of CO2 to methanol and conclude by proposing potential strategies to further improve the electrocatalytic CO2-to-methanol conversion.References Monteiro, M. C. O.; Dattila, F.; Hagedoorn, B.; García-Muelas, R.; López, N.; Koper, M. T. , Absence of CO2 electroreduction on copper, gold and silver electrodes without metal cations in solution. Nature Catalysis 2021, 4 (8), 654-662.Resasco, J.; Chen, L. D.; Clark, E.; Tsai, C.; Hahn, C.; Jaramillo, T. F.; Chan, K.; Bell, A. T., Promoter Effects of Alkali Metal Cations on the Electrochemical Reduction of Carbon Dioxide. Journal of the American Chemical Society 2017, 139 (32), 11277-11287.

Photocatalytic Conversion of CO2 By H2o As an Electron Donor over Mg-Doped SrTiO3

Atmospheric CO2 is considered as the main cause of climate change, which is known as one of the serious problems for the earth, and several approaches are employed to convert CO2 into value-added products, such as CO, HCOOH, CH3OH and CH4. Among those approaches, photocatalysis has been highly attracting the world-wide attention, because photocatalytic conversion of CO2, which is called as “artificial photosynthesis”, can be a solution for climate change in terms of its renewability, harmlessness and low cost. Ga-based mixed oxide photocatalysts such as ZnGa2O4 were reported as superior photocatalysts for the photocatalytic conversion of CO2 by using H2O3. Recently, our group reported that Ag and Co dual cocatalysts-loaded Al-doped SrTiO3 photocatalyst showed relatively high formation rate of CO for the photocatalytic conversion of CO2 by H2O under photoirradiation with a monochromatic light (365 nm)1, although Ga-based photocatalysts exhibited the activity under the photoirradiation with less than 300 nm. In this study, the effect of metal dopant in SrTiO3 on the photocatalytic conversion of CO2 was investigated. It was found that Mg-doped SrTiO3 showed higher formation rate of CO for the photocatalytic conversion of CO2 into CO under photoirradiation at 365 nm than Al-doped SrTiO3.Mg-doped SrTiO3 was synthesized by a flux method. After grinding mixture of SrTiO3, MgO, and SrCl2 flux, the obtained powder was calcined at 1418 K for 15 h. Ag and Co dual cocatalysts were loaded by chemical reduction method. An aqueous solution of NaH2PO2 reductant was added to the suspension containing Mg-doped SrTiO3, AgNO3, and Co(NO3)2, and it was kept at 353 K for 1.5 h with stirring. The photocatalytic conversion of CO2 by H2O was carried out using an external-irradiation-type reaction vessel. Ag and Co-loaded Mg-doped SrTiO3 was dispersed in 0.1 M NaHCO3 aqueous solution, and high purity CO2 gas was bubbled into the suspension at a flow rate of 30 mL min−1. Monochromatic UV LED lamp (365 nm) was used as a light source. The gaseous products were analyzed by TCD–GC (H2, O2) and FID–GC equipped with methanizer (CO).XRD patterns of pristine and Mg-doped SrTiO3 showed that diffraction peaks are shifted to the lower angle by Mg2+ doping, which might be corresponded to Mg2+ doping into Ti4+ site in the bulk of SrTiO3. SEM images displayed that a shape of Mg-doped SrTiO3 is an edge-shaved cube, while that of pristine SrTiO3 is irregular. In other words, {110} facets were observed in Mg-doped SrTiO3 in addition to {100} facets. According to the previous report2, the photoexcited carriers, electrons and holes, were transported to different crystal facets of the perovskite oxide, especially {100} and {110} facets, respectively. This anisotropic charge distribution would decrease the charge recombination rate in Mg-doped SrTiO3, resulting in the high photocatalytic activity for CO2 conversion.The attached figure shows formation rates of H2 (gray), O2 (white) and CO (black) and selectivity toward CO evolution (black diamond) for the photocatalytic conversion of CO2 by H2O over Ag and Co-loaded pristine SrTiO3, Al-doped SrTiO3, and Mg-doped SrTiO3. Mg-doped SrTiO3 exhibited much higher photocatalytic activity than pristine SrTiO3 and Al-doped SrTiO3. The formation rate of CO over Mg-doped SrTiO3 was 20 μmol h−1, which was 2.3 times larger than that over Al-doped SrTiO3. Surprisingly, the selectivity toward CO evolution was almost 100 % over both Al-doped and Mg-doped SrTiO3. Moreover, the stoichiometric amount of O2 evolution was observed during this reaction, indicating that H2O worked as an electron donor for the photocatalytic conversion of CO2.The control experiments revealed that the reduction of CO2 did not proceed in the absence of photocatalyst, photoirradiation, or additive (0.1 M NaHCO3). These results clearly indicated that the significant photocatalytic performance was observed by using the Ag and Co-loaded Mg-doped SrTiO3 photocatalyst under photoirradiation with a NaHCO3 additive in the suspension. To confirm that the generated CO is not derived from any organic contamination, the isotope-labeling experiments using 13CO2 gas was carried out. GC-MS analysis of the outlet gas in the photocatalytic conversion of 13CO2 over Mg-doped SrTiO3 clarified that 13C-labeled CO (m/z = 29) was evolved in priority to 12CO (m/z = 28). Accordingly, we concluded that CO gas evolved in our system is originated from CO2 gas bubbled into the suspension. Wang, et al., Chem. Sci., 2021, 12, 4940–4948Takata, et al., Nature, 2020, 581, 411–414Wang, et al., J. Mater. Chem. A 2015, 3, 11313–11319 Figure 1

Fabricating MOF@COF core-shell catalyst with remarkable CO2 adsorption capacity and charge carrier dynamic for efficient CO2 conversion

In this study, we utilized Zn-atz (MOFs) with a high CO2 adsorption capacity and composite it with COF-TD (COFs) via an imine bond to form Zn-atz@COF-TD. The resulting composite material exhibited a significantly higher CO2 adsorption capacity of reaching 39.0 cm3g−1, which was 2.3 times that of Zn-atz and 9.0 times that of COF-TD. The exceptional CO2 adsorption ability enhanced the concentration of CO2 around the active sites, which is beneficial for CO2 reduction. Moreover, the covalent bonding of Zn-atz to COF-TD through an imine bond provided a pathway for charge carrier transfer, facilitating electron-hole separation and migration. These two advantages synergistically accelerated the conversion of CO2 with high efficiency. Under the optimal reaction conditions, Zn-atz@COF-TD demonstrated a CO evolution rate of 8.94 μmolg−1h−1, which is 4.5 times that of Zn-atz and 2.3 times that of COF-TD. Isotope labeling experiments confirmed that the resulting CO was derived from CO2. Additionally, the photocatalysis reaction process is environmentally friendly as it does not require any sacrificial agent. Based on the results of in situ FT-IR spectra, a proposed reaction pathway of photocatalytic CO2 reduction is presented. This study offers novel insights into the utilization of MOFs@COFs-based materials with a core-shell structure in the field of photocatalysis.

Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples

Stable isotopes are powerful tools to assess metabolism. 13C labeling is detected using nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry (MS). MS has excellent sensitivity but generally cannot discriminate among different 13C positions (isotopomers), whereas NMR is less sensitive but reports some isotopomers. Here, we develop an MS method that reports all 16 aspartate and 32 glutamate isotopomers while requiring less than 1% of the sample used for NMR. This method discriminates between pathways that result in the same number of 13C labels in aspartate and glutamate, providing enhanced specificity over conventional MS. We demonstrate regional metabolic heterogeneity within human tumors, document the impact of fumarate hydratase (FH) deficiency in human renal cancers, and investigate the contributions of tricarboxylic acid (TCA) cycle turnover and CO2 recycling to isotope labeling invivo. This method can accompany NMR or standard MS to provide outstanding sensitivity in isotope-labeling experiments, particularly invivo.

Deep reaction network exploration of glucose pyrolysis

Resolving the reaction networks associated with biomass pyrolysis is central to understanding product selectivity and aiding catalyst design to produce more valuable products. However, even the pyrolysis network of relatively simple [Formula: see text]-D-glucose remains unresolved due to its significant complexity in terms of the depth of the network and the number of major products. Here, a transition-state-guided reaction exploration has been performed that provides complete pathways to most significant experimental pyrolysis products of [Formula: see text]-D-glucose. The resulting reaction network involves over 31,000 reactions and transition states computed at the semiempirical quantum chemistry level and approximately 7,000 kinetically relevant reactions and transition states characterized with density function theory, comprising the largest reaction network reported for biomass pyrolysis. The exploration was conducted using graph-based rules to explore the reactivities of intermediates and an adaption of the Dijkstra algorithm to identify kinetically relevant intermediates. This simple exploration policy surprisingly (re)identified pathways to most major experimental pyrolysis products, many intermediates proposed by previous computational studies, and also identified new low-barrier reaction mechanisms that resolve outstanding discrepancies between reaction pathways and yields in isotope labeling experiments. This network also provides explanatory pathways for the high yield of hydroxymethylfurfural and the reaction pathway that contributes most to the formation of hydroxyacetaldehyde during glucose pyrolysis. Due to the limited domain knowledge required to generate this network, this approach should also be transferable to other complex reaction network prediction problems in biomass pyrolysis.

Chemoselective synthesis of tertiary and secondary amines by reductive amination of aldehydes

A simple and efficient catalyst-free chemoselective reductive amination of primary amines and aldehydes to synthesis of tertiary and secondary amines with borane complex was developed. Primary amines are converted into tertiary and secondary amines in one pot reaction under mild condition with good functional group compatibility and It does not require any catalyst to participate in this reaction. The chemoselective control was achieved by switching the steric hindrance of borane complex. The strategy was successfully applied to synthetize Tetracaine (anaesthetic) and the potential mechanism was verified by isotope labeling experiments.

Nitrilotriacetic acid-assisted Mn(II) activated periodate for rapid and long-lasting degradation of carbamazepine: The importance of Mn(IV)-oxo species.

Periodate-based (PI, IO4-) oxidation processes for pollutant elimination have gained increased attention in recent years. This study shows that nitrilotriacetic acid (NTA) can assist trace Mn(II) in activating PI for fast and long-lasting degradation of carbamazepine (CBZ) (100% degradation in 2min). PI can oxidize Mn(II) to permanganate(MnO4-, Mn(VII)) in the presence of NTA, which indicates the important role of transient manganese-oxo species. 18O isotope labeling experiments using methyl phenyl sulfoxide (PMSO) as a probe further confirmed the formation of manganese-oxo species. The chemical stoichiometric relationship (PI consumption: PMSO2 generation) and theoretical calculation suggested that Mn(IV)-oxo-NTA species were the main reactive species. The NTA-chelated manganese facilitated direct oxygen transfer from PI to Mn(II)-NTA and prevented hydrolysis and agglomeration of transient manganese-oxo species. PI was transformed completely to stable and nontoxic iodate but not lower-valent toxic iodine species (i.e., HOI, I2, and I-). The degradation pathways and mechanisms of CBZ were investigated using mass spectrometry and density functional theory (DFT) calculation. This study provided a steady and highly efficient choice for the quick degradation of organic micropollutants and broadened the perspective on the evolution mechanism of manganese intermediates in the Mn(II)/NTA/PI system.

Insight into the effect of F− on acidity of H-SAPO-18 and its catalytic performance for conversion of methanol to olefins

In this study, F− was added to the synthesis gel to regulate the acid property of SAPO-18 molecular sieve and enhance its catalytic performance for the methanol-to-olefin (MTO) reactions. The results indicate that adding an appropriate amount of F− during synthesis can increase the crystallinity of SAPO-18 molecular sieve and reduce the overall strong acid density and external surface acid content. The H-SAPO-18-I-20-0.0025 molecular sieve exhibits a much higher catalytic lifetime (1000 min) and light olefins selectivity (45.2% to propene and 96.1% to C2-5=) in MTO at 400 °C than those of the traditional H-SAPO-18-1-0. The results of the isotope labeling experiments, GC-MS, and 13C MAS NMR results provided direct evidence that the aromatic-based cycle contributes more to the conversion of methanol into light olefins, and hexamethylbenzene serves as the most abundant hydrocarbon species that produces propene via the paring route.

Copper‐Catalyzed Olefinic C(sp2)−H Activation/Carbene Insertion/Ester Hydrolysis/Cyclization with Aryl Diazo Esters for the Synthesis of Multisubstituted Furanones

AbstractA copper‐catalyzed olefinic C(sp2)−H activation/carbene insertion/ester hydrolysis/cyclization sequence has been developed for the synthesis of substituted 2(5H)‐furanones employing readily available enaminones and aryl diazo esters as substrates. This method features operationally simple and good functional group tolerance. The transformation could be scaled up to gram quantities and the obtained 2(5H)‐furanone derivatives could be easily converted to a wide range of useful synthetic building blocks, indicative of the applicability of the synthetic strategy. Isotope labeling experiments demonstrated the ester group of diazo esters was hydrolyzed during the reaction.