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

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.

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,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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