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Base-Catalyzed Aqueous Methylenation of Imidazo[1,2-a]pyridines with Glyoxylic Acid: Synthesis of Bis(imidazo[1,2-a]pyridin-3-yl)methanes. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-18 Yinrong Wu,Xixiang Yang,Lin Yuan,Xiaodong Tang,Jianjun Chen
An efficient base-catalyzed method for the methylenation of imidazo[1,2-a]pyridines using glyoxylic acid was discovered. Various imidazo[1,2-a]pyridines were successfully converted to bis(imidazo[1,2-a]pyridin-3-yl)methanes in aqueous media. In addition, this strategy was extended to coupling imidazo[1,2-a]pyridines with other nucleophiles via methylene groups, yielding various substituted imidazo[1
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Synthesis of Sterically Hindered Monophosphino-o-Carboranes by Rh(I)-Catalyzed B(3,6)-H Arylation under Microwave Irradiation. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-18 Jin-Peng Liu,Yue Hu,Rui Guo,Sixuan Meng,Jian Chen,Jia Yuan,Guang-Ao Yu
Rh(I)-catalyzed B(3,6)-H arylation of monophosphino-o-carborane and a variety of aryl halides bearing ortho-substituted and di-ortho-substituted groups can be carried out under microwave irradiation. Sterically hindered B(3)-arylated and B(3,6)-diarylated products were obtained in 11-95% yields.
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Solvent-Controlled Regiodivergent Friedel-Crafts Reactions of 1-Naphthol with In Situ Generated Aza-o-Quinone Methides. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-18 Si-Kai Liu,Salha Alotaibi,Jen-Yu Kuan,Theo P Gonçalves,Kuo-Wei Huang,Jeng-Liang Han
In this study, we reported a solvent-controlled site-selectivity switchable Friedel-Crafts reaction of 1-naphthols with in situ generated aza-o-quinone methides. The ortho-selective Friedel-Crafts reaction was achieved in toluene, while the para-selective Friedel-Crafts reaction was accomplished in acetonitrile. With this protocol, a range of functionalized triarylmethanes were prepared. Moreover,
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Development of a Scalable Synthesis of a HPK1 Inhibitor Featuring a Direct α-Arylation of Boc-Protected N,N-Dimethylamine by Palladium-Mediated Negishi Cross-Coupling. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-18 Dahui Zhou,Matthew Del Bel,Thomas Knauber,Simon Berritt,John Braganza,Adam Brown,Anne-Marie Dechert Schmitt,Rebecca Gallego,Mingying He,Jennifer Lafontaine,Jean Matthews,Peter Morse,Sebastien Monfette,Neal Sach,Joseph Tucker,Lei Zhang,Ru Zhou,Pingyong Liao,Tongnan Liu,Fanxiu Meng,Qiming Mu,Bin Sun,Chaobo Wu,Xin Zhao,Sajiv Nair
The development of an improved synthesis of the potent HPK1 inhibitor, compound 1, is described. Two primary strategies were explored during this process: metallaphotoredox decarboxylative coupling and Negishi cross-coupling, both focusing on the direct installation of Boc-protected amine in a single step. Through the optimized Pd-catalyzed Negishi cross-coupling, a robust procedure was established
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Preparation and Regioselective Ring Opening Reactions of Fused Bicyclic N-Aryl Aziridines. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-18 Elliot F Hicks,Leanne M Fuentes Ruiz,Bryce E Gaskins,Michael K Takase,Brian M Stoltz
Presented herein is a systematic evaluation of ring opening reactions of bicyclic N-aryl aziridines. This class of compounds has not seen extensive study in the context of ring opening reactions making the site of reaction difficult to predict, potentially limiting their use as intermediates in the synthesis of nitrogen-containing molecules. Our recent successful ring opening strategy in the synthesis
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Stereoselective Synthesis of Multisubstituted γ-Imino α-Amino Acid Derivatives via Mannich Addition of β,β-Disubstituted Enesulfinamides to α-Alkynyl-Substituted α-Imino Esters. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-18 Yang Liu,Chong-Dao Lu
The metalloenamines, generated via the NH-deprotonation of β,β-disubstituted enesulfinamides using lithium diisopropylamide (LDA), participate in stereoselective nucleophilic addition reactions with β,γ-alkynyl-α-ketimino esters. This process yields multisubstituted γ-imino α-amino acid esters that contain acyclic vicinal quaternary-tetrasubstituted stereocenters, which are typically challenging to
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Sulfoxide-Controlled Chlorination of Pyrrolo[2,1-a]isoquinoline with Acetyl Chloride. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-18 Man Jiang,Jing Zhou,Hai-Lei Cui
A sulfoxide-controlled modification of pyrrolo[2,1-a]isoquinoline derivatives has been explored using acetyl chloride. In the presence of AcCl and PhSOPh, the dichlorination of methoxy-bearing pyrrolo[2,1-a]isoquinolines could be achieved at both the pyrrolic moiety and the phenolic ether moiety. Monochlorination of pyrrolo[2,1-a]isoquinoline derivatives occurred solely by the replacement of diphenyl
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Selective Reductions of Esters to Aldehydes: Extended Scope and Downstream Reactivity. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Rebeka Ločmele,Gábor Szilvágyi,József Répási,Gints Smits
In our study, we extended the applicability of ester hydrosilylation methodology employing (2-bromo-6-fluorophenyl)bis(2,3,5,6-tetrafluorophenyl)borane (SBR12) catalysts. Overall, the method features exceptionally low catalyst loading (as little as 0.01 mol %), along with mild reaction conditions and a high tolerance for various functional groups. We demonstrated the practicality of this technique
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Copper-Catalyzed Intermolecular Cyclopropanation of Benzofurans and Indoles. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 William A Carrick,Dorian Vallantin,Tabea Nett,Benjamin Darses,Jeffrey S Johnson
A method to cyclopropanate benzofurans and Cbz-protected indoles using a Cu(II) catalyst has been developed. Aryl diazoacetates react suitably with copper(II) hexafluoroacetylacetonate (Cu(II)hfacac2) to form a putative metal carbenoid that gives a productive dearomative reaction with substituted benzofurans and Cbz-protected indoles. The use of Cu(II) represents a shift toward more sustainable earth-abundant
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The Anthranil Core as a π-Conjugated Bridge in the Synthesis of Molecular Photosensitizers. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Laia Marín Moncusí,Carlos E Puerto Galvis,Eugenia Martínez-Ferrero,Emilio Palomares
Molecular photosensitizers based on the anthranil core were synthesized through a six-step linear synthesis featuring a Suzuki coupling at the C7 position and a controlled C3-H arylation. The introduction of donor and acceptor groups allowed the synthesis of unsymmetrical photosensitizers that were then investigated, revealing different spectroscopic and optoelectronic properties. Transient spectroscopy
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Synthesis of Functionalized Cyclohexenes through a Vinyl Alkenylation-Initiated [4 + 2] Cycloaddition Reaction. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Yongdi Xin,Bin Li,Biao Cheng,Qianting Zhou,Xinying Zhang,Xuesen Fan
Notwithstanding the prevalence of functionalized cyclohexene skeletons in natural products and pharmaceuticals, concise synthetic protocols for their effective assembly from simple starting materials are still scarce. Herein, we present a highly efficient and sustainable access toward functionalized cyclohexenes based on the cascade reaction of N-methoxyacrylamides with allenyl acetates. The formation
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Controlled Switching from Spirobi[pyrrolo[1,2-c]thiazoles] to Pyrrolo[1,2-c]thiazole-3-thiones during the Cyclization of 2-Acylethynylpyrroles with Carbon Disulfide. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Denis N Tomilin,Sophia A Stepanova,Igor A Ushakov,Alexander V Vashchenko,Boris A Trofimov
Base-catalyzed cycloaddition of 2-acylethynylpyrroles with carbon disulfide (NaOH, DMSO, room temperature) proceeds stereoselectively to provide spirobi[pyrrolo[1,2-c]thiazoles] and pyrrolo[1,2-c]thiazole-3-thiones, both integrated with Z-α,β-ethylenic ketones in 40-81 and 35-86% yields, respectively. The switching between spirobi[pyrrolo[1,2-c]thiazoles] and pyrrolo[1,2-c]thiazole-3-thiones is controlled
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Access to Unnatural Enantioenriched Amino Acids Derived from Phenylglycine through Nickel-Catalyzed Suzuki-Miyaura Coupling Involving Carbon-Oxygen Bond Insertion. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Jiaxiao Yang,Mamoudou Doucoure,Yasmine Charifi,Gustave Villard,Ying Xu,Joëlle Perard-Viret,Marie-Isabelle Lannou
We report herein the optimization of a nickel-catalyzed Suzuki-Miyaura coupling for the synthesis of unnatural bi- and polyaryl and heteroaryl amino acid derivatives (28 examples). The aim is to provide an inexpensive and efficient alternative to palladium-catalyzed reactions, exploiting nickel's reactivity toward oxygen-based electrophiles. To this end, easily racemizable hydroxyphenylglycine derivatives
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SET Cleavage of Peroxides: Influence of Reductant and Peroxide on the Reactivity and Regioselectivity of Alkoxy Radical Formation. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Amber Schuster,Boone W Evans,Jody G Redepenning,Jian Zhang,Patrick H Dussault
Alkoxy radicals are an important class of reactive intermediates frequently generated through single electron transfer (SET) reductions of organic peroxides. We investigated the reactions of a family of peroxide probes with a series of metal and photoredox reductants, with a focus on reactivity as well as regioselectivity of cleavage in terms of selectivity of alkoxy radical generation. A hydroperoxide
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Unexpected Suppression of Double-Proton Tunneling Induced by Quantum Barriers from Zero-Point Energy. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Edyta M Greer,Florence Uritsky,Benjamin Herrera,Frankie Benavides,Alexander Greer,Charles Doubleday
To assess tunneling, we studied the guanine-cytosine (GC) base pair tautomerization in the gas phase. We applied multidimensional semiclassical reaction path methodology with microcanonically optimized multidimensional tunneling (μOMT) using POLYRATE. The minimum energy path (MEP) has a single saddle point for the double proton transfer. Addition of vibrational zero-point energy (ZPE) to the MEP gives
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Dimolybdenum Catalysis: Deoxygenative Coupling of Aldehydes. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Xiang Gao,Rui Wu,Shifa Zhu
Described herein is the first example of dimolybdenum-catalyzed deoxygenative coupling of aldehydes using pinacol as a benign reductant. Both homocoupling and heterocoupling were successfully achieved. This facile protocol enables the rapid construction of a collection of symmetrical and unsymmetrical alkenes, including bioactive stilbenes, Pterostilbene, and DMU-211, with high (E)-selectivity. Detailed
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Base-Promoted S-Trideuteromethylation of Sulfenamides to Access Trideuteromethyl Sulfilimines. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-17 Kalyanakrishnan Arayil Vennoli,Afna Nizar,Parvathi Ikkara Sunil,Devashish Kalmegh,Shanawas Hussain Moulana Mahal,Alagiri Kaliyamoorthy
Recently, both sulfilimines and deuterated organic molecules have garnered considerable attention in organic synthesis, drug discovery, and agrochemicals. Herein, we present a base-mediated efficient synthetic route for synthesizing trideuteromethyl sulfilimines from sulfenamides utilizing cost-effective and readily accessible CD3OTs as an electrophilic trideuteromethyl source. A wide array of both
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Base-Mediated Substrate-Dependent [2 + 3] and [3 + 3] Annulation of Bisnucleophiles: Enabling the Modular Synthesis of Functionalized Spirocyclopentane Oxindoles and Tetrahydro-α-carbolines. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Jiaxu Feng,Yingying Wu,Lulu Xu,Xiangdi Wang
Herein, we represented two facile and efficient approaches for the synthesis of functionalized spirocyclopentane oxindoles and tetrahydro-α-carbolines from different bisnucleophiles with 3-iodo-2-iodomethyl-1-propene via [2 + 3] and [3 + 3] annulation. These methods exhibit good functional group tolerances, simple conditions, easily available start materials, and moderate to good yields.
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Copper-Catalyzed Diastereoselective Borylative α-(N-Aryl)aminoalkylation of Vinyl Arenes with Nitrones. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Jingyu Li,Long Chen,Ziqi Dang,Wei Dong,Zixin Ye,Zhen Qin,Ming Li,Shuxia Wang,Xiulian Zhang,Chuanzhou Tao
A copper-catalyzed three-component coupling of vinyl arenes, bis(pinacolato)diboron, and nitrones has been developed, which offers access to a diverse range of γ-(N-aryl)amino boronates via reductive workup, exhibiting good-to-excellent diastereoselectivities. This new protocol, which can be performed at a gram scale, utilizes nitrones as simple precursors and provides γ-amino boronates having versatile
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Solid-Phase Synthesis of Five-Membered Heterocycle-Fused Tryptanthrin via a Two-Site Oxidation Reaction. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Jimin Moon,Taeho Lee
Tryptanthrin (tryp) is being studied as a lead compound with pharmacological activity that is found in nature. To date, synthetic and pharmacological studies on trypanthrin have focused on substitution patterns on the A and D rings, while structural modifications of the A ring system have yet to be explored synthetically. In this study, we synthesized a tryp derivative containing a five-membered heterocyclic
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Computational Studies of Chiral Epoxide Radicals. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Kathleen M Morgan,Lauren A Brown,Camryn C Cole,Giavonna K Cooper,Alajah Nealy,DiJon Seltzer
Epoxides are strained heterocycles that are common commodity chemicals and synthetic intermediates. The goal of this study is to understand and compare the reactivity of simple epoxides and their radicals in the gas phase using G4 and W1BD calculations. The epoxides include the parent oxirane and monosubstituted analogs having -CH3, -NH2, -OH, -F, and -Cl substituents. The C-H bond dissociation energies
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Z-Axis-Oriented Pyrene Architectures: Regioselective Bipolar Engineering for Full Color-Tunable Emission. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Jiexi Liang,Chongyang Zeng,Tao Jiang,Xiaohui Wang,Carl Redshaw,Xing Feng
Controllably functionalizing pyrene at specific active sites along the Z-axis remains a significant synthetic challenge. In this work, we present a rationally designed synthetic strategy for the stepwise Z-axis functionalization of pyrene at the 1,3- and 6,8-positions, using a hydroxyl group at the 2-position as a directing group. This approach allows for the construction of novel Z-axis-oriented bipolar
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Deconvoluting the Effects of Substituents on Reaction Barriers through Machine Learning: The Case of Brønsted Acid-Mediated Nazarov Cyclizations. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Angus Keto,Elizabeth H Krenske
The barrier heights of Nazarov cyclizations are influenced by substituents in ways that can be challenging to predict. We explore the ability of machine learning (ML) models to predict the barriers by learning the activating and deactivating contributions of different substituents on the divinyl ketone. Random forest and graph neural network models are shown to achieve good predictive accuracies, with
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Insight into Diastereoselective Synthesis of β-Furan/Pyrrole-Substituted Cyclohexenone Derivatives through AlCl3-Catalyzed Cascade Rearrangement of Diels-Alder Cycloaddition Intermediates. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Xinkun An,Tingting Zhang,Haoyun Ma,Xie He,Yiyi Li,Mingan Wang
Herein, a strategy for the diastereoselective formal conjugate addition of heteroarenes and cyclic enone derivatives via the promotion of aluminum catalyst under mild conditions was reported. The formal Michael addition of a range of heteroarene dienes, including furans and pyrroles, to a variety of cyclohexanedienone derivatives containing a natural product and drug substrate occurred to achieve corresponding
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Photocatalyzed Intramolecular C-S Bond Formation: Green Synthesis of 2-Substituted Benzothiazoles. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-16 Yuxuan Han,Zhe Lv,Xiaoting Chen,Yadong Feng,Xiuling Cui
Visible-light-promoted oxidative cyclization reaction of thiobenzanilides for the intramolecular C-S bond construction has been developed. By employing acridinium salt as the photosensitizer, catalytic amount of tetramethylpiperidine-1-oxyl (TEMPO) as the hydrogen atom transfer (HAT) agent, and molecular oxygen from air as the terminal oxidant, 2-substituted benzothiazoles are efficiently synthesized
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Modular Synthesis of Trisubstituted 3-Oxazol-5(2H)-ones from α-Keto Acids, Ketones, and Ammonium Salt by Multicomponent Strategy. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Bin Tan,Enming Gao,Cheng Tian,Feng Zhao
In this report, we describe a direct and mild three-component reaction for the modular synthesis of 2,2,4-trisubstituted 3-oxazol-5(2H)-ones from ubiquitous α-keto acids, ketones, and ammonium salt. Significantly, a diverse library of trisubstituted 3-oxazol-5(2H)-ones (120 examples), including pharmaceutical derivatives, was efficiently obtained without the need for any extra catalysts or additives
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Hydrogen Tunneling in Thiobenzamide: A Case Study on Tunneling Through High-Energy Barriers. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 José P L Roque,Cláudio M Nunes,Epole Ntungwe,Antonio Fernández-Ramos,Rui Fausto
A few intriguing hydrogen quantum mechanical tunneling (QMT) reactions through high-energy barriers (>20 kcal mol-1) have been observed in cryogenic matrices. Building on these examples, we report here investigations into the QMT reactivity of thiobenzamide. Thiol isomers (1Tl) were generated in an argon matrix at 10 and 20 K. One thiol isomer (1Tl-aT) converts into another (1Tl-sT) via QMT S-H rotamerization
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Silylium-Ion-Promoted Formation of Methylenecyclobutenes by Formal (2 + 2) Cycloaddition of Allenylsilanes and Internal Alkynes. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Lei Deng,Honghua Zuo,Hendrik F T Klare,Martin Oestreich
A (2 + 2) cycloaddition of propargylsilanes and internal alkynes to afford densely substituted methylenecyclobutenes is reported. The propargylsilane is generated in situ by rapid silylium-ion-catalyzed isomerization of the corresponding allenylsilane through the intermediacy of a β,β'-bis(silicon)-stabilized vinyl cation. The stepwise cycloaddition is initiated by a silylium ion, and the (2 + 2) pathway
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Divergent Synthesis of Indoline-2-Phosphonates, Indole-2-Phosphonates, and Quinolines via Aza-Claisen Rearrangement of α-(Arylamino)phosphonates. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Babak Kaboudin,Mahsa Ghasemi,Mojtaba Ghashghaee,Haruhiko Fukaya,Hikaru Yanai
An efficient and practical method has been developed for the synthesis of indole-2-phosphonates from easily accessible α-(arylamino)phosphonates. The present synthesis includes the aza-Claisen rearrangement of α-(arylamino)phosphonates to give vinyl phosphonates, which was easily converted to the corresponding indoline products through the 5-exo-trig cyclization. The following dehydrogenative oxidation
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Gold(I)-Catalyzed Pathway-Switchable Syntheses of Azocine[4,5-b]indole and (1H-indol-3-yl)-Azepino[4,5-b]indole Derivatives. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Jiaji Li,Zhibin Zhao,Ziqiang Xu,Qing Jiang,Sen Zhang,Lianjie Zhang,Bin Lin,Lu Yang,Maosheng Cheng,Yongxiang Liu
A pathway-switchable gold(I)-catalyzed N-propargyl tryptamine cycloisomerization strategy was developed and successfully used for the syntheses of azocine[4,5-b]indole and (1H-indol-3-yl)-azepino[4,5-b]indole derivatives. The optimal reaction conditions for the two pathways were determined through detailed studies, and the scope of this pathway-switchable approach was explored using a series of N-propargyl
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FeCl3/TBHP-Mediated Oxidation of Indoles: Divergent Product Selectivity under Mechanochemical and Solution-Based Conditions. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Bhawani,Pratiksha Jangir, Sonam,Krishnan Rangan,Anil Kumar
A condition-controlled diversity-oriented approach to access different frameworks by the FeCl3/TBHP-mediated oxidation of indoles is developed. Oxidation of indoles produced 2-(indol-3-yl)indolin-3-ones in moderate to high (46-87%) yields under mechanochemical ball milling and benzoxazinones in good to excellent yields (9-90%) under solution-based conditions. The developed methods demonstrated a broad
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Switchable Four- and Five-Component Reactions with Perfect Regioselectivity Promoted by Photoredox/Sulfide Dual-Catalytic Quenching for Access to Diverse Complex Imides. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Kakeru Matsukuma,Masanori Tayu,Ryota Itai,Kotaro Imai,Sayaka Ohrui,Nozomi Saito
Multicomponent reactions, which involve the reaction of three or more components in a single step to efficiently produce a new molecular structure, have received growing attention in a range of research areas. In this study, four- and five-component reactions incorporating alkenes, carboxylic acids, alkyl radicals, and nitriles are developed for the imidoalkylation of alkenes with perfect regioselectivity
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Visible-Light SNAr Pyridination of Aryl Halides and Triflates with Acridine-Lewis Acid Photocatalysts. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Sabrina M Reich,Matthew R Lasky,Melanie S Sanford
This report describes the development of a visible light (440 nm) photocatalytic method for the cation radical-accelerated (CRA) SNAr pyridination of aryl (pseudo)halides using modular acridine-Lewis acid photocatalysts. A first-generation catalyst composed of acridine and Sc(OTf)3 is effective for the reaction of electronically diverse pyridines with electron-rich (primarily alkoxy- and alkyl-substituted)
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Total Synthesis of (-)-Enigmazole A by the Macrocyclization/Transannular Pyran Cyclization Strategy: Application to Structure-Activity Relationship Investigations. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-15 Kyoya Ohyama,Taisei Masuda,Keita Sakamoto,Atsushi Yoshimura,Kyoko Tatsumoto,Keisuke Murata,Haruhiko Fuwa
An 18-step total synthesis of (-)-enigmazole A was achieved by means of our macrocyclization/transannular pyran cyclization strategy. Specifically, the 18-membered macrolactone skeleton of (-)-enigmazole A was constructed from three readily available building blocks through a Horner-Wadsworth-Emmons olefination, a Yamaguchi esterification, a macrocyclic ring-closing metathesis, and a transannular oxa-Michael
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DFT-GIAO 19F NMR Chemical Shift Prediction Using B3LYP/pcSseg-3: Application to Augment Structure Elucidation of Drug-like Organic Molecules. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Rittik K Ghosh,Gabriel A Valdivia-Berroeta,Dongyue Xin,Nina C Gonnella
Accurate calculation of 19F chemical shifts for CF3, CF2, and CF fluorine types using density functional theory-gauge including invariant atomic orbitals (DFT-GIAO) approximation is described. Six methods, B3LYP/cc-pVDZ, B3LYP/pcSseg-3, ωB97X-D/cc-pVDZ, ωB97X-D/pcSseg-3, B3LYP/6-31+G(d,p), and PBE1PBE/Def2TZVP were evaluated for speed and accuracy. Based on our findings B3LYP/cc-pVDZ and B3LYP/pcSseg-3
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Design and Synthesis of a 3-Arylenoyltetramic Acid Library Employing a Consecutive Three-Component Coupling. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Miho Yoshiki,Shiori Koyama,Hironao Kobayashi,Shotaro Mimura,Tomonari Ri,Hiromichi Nishiyama,Yusuke Sasano,Yoshiharu Iwabuchi,Junko Fujimoto,Aoi Kimishima,Masako Honsho,Hiromasa Yokoe,Kazutada Ikeuchi,Yukihiro Asami,Naoki Kanoh
A facile method for synthesizing 3-arylenoyltetramic acids using consecutive coupling of a newly designed iodovinyldioxinone, arylboronic acids, and protected amino acids was established. The iodovinyldioxinone first undergoes Suzuki-Miyaura coupling with various arylboronic acids at room temperature to give 6-substituted dioxinones. These dioxinones generate acylketenes on heating, which react with
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Concise Total Synthesis of Sandramycin and Its Analogues via Cyclodimerization Using Mitsunobu Reaction. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Radhakrishnam R Ruddarraju,Yuya Komatani,Yasuaki Tokodai,Satoshi Ichikawa
Total synthesis of sandramycin was achieved via a cyclodimerization approach of the precursor pentapeptide by using the Mitsunobu reaction. This strategy allowed us to prepare a range of analogues efficiently. Their DNA binding ability and cytotoxicity against human cancer cell lines were also evaluated.
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Multicomponent Tandem Reactions for the Synthesis of gem-Dibromo Compounds via an ATRA/Elimination/Nucleophilic Substitution Process. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Renhua Su,Jiantao Zhang,Yanfu Jiang,Xian Jiang,Yifu Long,Peng Zhou,Weibing Liu
We developed a metal-free tandem atom transfer radical addition/elimination/nucleophilic substitution of alkenes with CBr4 and amines to synthesize a series of α-amino-substituted gem-dibromo compounds which are useful building blocks in diverse organic synthesis. Moreover, this transformation avoids the usage of any catalysts and external additives and also exhibits a broad substrate scope and high
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[3 + 3] Annulative Functionalization Approaches to Poly-Functionalized 8-Acylindolizines, 8-Enylindolizines, and Indolizine-Coumarin Hybrids. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Yerin Jeong,Sunmi Kim,Sunhee Lee,Dohui Ku,Hyunjin Oh,Ikyon Kim
Synthetic efforts to expand the indolizine chemical space via an annulative functionalization strategy are described. Cs2CO3-promoted [3 + 3] annulations under mild reaction conditions enabled facile decoration of a number of functional groups at the pyridine moiety by way of a domino N-alkylation-intramolecular aldol condensation procedure to afford a wide range of novel indolizines such as 8-acylindolizines
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The DMSO-Catalyzed CO2 Reduction with 9-BBN as a Source for the Selective N-Formylation, Room Temperature N-Methylation of Amines, N-Hydroxymethylation of Heterocycles, and C-N Couplings. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Ashok Kumar,Rohit Gupta,Ganesan Mani
The reduction of CO2 (1 atm) with 9-BBN in DMSO in the presence of amines at 90 °C selectively gave N-formamides in good to excellent yields. This method works with a range of substrates, including heterocyclic secondary amines and primary and secondary aliphatic and aromatic amines. Remarkably, the same CO2 (1 atm) reduction in the presence of a catalytic amount of DMSO and aromatic primary and secondary
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An Unusual I2/Base-Catalyzed C(sp3)-H Chalcogenation of Cyclohexanone-Fused 4-Hydroxy-2-pyridones and Extension to Several Cyano-Acetylated Derivatives. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Arun Dhurey,Animesh Pramanik
A metal-free protocol has been developed for successive construction of C-C, C-N, and C-S/Se bonds to access unexpected C8-chalcogenated cyclohexanone-fused 4-hydroxy-2-pyridones in very good yields. This approach involves acetic anhydride-mediated condensation of enaminones of cyclohexa-1,3-dione and cyanoacetic acid to generate cyclohexanone-fused 4-hydroxy-2-pyridones that undergo I2/K2CO3-catalyzed
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Copper-Catalyzed One-Pot Cascade Reactions of CF3CHN2, Nitriles, and Alkenes: Chemo- and Regioselective Access to 2-(Trifluoromethyl)pyrroles. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Chun-Hui Zhang,Zhi-Yuan Tao,Fa-Guang Zhang,Jing Nie,Jun-An Ma
Herein, we report a facile and versatile copper-catalyzed protocol for the chemo- and regioselective synthesis of highly substituted 2-(trifluoromethyl)pyrroles from readily available starting materials. This one-pot cascade reaction of CF3CHN2, nitrile, and nitroalkene proceeds efficiently under mild conditions, enabling access to a broad spectrum of 2-(trifluoromethyl)pyrroles. Furthermore, the utility
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Synthesis of N-Methylated Amines via Reduction of Carbamates Using Amidophosphine Borane. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-14 Ishita Paul,Devadkar Ajitrao Kisan,Soumyadip Dey,Abhijit Sau,Tarun K Panda
A hydride transfer strategy for the synthesis of N-methylated primary, secondary amines, and N-methylated heterocyclic amines is reported. This protocol effectively converts diverse carbamates into N-methylated amines using bench-stable amidophosphine borane as a reducing agent. The reaction demonstrates a broad substrate scope and functional group tolerance under mild conditions. Additionally, the
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Orchestrating Multiple Aryl Rearrangements: Deciphering the Dynamics of Competitive Shifts and Shuttles on Four Carbons. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-13 Nagaraju Ponugoti,Jogeswar Chhatria,Sooraj Kunnikuruvan,Parthasarathy Venkatakrishnan
Multiple aryl rearrangement and translocation reactions on aromatic scaffolds remain scarce and represent a compelling frontier in organic synthesis. Herein, we portray a comprehensive investigation of multiple sequential 1,2-naphthyl shift and aryl shuttle reactions on heteroaromatic scaffolds, including an unprecedented aryl shuttle on a bicyclic arene. For the first time, we delineate the competition
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PeriRxn, a Tool for Assessing Pericyclicity through Nucleus-Independent Chemical Shifts and Normalized Multicenter Bond Orders. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-13 William DeSnoo,Dean J Tantillo
Analyses of nucleus-independent chemical shifts (NICS) and normalized multicentered bond orders (nMCBO) along reaction coordinates were used to quantify the degree of cyclic delocalization occurring during various reactions as a criterion for determining whether reactions are pericyclic. The magnitude of the z-sampled average NICS, NICSzz¯, and nMCBO near the transition structure were found to be good
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Organocatalytic Reductive Amination of Aldehydes with 2-Propanol: Efficient Access to N-Alkylated Amines. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-12 Rahul Vishwakarma,Sikandar Singh,Nagaraju Vodnala,Shivani Singh,Chinmoy Kumar Hazra
Herein, we report on the development of a one-pot organocatalytic approach for the synthesis of N-alkylated secondary and tertiary amines. The reaction proceeds via the reduction of in situ generated imines, where the solvent acts as a hydride surrogate in the presence of TMSOTf, thereby facilitating the alkylation process. Mechanistic insights derived from control experiments and deuterium labeling
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N-Heterocyclic Carbene-Catalyzed Transformation of Formyl Sugars to Deoxy-Sugar Lactones. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-11 Norein Sakander,Shweta Gulabchand Gadecha,Irshad Ahmad Zargar,Narendra Nath Ghosh,Debaraj Mukherjee
The role of N-heterocyclic carbenes (NHCs) in catalyzing the transformation of sugar aldehydes into deoxy-sugar lactones has been systematically investigated. Imidazolium-derived NHCs efficiently facilitated the conversion of both pyranose- and furanose-based sugar aldehydes through the formation of Breslow intermediates, offering a mechanistically distinct and stereoselective pathway. The methodology
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Multimodal S(VI) Exchange Click Reactions Derived from SF2 Moieties: Comparative Kinetics and Stereochemistry of SuFEx and SuPhenEx Reactions. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-11 Yumei Zhu,Akash Krishna,Yang Chao,Xixi Li,Sidharam P Pujari,Guanna Li,Hong Huang,Hongxia Zhao,Jiajia Dong,Han Zuilhof
The reaction mechanism of multimodal SuFEx and SuPhenEx click chemistries was investigated in detail for substitution of both the first and second fluoride or p-nitrophenolate leaving groups in ∼RN = SOF2 and RN = SOF(p-NO2-phenol) substrates by temperature-dependent kinetics and density functional theory (DFT) calculations. Both the DFT calculations and the experimentally derived ΔH‡ indicate relatively
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Visible Light-Induced Hydroxyalkylation of 1,2,4-Triazine-3,5(2H,4H)-dione with Alcohols via Oxidative Cross-Dehydrogenative-Coupling. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-11 Xiaotong Fu,Ranran Feng,Yushi Tan,Hong-Yu Zhang,Yuecheng Zhang,Jiquan Zhao
An unprecedented C6-H hydroxyalkylation of 1,2,4-triazine-3,5(2H,4H)-dione was achieved using readily available and inexpensive alcohols as the coupling partner, low-toxicity 2-tert-butylanthraquinone as the photocatalyst, sodium bicarbonate as the base, and air as the green oxidant via oxidative cross-dehydrogenative-coupling. The reaction conditions are mildly carried out under visible-light induction
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Photocatalytic Acceptorless Conversion of Carboxylic Acids, Aldehydes, and Alcohols to Alkenes by a TiO2 and Cobaloxime Dual-Catalyst System. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-10 Eiki Maruyama,Xiongjie Jin,Kyoko Nozaki
TiO2 has been extensively used as a heterogeneous photocatalyst in both the fields of inorganic and organic chemistry. However, the combination of the TiO2 photocatalyst with transition-metal complexes for regulating the reactivity of radical species has been less explored. Here, we report the conversion of various oxygenates, such as carboxylic acids, aldehydes, or alcohols, to the corresponding one-carbon
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Access to 2-Amino Benzylic Thioethers via a Hydrolytic Tandem 1,4 Conjugate Addition Reaction of Benzothiazolium Bromides and N-(2-Chloromethyl)aryl Amides. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-10 Chenyi Li,Dan Hu,Yao Wang,Heng Yin,Fuyu Li,Wen Xia,Lixia Liu,Yulong Li
Organosulfides play an important role in the pharmaceutical field and organic synthesis. Herein, an unusual hydrolytic tandem 1,4 conjugate addition reaction between benzothiazolium bromides and N-(2-chloromethyl) aryl amides has been revealed for efficient and convenient preparation of functionalized thioethers. This strategy provides various functionalized thioethers in moderate to excellent yields
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Arylamine Photocatalyst-Induced Addition/Cyclization of 2-Allylaminobenzonitriles with gem-Difluoromethyl Radical for Assembling Phenanthridine Derivatives. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-10 Lin Shu,Huan Wang,Ziqing Jian,Zhike Zhou,Yanli Xu,Ye Zhang,Yanyan Chen
A transition metal-free photocatalytic addition/cyclization of 2-allylaminobenzonitriles with gem-difluoromethyl radicals has been developed, constructing phenanthridine derivatives in moderate to good yields. The strongly reducing arylamine was employed as a photocatalyst in the reaction, which tolerated tertiary amines and efficiently enabled the conversion of gem-difluoromethyl radical precursors
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Synthesis of Chiral Spirocyclopropanepenicillanates via [2 + 1] Annulation of 6-Alkylidenepenicillanates and Sulfur Ylides. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-10 João V R Gonçalves,Ricardo M Carvalho,Jéssica Macedo,Paloma Gonçalves,Inês Bártolo,Américo J S Alves,José A Paixão,Nuno Taveira,Teresa M V D Pinho E Melo
An unexplored reactivity of 6-(Z)-alkylidenepenicillanates was unveiled, describing the synthesis of compounds having a cyclopropane ring spiro-fused to the penicillanic core. This was achieved via the in situ generation of sulfur ylide intermediates from the corresponding sulfur salts, which react with 6-(Z)-alkylidenepenicillanates, leading to spirocyclopropanepenicillanates. The formal [2 + 1] cycloaddition
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Iridium/Silver-Catalyzed H/D Exchange for Perdeuteration of Indoles and Site-Selective Deuteration of Carbazoles: Application in Late-Stage Functionalization. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-10 Prakriti Dhillon,Subban Kathiravan,Jesper G Wiklander,Ian A Nicholls
A novel iridium/silver-based method for catalyzing C-H deuterium labeling of indoles and carbazoles using D2O is presented. The method leverages a carbonyl-based directing group to achieve isotopic incorporation. This method demonstrates broad substrate scope and excellent functional group tolerance, enabling diverse and precise labeling of biologically important heterocycles. Notably, the developed
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TEMPO Oxidative [3 + 2] Cycloaddition of N-Substituted Acrylamides and α-Diazoacetates: Access to Carbamoyl-Substituted Pyrazole-5-carboxylates. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-10 Lvyin Zheng,Beining Yang,Xiaoqing Zhu,Zhiying Zhang,Xiaofeng Hua,Peiyi Chen,Yinyun Lin,Wei Guo
We describe a transition-metal-free TEMPO-mediated oxidative [3 + 2] cycloaddition of N-substituted acrylamides and α-diazoacetates, providing access to carbamoyl-substituted pyrazole-5-carboxylates. This strategy offers several advantages, including the use of readily available starting materials, high atom economy, and excellent regioselectivity. The protocol delivers a series of carbamoyl-substituted
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Dearomative Difluoromethylation of N-Heterocycles and Pharmaceuticals with Bromo(difluoro)acetic Acid. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-10 Sandeep Kumawat,Tarun Bhatt,Kishore Natte
Given the significant prevalence of N-heterocycles in small-molecule pharmaceuticals, the selective N-difluoromethylation is of paramount importance in drug discovery and development. However, such integrated approaches remain underexplored, presumably due to the lack of efficient synthetic methods. In the present research, for the first time, we introduce a new and broadly applicable technique for
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Application of 19F NMR Spectroscopy for Determining the Absolute Configuration of α-Chiral Amines and Secondary Alcohols Using Trifluoromethylbenzoimidazolylbenzoic Acid. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-09 David Profous,Michal Kriegelstein,Petr Jurečka,Petr Cankař
Axially chiral 2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)benzoic acid (TBBA) was employed as a chiral derivatizing agent for determining the absolute α-configuration of primary amines and secondary alcohols via 19F NMR spectroscopy. The method utilizes the trifluoromethyl group as a sensor, detecting the shielding effects induced by individual alcohol or amine substituents. This approach was
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Mechanistic Insights into Rh-Catalyzed Regio- and Enantioselective Hydroformylation of Cyclopropyl-Functionalized Trisubstituted Alkenes. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-09 Aiswarya Purushothaman,Shuailong Li,Shilpa Shilpa,Shao-Tao Bai,Raghavan B Sunoj
Asymmetric hydroformylation (AHF) is a valuable method to convert cheaper feedstock alkenes into value-added products. In view of the contemporary importance of these reactions, we have examined the mechanism of AHF of cyclopropyl-functionalized trisubstituted alkenes by using syngas (CO and H2) catalyzed by [Rh(R,S)-Yanphos], offering high regio- and enantioselectivities by deploying a combination
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Synthesis of gem-Difluorinated N-Boc Amines from N-Boc Imines via Difluorinated Phosphonium Salts. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-09 Gregory A Lozhkin,Alexey L Trifonov,Alexander D Dilman
A one-pot metal-free protocol toward gem-difluorinated N-Boc-protected amines is described. At first, N-Boc imines react with in situ-generated phosphorus ylide, producing gem-difluorinated phosphonium salts, which subsequently behave as a source of difluoroalkyl radicals under photoredox conditions. The process works using a phenothiazine-type photocatalyst, Hantzsch ester, and electron-deficient
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Synthetic Studies toward the Aphidicolin Family of Diterpenoid Natural Products. J. Org. Chem. (IF 3.6) Pub Date : 2025-07-09 Jack Hayward Cooke,Safaa Jamshed,Richmond Sarpong
Herein, we report an investigation of several synthetic strategies to access the aphidicolin family of natural products. Some unsuccessful approaches include strategies featuring Diels-Alder cycloadditions, Cope rearrangement, divinyl cyclopropane-Cope rearrangement, and C-C cleavage "cut-and-sew" reactions. Separating key bond-forming and bond-breaking steps into a two-step "sew-and-cut" strategy