Search

An efficient chalcogenative annulation strategy for constructing functionalized saturated N-heterocycles from unactivated alkenes with dichalcogenides under electrochemical conditions has been presented. This protocol is applicable to mono-, di- or tri-substituted alkenes, providing a straightforward pathway to aziridines, azetidines, pyrrolidines, and piperidines with high regioselectivity. Moreover, the strategy is qualified to realize the oxychalcogenation of alkenes as well. [ABSTRACT FROM AUTHOR]

We describe the first total syntheses of tabernanthine and ibogaline. Entry to these iboga alkaloid natural products is enabled by a thermal coupling of indoles and aziridines to furnish the requisite nosyl tryptamine starting materials. This route features a Friedel‐Crafts type alkylation to form the key indole‐isoquinuclidine C−C bond. Finally, a regio‐ and diastereoselective hydroboration‐oxidation enables C−N bond formation to close the isoquinuclidine ring system and deliver tabernanthine and ibogaline in 10 and 14 % yield respectively. Both syntheses were completed in eight steps. [ABSTRACT FROM AUTHOR]

Piperazines constitute an important structural feature of many pharmaceuticals. For the discovery of new drugs, the ability to modify the lead compound's structure is crucial. Herein, we provide an efficient method for the synthesis of chiral 2,3,5-trisubstituted piperazine structures. Our route enables the synthesis of several novel chiral aryl aziridinyl ketones that could be converted into aziridine-fused bicyclic imines. The reduction of these imines and the nucleophilic ring-opening reaction of the aziridine ring allowed us to synthesize highly functionalized piperazine derivatives. [ABSTRACT FROM AUTHOR]

β‐Phenethylamines are widely represented in biologically and pharmacologically active organic small molecules. Here, we introduce N‐pyridinium aziridines as latent dual electrophiles for the synthesis of β‐phenethylamines. Bromide‐promoted ring opening generates β‐halopyridinium amines. Selective Ni‐catalyzed C−C cross‐coupling between organozinc nucleophiles and the benzylic C−Br electrophile affords a diverse family of β‐functionalized phenethylaminopyridinium salts, and coupling is stereoconvergent in the presence of chiral ligands. Subsequent Ni‐catalyzed reductive N−N bond activation within the β‐functionalized phenethylaminopyridinium salts furnishes the products of formal olefin carboamination. Other reductive N−N cleavage reactions are demonstrated to provide access to free primary amines, alkylated amines, heterocycles, and products derived from N‐centered radical chemistry. The developed reaction sequence can be implemented in the context of complex molecules and natural product derivatives. Together, the described results provide a general and modular synthesis of β‐phenethylamines and significantly expand the utility of N‐pyridinium aziridines as linchpins in chemical synthesis. [ABSTRACT FROM AUTHOR]

A general and atom-efficient synthesis of quinoline-C2-substituted β-hydroxyarylethylamino derivatives was achieved by copper-catalyzed [3+3]-cycloaddition reaction of N -oxide with N -Ts aziridines. Notably, temperature has a huge impact on this transformation as evidenced by the fact that, at 80 °C, exclusively the [3+3] cycloadduct was isolated whereas, at elevated temperature (140 °C), it has been converted into the aminated product with good yield. Notably, there is no byproduct in the overall process. The use of base-free conditions, excellent site selectivity, and good functional group tolerance are the important features of the process. [ABSTRACT FROM AUTHOR]

Elevated concentrations of CO2 in the atmosphere pose significant challenges, notably contributing to the greenhouse effect. CO2 as an abundant C1 resource converting into high-value oxazolidinones is a promising avenue for effective carbon fixation. Herein, a highly stable binuclear cerium–organic framework, [Ce2(DCTP)2(DMA)2(OAc)2]n (1), has been successfully designed and synthesized, which maintains the intact three-dimensional framework after immersing in solutions with pH ranging from 1 to 12 and various common solvents for 24 hours, respectively. Explorations on CO2 conversion indicate that compound 1 exhibits remarkable catalytic efficiency in the cycloaddition reaction of CO2 with aziridines to form oxazolidinones under relatively low CO2 pressure. 1 can be easily regenerated five times without a significant decrease in yield. Mechanistic experiments show that the high catalytic activity of 1 is attributed to the stable three-dimensional framework, high Lewis acidity, and ample cerium active sites. Notably, 1 is a rare lanthanide metal–organic framework-based (Ln-MOF-based) catalyst for the cycloaddition of CO2 with aziridines under mild pressure. [ABSTRACT FROM AUTHOR]

The asymmetric [3+2] cycloaddition of azomethine ylides generated from the corresponding imino ester-to-trans-β-nitrostyrene catalysis by chiral aziridine-containing phosphines and phosphine oxides is described. Of the sixteen stereoisomers that could be formed as a result of the title reaction, three were formed, two of which were obtained in an enantiomerically enriched or pure form, and one in a racemic form. One of the products underwent epimerization under basic reaction conditions. [ABSTRACT FROM AUTHOR]

A new strategy for the synthesis of 3‐substituted phthalides has been developed via a Lewis acid‐catalyzed intramolecular ring opening of aziridines with esters. Broad substrate scope, good yields and mild conditions made the cyclization reaction very suitable for the rapid construction of libraries of 3‐substituted phthalide compounds. [ABSTRACT FROM AUTHOR]

The first palladium‐catalyzed allylation of isocyanoacetates with vinyl aziridines has been developed. The reaction conditions were suitable for a variety of α‐aryl isocyanoacetates as well as N‐substituted vinyl aziridines, affording the corresponding allylation products in moderate to high yields (up to 98 %) along with excellent stereoselectivity and regioselectivity. Transformations of the allylation products into trans‐4,5‐dehydrolysine analogues and a highly functionalized proline ester derivative were further demonstrated, and a preliminary asymmetric version of the reaction has also been evaluated. [ABSTRACT FROM AUTHOR]

In previous works, we demonstrated that tertiary 3‐chloropiperidines are potent chemotherapeutics, alkylating the DNA through the formation of bicyclic aziridinium ions. Herein, we report the synthesis of novel secondary 3‐chloropiperidine analogues. The synthesis incorporates a new procedure to monochlorinate unsaturated primary amines utilizing N‐chlorosuccinimide, while carefully monitoring the temperature to prevent dichlorination. Furthermore, we successfully isolated highly strained bicyclic aziridines by treating the secondary 3‐chloropiperidines with a sufficient amount of base. We conclude this work with a DNA cleavage assay as a proof of principle, comparing our previously known substrates to the novel compounds. In this, the secondary 3‐chloropiperidine as well as the isolated bicyclic aziridine, proved to be more effective than their tertiary counterpart. [ABSTRACT FROM AUTHOR]

The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π–stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands. [ABSTRACT FROM AUTHOR]

The oxirane and aziridine rings are valuable building blocks in modern synthetic chemistry and catalytic asymmetric ring opening reactions of these three membered ring systems have emerged as a powerful chemical tool for the synthesis of natural products and biologically active compounds. In this context, the regioselective ring‐opening of structurally or electronically unbiased epoxides and aziridines is challenging. Recently, metal‐catalyzed substrate directed strategies have successfully applied in the regio‐ and enantioselective ring opening of functionalized epoxy alcohols by the Yamamoto group. Subsequently, our group realized the ring opening reactions of functionalized 2,3‐aziridinyl alcohols with the dinuclear zinc complex. These enantioselective nucleophilic ring opening reactions of functionalized epoxy alcohols and aziridinyl alcohols allow for the facile synthesis of amino alcohol derivatives and the introduction of new concepts in catalysis. [ABSTRACT FROM AUTHOR]

We report an approach to the diastereoselective synthesis of 1,2‐disubstituted heterocyclic aziridines. A Brønsted acid‐catalyzed conjugate addition of anilines to trisubstituted heterocyclic chloroalkenes provides an intermediate 1,2‐chloroamine. Diastereocontrol was found to vary significantly with solvent selection, with computational modelling confirming selective, spontaneous fragmentation in the presence of trace acids, proceeding through a pseudo‐cyclic, protonated intermediate and transition state. These chloroamines can then be converted to the aziridine by treatment with LiHMDS with high stereochemical fidelity. This solvent‐induced stereochemical enrichment thereby enables an efficient route to rare cis‐aziridines with high dr. The scope, limitations, and mechanistic origins of selectivity are also presented. [ABSTRACT FROM AUTHOR]

Under the catalysis of a Cu(I) or Ag(I) salt with a chiral diphosphine ligand, the enantioselective nucleophilic ring opening of racemic 2‐styrenylaziridines via kinetic resolution or dynamic kinetic asymmetric transformation (DyKAT) and of meso aziridines via desymmetrization with alcohols was realized. The reaction provided a range of chiral vicinal amino ether derivatives in 47%‐98% yields and with 50%–98% ee. The reaction could be extended to aliphatic carboxylic acids as nucleophiles. The synthetic utility was demonstrated in a four‐step formal synthesis of a diastereomer of the antirythmetic agent vernakalant. [ABSTRACT FROM AUTHOR]

A series of optically pure aziridine phosphines and their corresponding phosphine oxides were synthesized through established chemical methodologies. The compounds were systematically investigated for their biological properties. Notably, all synthesized compounds demonstrated moderate antibacterial activity only against the reference strain of Staphylococcus aureus. However, compounds 5 and 7 exhibited noteworthy cell viability inhibition of human cervical epithelioid carcinoma HeLa cells and endometrial adenocarcinoma Ishikawa cells. Further studies of these compounds revealed additional biological effects, including disruption of the cell membrane in high concentrations, cell cycle arrest in the S phase, and the induction of reactive oxygen species (ROS). Comparative analysis of the two classes of chiral organophosphorus derivatives of aziridines indicated that chiral phosphine oxides displayed significantly higher biological activity. Consequently, these findings suggest that chiral phosphine oxides may be potential candidates for the development of anticancer drugs. In light of the significant interest in preparations whose structure is based on a three-membered aziridine ring in terms of potential anticancer therapy, this research fits into the current research trend and should constitute a valuable addition to the current state of knowledge and the existing library of aziridine derivatives with anticancer properties. [ABSTRACT FROM AUTHOR]

The coupling of diaziridines with donor–acceptor aziridines (DAAs) has been achieved using Zn-catalysis to furnish imidazopyrazole-4,4-dicarboxylates via [1,4]-hydride shift. The use of Zn-catalysis, [1,4]-hydride shift, natural product modification and a late-stage molecular docking study are important practical features. [ABSTRACT FROM AUTHOR]

Chiral cyclopentadienyl‐rhodium(III) CpxRh(III) catalysis has been demonstrated to be competent for catalyzing highly enantioselective aziridination of challenging unactivated terminal alkenes and nitrene sources. The chiral CpxRh(III) catalysis system exhibited outstanding catalytic performance and wide functional group tolerance, yielding synthetically important and highly valuable chiral aziridines with good to excellent yields and enantioselectivities (up to 99 % yield, 93 % ee). This protocol presents a novel and effective strategy for synthesizing enantioenriched aziridines from simple alkenes. Various transformations were performed on the aziridine products, illustrating the versatility and synthetic potential of this protocol for constructing highly functionalized compounds. [ABSTRACT FROM AUTHOR]

This manuscript describes the development of alkyne addition to the aziridine moiety of aziridinoquinoxalines using dual Ir(III)/Cu(I) catalytic system under green light‐emitting diode (LED) photolysis (λmax=525 nm). This mild method features high levels of chemo‐ and regioselectivity and was used to generate 30 highly functionalized substituted dihydroquinoxalines in 36–98 % yield. This transformation was also carried asymmetrically using phthalazinamine‐based chiral ligand to provide 9 chiral addition products in 96 : 4 to 86 : 14 e.r. The experimental and quantum chemical explorations of this reaction suggest a mechanism that involves Ir(III)‐catalyzed triplet energy transfer followed by a ring‐opening reaction ultimately leading to the formation of azomethine ylide intermediates. These azomethine intermediates undergo sequential protonation/copper(I) acetylide addition to provide the products. [ABSTRACT FROM AUTHOR]

Azetidines, being four‐membered N‐heterocycles, possess significant potential in contemporary medicinal chemistry owing to their favorable pharmacokinetic properties. Regrettably, the incorporation of functionalized azetidines into pharmaceutical lead structures has been impeded by the absence of efficient synthetic methods for their synthesis. In this study, a Rh‐catalyzed one‐carbon ring expansion of aziridines with vinyl‐N‐triftosylhydrazones is presented, which facilitates the synthesis of high value‐added 2‐alkenyl azetidine products. This research represents the first example of ring expansion of aziridines enabled by vinyl carbenes. Additionally, a one‐pot two‐step protocol, initiated from cinnamaldehyde, was successfully achieved, offering a step‐economical and facile approach for the synthesis of these compounds. The pivotal aspect of this successful transformation lies in the in situ formation of an alkenyl aziridinium ylide intermediate. Experimental investigations, coupled with computational studies, suggest that a diradical pathway is involved in the reaction mechanism. [ABSTRACT FROM AUTHOR]

A vicinal diamine motif can be found in numerous natural compounds and pharmaceuticals, making it an important synthetic target. Herein, we report a telescoped synthesis of vicinal diamines under continuous flow conditions. This approach involves the electrochemical aziridination of alkenes with primary amines, followed by the strain-release driven ring-opening using various nitrogen nucleophiles. The efficacy of the developed method was demonstrated through the synthesis of diverse symmetrically and non-symmetrically substituted vicinal diamines, as well as vicinal amino azides, which can be further hydrogenated to diamines in flow. Additionally, O-centered nucleophiles were employed for the ring-opening of aziridines in our telescoped synthesis, yielding vicinal amino ethers and alcohol. This process offers a streamlined and efficient pathway for the direct synthesis of valuable products from readily available starting materials, bypassing the isolation of unstable aziridine intermediates. [ABSTRACT FROM AUTHOR]

Isothiourea is an important class of sulfur-containing molecules showing unique catalytic and biological activities. As such, polyisothiourea is envisioned to be an interesting type of polymer that potentially exhibits a number of interesting properties. However, there is no access to synthesizing well-defined polyisothiourea, and currently isothiourea-containing polymers are mainly prepared by immobilizing onto other polymer's side chain. Herein, we report the first facile synthesis of polyisothioureas via alternating copolymerization of aziridines and isothiocayanates. Mediated by the catalytic system of phosphazene superbases/alcohol, a broad scope of aziridines and isothiocayanates could be transformed into polyisothioureas with adjustable substitutions (11 examples). The structures of obtained polyisothioureas were fully characterized with 1H-NMR, 13C-NMR, and 1H-13C HMBC NMR. Moreover, the polyisothioureas show tunable thermal properties depending on substitutions on the isothiourea linkages. The novel structure of these polyisothioureas will enable a powerful platform for the discovery of next-generation functional plastics. [ABSTRACT FROM AUTHOR]

The bulk radical polymerization of bis(aziridine) with molten elemental sulfur resulted in brittle, cross‐linked polymers. However, when the bis(aziridine) was treated with elemental sulfur in the presence of an organobase, the ring‐opening reaction of aziridine with oligosulfide anions occurred, leading to the formation of linear polymers by step‐growth polymerization. These newly synthesized polymers possess repeating units containing a sulfonamide or amide functional moiety and oligosulfide bonds with an average sulfur segment of about two. A small molecular model reaction confirmed the nucleophilic addition reaction of elemental sulfur to aziridine. It was verified that S−S dynamic bond exchange takes place in the presence of an organic base within the linear chains. The mixture of the synthesized polysulfides with pyridine exhibits exceptional adhesive properties when applied to steel, and aluminum substrates. Notably, these prepared adhesives displayed good reusability due to the dynamic S−S exchange and complete recyclability due to their solution processability. This elemental sulfur‐involved polymerization approach represents an innovative method for the synthesis of advanced sulfur‐containing polymers, demonstrating the potential for various applications in adhesives and beyond. [ABSTRACT FROM AUTHOR]

The BF3⋅OEt2‐catalyzed reaction of azulene with N‐protected aziridines represents a general, efficient (up to 91% yield) and regioselective approach to phenethylamine‐azulene conjugates. Stereochemical studies and DFT calculations lend support to a concerted SN2‐type mechanism governing the ring‐opening of the aziridine. [ABSTRACT FROM AUTHOR]

Commercially available poly(lactic acid) exhibits poor hydrolytic stability, which makes it impossible for use in durable applications. Therefore, a novel hydrolysis inhibitor based on an aziridine derivative as well as a novel stabilizer composition, containing an aziridine derivative and an acid scavenger, were investigated to improve the hydrolytic stability. To evaluate the stabilizing effect, the melt volume rate (MVR) and molecular weight were monitored during an accelerated hydrolytic aging in water at elevated temperatures. Temperatures were selected according to the glass transition temperature (~60 °C) of PLA. It was shown that the novel hydrolysis inhibitor as well as the novel stabilizer composition exhibited excellent performance during hydrolytic aging, exceeding commercially available alternatives, e.g., polymeric carbodiimides. A molecular weight analysis resulted in a molecular weight decrease of only 10% during approximately 850 h and up to 20% after 1200 h of hydrolytic aging, whereas poly(lactic acid) stabilized with a commercial polycarbodiimide revealed comparable molecular weight reductions after only 300 h. Furthermore, the stabilization mechanism of the aziridine derivative alone, as well as in the synergistic combination with the acid scavenger (calcium hydrotalcite), was investigated using nuclear magnetic resonance (NMR) spectroscopy. In addition to an improved hydrolytic stability, the thermal properties were also enhanced compared to polymeric carbodiimides. [ABSTRACT FROM AUTHOR]

A sequential one‐pot direct strategy for the synthesis of 2‐hydroxy‐2‐substituted‐2H‐benzo[b][1,4]oxazin‐3(4H)‐ones is developed under ambient conditions with moderate to good yields (up to 75 %) by regioselective ring‐opening of spiro‐epoxy/aziridine oxindoles with 50 % aq. H2O2 followed by rearrangement reaction in presence of amberlyst‐15 catalyst. Further, sequential reaction with aldehydes/ketones and carbonyldiimidazole (CDI) gave spiro[benzo[b][1,4]oxazine‐2,4′‐[1,3]dioxolan]‐3(4H)‐ones and spiro[benzo[b][1,4]oxazine‐2,4′‐[1,3]dioxolane]‐2′,3(4H)‐diones, respectively. [ABSTRACT FROM AUTHOR]

An in situ generated photoactive copper(I)‐complex‐catalyzed aziridination reaction of cyclic N‐sulfonyl imines with α‐aryl‐substituted vinyl azides irradiated by blue‐LEDs light is reported for the first time. This novel SET process represents a mild, sustainable, and pragmatic method for accessing synthetically resourceful sulfamidate‐fused aziridines in acceptable chemical yields with excellent diastereoselectivities. Delightedly, pharmacologically attractive benzo[f][1,2,3]oxathiazepine dioxides and fused isoxazoline frameworks were achieved through our newly developed metal‐free based ring‐expansion techniques, highlighting the synthetic value of accessed aziridines. Finally, the possible mechanism for [2+1] aza‐cyclization was presented based on the conduction of a series of control experiments. [ABSTRACT FROM AUTHOR]

N‐Trifluoromethylated organics may be applied in drug design, agrochemical synthesis, and materials science, among other areas. Yet, despite recent advances in the synthesis of aliphatic, cyclic and heterocyclic N‐trifluoromethyl compounds, no strategy based on trifluoromethyl nitrene has hitherto been explored. Here we describe the formation of triplet trifluoromethyl nitrene from azidotrifluoromethane, a stable and safe‐to‐use precursor, by visible light photocatalysis. The addition of CF3N to alkenes via biradical intermediates afforded previously unknown aziridines substituted with trifluoromethyl group on the nitrogen atom. The obtained aziridines were converted into either N‐trifluoromethylimidazolines, via formal [3+2] cycloaddition with nitriles, mediated by a Lewis acid, or into N‐trifluoromethylaldimines, via ring opening and aryl group migration mediated by a strong Brønsted acid. Our findings open new opportunities for the development of novel classes of N‐CF3 compounds with possible applications in the life sciences. [ABSTRACT FROM AUTHOR]

Transition metal-catalyzed asymmetric nitrene transfer is a powerful method to generate enantioenriched amines found in natural products and bioactive molecules. A highly chemo- and enantioselective intramolecular silver-catalysed aziridination of 2,2,2-trichloroethoxysulfonyl (Tces)-protected carbamimidates gives [4.1.0]-bicyclic aziridines in good yields and up to 99% ee. [ABSTRACT FROM AUTHOR]

The development of innovative methods for the construction of heterocycles is an important topic in synthetic and medicinal chemistry. Ring expansion strategies, involving the cyclization of strained aza rings, have been well developed in the synthesis of diverse heterocyclic compounds. This microreview summarizes recent advances in the ring expansion reactions of aziridines, oxetanes, and azetidines to access a series of functionalized 2-oxazolines, which are versatile structural motifs in drugs and bioactive molecules. [ABSTRACT FROM AUTHOR]

The asymmetric [3+2] cycloaddition of azomethine ylides generated from the corresponding imino ester-to-trans-β-nitrostyrene catalysis by chiral aziridine-containing phosphines and phosphine oxides is described. Of the sixteen stereoisomers that could be formed as a result of the title reaction, three were formed, two of which were obtained in an enantiomerically enriched or pure form, and one in a racemic form. One of the products underwent epimerization under basic reaction conditions.

Azomethine ylides are typically in situ generated synthons for making N‐heterocycles through cycloaddition reactions. But an offbeat aspect about them is the isomeric nature of aldiminium‐based azomethine ylides and (alkyl/aryl)(amino)carbenes, interconvertible by a formal 1,3‐H+ transfer. Herein, two thermally robust azomethine ylides with a N‐appended picolyl sidearm are isolated, which cyclize to pyaziridines at 80 °C but unprecedentedly result N−picoCAAC‐CuCl (CAAC=cyclic(alkyl)(amino)carbene) complexes when heated with CuCl at merely 60 °C. The pendant Npy, as revealed by computational analysis, plays a crucial role in this unusual 1,3‐H+ shift using a deprotonation‐protonation sequence, as well as in placing the CuCl at the carbenic site in tandem. The softer nature of Cu(I) is also critical. Chelating CAACs are rare and one with a N‐tethered additional donor is priorly unknown. Both N‐picoCAAC and pyaziridine are bidentate chelators giving highly active cationic Rh(I) catalysts for hydrosilylating unactivated olefins by Et3SiH. Notably, the pyaziridine‐Rh(I) is superior than the N‐picoCAAC‐Rh(I) catalyst. [ABSTRACT FROM AUTHOR]

An available method for a synthesis of N-substituted (E)-2-(diphenylphosphoryl)aziridines with high yields by the reaction of (1,2-dibromoethyl)(diphenyl)phosphine oxide with a number of primary amines, in particular, methyl-, ethyl-, isopropyl-, tert-butyl-, cyclohexyl- and benzylamines at room temperature in the presence of sodium hydroxide, has been developed. The antibacterial activity of the synthesized compounds was evaluated. [ABSTRACT FROM AUTHOR]

An unprecedented Pd‐catalyzed fluorinative bifunctionalization of aziridines and azetidines was successfully developed via regioselective C−C and C−F bond cleavage of gem‐difluorocyclopropanes, leading to various β,β′‐bisfluorinated amines and β,γ‐bisfluorinated amines. This reaction was achieved by incorporating a 2‐fluorinated allyl group and a fluorine atom scissored from gem‐difluorocyclopropane in 100 % atom economy for the first time. The mechanistic investigations indicated that the reaction underwent amine attacking 2‐fluorinated allyl palladium complex to generate η2‐coordinated N‐allyl aziridine followed by fluoride ligand transfer affording the final β‐ and γ‐fluorinated amines. [ABSTRACT FROM AUTHOR]

Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery. [ABSTRACT FROM AUTHOR]

Application of a binary Ga‐based catalyst system for the coupling of CO2 and aziridines to form oxazolidinones is presented. It has been possible to optimize the catalyst system for the selective formation of a single regioisomer, in excellent yield, under relatively mild reaction conditions. The optimized catalyst system has been successfully applied to a range of substituted aziridines derived from styrene oxide. It has been observed that aziridines bearing two aromatic substituents result in piperazine formation through an unexpected dimerization reaction. These piperazine products can be selectively formed in the absence of CO2 or are favored at lower reaction temperatures. A detailed DFT study into the reaction mechanism for the formation of both products has been carried out and an unusual ligand assistance in the case of oxazolidinone synthesis has been identified. More specifically, this ligand interaction promotes the initial ring‐opening of the aziridine and this work presents the first fully elucidated mechanism involving this intermediate. [ABSTRACT FROM AUTHOR]

Carbon dioxide is a cheap, easily available, and practically inexhaustible source of synthetic carbon (C1-synthon). Among various transformations of CO2, the synthesis of cyclic carbonates from epoxides and cyclic carbamates from aziridines can be referred to as priority areas in the development of contemporary chemical synthesis and catalysis. Cyclic carbonates found wide application in modern industry (electrolytes, solvents, reagents, polymers) and their use and production will be constantly increased. The development of effective catalytic processes that would allow the synthesis of carbonates under mild conditions (atmospheric pressure of CO2 or lower, temperature 25°C) and low loads of durable and affordable catalysts is at the forefront of research. In the present review we analyze the existing directions of research on the catalytic systems based earth-abundant metals Al3+, Fe2+(3+), and Zn2+ for the synthesis of cyclic carbonates from epoxides and cyclic carbamates from aziridines. [ABSTRACT FROM AUTHOR]

Keywords: photocatalysis; Barbier reaction; aziridines; azetidines; C-N bond cleavage EN photocatalysis Barbier reaction aziridines azetidines C-N bond cleavage 1385 1390 6 07/11/23 20230725 NES 230725 Graph C-C bond-formation processes are an essential class of reactions for the construction of the skeletons of organic compounds. Photocatalysis, Barbier reaction, aziridines, azetidines, C-N bond cleavage After the reduction, the radical-anion intermediate B I b smoothly undergoes C-N bond cleavage to deliver the benzyl radical intermediate B II b . [72] Here, we report a visible-light photocatalytic Barbier-type reaction of aziridines and azetidines with nonactivated aldehydes through reductive cleavage of C-N bonds [75] (Scheme 1 C). [Extracted from the article]

A new type of metal-free [5+1] cycloaddition reaction of donor–acceptor aziridines with 2-(2-isocyanoethyl)indoles is reported herein. This method exhibits broad substrate scope and atom-economy. A series of 2H-1,4-oxazines containing an indole heterocycle skeleton were obtained in up to 92% yield under mild reaction conditions. Control experiments revealed that free indole N–H is crucial for the above transformations. The theoretical calculation studies provided guidance on the in-depth insight into the reaction mechanism and the hydrogen-bond between the free indole N–H and carbonyl group was identified to lower the free energy barrier in the transition states. [ABSTRACT FROM AUTHOR]

Herein a concise and efficient method for the synthesis of aziridines has been developed. The reaction proceeds through a formal intermolecular [2+1] cycloaddition reaction of saccharin‐derived cyclic ketimines with sulfur ylides. This methodology features high atom‐economy, broad substrate scope and an operationally simple procedure, affording the aziridines with excellent yields and diastereoselectivity (>20 : 1 dr). In the presence of base, the aziridine products could be readily converted to benzothiazines by an unusual rearrangement reaction. [ABSTRACT FROM AUTHOR]

Catalytic reactions of 3-membered heterocycles, such as epoxides and aziridines, with CO2 in the presence of metal–salen complexes are considered in this review (salens is a class of ligands, derived from diamines and salicylaldehyde or its substituted analogs). These reactions lead to copolymers or cyclic carbonates/oxazolidinones, which are important products of modern fine and industrial organic synthesis. The influence of metal ion, substituents in salen and the nature of cocatalyst on the catalytic performance of the systems based on metal–salen complexes, reported during two recent decades, is analyzed. It was shown that formation of bi- or polynuclear complexes, as well as incorporation of the organic cocatalyst (such as tetraalkylammonium cation) in the molecule of the metal-containing catalyst improved the catalytic performance of metal–salen species due to cooperative effect on several active sites in activation of epoxide and its reaction with CO2. The ways for creation of heterogeneous metal–salen catalysts for reactions of 3-membered heterocycles with CO2 are also summarized. [ABSTRACT FROM AUTHOR]

In recent years, various catalytic synthetic methods, starting with allenes, have been developed to produce a wide range of bicyclic methylene aziridines (MA). MA are valuable intermediates for the preparation of complex amine-containing stereotriads, tetrads, and heterocycles potentially useful in the synthesis of natural products and pharmaceuticals. This work reports the possibilities of using ring opening reactions of MA in the synthesis of biologically relevant heterocyclic motifs such as aziridineurea, 2H-azirine and 4,5-disubstituted oxazolidin-2-one. We performed detailed studies on the reaction between model MA with vinylmagnesium bromide and found that along with formal nucleophilic vinylic substitution product minor fraction of 2-methyl-1-(3-methyl-2H-azirin-2-yl)propyl pent-4-enoate was isolated. We showed that investigated reactions are stereoretentive, ruling out a SNVπ pathway, but the detailed mechanism remains open to speculation. Thus, reactivity patterns shown here for MA reactions can be useful in predicting reaction paths with other C- and N-nucleophiles. 2D NMR spectra of the key products were studied in detail including COSY, NOESY and HSQC experiments. [ABSTRACT FROM AUTHOR]

A series of optically pure aziridine phosphines and their corresponding phosphine oxides were synthesized through established chemical methodologies. The compounds were systematically investigated for their biological properties. Notably, all synthesized compounds demonstrated moderate antibacterial activity only against the reference strain of Staphylococcus aureus. However, compounds 5 and 7 exhibited noteworthy cell viability inhibition of human cervical epithelioid carcinoma HeLa cells and endometrial adenocarcinoma Ishikawa cells. Further studies of these compounds revealed additional biological effects, including disruption of the cell membrane in high concentrations, cell cycle arrest in the S phase, and the induction of reactive oxygen species (ROS). Comparative analysis of the two classes of chiral organophosphorus derivatives of aziridines indicated that chiral phosphine oxides displayed significantly higher biological activity. Consequently, these findings suggest that chiral phosphine oxides may be potential candidates for the development of anticancer drugs. In light of the significant interest in preparations whose structure is based on a three-membered aziridine ring in terms of potential anticancer therapy, this research fits into the current research trend and should constitute a valuable addition to the current state of knowledge and the existing library of aziridine derivatives with anticancer properties.

Commercially available poly(lactic acid) exhibits poor hydrolytic stability, which makes it impossible for use in durable applications. Therefore, a novel hydrolysis inhibitor based on an aziridine derivative as well as a novel stabilizer composition, containing an aziridine derivative and an acid scavenger, were investigated to improve the hydrolytic stability. To evaluate the stabilizing effect, the melt volume rate (MVR) and molecular weight were monitored during an accelerated hydrolytic aging in water at elevated temperatures. Temperatures were selected according to the glass transition temperature (~60 °C) of PLA. It was shown that the novel hydrolysis inhibitor as well as the novel stabilizer composition exhibited excellent performance during hydrolytic aging, exceeding commercially available alternatives, e.g., polymeric carbodiimides. A molecular weight analysis resulted in a molecular weight decrease of only 10% during approximately 850 h and up to 20% after 1200 h of hydrolytic aging, whereas poly(lactic acid) stabilized with a commercial polycarbodiimide revealed comparable molecular weight reductions after only 300 h. Furthermore, the stabilization mechanism of the aziridine derivative alone, as well as in the synergistic combination with the acid scavenger (calcium hydrotalcite), was investigated using nuclear magnetic resonance (NMR) spectroscopy. In addition to an improved hydrolytic stability, the thermal properties were also enhanced compared to polymeric carbodiimides.

Herein, a nickela‐electrocatalyzed cross‐electrophile coupling of readily available aryl aziridines and aryl bromides under mild and sustainable electrochemical conditions to access synthetic useful β‐arylethylamines is developed. This protocol is characterized by its exquisite chemo‐ and regioselectivity, broad substrate scope and good functional group compatibility. Mechanistic studies confirmed that the regioselectivity and reactivity observed are a result of electro‐induced ring‐opening of aziridines under electroreductive conditions to generate a benzyl radical intermediate as the active species. Furthermore, this strategy also enables cross‐coupling with CO2 to access β‐amino acids under mild conditions. [ABSTRACT FROM AUTHOR]

Aziridines are highly valued synthetic targets in organic and medicinal chemistry. The organocatalytic synthesis of such structures with broad substrate scope and good diastereoselectivity, however, is rare. Herein, we report a broadly applicable and diastereoselective synthetic method for the synthesis of trans‐aziridines from imines and benzylic or alkyl halides utilizing sulfenate anions (PhSO–) as the catalyst. Substrates bearing heterocyclic aromatic groups, alkyl, and electron‐rich and electron‐poor aryl groups were shown to be compatible with this method (33 examples), giving good yields and high diastereoselectivities (trans : cis >20 : 1). Further functionalization of aziridines containing cyclopropyl or cyclobutyl groups was achieved through ring‐opening reactions, with a cyclobutyl‐substituted norephedrine derivative obtained through a four‐step synthesis. We offer a mechanistic proposal involving reversible addition of the deprotonated benzyl sulfoxide to the imine to explain the high trans‐diastereoselectivity. [ABSTRACT FROM AUTHOR]

The activations of carbonyl compounds bearing cyclopropyl, epoxyl, azirine and aziridinyl groups by N‐heterocyclic carbene (NHC) organic catalysts are reviewed. The reactions are introduced and discussed from 3 aspects according to the activation modes involved in these transformations. A brief summary on the achievements and the remaining challenges in NHC‐catalyzed activation of cyclopropanes and their analogues is given at the end of this minireview. Our own perspectives on the future development within this highly active research field are also provided. [ABSTRACT FROM AUTHOR]

An unprecedented oxidative cyclodimerization reaction of 2H-azirine-2-carboxylates to pyrimidine-4,6-dicarboxylates under heating with triethylamine in air is described. In this reaction, one azirine molecule undergoes formal cleavage across the C-C bond and another across the C=N bond. According to the experimental study and DFT calculations, the key steps of the reaction mechanism include nucleophilic addition of N,N-diethylhydroxylamine to an azirine to form an (aminooxy)aziridine, generation of an azomethine ylide, and its 1,3-dipolar cycloaddition to the second azirine molecule. The crucial condition for the synthesis of pyrimidines is generation of N,N-diethylhydroxylamine in the reaction mixture in a very low concentration, which is ensured by the slow oxidation of triethylamine with air oxygen. Addition of a radical initiator accelerated the reaction and resulted in higher yields of the pyrimidines. Under these conditions, the scope of the pyrimidine formation was elucidated, and a series of pyrimidines was synthesized. [ABSTRACT FROM AUTHOR]

Here, we report an asymmetric electrochemical organonickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides in an undivided cell, affording β-phenethylamines in good to excellent enantioselectivity with broad functional group tolerance. The combination of cyclic voltammetry analysis of the catalyst reduction potential as well as an electrode potential study provides a convenient route for reaction optimization. Overall, the high efficiency of this method is credited to the electroreduction-mediated turnover of the nickel catalyst instead of a metal reductant-mediated turnover. Mechanistic studies suggest a radical pathway is involved in the ring opening of aziridines. The statistical analysis serves to compare the different design requirements for photochemically and electrochemically mediated reactions under this type of mechanistic manifold. Metal reductants show low efficiency in enantioselective nickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides. Here, the authors improve the reaction efficiency through an electrochemical method. [ABSTRACT FROM AUTHOR]

Cyclophellitol aziridines have found wide application as mechanism‐based, covalent, and irreversible inhibitors of retaining glycosidases. These compounds, like their parent compound, cyclophellitol (a natural product retaining β‐glucosidase inactivator), make use of the mechanism of action of retaining glycosidases, which process their substrate through the formation of a transient covalent intermediate. In contrast, inverting glycosidases, the other main family of glycosyl hydrolases, do not employ such a covalent intermediate, and, as a consequence, useful scaffolds for mechanism‐based inhibitor design have yet to be discovered. In this work, we explore chemistries that allow for the construction of cyclitol aziridines with the aziridine electrophile attached in an exocyclic fashion, more distal from the anomeric carbon – thus putatively closer to an inverting glycosidase active site nucleophile. The developed chemistries have allowed for the synthesis of a focused library of differently N‐substituted, α‐and β‐glucopyranose configured cyclitol aziridines for future evaluation as inhibitors or inactivators of α‐and β‐glucosidases alike. [ABSTRACT FROM AUTHOR]

TFA promoted deprotection of O−Ts activated N‐Boc hydroxylamines triggers aminofunctionalization‐based polycyclizations of tethered alkenes. The processes involve intramolecular stereospecific aza‐Prilezhaev alkene aziridination in advance of stereospecific C−N cleavage by a pendant nucleophile. Using this approach, a wide range of fully intramolecular alkene anti‐1,2‐difunctionalizations can be achieved, including diaminations, amino‐oxygenations and amino‐arylations. Trends associated with the regioselectivity of the C−N cleavage step are outlined. The method provides a broad and predictable platform for accessing diverse C(sp3)‐rich polyheterocycles of relevance to medicinal chemistry. [ABSTRACT FROM AUTHOR]