ASAP (As Soon As Publishable)
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April 24, 2025

Copper-Catalyzed Reductive Hydroamination of Alkenes and 1,3-Dienes with Nitroarenes
Zi-Heng Zhang - ,
Shuang-Shuang Ma - ,
Yuan-Yuan Jiang - ,
Jin-Qing Lin *- , and
Bao-Hua Xu *
In this study, copper-catalyzed reductive hydroamination of alkenes and 1,3-dienes with nitroarenes was developed. Such umpolung hydroamination of unsaturated C═C double bonds exhibited Markovnikov selectivity, and the hydroamination of 1,3-dienes preferred 1,2-addition. Mechanistic studies suggested the system proceeds through a radical pathway with the concomitant activation of both substrates to nucleophilic alkyl radical species and electrophilic nitro-based intermediates, respectively. The attack of alkyl radical species on the N atom of nitro-based intermediates yielded the desired amines. However, this C–N cross-coupling strongly competed with the self-reduction of each species under such a system.

Mechanosynthesis of β-Naphthol Derivatives via Triflic Anhydride-Mediated Reaction of Arylacetic Acids with Arylalkynes
Xu-Ling Xia - ,
Liang Li - ,
Jun-Shen Chen - ,
Li-Feng Guo - , and
Guan-Wu Wang *
The mechanosynthesis of β-naphthol derivatives was accomplished through triflic anhydride-mediated cyclization reactions of arylacetic acids with arylalkynes in moderate to good yields by ball milling at room temperature. The present protocol featured solvent-free and simple conditions, a short reaction time, and easily available and inexpensive reagents.
April 23, 2025

One-Pot Synthesis of Tricyclic Benzoxazines and Benzoxazepine by Heterogeneous Biochemo Multienzyme Cascade Reaction
Eliana Capecchi - ,
Elisabetta Tomaino *- ,
Bruno M. Bizzarri - , and
Raffaele Saladino *
This publication is Open Access under the license indicated. Learn More
Benzoxazine and benzoxazepine derivatives with tricyclic five-, six-, and seven-membered lactone and lactam rings were synthesized in one-pot conditions by using biochemo multienzyme cascade of lipase M and tyrosinase. The reaction involves tyrosinase-mediated ortho-hydroxylation of the phenolic moiety, followed by 1,6-Michael addition and tandem intramolecular ring closure. The method achieves high atom economy, minimizes purification steps, and provides a sustainable alternative to conventional multistep syntheses. Enzymes showed excellent reusability, further enhancing the green approach.

Nucleophile-Controlled Regiodivergent Domino Reactions of Enetriones with γ-Bromocrotonates: Access to 1,3-Dienic Esters and Tetrasubstituted Pyrans
Dan Xiong - ,
Sen Zhang - ,
Zhiyue Li - ,
Hui Yao *- ,
Linxuan Li - ,
Nianyu Huang *- , and
Nengzhong Wang *
Herein, we developed an efficient nucleophile-controlled regiodivergent domino reaction between enetriones and γ-bromocrotonates. This method allowed for the rapid synthesis of a range of 1,3-dienic esters and tetrasubstituted pyrans under metal-free conditions. In the presence of pyridine, a SN2 substitution/Michael addition/elimination sequence formed 1,3-dienic esters in satisfactory yields with high E-stereoselectivities. Alternatively, a SN2 substitution/Michael addition/cyclization/cyclopropanation/cyclopropane ring-opening process forged tetrasubstituted pyrans in good yields with the help of Et3N. It is interesting to note that the site-selective reactions of γ-bromocrotonates at the α- or γ-position were readily realized by modulating pyridine and Et3N. Furthermore, the simple pyridine and Et3N act as both nucleophiles in SN2 substitution reactions and Lewis bases in deprotonation processes.

PhICl2/KSeCN Mediated Synthesis of Selenopheno[3,2-b]indoles and 3-Selenocyanato-2-benzoselenophene Indoles from 1,3-Diynes via Double Electrophilic Cyclization
Jianing Zhang - ,
Fengxia Sun - ,
Xiangyu Zhan - , and
Yunfei Du *
A hypervalent iodine-enabled double intramolecular electrophilic cyclization of 1,3-diynes has been employed in the synthesis of selenopheno[3,2-b]indoles and 3-selenocyanato-2-benzoselenophene indoles. A plausible mechanism involving the in situ formation of the reactive Cl-SeCN species from the reaction of PhICl2 and KSeCN, followed by cascade cyclization involving C–N/C–Se bond formations, was postulated.

Synthesis of Thienoacenes via Cascade Copper-Catalyzed C–S Coupling and Thienannulation Reactions and Their Thermoelectric Properties
Jiaxuan Dong - ,
Yifan Lv - ,
Yiyang Li - ,
Kexin Xu - ,
Xinrui Cui - ,
Cun-Yue Guo *- , and
Baolin Li *
Thienoacenes are a prominent class of fused-ring conjugated organic compounds and have attracted considerable attention due to their high coplanarity, good stability, high charge-carrier mobility, etc. However, most current synthetic methods toward thienoacenes require costly starting materials and reagents, as well as a lengthy synthetic procedure with low overall yields. Herein, a nonprecious copper-catalyzed system without additional ligands was developed to facilitate C–S coupling and 5-endo-dig thienannulation reaction, leading to the synthesis of a range of thienoacenes including dithieno[3,2-b:2′,3′-d]thiophenes (DTTs) and thieno[2′,3′:4,5]thieno[3,2-b]thiophene[2,3-d]thiophene (TTAs) with yields of up to 90% (for single-sided thienannulation reactions) and 65% (for double-sided thienannulation reactions). In addition, three π-extended DTTs were studied as potential thermoelectric materials, and their composites with single-walled carbon nanotubes (SWCNTs) exhibited high thermoelectric performance with the power factor up to 399.01 ± 16.26 μW m–1 K–2 at room temperature, which is the highest reported for thermoelectric composites comprising small-molecule thiophene derivatives and SWCNTs, signifying a step forward in the development of high-performance thermoelectric composites based on thiophene derivatives.

Synthesis of 3-Amino-β-lactams through Selective Imination of 3-Oxo-β-lactams
Sari Deketelaere - ,
Emma Vandenheede - ,
Nicola Piens - ,
Lore Cools - ,
Lieselotte Crul - ,
Lotte Demeurisse - ,
Karen Mollet - ,
Christian V. Stevens - , and
Matthias D’hooghe *
3-Oxo-β-lactams are known to deliver different types of reaction products upon treatment with primary amines, predominantly governed by the nature of the C4 substituent. In this work, a C4 substituent-independent protocol for the conversion of 3-oxo-β-lactams to the corresponding 3-imino-β-lactams was developed. By using primary amine hydrochloric acid salts in combination with 2,4,6-collidine, or free primary amines in combination with acetic acid, the undesired ring opening of 4-aryl- and (S)-4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidine-2,3-diones toward ethanediamides and α-aminoamides, respectively, is avoided, enabling the smooth transformation of any 3-oxo-β-lactam into its imine counterpart. As demonstrated by the ensuing synthesis of 3-alkylamino-β-lactams, 3-imino-β-lactams serve as building blocks for the construction of functionalized 3-amino-β-lactams, with the latter being key motifs in drug discovery.

Cross-Dimerization Giving Silyl-Substituted Conjugated Hexatrienes: An Approach to 1,6-Diarylhexa-1,3,5-trienes
Fuma Sakamoto - ,
Eri Arata - ,
Ryo Saito - ,
Sayori Kiyota - ,
Nobuyuki Komine - , and
Masafumi Hirano *
A new approach to 1,6-diarylhexa-1,3,5-trienes (DAHs) has been achieved. Cross-dimerization of 1-aryl-2-silylethyne (1) with benzyl((E)-buta-1,3-dien-1-yl)dimethylsilane (2c) catalyzed by [Ru(η6-naphthalene)(η4-1,5-cycloocatdiene)] produces (1E,3E)-(6-aryl-5-silylhexa-1,3,5-trien-1-yl)benzyl(dimethyl)silane (3), where the dominant stereochemistry at the 5-position in 3 is the E-form. Subsequent Hiyama cross-coupling of 3 with aryl iodide catalyzed by [Pd2(dibenzylideneacetone)3]·C6H6 in the presence of TBAF·3H2O gives a series of (1E,3E,5E)-1,6-diarylhexa-1,3,5-trienes (DAH), showing that the C(5)═C(6) double bond rotates in the event of protodesilylation. The controlled experiments suggest that the Hiyama cross-coupling of the terminal silyl group in 3 takes place first, and then protodesilylation of the internal silyl group occurs to give (1E,3E,5E)-DAHs. An X-ray structure analysis reveals the molecular structure of (1E,3E,5E)-1-(4-acetylphenyl)-6-phenylhexa-1,3,5-triene. The photochemical study of some new DAHs has been conducted, showing bright fluorescence upon irradiation with a large Stokes shift (∼4026 cm–1) by π–π* transition according to TD-DFT calculations.

Photocatalytic Approach Toward the Synthesis of Amides via S–C Cleavage: A Mild Approach
Shikha Pandey - ,
Sandeep Kumar - ,
Vishal Singh - ,
Vandana Srivastava - , and
Sundaram Singh *
A metal-free photocatalytic methodology for the synthesis of amides has been developed using eosin Y as a photocatalyst under ambient conditions. This approach provides a sustainable and efficient alternative for amide formation by eliminating the need for metal catalysts, and operates efficiently at room temperature. The use of eosin Y promotes high selectivity and reactivity, providing a green and cost-effective pathway for the synthesis of amides.

Scalable Multistep One-Pot Synthesis of Natural and Modified Nucleoside Triphosphates
Sergei Negria - ,
Yinglong Jia - ,
Noah A. Setterholm - ,
Bhawna Barpuzary - , and
John C. Chaput *
Polymerases are among the most powerful tools in the molecular biology toolbox; however, access to large quantities of chemically modified nucleoside triphosphates for diverse applications remains hindered by the need for purification by high-performance liquid chromatography (HPLC). Here, we describe a scalable approach to modified nucleoside triphosphates that proceeds through a P(III)–P(V) mixed anhydride intermediate obtained from the coupling of a P(III) nucleoside phosphoramidite and a P(V) pyrene pyrophosphate reagent. The synthetic strategy allows the coupling, oxidation, and deprotection steps to proceed as stepwise transformations in a single one-pot reaction. The fully protected nucleoside triphosphates are purified by silica gel chromatography and converted to their desired compounds on scales exceeding those achievable by conventional strategies. The power of this approach is demonstrated through the synthesis of several natural and modified nucleoside triphosphates using protocols that are efficient and straightforward to perform.

The Importance of Atomic Charges for Predicting Site-Selective Ir-, Ru-, and Rh-Catalyzed C–H Borylations
Shannon M. Stephens - and
Kyle M. Lambert *
This publication is Open Access under the license indicated. Learn More
A supervised machine learning model has been developed that allows for the prediction of site selectivity in late-stage C–H borylations. Model development was accomplished using literature data for the site-selective (≥95%) C–H borylation of 189 unique arene, heteroarene, and aliphatic substrates that feature a total of 971 possible sp2 or sp3 C–H borylation sites. The reported experimental data was supplemented with additional chemoinformatic descriptors, computed atomic charges at the C–H borylation sites, and data from parameterization of catalytically active tris-boryl complexes resulting from the combination of seven different Ir-, Ru-, and Rh-based precatalysts with eight different ligands. Of the over 1600 parameters investigated, the computed atomic charges (e.g., Hirshfeld, ChelpG, and Mulliken charges) on the hydrogen and carbon atoms at the site of borylation were identified as the most important features that allow for the successful prediction of whether a particular C–H bond will undergo a site-selective borylation. The overall accuracy of the developed model was 88.9% ± 2.5% with precision, recall, and F1 scores of 92–95% for the nonborylating sites and 65–75% for the sites of borylation. The model was demonstrated to be generalizable to molecules outside of the training/test sets with an additional validation set of 12 electronically and structurally diverse systems.

N-Heterocyclic Carbene-Catalyzed [4 + 2] Annulation of Enolizable Thioesters for the Synthesis of 2-Pyrones
Jinfeng Zhang - ,
Chen Zhu - ,
Xu Cao - ,
Hui Jin *- , and
Lixin Zhang *
An N-heterocyclic carbene (NHC)-catalyzed [4 + 2] annulation enables the direct synthesis of 2-pyrones from α-chlorothioesters and β,γ-unsaturated α-keto esters or chalcones. The method utilizes NHC-activated α-chlorothioesters to generate key intermediates for 2-pyrone formation with high functional group tolerance. Moreover, the 2-pyrones were transformed into polysubstituted benzene and naphthalene derivatives, showcasing their synthetic value.
April 22, 2025

Visible-Light-Induced 4CzIPN-Catalyzed Alkylamination of Alkenes via Cyclobutanone Oxime Esters and Anilines
Jiang-Hong Liu - ,
Ze-Yu Tian - ,
Zhen-Ye Wu - ,
Tian-Le Huang - ,
Li Hai - ,
Li Guo *- ,
Yong Wu *- , and
Zhongzhen Yang *
We disclosed an organophotoredox-catalyzed three-component oxidative radical-polar crossover strategy for constructing 1,2-alkylamination products. Cycloketone oxime derivatives were used as cyanoalkyl radical precursors and anilines were used as the nucleophiles. This facile protocol shows a good reaction yield and broad substrate scope.

Thermal Cα–C6 Cyclization of Enediynes
Haonan Cheng - ,
Wenbo Wang - ,
Yun Zeng - ,
Houjun Zhang - ,
Xiaohua Huang - ,
Fangxu Pu - ,
Xiaofan Zhang - ,
Aiguo Hu *- , and
Yun Ding *
Canonical thermal cycloaromatizations (Bergman, C1–C6; Myers-Saito, C2–C7; Schmittel, C2–C6; Schreiner-Pascal, C1–C5) are limited to the formation of five- or six-membered rings, while the formation of larger rings from enediyne (or enyne-allenes) has no precedent experimental exploration. Herein, we present a novel thermal cyclization of enediyne, leading to the formation of a stable seven-membered cyclization product. The structure of this product was elucidated by using NMR and single-crystal X-ray diffraction techniques. The presence of a maleic hydrazide moiety is postulated to facilitate the proton transfer, resulting in the rearrangement of enediyne to enyne-allene, culminating in ring closure through Cα–C6 cyclization. The reaction mechanism was further explored by using density functional theory (DFT), revealing a low activation barrier for the Cα–C6 cyclization at 19.6 kcal/mol. The newly formed seven-membered ring exhibits strong Möbius aromaticity, as confirmed by calculations of the nucleus-independent chemical shift (NICS) and anisotropy of the induced current density (ACID). In the subsequent reaction, the fusion of the oxazolidin-2-one ring and the elimination of the isobutene molecule release a significant amount of energy, further driving the formation of the final product.

Chemoselective Double Allylic Substitutions with Carbon Nucleophiles: Access to Tetrahydroindoles and Tetrahydrocarbazoles
Bocheng Chen - ,
Lucas Pagès - ,
Cyrille Kouklovsky - ,
Sébastien Prévost *- , and
Aurélien de la Torre *
A chemoselective double allylic substitution involving two different carbon nucleophiles is described. The reaction relies on a dual catalytic approach, with a Lewis acid promoting the first allylic substitution and Pd promoting the second step. Starting from simple allylic diols, a diversity of polycyclic structures can be obtained, including tetrahydroindole, tetrahydrocarbazole, and tetrahydronaphthalene.

Straightforward Access to 4-Sulfenylated Isocoumarins via Sulfoxides/MOMCl-Enabled Regioselective Cleavage and Reconfiguration of C–S Bonds
Linlin Xing - ,
Shiyan Cao - ,
Hezhuang Feng - ,
Haixia Zheng - ,
Haoyuan Fan - ,
Kai Wang - ,
Yongjun Zheng - ,
Yong Zhang - , and
Yunfei Du *
The combination of sulfoxides with MOMCl has been found for the first time to mediate electrophilic cyclization and install a variety of sulfenyl groups onto isocoumarin skeletons via regioselective cleavage and reconfiguration of C–S bonds. Notably, MOMCl, a mild and readily available alkyl chloride, was indispensable and played a significant role as an activator under neutral conditions in this transformation, thus expanding the scope of acid-labile substrates.

Visible-Light-Mediated Addition Reactions of Sulfur-Containing Reagents with α-Trifluoromethyl Alkenes
Yi-Rong Chen - ,
Jia-Hui Han - ,
Weidong Rao - ,
Ping Song *- ,
Shu-su Shen - ,
Daopeng Sheng - , and
Shun-Yi Wang *
Herein, we described the addition reactions of sulfur-containing reagents (sodium sulfinates, dithiosulfonates) with α-trifluoromethyl alkenes under visible light. A series of trifluoromethyl sulfonates were synthesized via the visible-light-induced radical addition reaction of sodium sulfinates and α-trifluoromethyl alkenes to obtain protons from the solvent. A series of dithiosulfonated derivatives were synthesized via visible-light-induced bifunctionalization reaction of α-trifluoromethyl alkenes with dithiosulfonates.This strategy has the advantages of mild reaction conditions, good substrate universality and high yield up to 99% yield.

Visible-Light-Driven Tandem Cyclization of o-Hydroxyaryl Enaminones: Access to 3-(α-Arylsulfonamido)trifluoroethyl Chromones
Jinwei Yuan *- ,
Qiyang Liu - ,
Xuanlin Liu - ,
Da Wang - ,
Meng Yan *- ,
Xianghui Meng - ,
Ji Ma *- , and
Lingbo Qu
A visible-light-driven intermolecular tandem α-amidotrifluoroethylation/cyclization of enaminones using a previously unreported N-trifluoroethylaminopyridinium salt was achieved in the absence of transition metal catalysts or bases. Notable features of this synthetic method include mild conditions, high selectivity, excellent functional group compatibility, and satisfactory yields. Preliminary mechanistic studies indicate that the reaction proceeds via a radical pathway, involving an in situ generated N-trifluoroethyl radical, followed by a 1,2-H shift.

Typical Electron-Withdrawing Groups Are ortho, meta-Directors Rather than meta-Directors in Electrophilic Aromatic Substitution
Paul R. Rablen *
This publication is Open Access under the license indicated. Learn More
Electron-withdrawing groups are traditionally considered meta-directing in aromatic substitution reactions. However, when the pre-existing substituent is a π-acceptor, both experiment and calculation indicate that substantial amounts of ortho as well as meta substitution occur, with very little para reactivity. A simple perturbative MO argument rationalizes this finding. It is therefore suggested that these substituents are best understood as ortho, meta-directors, with a preference for meta, just as electron-donating groups are considered ortho, para-directors, with a preference for para.
April 21, 2025

Electrochemical Cascade Reactions of 1,2,3-Benzotriazinones with Alkynes to Assemble 3,4-Dihydroisoquinolin-1(2H)-ones
Sanfei Nian *- ,
Xudong Wu - ,
Anwu Chen - ,
Zhiming Lei - ,
Qiuyue Song - ,
Quan Huang - ,
Min Liu - ,
Shengming Lu - ,
Jinkang Chen *- , and
Daijing Wei
An unexpected electrochemical cascade reaction of 1,2,3-benzotriazinones with alkynes to assemble 3,4-dihydroisoquinolin-1(2H)-ones has been developed, which avoids the use of pressurized H2, any metal catalysts, and stoichiometric redox agents. This route tolerates a wide range of functional groups in both reactants and can be performed under an air atmosphere. The process of continuous cathodic reduction was demonstrated by control experiments and cyclic voltammograms. Moreover, the gram-scale reaction confirmed the potential of this environmentally benign method for practical applications.

Substrate- and Reagent-Controlled Dimerization of Vinyl para-Quinone Methides
Ryan G. Baker - ,
Kyle D. Reichl - ,
Michael J. Smith - ,
Michael Ricca - ,
Margaret A. Mickelberg - , and
John A. Porco Jr.*
Substrate and reagent-controlled dimerization of vinyl para-quinone methides (VPQMs) is reported. When subjected to Brønsted acidic conditions, VPQM dimerization occurs via a formal 1,8-addition to provide griffipavixanthone (GPX)-type congeners. Under optimized Lewis acidic conditions, a change in regioselectivity affords limonene-containing dimers by a 1,6-addition/cyclization process. This divergent reactivity has been explored on several substrates of differing complexity, providing access to analogues of the natural product griffipavixanthone (GPX) as well as a range of novel, substituted limonene dimers.

Strain-Releasing Hydrogenation of Donor–Acceptor Cyclopropanes and Cyclobutanes via Electrochemical Site Selective Carbonyl Reduction
Nakshatra Banerjee - ,
Rakesh Kumar - ,
Biswadeep Manna - , and
Prabal Banerjee *
An acid or hydrogen gas-free electrochemical protocol is established for the hydrogenation of strained rings (cyclopropane and cyclobutane) at room temperature and atmospheric pressure. The mechanistic study revealed that the reaction was initiated via the reduction of the carbonyl group. The methodology is highly specific toward strained rings such as cyclopropane and cyclobutane, which exhibit broad functional group tolerance.

Intra-/Intermolecular 1,2-Diamination of Alkenyl Oximes with O-Benzoylhydroxylamines Enabled by Copper Catalysis
Jiangfei Chen - ,
Qi Xue - ,
Shenyu Ren - ,
Yi-Lin Liu *- ,
Yang Li *- , and
Jin-Heng Li *
We here describe a versatile, convenient, and efficient approach to synthesize cyclic nitrone compounds by diamination of alkene, which was catalyzed by simple copper salts under basic conditions with good chemoselectivity. The method utilized γ,δ-unsaturated ketoximes with O-benzoylhydroxylamines as an electrophilic nitrogen source to realize intra-/intermolecular 5-exo-trig cyclization of internal alkenes of unsaturated ketoximes without external oxidants required, and a series of substitution patterns, both donor and withdrawing substituted moieties, are well-tolerated, leading to target products in moderate to good yields.
April 20, 2025

Phenyldithiafulvene-Substituted Ferrocene Derivatives as Redox-Regulated Molecular Switches
Fatma Takfa - ,
Liam H. Britt - , and
Yuming Zhao *
We designed a new type of redox-active molecular triad in which two electron-donating dithiafulvene (DTF) groups are connected to a central ferrocene (Fc) hinge unit through phenylene linkers. Three structural isomers of the (DTF)2–Fc system were synthesized through Suzuki–Miyaura cross-coupling followed by phosphite-promoted olefination reactions. The molecular structures and solid-state properties of these compounds were investigated by X-ray single-crystallographic analysis. Their electronic absorption and electrochemical properties in the solution phase were examined using UV–vis spectroscopy and cyclic voltammetry. Our studies showed that these compounds possess multistage redox activities due to the presence of electron-donating DTF and Fc groups, while detailed redox behaviors are dependent on the substitution patterns and steric crowdedness of each compound. To gain deeper insight, we performed density functional theory (DFT) and molecular dynamics (MD) simulations to examine the conformational and electronic properties of these compounds in neutral and different oxidation states. Furthermore, the para-substituted (DTF)2–Fc was found to show intriguing supramolecular interactions with γ-cyclodextrin.

N-Heterocyclic Carbene-Carbodiimide (NHC-CDI) Adducts: A Systematic Investigation of Electronic Modifications on Kinetic and Thermodynamic Properties of Adduct Association and Dissociation
Le Dung Pham - ,
Briana Krupinsky - ,
Anthony W. Schlimgen - , and
Jessica R. Lamb *
N-Heterocyclic carbene-carbodiimide (NHC-CDI) adducts are versatile compounds that can be used as ligands and (pre)catalysts, but their systematic structure–property relationships are underexplored. Herein, we investigated how structural electronic variations on both the NHC and CDI affect the inherent kinetic and thermodynamic properties of the adducts. Using in situ carbene trapping and variable-temperature NMR spectroscopy, we measured the rates of dissociation and the equilibrium constants and then used Eyring and van’t Hoff analyses to calculate ΔG‡ and ΔG, respectively. Linear free-energy relationships indicate that changing the para position of the CDI substituents yields a similar effect to changing the NHC core. These CDI structural modifications affected the adducts’ thermodynamics (ΔG) more than the kinetics (ΔG‡) and were found to be influenced more by inductive, rather than resonance, factors. Preliminary results suggest a steric threshold beyond which steric effects dominate electronic effects in governing the strength of the adduct bond. This systematic investigation provides valuable insight into the design of NHC-CDIs for current and future applications.

Optimized Monomer-Based Synthesis of Poly-N-amino Peptides
Avraz F. Anwar - and
Juan R. Del Valle *
We report an optimized protocol for the solid-phase synthesis of backbone-N-aminated peptides. Electrophilic N-amination of amino acid zwitterions provides crude α-hydrazino acids that can be used directly in SPPS. In situ formation of Fmoc-protected amino acid chlorides with Ghosez’s reagent enables base-free couplings to α-hydrazino acids on an automated system. TFA-free cleavage and global deprotection affords poly-N-amino peptides in high crude purity and in a fraction of the time required by previously reported methods.

Mn(acac)3/Hydrazide-Catalyzed Aerobic Oxidative Cross-Dehydrogenative Couplings of 1,2,3,4-Tetrahydroisoquinolines and Their Mechanistic Studies
Ga Young Kim - ,
Sehee Park - ,
Gayeong Park - ,
Yeongyeong Kang - ,
Hyungjun Kim *- , and
Jinho Kim *
Aerobic oxidative cross-dehydrogenative couplings of 1,2,3,4-tetrahydroisoquinolines were developed using a Mn(acac)3 and ethyl 2-(4-nitrophenyl)hydrazine-1-carboxylate cocatalytic system. Nucleophiles, including nitroalkanes, dialkyl malonates, acetophenones, indoles, phosphonates, and phosphine oxides, were successfully employed to produce α-functionalized 1,2,3,4-tetrahydroisoquinolines. Control experiments revealed that radical species are not involved in the mechanism. Additionally, 1H NMR and HRMS analyses in the stoichiometric reaction identified an aminal structure as a crucial intermediate. Computational studies further support the plausibility of a hydride transfer process in the oxidation of 1,2,3,4-tetrahydroisoquinolines instead of the triazane pathway, which was predominantly proposed in the DEAD-mediated reaction.

Rh-Catalyzed Synthesis of Isobenzofurans via Donor/Donor-Type Metal Carbenoids and Their [4 + 2] Cycloaddition
Naoki Morita - ,
Shinnosuke Yoshikawa - ,
Eisuke Ota - , and
Junichiro Yamaguchi *
A rhodium-catalyzed synthesis of isobenzofurans via donor- and donor-type metal carbenoids has been developed. Nosylhydrazones were used as carbene precursors, generating rhodium carbenoid species under basic conditions. These intermediates underwent intramolecular cyclization with ester groups to afford isobenzofurans, which subsequently participated in a highly endo-selective [4 + 2] cycloaddition with maleimides and other dienophiles. The reaction exhibited a broad substrate scope, accommodating various ester and aryl substituents while maintaining excellent regio- and stereoselectivity. Mechanistic studies, including control experiments, NMR analysis, and computational calculations, revealed that the reaction proceeds through a rhodium carbenoid intermediate, leading to the formation of isobenzofuran prior to cycloaddition. The endo-selectivity was found to originate from the difference in activation energies between the transition states, as supported by computational studies. Additionally, the isolation of the diazo intermediate and its direct conversion to isobenzofuran confirmed the stepwise nature of the transformation. This study expands the utility of donor- and donor-type carbenoids in organic synthesis, demonstrating their effectiveness in constructing highly reactive isobenzofurans under mild conditions.
April 19, 2025

A Unified Strategy for the Synthesis of Diverse Bicyclo[2.2.2]octadiene Ligands
Wen-Tao Chen - ,
Wen-Cai Luo - ,
Jun-Ting Liang - ,
Yu-Tao He *- , and
Ya-Jian Hu *
A new approach for the enantioselective synthesis of various bicyclo[2.2.2]octadiene ligands has been developed, which features a chiral oxazaborolidinium-catalyzed asymmetric Diels–Alder reaction to construct the bicyclo[2.2.2]octane framework. The pivotal ketone 12 served as a common intermediate that was finally transformed into the desired C1- and C2-symmetric chiral dienes. This work provides an alternative method to the reported chiral diene synthesis and would be beneficial to exploration of the potentials of this type of versatile ligand in new asymmetric transformations.

Synthesis of Functionalized Indolizines through 1,3-Dipolar Cycloaddition of Zwitterionic Ketenimines and Pyridinium Salts
Farhad Golmohammadi - ,
Chiman Osmani - ,
Frank Rominger - , and
Saeed Balalaie *
A straightforward and efficient strategy for the synthesis of fully functionalized indolizines has been developed through a transition metal- and oxidant-free [3 + 2] cycloaddition reaction of zwitterionic ketenimines and pyridinium salts. This versatile method proceeds under mild conditions, affording functionalized indolizines in moderate to good yields. This efficient approach involves an intermolecular [3 + 2] cycloaddition, followed by enamine/imine tautomerization and aromatization. Notably, this method demonstrates broad functional group compatibility and allows for facile scalability, making it a valuable tool for the synthesis of indolizine-based frameworks in organic and medicinal chemistry.
April 18, 2025

Pd-Catalyzed Synthesis of Acyclic 1,2-Dioxygenated Dienes and Their Regioselective Decarboxylative Diels–Alder Cycloaddition/Aromatization Reactions to Access Multisubstituted Phenols
Shuaikang Zhou - ,
Siyi Qin - ,
Xifang Zhang - ,
Ying Song *- , and
Yuanfei Zhang *
A Pd-catalyzed protocol that provides efficient access to acyclic 1,2-dioxygenated dienes has been established. The installation of the bifunctional carbonate electrofuge to the diene cores enabled such dienes to undergo a regioselective decarboxylative Diels–Alder cycloaddition/aromatization reaction, affording diverse synthetic challenging multisubstituted phenols with ease.

Rapid and Additive-Free Synthesis of β-Sulfido Sulfonyl Fluorides through N-Methyl-2-pyrrolidinone (NMP)-Promoted Thia-Michael Addition
Junwei Han - ,
Qiushuo Zheng - ,
Xin Ding - ,
Yuqin Wen - ,
Nengrong Chen - ,
Wanzhen Lin *- , and
Fa-Jie Chen *
β-Sulfido sulfonyl fluorides, incorporating a clickable sulfonyl fluoride and a thioether motif, are valuable intermediates in chemical biology, materials science, and drug discovery. Herein, we developed a rapid and additive-free synthesis of these compounds via N-methyl-2-pyrrolidinone (NMP)-promoted thia-Michael addition of thiols to ethene sulfonyl fluoride (ESF). The reaction proceeds smoothly under neutral conditions without the need for a base or catalyst, achieving high efficiency within 20 min. This method demonstrates a broad substrate scope, tolerating thiophenols, alkylthiols, thioglycosides, and cysteine-containing peptides. The resulting β-sulfido sulfonyl fluorides enable diverse transformations, such as sulfur(VI) fluoride exchange (SuFEx) reaction and thioether oxidation, facilitating applications in drug conjugates and materials, such as additives for lithium-ion battery electrolyte components.

Late-Stage Functionalization Strategies of 1,2,3-Triazoles: A Post-Click Approach in Organic Synthesis
Mangal S. Yadav - ,
Vinay K. Pandey - ,
Manoj K. Jaiswal - ,
Sumit K. Singh - ,
Anindra Sharma - ,
Mayank Singh - , and
Vinod K. Tiwari *
The 1,2,3-triazole scaffolds are an important class of biologically privileged heterocyclic compounds with several key applications in chemistry, biology, medicine, agriculture, and material science. The “postclick” functionalization of 1,2,3-triazoles may emerge as a promising tactic for the construction of molecular architectures of therapeutics and is considered to be a growing area of investigation. This interest extends beyond the regioselective Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) method that involves the trapping of Cu(I)-triazole with suitable precursors. In this Perspective, we highlight the growing impact of postclick strategies in organic synthesis required for the late-stage functionalization of 1,2,3-triazoles with a hope that this emerging concept may provide ample opportunities in modern organic synthesis of notable applications in medicinal chemistry, biology, and materials science.

Asymmetric and Symmetric S-zig-zag-Fused BODIPYs: Synthesis and Photophysical and Oxidative Properties
Ruihan Yang - ,
Lu Li - ,
Shulin Gao - ,
Zhehui Weng - ,
WeiLi Li - ,
Zhaohui Wang - ,
Xiangguang Li *- ,
Yanhua Yang *- , and
Wei Jiang *
We present a new, straightforward, and versatile approach that utilizes regioselective brominated precursors to synthesize both asymmetric and symmetric S-zig-zag-fused BODIPYs (s-TFB and bis-TFB) in moderate yields (45% and 40%, respectively). X-ray structure analyses reveal that the planar rigidity of the BODIPY skeleton is progressively enhanced with an increasing number of thiopyran rings. The annulation of S-heteroaromatic rings at the zig-zag edge of the BODIPY core results in blue-shifted absorption and emission spectra, with bis-TFB exhibiting maxima at 530 and 539 nm and elevated LUMO energy levels. In contrast, oxidation of s-TFB and bis-TFB with m-CPBA demonstrates significant site selectivity, affording four oxidation products, namely s-s-SFB, s-bis-SFB, bis-s-SFB, and bis-bis-SFB, in yields ranging from 22% to 36%. These oxidated S-zig-zag-fused BODIPY derivatives display large red-shifted absorption and emission spectra (e.g., 648 and 735 nm for s-bis-SFB), along with more stable HOMO and LUMO energy levels and reduced HOMO–LUMO gaps. This S-zig-zag-fused cyclization/oxidation strategy enables precise tuning of the BODIPY optoelectronic properties, opening new avenues in dye design and application.

Palladium-Catalyzed Ring-Opening Defluorinative Hiyama Cross-Coupling of gem-Difluorocyclopropanes with Arylsilanes
Zhi-Shang Wang - ,
Dong-Guo Hong - ,
Hongfang Li - ,
Teck-Peng Loh *- , and
Ming-Zhu Lu *
We report an efficient palladium-catalyzed ring-opening defluorinative Hiyama cross-coupling of gem-difluorocyclopropanes with structurally diverse (hetero)arylsilanes through C–C bond activation and C–F bond cleavage. This regioselective ring-opening defluorinative Hiyama cross-coupling features a broad substrate scope with excellent functional group compatibility, affording a diverse variety of linear 2-fluoroallylic scaffolds in good yields with high Z-selectivity.
April 17, 2025

Rational Design of Supramolecular Receptors for Consistent Binding Affinities under High-Salinity Conditions
Borja Gómez-González - ,
Nuno Basílio - ,
Belén Vaz - ,
M. Rita Paleo - ,
F. Javier Sardina - ,
Moisés Pérez-Lorenzo *- , and
Luis García-Río *
The development of water-soluble multicharged macrocycles has opened promising pathways in biomedical applications, enabling selective molecular recognition for therapeutic and diagnostic uses. Yet, traditional polyanionic and polycationic receptors often face performance limitations under realistic operating conditions. A major drawback is the natural tendency of these polycharged hosts to experience increasing screening effects as concentration rises due to self-ion pairing phenomena, which can reduce binding efficiency by several orders of magnitude. These issues are further intensified when polyionic receptors are used in high-salinity environments, typically used to replicate physiological settings, where the abundance of ions introduces additional screening effects that diminish the supramolecular affinity for a wide range of guests. This study presents a new approach that leverages zwitterionic synthetic receptors with rationally engineered architectures to overcome these challenges. By incorporation of specific structural features, self-ion pairing is eliminated, effectively making host concentration no longer a controlling factor in the thermodynamics of the complexation process. Additionally, these dual-charged hosts achieve self-contained stabilization, naturally shielding recognition sites from external ion interference under high-salinity conditions. Furthermore, the ability of these supramolecular hosts to encapsulate zwitterionic guests, a challenging task due to the strong solvation of these molecules in aqueous solution, adds significant value to the functional versatility of these macrocycles. Altogether, these findings represent a significant advancement in the design of stable and adaptable receptor systems for complex environments.

Scandium Triflate Catalyzed Cycloadditions of Vinyl Diazo Compounds and In Situ Formed Naphthoquinone Methides
Yi-Xiao Yin - ,
Jie Zhan - ,
Ren Liu - ,
Pran Gopal Karmaker - ,
Qing Zhou *- ,
Wen-Dao Chu - , and
Quan-Zhong Liu *
Vinyl diazo carbonyl compounds have received great attention and are widely employed in the cycloadditions of in situ formed reactive intermediates. Metal carbenes are predominantly involved in cycloadditions, and transformations of vinyl diazo compounds that do not proceed via the metal carbene pathway have been seldom reported. Herein, scandium-catalyzed cycloadditions of vinyl diazo compounds and in situ formed 2-naphthoquinone-8-methides are achieved, and naphthalene-fused polycyclic products were obtained in up to 88% yield. In the transformation, the nucleophilic conjugate addition of vinyl diazo compounds to in situ formed 2-naphthoquinone-8-methides generates vinyl diazonium intermediates, which undergo an intramolecular Friedel–Crafts reaction and intramolecular transesterification to yield the final product.

Inherently Chiral Seven- and Eight-Membered Rings: Enantioselective Synthesis and Applications
Yu Luo - ,
Shuang Luo - , and
Qiang Zhu *
Compared to smaller or larger rings, seven- and eight-membered carbo- and heterocycles are typically nonplanar and exhibit greater conformational rigidity. This property alone can impart chirality to certain 7- or 8-membered ring systems. Herein, we summarize recent achievements in the enantioselective synthesis of this class of inherently chiral medium rings, including both ring construction and ring modification, as well as the applications of chiral ligands and catalysts derived from these rigid cyclic scaffolds in asymmetric catalysis.
April 16, 2025

Calcium Impregnated Silica Gel in the Domino Reaction Involving Irreversible Aldol Addition, Dehydration, and Michael Addition
Jih Ru Hwu *- ,
Khagendra Prasad Bohara - ,
Animesh Roy - ,
Wen-Chieh Huang - ,
Kuo-Chu Hwang - ,
Chun-Cheng Lin - ,
Kao Shu Chuang - ,
Shu-Yu Lin - , and
Shwu-Chen Tsay
This publication is Open Access under the license indicated. Learn More
An innovative method was developed for the performance of aldol additions in an irreversible fashion by the use of calcium metal impregnated silica gel (Ca@SiO2) as a remarkable reducing reagent. In this approach, Ca@SiO2 drove the reaction forward, prevented reversibility, and ensured the formation of the desired products. Thus, in the presence of Ca@SiO2 (3.0 equiv), aldehydes (1.0 equiv) condensed with ketones (1.0 equiv) in 2-MeTHF to yield α,β-unsaturated enones in 71–90% yields at 25 °C. Additionally, a domino reaction involving successive aldol addition, dehydration, and Michael addition was developed for the preparation of 1,5-diketones. Accordingly, when aldehydes (1.0 equiv) were allowed to react with ketones (2.2 equiv) and Ca@SiO2(4.0 equiv), 1,5-diketones were produced in 67–88% yields. These reactions involved radical processes, where Ca@SiO2 abstracted two α hydrogen atoms from ketones and the oxygen atom from aldehydes to form CaH2@SiO2 and CaO@SiO2, respectively. These species were confirmed by powder X-ray diffraction analysis. The resultant impregnated silica gel species were solid and insoluble in the reaction mixtures, which made the addition reactions irreversible. This method represents a significant advancement in aldol condensation reactions and offers the advantages of both atom economy and atom efficiency.

Oxidation-State-Dependent Photochemistry of Sulfur-Bridged Aza-Anthracenes
Ryoga Hojo - ,
Hikaru Noguchi - ,
Jessica Toigo - ,
Michael O. Wolf *- , and
Zachary M. Hudson *
Aromatic systems with bridged sulfur units in varying oxidation states have enabled photoresponsive materials for anticounterfeiting and supramolecular assembly. However, only a few sulfoxide-bridged chromophores exhibit photoinduced sulfur extrusion, leading to drastic photophysical changes that make them useful as stimuli-responsive materials. Here, we present nitrogen-substituted anthracene (aza-anthracene) with a sulfur bridge in different oxidation states. Overall, aza-anthracene produces red-shifted green-to-red chromophores with similar sulfoxide photoconversion behavior compared to the anthracene analog.

Merging Electrosynthesis and Biocatalysis to Access Sulfur-Based Chiral α-Fluorinated Carboxylic Acids
Parmjeet Kaur - and
Vikas Tyagi *
We describe a sustainable process to synthesize chiral sulfur-based organofluorine compounds by integrating electrosynthesis and biocatalysis within a single vessel while using water as a solvent. In this context, differently substituted 2-fluoro-3-mercaptopropionic acids have been synthesized in good isolated yields using thiophenols and fluorine-containing α,β-unsaturated alkenes. In addition, molecular docking and control experiments were carried out that suggest the formation of radical species during the electrolysis and participation of the lipase active site during the biocatalysis. The scalability and applicability of the developed protocol have been illustrated through the synthesis of a key intermediate of the MMP-3 inhibitor and by performing a gram-scale reaction. Further, the compatibility of the lipase enzyme with electricity highlights the promising potential of enzymatic electrosynthesis in advancing environmentally friendly organic transformations.

Photoredox/Palladium-Catalyzed Reduction Alkylation of Imines and Ammonium Salts via Dual C–N Bond Cleavage
Tao Ju *- ,
Zhi-Hao Wang - ,
Ai-Ling Lu - ,
Jing Sun - ,
Kun Huang - ,
Wen Xiong *- ,
Ying Han *- , and
Chao-Guo Yan
Here, we report a photoredox/palladium-catalyzed reduction alkylation of imines and ammonium salts via dual C–N cleavage. This reaction proceeds under mild, green, and operationally simple conditions, offering a broad scope of secondary amine compounds with alpha quaternary carbon. Mechanistic studies indicate that the α-amino carbanion, generated by a successive single-electron transfer process, is a key intermediate in photoredox/palladium catalysis.

Solvent-Controlled and Highly Chemoselective Reduction of α,β-Unsaturated Ketones and Aldehydes
Yu-kun Zhang - ,
Eman Fayad - ,
Hanadi A. Katouah - , and
Hua-Li Qin *
Herein, we establish two highly efficient reductions of α,β-unsaturated ketones and aldehydes via Raney nickel-catalyzed hydrogenation with distinct chemoselectivity, which is controlled by the solvent. This methodology demonstrates a brilliant result when reducing α,β-unsaturated ketones and aldehydes to ketones or alcohols. High isolated yields were obtained for a series of benzalacetone- and cinnamaldehyde-derived substrates without additional column chromatographic purification. The practicability of the methodology was demonstrated by reducing the natural products and synthesizing the approved drug.

Iron-Catalyzed Thioarylation of Arenes Using Saccharin-Derived Reagents
Lachlan J. N. Waddell - ,
Oluwajuwon A. M. Okunade - ,
Amy C. Dodds - ,
Michael C. H. Lok - ,
R. Nisha Khanizeman - , and
Andrew Sutherland *
This publication is Open Access under the license indicated. Learn More
Biaryl sulfides are important scaffolds found in various natural products and pharmaceutically active compounds. One of the main approaches for the synthesis of this compound class involves the substitution of arenes using electrophilic thioaryl species. However, these methods generally require acidic activation of the electrophile, more forcing conditions, and long reaction times. Here, we describe the combination of the super Lewis acid iron(III) triflimide with saccharin-based thioarylation reagents for the rapid synthesis of unsymmetrical biaryl sulfides under mild conditions. This approach was effective with electron-deficient thioaryl species that performed poorly with previous methods, allowing the efficient functionalization of bioactive compounds.

Synthetic Studies toward the Total Synthesis of Scabrolide A
Sabnam Begum - and
Tushar Kanti Chakraborty *
Herein, we report a concise route to the [5-5-6]-fused tricyclic core of scabrolide A and our efforts toward the construction of the fourth cycloheptane ring of the molecule via a 7-endo-trig radical cyclization. The tricyclic cyclohexenone core was assembled by a ring-closing metathesis (RCM) reaction followed by oxidation and concomitant isomerization of the double bond. These promising results have potential implications in the synthesis of similar tricyclic cores of many other congeners within this family of furanobutenolide-derived polycyclic cembranoids and norcembranoids.

Z-Selective Synthesis of Trisubstituted Alkenes by the HWE Reaction Using Modified Still–Gennari Type Reagents
Ignacy Janicki *
This publication is Open Access under the license indicated. Learn More
Application of new reagents in the Z-selective synthesis of trisubstituted alkenes via modified Horner–Wadsworth–Emmons carbonyl olefination is presented. The reagents tested are ethyl bis(1,1,1,3,3,3-hexafluoroisopropyl)phosphonoalkanoates, structurally similar to Still–Gennari type reagents. A set of various trisubstituted Z-alkenes was obtained in very high or quantitative yields with excellent Z-selectivity. Remarkably, the procedure was very successful for the synthesis of Z-2-aryl-substituted cinnamic acid esters, maintaining exclusive Z-selectivity even at an increased temperature.
April 15, 2025

Ortho-Hydroxy-Substituted Diaryliodonium Salts Enabled Intramolecular Aryliodonium Rearrangement in Synthesis of Ortho-Iodo Diaryl Ethers
Taiyou Liu - ,
Cheng Pan - ,
Limin Wang - ,
Zhen-Jiang Xu - , and
Jianwei Han *
A new family of ortho-hydroxy-substituted diaryliodonium salts was synthesized with 1-acetoxy-2-iodobenzenes, in which the acetyl group was cleaved in a one-pot synthesis. The ortho-hydroxyl-substituted diaryliodonium salts underwent further intramolecular aryl migration reaction, giving ortho-iodo diaryl ethers either with or without the presence of bases.

DNA-Compatible N-Formylation of Amines by Using TMSCF2Br
Huilin Liao - ,
Xianfu Fang - ,
Huihong Wang - ,
Chang Chen - ,
Gong Zhang - ,
Yangfeng Li *- , and
Yizhou Li *
DNA-encoded libraries (DELs) have emerged as powerful tools in drug discovery. Protected amino acids serve as essential building blocks in the construction of DELs, resulting in the widespread presence of amino groups within these libraries. N-formylation of free amines not only enhances the activity of lead compounds but also functions as an effective amino-protecting strategy. In this study, we introduce trimethyl(bromodifluoromethyl)silane (TMSCF2Br) as a novel N-formylation reagent for DEL synthesis. This approach demonstrates robustness in DEL-compatible synthesis and enables library diversification through functional group transformation (FGT). Additionally, we achieved efficient removal of formyl groups, enabling the formyl group to be strategically used for on-DNA amino protection orthogonal to Fmoc and Boc groups.

Synthesis of Phenanthrenes and Naphthoquinone Fused Benzoxepines via Hauser–Kraus Annulation of Sulfonylphthalide with Morita–Baylis–Hillman Adducts of Nitroalkenes
Chenikkayala Siva Sankara - ,
Shweta Prakash Gaikwad - ,
Suman Das Adhikary - ,
Thekke V. Baiju - ,
Rajni Kumari - , and
Irishi N. N. Namboothiri *
The Hauser–Kraus annulation of sulfonylphthalide with Morita–Baylis–Hillman (MBH) adducts of nitroalkenes provides access to phenanthrenes and naphthoquinone fused dihydrobenzoxepines. The H–K annulation results in naphthoquinones bearing a key alcohol group in protected form, which leads to naphthoquinone fused tetracyclic oxepines upon reaction with formaldehyde. These alcohols yield functionalized phenanthrenes via oxidation and [3 + 3] annulation with β-ketoesters.

Access to C5-Sulfonylated Tetrahydropyridazines via Photoinduced Cascade Sulfonylation-Cyclization of N-Cinnamyl Aldehyde Hydrazones
Changduo Pan *- and
Miao Zeng
Direct installation of a sulfonyl functional group into the C5-position of tetrahydropyridazine was achieved using N′-benzylidene-N-cinnamylacetohydrazide as a new building skeleton via the photocatalytic carbosulfonylation/annulation procedure. Various substituted C5-sulfonylated tetrahydropyridazines were obtained in good to excellent yields employing aryl- or alkylsulfonyl chlorides as the sulfonyl radical sources. This reaction was realized through the selective addition of sulfonyl radical to the C2 position of cinnamyl followed by the 6-endo-trig annulation to the hydrazone CH═N bond.

Hydrogen-Bonding Assisted Catalytic 1,2-Addition Reaction of Trifluoropyruvate with 2,4-Dihydrocylopenta[b]indoles
Kexin Pang - ,
Xin Li - ,
Man Wang - ,
Ran Song - ,
Daoshan Yang - , and
Jian Lv *
CF3-substituted tertiary alcohols are valuable as biologically active compounds, but the synthesis of the corresponding cyclopentadiene derivatives remains challenging. The DABCO-catalyzed 1,2-addition reaction of trifluoropyruvates with 2,4-dihydrocyclopenta[b]indoles has been developed, affording CF3-substituted tertiary alcohols in up to 90% yield and with up to >99:1 dr. The catalytic reaction is facilitated by hydrogen bonding (N–H···N) between the cyclic tertiary amine and the indole moiety. Additionally, Et3N (1.0 equiv) can promote the retro-1,2-addition reaction of the CF3-subsituted tertiary alcohols, yielding dihydrocyclopenta[b]indole 1 in up to 72% yield.

Dearomative Ring-Opening of N-Fused Heteroarenes: Access to Tetrasubstituted Alkenes and Ketimines
Qianling Wu - ,
Xiaojing Wang - , and
Qijian Ni *
We report a novel and efficient strategy for constructing tetrasubstituted alkenes and α-iminonitriles from 3-aminoindolizines and 3-aminoimidazo[1,2-a]pyridines. This approach involves a dearomative ring-opening of N-fused heteroaromatic amines coupled to a DDQ-mediated oxidative process under mild, metal-free conditions. The methodology demonstrates broad substrate scope, excellent functional group tolerance, and scalability, offering a versatile platform for synthesizing complex alkenes and nitrile-containing frameworks.

Synthesis of Spirocyclic Phthalans via Ru-Catalyzed [2 + 2 + 2] Cycloaddition of 1,6-Diynes with Ex-Situ Generated Acetylene
Yoshihiko Yamamoto *- ,
Kenichi Yoshimura - , and
Takeshi Yasui
Spirocyclic motifs are attracting increasing attention owing to their three-dimensional geometries that endow bioactive molecules with superior physical and biological properties. We developed an efficient method for constructing spirocyclic phthalans via the Ru-catalyzed [2 + 2 + 2] cycloaddition of cycloalkanone-derived 1,6-diynes with acetylene gas ex-situ-generated from calcium carbide and H2O.
April 14, 2025

Synthesis of Viriditins A and B by Selective Coupling of Trans-1,2-Dichloroethylene
Feddro Gilbert Wijaya - ,
Sopan Pralhad Khandare - ,
Dániel Csókás - ,
Raghunath O. Ramabhadran - , and
Roderick W. Bates *
A synthesis of (−)-viriditin A and (−)-viriditin B has been completed sequentially using a Suzuki coupling and a Heck reaction of trans-1,2-dichloroethylene. The selectivity for monocoupling of trans-1,2-dichloroethylene is attributed to a lower-energy transition state for the oxidative addition step.

Synthesis and Chiroptical Properties of Biscarbazole-Embedded Diaza[7]helicenes
Gourav M. Upadhyay - ,
Asim Swain - ,
Esha H. Bhalodi - ,
Prince Ravat *- , and
Ashutosh V. Bedekar *
In this study, we report the synthesis and chiroptical properties of biscarbazole-embedded diaza[7]helicenes. Although the classical photocyclization pathway was unsuccessful, the strategic introduction of a bromo group successfully yielded the desired helical compounds. Interestingly, using methoxy groups instead of bromo groups led to the formation of an unusual degraded product during photocyclization. The synthesized molecules were resolved into their enantiomers, and their chiroptical properties were investigated by using steady-state absorption and emission spectroscopy. Additionally, the excited-state dynamics were examined through time-resolved fluorescence decay measurements. Quantum chemical calculations were performed to rationalize the observed optical properties.

Substrate-Controlled Pentafluorosulfanylation of Activated Alkenes Containing the Benzimidazole Moiety with SF5Cl
Xinqiang Tan *- ,
Yuezhen Li - ,
Shijie Liu - ,
Ziyou Hao - ,
Yingchang Guo - ,
Ruiping Fan - ,
Yunhui Yan - ,
Jianmei Yuan - ,
Lizhen Fang - ,
Ping-Xin Zhou - ,
Hao Tang *- , and
Yingling Wang *
We report herein a method of substrate-controlled pentafluorosulfanylation of activated alkenes containing the benzimidazole moiety with SF5Cl, which provides a highly efficient way to access SF5-containing benzo[4,5]imidazole[2,1-a]isoquinolin-6(5H)-ones, as well as SF5-containing N-benzoyl benzimidazoles. Besides the pentafluorosulfanyl group (−SF5), the current method can be applied to the tetrafluorosulfanyl group (−SF4−) incorporation. A radical mechanism involving single electron transfer (SET) or the atom transfer radical addition (ATRA) process is proposed.

Pd/NBE-Catalyzed One-Pot Modular Synthesis of Tetrahydro-γ-carbolines
Chuantao Huang - ,
Wenlin Zhang - ,
Ying Liu - ,
Zhixin Zhang - ,
Jun Gong - ,
Xiaobo Wang - ,
Ping Xue - ,
Li Feng *- , and
Helin Lu *
Tetrahydro-γ-carbolines are especially outstanding fused heterocyclic ring systems possessing significant biological activities in the central nervous system. Here, using commercially available NBE derivatives (NBEs), we report an efficient protocol for the one-pot modular synthesis of 4-substituted tetrahydro-γ-carbolines via Catellani/aza-Michael addition cascade from easily available 3-iodo-1-tosyl-1H-indole, aziridines and olefins. This approach exhibits a wide substrate scope, good yields, scalability, and potential extension toward the synthesis of Mebhydroline analogues.

An Unusual Friedel–Crafts Reaction and Violation of the Markovnikov Rule in the Formation of an Adamantyl Arene
B. Andes Hess Jr*- and
Lidia Smentek
This publication is Open Access under the license indicated. Learn More
Yoshihara, Hiroki, Yagi, and Itami utilized an unusual Friedel–Crafts-like alkylation in the synthesis of an adamantane-annulated arene. The precursor was a 3° carbocation, which they proposed undergoes a Wagner–Meerwein shift to a 2° carbocation, which subsequently alkylates a benzene ring. This mechanism was supported by their DFT calculations. However, their choice of the B3LYP functional often finds false transition structures. A more appropriate functional showed that the alkylation occurs via a concerted reaction.

Photomediated Radical Cascade Addition–Cyclization of N-Butenoyl Tetrahydroquinolines: Accessing Functionalized Julolidines
Ajal P. Shaji - ,
Nachiketh Sudarshan - ,
Burkhard König - , and
Purushothaman Gopinath *
Herein, we describe the photomediated radical cascade addition–cyclization of N-butenoyl tetrahydroquinolines to access various functionalized julolidine-5-one. The scope of the methodology was illustrated with several sulfonyl chlorides and tetrahydroquinolines. Other radical precursors, such as trifluoromethyl, bromoacetonitrile, bromoacetates, etc., also worked efficiently, demonstrating the broad utility of the method. Finally, large-scale synthesis of sulfonyl-substituted julolidine-5-one and downstream conversions of the synthesized julolidine derivatives were carried out to illustrate the synthetic utility of the methodology.

The Synthesis of a Naloxone-Related Oxidative Drug Product Degradant
Marie-Angélique F. S. Deschamps - ,
John S. Carey *- , and
Joseph P. A. Harrity *
This publication is Open Access under the license indicated. Learn More
Naloxone is a nonselective opioid receptor antagonist used to reverse the effects of opiate-related overdose. Studies aimed toward identifying naloxone degradants present in a buprenorphine/naloxone combination drug product revealed several compounds whose structures could not be confirmed by comparison to authentic samples. We report herein the confirmation of the structural assignment of one of these compounds (so-called, “Degradant E”) by chemical synthesis starting from naloxone. Key features of the developed route include the conversion of the N-allyl group to the corresponding Boc carbamate as a means of facilitating the chemoselective oxidative cleavage of the C6–C7 bond. In addition, the use of a pivalate ester derivative of naloxone’s phenol group offered a convenient means of isolating Degradant E as the corresponding HCl salt using an acid-promoted global ester hydrolysis in the final step.

Electrochemistry of Azobenzenes and Its Potential for Energy Storage
Dominic Schatz - and
Hermann A. Wegner *
This publication is Open Access under the license indicated. Learn More
Azobenzenes are promising materials for energy storage due to their reversible photoisomerization and redox properties. Given the critical role of redox behavior in the latter application, an investigation of their redox processes is essential. We propose a classification of azobenzenes into two categories: benzenoid-type and quinoid-type, based on the mechanism of their oxidation. Benzenoid-type compounds have been extensively studied due to their reversible reduction. Quinoid-type compounds exhibit oxidative and reductive versatility, making them promising for further research in energy storage.
April 13, 2025

Catalytic System-Controlled [4 + 1] and [4 + 2] Annulation for the Construction of Pyrazolo[1,2-a]indazoles and Pyrazolo[1,2-a]cinnolines from Pyrazolidinones and Diazo Indandiones
Qiannan Xiao - ,
Shulei Hu - ,
Feifei Fang - ,
Mengdi Yan - ,
Shurui Zhang - ,
Yiting Liu - ,
Hong Liu - ,
Dechuan Wang *- , and
Jiang Wang *
Pyrazolo[1,2-a]indazoles and pyrazolo[1,2-a]cinnolines can be constructed selectively via catalytic system-controlled C(sp2)-H activation/[4 + 1] cyclization and C(sp2)-H activation/[4 + 2] cyclization reaction, utilizing pyrazolidinones and diazo indandiones. Employing two different Rh(III) catalysts, we successfully synthesized two distinct types of nitrogen-containing heterocyclic compounds, pyrazolo[1,2-a]indazoles and pyrazolo[1,2-a]cinnolines, respectively. Moreover, an inexpensive Ru(II) catalyst could also effectively generate pyrazolo[1,2-a]cinnolines with moderate to good yields. Overall, these methodologies offer advantages such as regioselectivity, broad substrate scope, operational simplicity, and product availability.

DNA-Compatible Huisgen [3 + 2] Cycloaddition of In Situ Formed Nitrile Oxides with Alkenes or Alkynes to Synthesize Isoxazolines or Isoxazoles
Gaonan Wang *- ,
Xiaona Zhang - ,
Hui Zhu - ,
Xiaodong Shi - ,
Zhuo Wen - ,
Qi Zhang - ,
Alexander L. Satz - ,
Wenji Su - ,
Letian Kuai - , and
Dongcheng Dai *
DNA-encoded chemical library (DECL) technology is recognized as a robust screening platform for drug discovery. Developing new DNA-compatible reactions is crucial for expanding the chemical space of DECLs. Cyclization reactions, particularly those involving the formation of heterocycles, offer unique and efficient methods for accessing privileged scaffolds or lead-like small molecules. In this study, we introduce two new methods that utilize readily accessible aldehydes to create substituted isoxazolines and isoxazoles by the 1,3-dipolar cycloaddition reaction. These methods demonstrate high conversion efficiency and can be applied to a wide range of substrates. The reactions are DNA-compatible and do not cause significant DNA degradation.
April 11, 2025

Unanticipated Three-Component Cascade and Sequential Cyclization: Highly Diastereoselective Synthesis of Polyfunctionalized Cyclohexanes
Qing He *- ,
Rui Zhou - ,
Bin Liu - ,
Ronghua Wang - ,
Xiangkai Kong - ,
Siyu He - ,
Jianta Wang - ,
Lingling Fan *- ,
Xiaozhong Fu *- , and
Lei Tang *
Herein, we reported a DBU-catalyzed cascade and sequential [1 + 2 + 3] annulation of malononitrile with α,β-unsaturated ketones to access polyfunctionalized cyclohexanes with high yield and excellent diastereoselectivity (>93% yield, >19:1 dr). Intriguingly, this appears to be the new strategy for using α,β-unsaturated ketones either as 2C or 3C synthon to react with dinucleophile 1C synthon to construct six-membered carbocycles in one-pot manner. In addition, these synthesized compounds suppressed the growth of phytopathogenic fungi in vitro. Among them, compound 3l exhibited excellent and broad antifungal activity, which possesses potential as an agricultural antifungal agent.

Dual-State Emissive and Substituent-Tunable pH-Sensitive Bis-Heterocyclic Fluorescent Probes
Preeti Ashokkumar Chaudhran - ,
Sakshi Y. Mastoli - ,
Abhishek Dey - ,
Shubhini A. Saraf - , and
Abha Sharma *
A library of fluorescent molecules based on imidazopyridine linked with benzothiazole and benzimidazole was assessed for pH sensitivity and the effect of substituents thereon, also leading to dual-state emission. A broad range of pH (1–13) was evaluated, where the benzothiazole-based (BnTA) compounds responded in acidic pH, whereas the benzimidazole-based (BnIm) compounds behaved differently at different pH with recognizable color change on shifting from acidic to neutral and then to basic. NMR titrations revealed the effect of substituents on governing the site of protonation and deprotonation. Further, the mechanism of fluorescence was comprehended through theoretical calculations. On assessing the solid state fluorescence briefly, 2e showed mechanochromic behavior, showing green fluorescence in the solid state, which vanished upon grinding, and upon fuming with acetone, the fluorescence turned yellowish orange, which reverted to the initial fluorescence upon long-term exposure of acetone. The cellular uptake and fluorescence response of 2l in pH were also evaluated. The colocalization experiment suggested that 2l crossed the nuclear membrane and stained the nucleus, showing its possible in vitro application. The compound serves as a potential lead for other applications likewise, such as optoelectronics, data encryption, and pH sensors.

Synthesis of Polyfluorinated Biaryls via Palladium-Catalyzed Decarboxylative Cross-Coupling of Zinc Polyfluorobenzoates with Aryl Fluorosulfates
Bo-Wen Yang - ,
Jun Xu - ,
Jie Pan - ,
Xue-Qiang Chu - ,
Jian-Ping Chen - ,
Hao Xu *- ,
Chengping Miao *- ,
Weidong Rao - , and
Zhi-Liang Shen *
A palladium-catalyzed decarboxylative cross-coupling of zinc polyfluorobenzoates with aryl fluorosulfates, which proceeded efficiently via C–O bond cleavage to afford the corresponding polyfluorinated biaryls in moderate-to-good yields, was developed. The reactions exhibited both good substrate scope and broad functional group compatibility, and it could be scaled-up easily. The synthetic simplicity and practicability of the reaction was further demonstrated by one-pot manipulation by directly mixing polyfluorobenzoic acid and Zn(OH)2 in the coexistence of aryl fluorosulfate and a palladium catalyst in one flask. Further studies showed that aryl fluorosulfate is more robust than other aryl halides and pseudohalides as a arylating reagent, and zinc polyfluorobenzoate is a more effective decarboxylative polyfluoroarylating agent than their magnesium and potassium counterparts.

Construction of Thiochroman-4-ols through a (4 + 2) Annulation Strategy Using Allenyl Sulfones as Substrates
Lilia Anani - ,
Jean-François Lohier - ,
Annie-Claude Gaumont - ,
Jean-François Brière - ,
Sylvain Oudeyer - , and
Stéphane Perrio *
Herein, we report an efficient and straightforward access to highly functionalized thiochroman-4-ol derivatives by the construction of S–C and C–C bonds in a domino fashion. The methodology is based on a (4 + 2) annulation reaction involving α-substituted allenyl sulfones and aromatic thiolates displaying an ortho α-ketoester group as substrates. The anionic sulfur species were generated in situ by reduction of the corresponding disulfides, using a Rongalite/K2CO3 system. The practicality of the strategy was further demonstrated by gram-scale synthesis, postmodifications, and compatibility with other types of electron-deficient allenes (allenoate and allenone).

Synthesis of PSI Oligosaccharide for the Development of Total Synthetic Vaccine against Clostridium difficile
Hong-Jay Lo *- ,
Ravinder Mettu - ,
Chiang-Yun Chen - ,
Shiou-Ting Li - , and
Chung-Yi Wu *
This publication is Open Access under the license indicated. Learn More
Clostridium difficile causes serious nosocomial diarrhea in humans. In particular, C. difficile ribotype 027 strain, which is more virulent in nature, is associated with higher mortality rates. To prevent disease caused by C. difficile, capsular polysaccharides such as PSI, PSII, and PSIII from the outermost protective layer of C. difficile bacterium are good targets in the development of vaccine against C. difficile. In this study, we report for the first time an efficient synthesis of phosphorylated PSI oligosaccharide and its derivatives in various lengths. We have also developed a one-pot strategy for the synthesis of a pentasaccharide repeating unit and used this approach to successfully synthesize the protected pentasaccharides in the gram scale.

Enantioselective Access to Decahydroquinolines Bearing a C4a or C8a Quaternary Stereocenter from a Common Intermediate Total Synthesis of (−)-Myrioxazine A
Arnau Calbó - ,
Miriam Piccichè - ,
Llorenç Rubert - ,
Eisuke Comas-Iwasita - ,
Rosa Griera - ,
Carolina Estarellas - ,
F. Javier Luque *- ,
Joan Bosch - , and
Mercedes Amat *
(R)-Phenylglycinol-derived perhydrooxazoloquinoline 2 provides stereoselective access to angularly substituted enantiopure decahydroquinolines (DHQs). Reaction of 2 with appropriate Grignard reagents leads to cis-DHQs bearing a C8a aza-quaternary stereocenter, whereas reaction of 2 with Michael acceptors followed by reductive removal of the 2-phenylethanol of the chiral inductor gives rise to cis- or trans-DHQs bearing a C4a all-carbon quaternary stereocenter depending on the hydride used for the cleavage of the oxazolidine C–O bond. Theoretical studies have clarified the mechanistic intricacies of the reaction of 2 with Michael acceptors, providing arguments for a proper understanding of the observed stereoselectivity. Finally, the reaction of 2 with formaldehyde is reversible, allowing the regioselective formation of either the angularly substituted hydroxymethyl derivative 12 or the C8-substituted derivative 13 depending on the reaction temperature. An expeditious synthesis of the Myrioneuron-type alkaloid (−)-myrioxazine A from 13 is reported.

Directing Group-Controlled Regioselective [4 + 3] Annulation of Indole-2-Carboxamides with MBH Carbonates toward Highly Substituted Indole-1,2-Fused Diazepanones
Shutao Wang - ,
Wenyao Zhang - ,
Zhuoqi Zhang - ,
Jinbao Xiang *- , and
Lianyou Zheng *
A Lewis base-catalyzed [4 + 3] annulation between dinucleophilic indole-2-carboxamides and Morita–Baylis–Hillmann (MBH) carbonates was developed to access densely substituted indole-1,2-fused diazepanones. This reaction is initiated by a Lewis base-catalyzed N-allylic alkylation of the indole scaffold with MBH carbonates, followed by intramolecular Michael cyclization. Notably, the selectivity of this process is controlled by a removable o-methoxyphenyl (OMP) directing group attached to the indole-2-carboxamides. The wide scope of substrates, high regio- and stereoselectivity, and diverse transformations highlight the potential synthetic utility of this method in drug discovery.
Correction to “Highly Regio- and Diastereoselective Tethered Aza-Wacker Cyclizations of Alkenyl Phosphoramidates”
Anand H. Shinde - ,
Annu Anna Thomas - ,
Joel T. Mague - , and
Shyam Sathyamoorthi *
This publication is free to access through this site. Learn More
April 10, 2025

Sulfinylation of Tertiary Alkyl Halides via a Halogenophilic Substitution (SN2X) Reaction
Kai-Cheng Liang - ,
Tian-Peng Ling - ,
Hai-Tao Qin *- , and
Feng Liu *
The halogenophilic SN2X reaction involving a nucleophilic attack on the X group from the front is less sensitive to backside steric hindrance. Herein, we report a mild and efficient SN2X reaction for sulfinylation of activated tertiary alkyl halides, which could provide a novel method for accessing sulfoxides decorated with a congested carbon center. Preliminary mechanistic studies indicated that the generated sulfinyl bromides would be the key electrophilic intermediates in the reaction.

N-Iodosuccinimide-Promoted Synthesis of Indolo[3,2-c]quinolizines via Cascade Intramolecular C–N Bond Formation/Aromatization with 3-(1H-Indol-3-yl)-2-(pyridin-2-yl)propanoates
Chen Chen - ,
Xixiang Yang - ,
Jiaxin Wang - ,
Weiya Kong - ,
Jianjun Chen *- , and
Xiaodong Tang *
An NIS-promoted cascade of intramolecular C–N bond formation/aromatization with 3-(1H-indol-3-yl)-2-(pyridin-2-yl)propanoates is described for synthesizing a polycyclic indole skeleton, indolo[3,2-c]quinolizine, as well as 1,9-dihydropyrazolo[4’,3′:5,6]pyrido[2,3-b]indole. The advantages of this protocol include accessible starting materials, mild conditions, simple operation, and good yields. Indolo[3,2-c]quinolizines exhibited good fluorescence properties and effective staining for live cells, targeting lysosomes and mitochondria. Additionally, the products showed significant antiproliferative activity against tumor cells in the MTT assay.

Manual Grinding and Sunlight Synergistically Promoted Sulfonylation of Alkenyl Sulfonium Salts with Sulfinic Acids
Li-Hua Yang - ,
Lin Chen - ,
Wen-Shi Yao - ,
Han-Yue Peng - ,
Xiang-Qin Xu - ,
Sha Peng *- , and
Long-Yong Xie *
An environmentally friendly and practical method for the synthesis of various vinyl sulfones was developed through the direct sulfonylation of alkenyl sulfonium salts with sulfinic acids. The reaction was effectively triggered by the combined actions of milling, sunlight, and photocatalysts under solvent-free conditions, offering advantages such as a short reaction time (5–10 min), room temperature, and a straightforward workup procedure. Preliminary mechanistic studies suggested that a sulfonyl radical may be involved in this mechanophotocatalytic transformation process.

Pd-Catalyzed Selective Arylative Cascade Cyclization of 1,6-Diynes and Dibenzoxaborins for Fused Naphthalene Derivatives
Muniganti Naveen Kumar - ,
Shivunapuram Mahesh - ,
Jagadeesh Babu Nanubolu - , and
Maddi Sridhar Reddy *
A palladium-catalyzed new mode of cascade arylative cyclization of 1,6-diynes is disclosed using dibenzoxaborin as an arylating agent featuring transmetalation and selective migratory insertion as the key steps. This process enables the efficient construction of polysubstituted fused naphthalene skeletons via the formation of three new C–C bonds through dual regioselectivity in both arylation as well as C–H functionalization. Some control experiments and kinetic isotope effect (KIE) studies were conducted to elucidate the reaction mechanism, and some product diversifications were achieved to showcase the synthetic potential.

TCT-Mediated and Water-Controlled Synthesis of Benzofuran-3(2H)-ones Bearing a Quaternary Carbon Center via a Radical Process Using Dimethyl Sulfoxide as a Dual Synthon
Qing Chen - ,
Zhao Du - ,
Chuanqi Liu - ,
Xiaoqian Wang - ,
Wantong Yue - ,
Yilei Wang - , and
Zhihua Peng *
An efficient and attractive method for the synthesis of valuable benzofuran-3(2H)-one derivatives bearing a quaternary center in one step by employing dimethyl sulfoxide (DMSO) as a dual synthon under metal-free conditions has been developed. In this reaction, DMSO activated by cyanuric chloride (TCT) provides two different units (CH3 and SMe) in the target molecules, and the construction of the quaternary carbon center in the benzofuran-3(2H)-ones can be controlled by the addition of water. Furthermore, the functional group compatibility and synthetic value were demonstrated by scope evaluation and gram-scale experiments. The mechanistic studies show that the reaction may proceed via a radical process.

Tf2O/DMSO-Promoted Umpolung Phosphorylation for C(sp2)–P or C(sp3)–P Bond Formation
Da-Wei Shi - ,
Ming Li - ,
Rui-Jia Yang - ,
Xin-Yu Zhao - ,
Ting Zhang - ,
Jiayi Huangfu - ,
Ling Xu - ,
Ke Wang - ,
Yi-Xuan Ma - , and
Bin Yang *
We have developed an umpolung method utilizing the Tf2O/DMSO-based system for C(sp2)–P bond or C(sp3)–P bond formation. This method employs both P(O)–H and P(O)–OH compounds as phosphorus sources and demonstrates excellent compatibility with a wide range of Grignard reagents. Without the requirement of precious transition metals or additives, this one-pot protocol provides a practical and efficient synthetic pathway to a variety of aryl and alkyl phosphine oxides. The broad substrate scope and diverse synthetic applications highlight the practical utility of this method.

Visible-Light-Mediated, LMCT-Enabled C(sp3)-H Bond Alkylation of Alkanes and Silanes via C-4 Functionalization of Coumarins
Parashuram Sharma - ,
Tavinder Singh - ,
Nisha Rawat - , and
Anand Singh *
A visible-light-promoted FeCl3-catalyzed protocol for the generation of alkyl and silyl radicals from alkanes and silanes, respectively, is described. Employing a chlorine radical as a hydrogen atom transfer agent, alkyl, and silyl radicals were accessed and functionalized by addition to coumarins, ultimately resulting in a redox-neutral alkylation/silylation. The reaction occurs without an exogenous oxidant and under mild conditions, highlighting the potential of 3D-metal compounds in achieving challenging bond activations via photochemical excitation.

B(C6F5)3-Catalyzed Reductive Deoxygenation of Isatins for Indole Synthesis
Seung Deok Son - ,
Hoe Young Choi - , and
Haye Min Ko *
An efficient method for reductive deoxygenation of isatin derivatives using catalyst B(C6F5)3 and methylphenylsilane is described. This reaction proceeds rapidly under mild conditions, and the protocol provides a broad substrate scope. Notably, while general synthetic methods utilizing a combination of B(C6F5)3 and hydrosilanes smoothly reduce indoles to generate indolines, the present strategy represents the first reductive deoxygenation reaction for the formation of indoles without further reduction.
March 31, 2025

Conjugated 1,8 and 1,6 Addition of Bis-Trimethylsilylketene Acetal to Activated p-Quinone Methides via Trifluoromethanesulfonic Anhydride
Luis J. Benitez-Puebla - ,
Ricardo Ballinas-Indili *- ,
Marcos Flores-Alamo - ,
José M. Guevara-Vela - ,
Tomas Rocha-Rinza - ,
Saulo Rosales-Amezcua - , and
Cecilio Alvarez-Toledano *
This publication is Open Access under the license indicated. Learn More
In this work, we studied the conjugated additions of bis-trimethylsilylacetalketene acetals (bis-TMSKA) to para-quinone methides (p-QMs), which are one of the most explored molecules for the study of conjugated additions and gained significant attention in organic chemistry due to their versatile reactivity, particularly in Michael addition reactions. In this study, trifluoromethanesulfonic anhydride (Tf2O) was used as an activating agent for p-QMs, aiming to achieve 1,6-Michael addition products and the least reported 1,8-Michael addition with pyridine substituents. The reactivity of p-QMs derived from pyridine demonstrated distinct reaction pathways, leading to the formation of δ and γ lactones. The investigation also involved synthesizing a 1-indanone derived from the carboxylic acids obtained from the 1,6-addition.

Mechanochemical Functionalization of Heterocycles by C–H Activation: An Update
Mainak Banerjee *- ,
Abboy Chatterjee - ,
Shaurya Aneja - , and
Amrita Chatterjee *
The mechanochemical C–H activation of heterocycles presents a sustainable, solvent-free alternative to the traditional solution-phase synthesis. Heterocycles are fundamental molecular scaffolds in medicinal chemistry and drug discovery. This review highlights recent advances in mechanochemical methods for metal-catalyzed and metal-free C–H functionalization/derivatization, including arylation, alkenylation, acylation, borylation, trifluoromethylation, etc., applied across various heterocyclic compounds. Emphasizing green aspects, this synopsis provides a comprehensive overview of mechanochemical innovations, their unique features and advantages, transformative potential for ecofriendly synthesis, and future prospects of sustainability.