ASAP (As Soon As Publishable)

Substituted alkenes, crucial in organic chemistry, are typically accessed from internal alkynes by using transition-metal catalysis. Herein, we report a novel approach to the Lewis acid-catalyzed synthesis of trisubstituted alkenes bearing a quaternary carbon from internal alkynols and 2-pyrrolyl arylamines. This method involves allene formation followed by intramolecular [5 + 1] annulation to furnish a diverse range of trisubstituted alkenes with excellent regioselectivity and poor diastereoselectivity. Further, we demonstrated the gram-scale synthesis and synthetic transformations and proposed the reaction mechanism based on the isolation of intermediates.

A step-economical and efficient strategy for the enantioselective synthesis of tetradeuterated γ-nitroketones using a cost-effective and readily available deuterium source is highly desirable. Herein, we report a nickel-catalyzed one-pot H/D exchange and highly enantioselective Michael addition of α,β-unsaturated 2-acyl imidazoles with nitromethane in the presence of D₂O. This protocol demonstrates excellent efficiency, high enantioselectivity, and a broad substrate scope, offering a practical and versatile approach to accessing deuterium-labeled compounds.

The design of high-energy density energetic materials (HEDMs) and the exploration of energy limits have long been prominent research areas, presenting both significant opportunities and challenges. In this study, we report the synthesis of 1,2-bis(4-azido-3,5-dinitropyrazolyl) diazene (BLG-101) utilizing an energetic block design strategy based on a long nitrogen chain. BLG-101 exhibits a high crystal density of 1.924 g·cm^–3, with a measured density of 1.89 g·cm^–3, and demonstrates excellent enthalpy of formation alongside favorable thermal stability. Notably, BLG-101 showcases exceptional detonation performance, achieving a detonation velocity (V_D) of 9800 m·s^–1 and a heat of detonation (Q) of 6893 kJ·kg^–1, surpassing those of the classical high-energy compound CL-20, which has a V_D of 9445 m·s^–1 and a Q of 6134 kJ·kg^–1. However, BLG-101 has a higher mechanical sensitivity (IS = 3.6 J, FS = 32 N) than CL-20 (IS = 4 J, FS = 48 N). The integrated design approach, which synergistically combines nitro, azide, and elongated nitrogen chain structures within a pyrazole framework, significantly enhances the energetic performance of nitropyrazole compounds. This innovative strategy not only overcomes the current energy limitations associated with nitropyrazole derivatives but also provides a novel pathway for the design and synthesis of new energetic compounds with high energy density.

The combination of a natural amino acid (AA) (l-Glu, l-Tyr, and l-Lys) and tetrabutylammonium iodide was efficiently employed as a catalytic framework for the Meinwald rearrangement of various epoxides into their respective ketones under microwave irradiation and solvent-free conditions. The designed catalytic system has shown a good catalytic performance in the conversion of epoxides with different functional groups. The reaction is regioselective toward ketone formation, and these have been obtained in good to excellent yields. l-Glu was found to be the most active AA for this catalytic transformation. A mechanistic proposal, supported by computational simulations, is also provided to reinforce our experimental findings. The suggested reaction mechanism was obtained by computing the minimum energy path at the density functional theory level through the climbing-image nudged elastic band method. A localized molecular orbital analysis based on intrinsic bond orbitals was also performed to better understand the catalytic role of the AA -TBAI combination along the computed reaction path. A key role of both the carboxylic moiety and the iodide anion was identified in different reaction steps of our proposed mechanism, facilitating hydride transposition to form the final product.

We have developed a palladium-catalyzed ester carbonylation reaction that enables the synthesis of ester-substituted benzofuran derivatives in a single step through the introduction of alkyl halides undergoing in situ hydrolysis and alkynyl aryl iodides. This method demonstrates broad applicability to both primary and secondary alkyl halides while maintaining excellent functional group compatibility under low palladium loading conditions. Notably, this strategy significantly expands the scope of the ester carbonylation reactions.

The sex pheromone of the long-tailed mealybug has been synthesized in both racemic and enantiopure forms from simple racemic acyloin acetate and chiral acyloins (both R and S). An efficient iron-mediated intramolecular radical cyclization has been used to achievethe efficient formation of a cyclopentane core and bicyclic lactone bearing two quaternary centers under mild conditions. The resulting cyclopentane core and bicyclic lactones were elaborated to give the target pheromone.

Quinolines, a significant part of nitrogen-containing heterocycles, are widely found in functional compounds. Herin, a photochemical radical cyclization reaction of o-vinylaryl isocyanides and aryldiazonium tetrafluoroborates, has been reported to build 2,4-diaryl quinolines. Readily accessible aryl diazonium salts were utilized as aryl radical precursors at room temperature. This approach allowed good functional group tolerance and substrate applicability.

A formal [4 + 1] addition of NaSH to bromoisocyanoalkenes provides substituted thiazoles via a versatile strategy that affords an array of 4- or 5-monosubstituted or 4,5-disubstituted thiazoles. The unique assembly is achieved by a rare S_NV_π displacement of NaSH on (Z)-bromoisocyanoalkenes. The versatile strategy addresses the dearth of conjugate additions to alkenes substituted with isocyanides as the sole electron-withdrawing group to provide an array of substituted thiazoles.

Herein, an efficient Rh-catalyzed C–H activation/annulation between α,β-unsaturated amides and coumarin-derived iodonium ylides has been developed, affording novel pyrano[3,2-c]chromene-2,5-diones and analogues in high yields. Most products could be easily isolated by precipitation in ethanol, followed by simple filtration. Additionally, this protocol demonstrated the benefits of environmentally friendly conditions, air compatibility, good functional group compatibility, scale-up synthesis with low catalyst loading, and a recyclable Rh catalyst. Importantly, compounds 3m and 3w demonstrated moderate agonist activity on the TASK-3 channel, with I/I₀ values of 1.7650 ± 0.1058 and 1.400 ± 0.0589, respectively.

A simple and practical method has been developed for the carbonylative esterification of imidazo[1,2-a]pyridines via C(sp²)–H bond functionalization using alkyl alcohols under mild reaction conditions. The carbonyl fragment is sourced from radical-mediated C–C cleavage of the alcohols, providing a green, safe, and economic alternative to traditional carbonyl sources like carbon monoxide. Through this strategy, a number of imidazo[1,2-a]pyridine-3-carboxylates were obtained from simple substrates by a single step.

We disclose the total synthesis of naturally occurring isocoumarins: (S)-fusarimarin B, (S)-diaporthin, (10S)-8-methoxydiaporthin, (S)-orthosporin, (S)-monarubin B, (S)-lunatinin, and isochromans aspergillumarin A, aspergillumarin B, and penicimarin B. The synthetic strategy highlights an efficient Ag(I)-mediated 6-endo-dig cyclization of properly substituted 2-alkynylated benzoates to yield the corresponding isocoumarins in excellent yields. The obtained isocoumarins, upon asymmetric hydrogenation with the Ru-BINAP catalyst, provided the corresponding isochromans with excellent yields and enantioselectivity. A Sonogashira cross-coupling reaction of properly functionalized terminal alkynes and substituted aryl bromides was employed to access 2-alkynylated benzoates. This report constitutes the first asymmetric synthesis of three naturally occurring isocoumarins: (S)-fusarimarin B, and (S)-monarubin B.

A novel and environmentally friendly strategy has been developed for the efficient electrochemical synthesis of β-keto sulfones. This method enables the synthesis of β-keto sulfones by reacting easily available sulfonylhydrazide with enol acetate under mild conditions, especially without the need for transition metal catalysts or oxidants, which can achieve high yields. The scope of this reaction was systematically explored with various sulfonyl hydrazides and enol acetates. The scale-up synthesis of β-keto sulfones was successfully accomplished using an electrochemical flow cell, demonstrating the industrial applicability of this approach. Moreover, the underlying reaction mechanism was further investigated through free radical scavenging experiments and cyclic voltammetry studies.

Cyanine dyes are widely used fluorophores with a range of labeling applications. However, there exists a lack of common, general methods for their synthesis that are applicable to dyes with a broad range of emission wavelengths. Herein, we describe a rapid, microwave-assisted, one-pot procedure for the synthesis of symmetrical trimethine, pentamethine, and heptamethine cyanine dyes in near-quantitative yields. A variation of the procedure allows the moderate-to-high-yielding synthesis of unsymmetrical cyanine dyes bearing −COOH substituents for functionalization.

In this paper, the application of α-methyl secondary enaminones in the synthesis of tetrahydrofuropyridines is described. The key step of the methodology is the in situ generation of 1-azadiene from oxidation of α-methyl secondary enaminone, followed by a subsequent inverse-electron-demand hetero-Diels–Alder reaction proceeded to give the desired product. Mechanistic studies and density functional theory (DFT) calculations revealed the detailed reaction pathway. Gram-scale preparation experiments and further transformation of the product demonstrate the potential applicability of this method. In addition, the amide derivatives could be obtained by employing β-methyl secondary enaminones as substrates under similar oxidative conditions. The present work opens a new window to the application of rarely reported α-methyl secondary enaminones.

Visible-light switchable stilbenes with a stable Z isomer that can function in aqueous media are notably rare in the literature. The synthesis and characterization of a set of 12 novel molecules featuring an aryl-substituted heterostilbene motif, a class of visible-light switchable stilbenes, are presented here. Leveraging an electronic push–pull mechanism, strategic selection of electron donors, and an indolinium moiety as the acceptor, we achieved precise tuning of the switching wavelengths.

For the first time, a photoredox-catalyzed alkoxycarbonylation/tricyclization reaction was developed by employing readily accessible enediynes and alkyloxalyl chlorides as starting materials, enabling the synthesis of ester-substituted polycyclic N-heteroaromatics under mild conditions through a radical-mediated mechanism. This photocatalytic strategy is notable for its exceptional compatibility with diverse functional groups, scalability, and efficiency in the formation of rings and chemical bonds. Notably, continuous flow photocatalysis technology markedly improved these reactions compared to the equivalent batch reactions, efficiently decreasing the reaction times to merely 40 min.

We report the electron-deficient CpRh(III) [Cp^ERh(III)] complex-catalyzed branch selective alkenylation with aliphatic alkenes and annulation with internal alkynes using N-2-pyridylanilines. In these reactions, the electron-deficient Cp^ERh(III) catalyst is more active than the electron-rich Cp*Rh(III) catalyst, used commonly in C–H activation, and the reactions proceed with a catalytic amount of a Cu(II) oxidant under air and at lower temperatures than conventional methods. From mechanistic considerations, steric repulsion between the ligand and the directing group may be responsible for the branch selective alkenylation.

Steroids have consistently drawn scientific attention due to their diverse structures and exceptional pharmacological activities. However, halogenated natural steroids remain relatively rare, especially for those derived from plants. In this study, two chlorinated C₁₉ steroids hocarnoids A (1) and B (2) were identified from the folk medicinal plant Hoya carnosa, representing the first examples of plant derived C-16 chlorinated steroids. Semisynthesis of compounds 1 and 2 was completed in 4 and 5 linear steps with 28.2% and 25.3% overall yields through a modified approach, corroborating further their structures. A total collection of 11 C₁₉ steroids, including intermediates obtained during the synthesis, were evaluated for the anti-inflammatory activity against lipopolysaccharide (LPS)-induced inflammation-related RAW 264.7 macrophages. Among them, the natural product hocarnoid A (1) displayed the strongest anti-inflammatory activity with an IC₅₀ value of 3.62 ± 0.08 μM, which also attenuated the mRNA levels of proinflammatory cytokines IL-1β, IL-6, IL-10, and TNF-α.

Sinudenoids B–D represent a biologically significant and structurally intricate family of natural products distinguished by their unique [5–5–6–6] tetracyclic skeleton. Herein, we present an efficient strategy for the asymmetric synthesis of their [5–5–6–6] tetracyclic framework. Key features of our approach include a convergent synthetic strategy driven by esterification, a pivotal Ireland-Claisen rearrangement to construct a C11–C12 bond, followed by efficient lactonization and isomerization, and a ring-closing metathesis to complete the [5–5–6–6] tetracyclic skeleton.

Multi(boronate) esters are useful building blocks in modern chemical synthesis. Herein, we have developed an efficient, transition metal- and solvent-free method for the regioselective boration of alkenes and alkynes. The alkali metal Lewis base (NaOMe)-mediated reactions, using bis(pinacolato)diboron (B₂pin₂) as the boron reagent, resulted in the diboration of alkenes at room temperature and the triboration of alkynes at 60 °C to produce synthetically useful alkyl 1,2-bis(boronate) esters and 1,1,2-tris(boronate) esters, respectively, in excellent yields and with high regioselectivity. This environmentally benign protocol demonstrates a broad substrate scope and good functional group tolerance for alkenes and alkynes. The gram-scale reaction further highlights the practical usefulness of the method. The proposed reaction pathway has been evaluated based on stoichiometric reactions and DFT studies.

We investigated the chemical consequences of direct irradiation of alkyl bis(catecholato)silicates. We provide evidence for alkyl radical formation through EPR spin-trapping experiments, relative kinetics of radical formation, and direct observation of the nitro group-stabilized semiquinone radical.

A mild and practical method for synthesizing amidoindoles and amidopyrroles was described via the direct amidation of indoles or pyrroles with isocyanates promoted by 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). In this reaction, HFIP acted as a strong hydrogen bond-donating solvent to activate isocyanates, enabling the amidation of electron-rich nitrogen-containing heterocycles.

A base-catalyzed protocol is reported for the construction of 1,3-thiazolidine-2-thione scaffolds bearing quaternary carbon centers from carbon disulfide and α-tertiary propargylamines. The reaction proceeds using low catalyst loading, under ambient temperatures, and in the absence of solvent. Various α-tertiary propargylamines have been employed, affording a series of previously unreported thiazolidine-2-thione compounds and avoiding purification via column chromatography in certain cases. We also describe a one-pot strategy for the synthesis of the same products through a KA² coupling–CS₂ incorporation approach. The reaction mechanism and substituent-dependent catalytic behavior were studied through a combination of detailed experimental and computational studies.

Concerned with traditional nitration methods requiring high temperatures, strong acids, or oxidizing agents, we developed an acid-free, selective photocatalytic nitration method using riboflavin tetraacetate and Fe(NO₃)₃·9H₂O under visible light. This method efficiently nitrates various arenes and bioactive molecules with high selectivity and functional group tolerance, offering a sustainable alternative to traditional nitration techniques.

Polycyclic aromatic hydrocarbons (PAHs) with open-shell or redox characteristics are highly desirable due to their intriguing electronic properties and potential applications. Here, we demonstrate a series of phenylenediamine-linked nanographenes (NGs) 1–3 by connecting two aza-hexa-peri-hexabenzocoronene (HBC) units to p-phenylene, p,p’-biphenylene, and p,p”-terphenylene, respectively, and unveil their 3D conformations, electronic structures, and redox properties. As proved by X-ray crystallographic analysis and quantum chemical calculation, 1–3 adopted anti-folded, Z-shaped 3D structures with rotatable single bonds. The structure-dependent redox capabilities were disclosed. For 1, a stable monoradical cation was generated by one-electron oxidation as the terminal product. X-ray crystallographic analysis revealed an unprecedented syn-folded structure of monoradical 1⁺. However, 2 and 3 were demonstrated as redox-active molecules from neutral to dication that each oxidative state can be precisely controlled by chemical oxidation/reduction.

Herein, we developed alkyl radical generation from C(sp³)–H bonds of alkanes via a photoinduced HAT-process without employing an external metal, photocatalyst, and organic peroxide. The generated alkyl radical participates in radical addition and cascade cyclization of N-arylacrylamides/N-acryloyl benzamides to deliver structurally diverse and valuable functionalized oxindoles and isoquinolinediones in moderate to good yields. Preliminary mechanistic studies indicated the generation of aryl radical through homolytic cleavage of Ar–I bonds via direct photoexcitation of aryl iodide.

We report the asymmetric total synthesis of optically active nervione in both (+) and (−) forms, a natural product initially isolated from Nervilia concolor in 2022. Beginning with commercially available resorcinol, optically pure nervione was synthesized in 10 steps, employing a combination of ortho-directed strategies and a crucial late-stage, Lewis acid-mediated, highly diastereoselective reduction. Discrepancies observed in circular dichroism (CD) spectra prompted the reassignment of nervione’s absolute configuration from (3S, 8R) to (3R, 8S).

A new general strategy for accessing pyrano[3,2-b]indol-2-ones, a promising fused hybrid heterocyclic system, has been devised from o-nitroynones and β-ketoesters through a one-flask cascade process involving tandem Michael addition, intramolecular cyclization, and Cadogan-Sundberg reductive cyclization. The utility of this approach has been further amplified by leveraging the cycloaddition proclivity of the α-pyrone moiety in pyrano[3,2-b]indol-2-ones toward a concise entry to carbazoles. Illustrative synthesis of the carbazole natural products hyellazole and chlorohyellazole is also disclosed.

Azetidines represent an attractive and emerging design option in medicinal chemistry owing to their small size and polar nature, as well as their potential to significantly impact the physicochemical properties of drug molecules. However, traditional methods for the synthesis of 3,3-disubstituted azetidines usually require higher step counts or exhibit poor functional group compatibility. Herein, we report a modular synthesis strategy for 3,3-disubstituted azetidines based on azetidinylation reagents. The practicality of this method is further exemplified by the use of readily available starting materials, mild reaction conditions, and a very broad substrate scope.

A unique β-position [3 + 2]-cycloaddition between γ-deconjugated butenolides and spiro-epoxyoxindoles catalyzed by Sc(OTf)₃ has been disclosed. A variety of unexpected [3 + 2]-cycloaddition adducts of spiro-oxindoles fused with bicyclic γ-lactones and three consecutive stereocenters have been successfully constructed in good yields (up to 88%) with excellent diastereoselectivities (>20:1) in one single operation under mild conditions, which is difficult to achieve by traditional strategies.

A method for the asymmetric propargylation and allenylation of isatins catalyzed using chiral Box-copper/zinc catalysts is described. By modulation of the metal and solvent, a series of chiral 3-hydroxy-3-propargyl-2-oxindoles and 3-hydroxy-3-allenyl-2-oxindoles are selectively synthesized in good yields with excellent enantio- and regioselectivities.

Chemical utilization of carbon dioxide (CO₂) has emerged as a sustainable access for synthesizing high-value chemicals. Continuously designing the more practical reaction systems is of large importance. Herein, an unprecedented and powerful copper-PMHS reductive system of o-aminobenzamides with CO₂ is disclosed. Synthetically, a diverse range of quinazolinones (>70 examples) are rapidly assembled with excellent functional group tolerance in good yields. Moreover, building other types of heterocycles such as benzothiazoles and benzimidazoles is also allowable. Mechanistically, differing from the reported carbonylation cases, this finding represents a scarce example of CO₂ as a single-carbon atom synthon in the PMHS system.

A method for iodinating deactivated aryl rings is reported using a greatly reduced quantity of H₂SO₄ (<1 vol %) compared with traditional methods, which often requires it as a bulk solvent. A new aryl iodine(III) system oxidizes I₂ in organic solvents (CH₂Cl₂, CHCl₃) with trifluoroacetic anhydride as a water scavenger. Catalytic H₂SO₄ is used in the case of highly deactivated rings. The aryl iodine(III) oxidants 4-nitrophenyliodine bis(trifluoroacetate) (NPIFA), 3-iodosylbenzoic acid (3-IBA), and 2,4-dichloro-5-iodosylbenzoic acid (3-IBACl₂) are applied based on separability and reactivity of target substrates, and their reduced forms are recovered by simple acid/base extractions, demonstrating excellent reusability. Leveraging this, iodinated products are isolated without the need for chromatography. The method is suitable for use under benchtop conditions and exhibits high efficiency in iodine and the oxidant, as well as excellent positional selectivity in the substrates tested.

The convergent synthesis of a series of chromane derivatives by a triflimide-catalyzed annulation of o-hydroxy benzylic alcohols with alkenes is reported. The Brønsted acid-catalyzed reaction proceeds from simple starting materials under mild conditions and provides chromane products of varying substitution patterns.

Cross-coupling reactions using ketones directly as alkenyl electrophiles proceed efficiently in the presence of a cooperative Ru and amine catalytic system. The amine catalyst functions as the transient leaving group of an in situ generated enamine, where the alkenyl C–N bond is cleaved with the aid of a pyridine directing group and the Ru catalyst. A ketone with a 3-substituted pyridyl group is essential for a smooth reaction.

Formation of imine organic cages relies on the error correction of dynamic covalent chemistry. Here, we demonstrate kinetically trapped rylene diimide [2 + 3] cages formed in high yields, and we investigate the effect of substituents on their formation kinetics and stability. Thereby, we identified that alkoxy groups in 2,4,6-trialkoxy-1,3,5-triformylbenzene, which are used to stabilize covalent organic cages or COFs, act as stereoelectronic chameleons. They increase the electrophilicity of the tritopic aldehyde and the rate of the imine bond formation but simultaneously diminish its kinetic stability in solution. We also show that aldehydes present in the solution may have a detrimental effect on the cage’s kinetic stability. In addition, we observed [2 + 2] macrocycles as intermediates in the cage formation and decomposition. We propose that these intermediates represent interesting targets to explore the threshold at which an imine assembly with a rung structure may turn from thermodynamic to kinetic control. Generally, this work underscores critical factors governing the chemistry of kinetically trapped imine assemblies, such as steric bulk, (stereo)electronics, presence of catalysts, and water concentration.

A photocatalytic diazo triplet carbene-promoted C(sp³)–H oxidative coupling of isochromans and triazoles was developed in up to 83% yield at room temperature in air. The radical-like triplet carbenes were used as efficient HAT acceptors, and the possible synergistic HAT enabled the unprecedented process with a high regioselectivity.

α-Cyanoacrylamide derivatives of ibrutinib are reversible inhibitors of Bruton’s tyrosine kinase (BTK), an important target in B-cell-mediated cancers. We prepared the methyl derivative 1 as part of a larger study and observed interesting complex isomerization behavior that warranted further investigation. Herein, we characterize the solution-state configurational and conformational behavior of 1 by 1D and 2D temperature-dependent NMR and LC–MS. Synthesis of 1 by various routes leads to mixtures of E and Z configurational isomers about its alkene centered at C-31 and C-32. Isomers (E)-1 and (Z)-1 can be separated by reversed-phase HPLC and are stable at room temperature in solution. Interestingly, each configurational isomer undergoes cis/trans conformational isomerization about their respective acrylamide bonds at N-28 with rates dependent on the alkene configuration at C-31. Further, the configurational integrity of the alkene can be compromised at elevated temperatures. Warming pure (E)-1 affords a mixture of E- and Z-isomers resulting in the same relative ratio as observed in the initial synthesis of the compound, with each again exhibiting conformational isomerization about their amide bonds. Warming pure (Z)-1 affords the same results. Knowledge of the isomerization behavior of α-cyanoacrylamides can inform the synthesis, purification, and utility of this class of molecules.

Diketopiperazine (DKP), a versatile scaffold, is extensively used in the synthesis of complex natural products, bioactive molecules, and smart materials in organic chemistry. Recently, activated DKPs, such as Boc-DKPs, have emerged as key building blocks for peptide elongation in peptide synthesis. In this study, we developed a facile protocol for synthesizing mono-Boc-protected DKPs from readily accessible N-4-methoxybenzyl (N-PMB)-amino acids and amino acid methyl esters. This protocol involved a sequence of reactions encompassing the formation of dipeptides from N-PMB-amino acids and amino acid methyl esters, cyclization of N-PMB-dipeptides to form PMB-DKPs, Boc-protection of PMB-DKPs, and subsequent PMB-deprotection of PMB-DKP-Boc to afford mono-Boc-DKPs. The protocol demonstrated a broad substrate scope, accommodating diverse amino acids with various side chains, affording mono-Boc-DKPs in good yields with excellent stereoselectivities (>20:1 dr). The synthetic utility of mono-Boc-DKPs was showcased in peptide synthesis by synthesizing pentapeptide Boc-l-Tyr(t-Bu)-Gly-l-Phe-Gly-l-Val-OtBu by 2-fold peptide elongation with two mono-Boc-DKPs. Furthermore, we synthesized Leu-enkephalin pentapeptide by reacting cyclo(Boc-l-Tyr(t-Bu)-Gly-) with H-Gly-l-Phe-l-Leu-Ot-Bu, resulting in a good yield and excellent optical purity.

An approach to cyclohepta[b]indoles via the formal (4 + 3) annulation of readily synthesized 2-indolyl-derived 1,3-dicarbonyl compounds to acrolein and enones was developed. The process is initiated by catalytic Michael addition, wherein the adduct was generated in situ. The subsequent addition of a Bro̷nsted acid catalyst triggers a cascade process that includes intramolecular Friedel–Crafts hydroxylalkylation followed by dehydration. The cascade reaction is relatively undemanding since even degrading chloroform is able to initiate it. The obtained tetrahydrocyclohepta[b]indoles were prone toward easy dimerization, underscoring the high reactivity of the double bond in the seven-membered ring.

A photocatalytic radical sulfonarylation of N-arylacrylamides via a three-component cascade cyclopropyl alcohol ring opening/sulfur dioxide insertion/sulfonyl radical addition/cyclization sequence has been developed. This method employs cyclopropyl alcohols as the precursors of β-carbonyl alkyl radicals and Na₂S₂O₅ as a cheap source of sulfur dioxide. By using this cascade procedure, a wide variety of γ-keto-sulfone-substituted oxindoles were facilely synthesized.

We report a ferrocene-mediated electrochemical intermolecular oxidative annulation between malonates and styrenes that avoids the use of excess oxidants such as Mn(OAc)₃. The reaction proceeds via presumably the generation of a malonyl radical that adds to the styrene. After further anodic oxidation, the resulting benzylic carbocation is intercepted by one of the esters to deliver the desired γ-lactones.

The synthesis of 2- and 6-substituted-3-aminopiperidines from Weinreb amides containing an allylamino fragment is reported. Involving the simultaneous hydrozirconation of the C═C and the C═O bonds, the cyclization was promoted by the BF₃-mediated generation of an iminium. Proven to be highly diastereoselective, the sequence can be applied to diversely substituted unsaturated Weinreb amides and valorized through the preparation of bicyclic heterocycles.

An efficient Rh(III)-catalyzed annulation between 3-aryl-2H-benzo[b][1,4]oxazines and α-diazo-β-ketoesters was developed, affording a series of polycyclic heteroarenes in moderate to excellent yields with good functional group compatibility. The procedure featured high efficiency, redox neutrality, twofold ortho-C-H activation, and dual [4 + 2] annulation. Moreover, several important intermediates and products have been isolated as powerful evidence for the proposed reaction mechanism.

Tether-directed electrosynthesis of [60]fullerene derivatives fused with 5-membered azacycle and 13-membered carbocycle, that is, bicyclic 1,4,9,12- and 1,2,4,15-adducts, has been achieved unexpectedly for the first time. The novel bicyclic [60]fullerene derivatives are obtained by the electrochemical reduction of [60]fullerene-fused indolines or lactams and subsequent regioselective cyclization with 2,2″-bis(bromomethyl)-1,1′:3′,1″-terphenyl. The product structures have been characterized by spectroscopic data and single-crystal X-ray analysis.

A lone pair-π interaction was employed to alter the reactivity of three isochalcogenourea catalysts in a model silylation reaction. Even though a lone pair-π interaction is a relatively weak interaction, working cooperatively with a bond-forming step allowed the interaction to alter the reactivity of the catalyst over the inherent nucleophilicity in an alcohol silylation reaction.

Bicyclo[3.2.1]octanes widely exist in natural products and bioactive compounds. However, the efficient construction of these skeletons remains a challenge. Herein, we reported a convenient synthesis of diaza-oxabicyclo[3.2.1]octanes and dioxa-azabicyclo[3.2.1]octanes by intramolecular cascade cyclizations. The reaction was performed under transition metal-free conditions and with good functional group tolerance. This work provides divergent approaches to bicyclo[3.2.1]octane frameworks.

The fascinating skeleton 3,2′-pyrrolidinyl spirooxindole exhibits diverse pharmacological activity. Despite advancements in the construction of this skeleton, the application rearrangement strategy for the synthesis of 3,2′-pyrrolidinyl spirooxindole remains underexplored. Herein, we reported an efficient method for the construction of 3,2′-pyrrolidinyl spirooxindole by the [2,3]-rearrangement reaction between 3-diazoindolin-2-one and arecoline under mild reaction conditions, which had a good functional group tolerance and high yield. This work not only facilitates the study of selective rearrangement of ammonium ylide but also contributes significantly to the synthesis of spiro compounds.

Dual functionalization in organic synthesis represents a powerful strategy aimed at achieving multiple transformations within a single reaction cycle, thereby streamlining synthetic processes, enhancing efficiency, and imparting economic paths for complex molecules. Here, we report a heterogeneous perovskite nanocrystal (NC) photocatalytic system that can simultaneously drive two photoredox cycles in a single reaction. The dual process incorporates two distinct functional groups (N-heterocycles and bromines) into N-arylamines under the influence of a single catalyst (CsPbBr₃ NCs), allowing for the concurrent formation of two distinct architectures of 3-bromo-N-arylindoles. Mechanistically, long-lived charge separation and charge carrier accumulation at the NC surface enable perovskite to drive these two photoredox cycles simultaneously. The dual approach exploits light-induced holes to drive an amine oxidation in one cycle (I) and cooperatively utilizes dibromomethane (CH₂Br₂), a solvent-grade mild reagent for site-selective bromination, to achieve the other photoredox cycle (II). We find that chiral perovskite induces enantioselective axial C–N bond formation, but is inactive for axial C–C bond formation of arylindoles. Merging two photoredox cycles simultaneously to achieve dual functionalization is rare; thus, the perovskite NC photocatalysis not only aligns with the principles of green chemistry but also holds immense potential for the rapid and economical design of complex molecules.

Non-covalent interactions are a highly promising tool for the development of transition-metal-free chemospecific synthetic transformations. Here, we demonstrate the implementation of non-covalent interactions as a simple, precise, and flexible synthetic toolbox, allowing the controlled transformation of o-dimethylaminoaryloximes into nitriles and hard-to-reach nitrogen heterocycles under mild conditions. This diverse reactivity is activated via hydrogen bonding and facilitated via the “buttressing effect” of the substituents next to the NMe₂ group. All transformations require only simple and easily available acids and solvents, which generally provide precise control over the direction of the reaction, allowing the selective synthesis of nitriles, fused pyrazoles, isoxazoles, and pyrroles.

The enol-Ugi condensation, a versatile multicomponent reaction, provides a rapid and efficient route to enamine peptidomimetics. In this study, we investigated the factors influencing the conformational behavior of three enol-Ugi adducts with distinct structural features. Through DFT calculations and NCI analysis, we identified that noncovalent interactions, including hydrogen bonds and π–π interactions, play a pivotal role in restricting conformational flexibility. While six-membered cyclic enamines 6 and 7 exhibited varying degrees of rotational freedom, the indanone-derived enamine 8 displayed a locked conformation resembling a retropeptidic turn. These findings highlight the potential of tailoring enol-Ugi adducts to mimic biologically relevant peptidic motifs, opening new avenues for drug discovery and design.

N-tert-butyl-glycine (NtBu) is a known peptoid structure-inducing monomer. The hindered tert-butyl group exerts a major effect on the cis/trans isomerization of the NX-NtBu peptoid-amide bond, which adopts exclusively the cis-geometry. Incorporating this monomer into peptoid oligomers is therefore an excellent way of promoting specific secondary structures such as turns and polyproline type-I helices. However, the steric hindrance of the tert-butyl group has so far prevented the solid-phase synthesis of peptoid oligomers incorporating NtBu monomers. We report here for the first time solid-phase syntheses of NtBu-containing peptoids using a modified submonomer protocol. We have found that the success of the critical DIC-mediated acylation step depends on the addition of a base and/or basic pretreatment of the resin prior to the reaction. The use of chloroacetic acid instead of bromoacetic acid also improved the efficacy of the syntheses, as did a halogenoacetic acid preactivation stage. To demonstrate the effectiveness of the modified submonomer protocol, we synthesized homooligomers at sequence lengths of up to 12-mer and also applied it to the synthesis of various peptoids with highly congested NCα-gem-dimethyl side chains.

Phosphinylation of π-scaffolds is of huge current interest; however, the ensuing C–P(O) bond formation necessitates catalyst, light, heat, etc. We report that electron-deficient halogenated naphthalene diimide (NDI) scaffolds can enable catalyst-free, room-temperature phosphinylation via a possible single-eT-mediated reaction. The arylphosphinylated NDIs show multielectron acceptor property, and LUMO of −4.24 eV, rendering the Ph₂PO group equally potent as the electron-withdrawing C≡N group. Thus, in situ reduction can be propelled leading to radical anions and dianions.

Biological substrate specificity ensures that organisms interact accurately with biomolecular receptors, crucial for key functions such as signaling and immunity. Nevertheless, this phenomenon is still poorly understood, with host–guest chemistry offering a suitable platform for studying simplified models. Herein, we report an in-depth study of the host–guest chemistry of alkyltriphenylphosphonium cations with cucurbit[8]uril (CB[8]), initiated by the serendipitous discovery of salt forming a tightly bound pseudoheteroternary 1:1 complex with CB[8]. A first generation of model substrates was designed to explore an unusual binding mode characterized by the simultaneous introduction of two distinct guest fragments within the host cavity. Structural features of the complexes were elucidated using ESI-MS and NMR 1D/2D techniques; thermodynamic properties were assessed by isothermal titration calorimetry, and kinetic parameters were derived from selective inversion–recovery NMR. Experimental results aligned well with electronic structure calculations, revealing a reproducible binding motif with submicromolar affinities. This peculiar complexation mode involves a synergistic effect caused by steric crowding around the P⁺ atom, facilitating the insertion of two aromatic units into CB[8] while hindering association with CB[7]. Based on these findings, a second generation of minimalistic substrates was developed, preserving the synergistic interaction mode and exhibiting specific binding to CB[8].