Insertion Products Research Articles

Synthesis and Reactivity of a Bipyridyl Tantalum Complex.

The bipyridyl tantalum complex (2,6-iPr2C6H3O)3Ta(bipy) (2) is synthesized by the reaction of (2,6-iPr2C6H3O)3TaCl2 (1) and 2,2'-bipyridine in the presence of excess potassium graphite (KC8). Complex 2 coordinates readily with pyridine and 4-(dimethylamino)pyridine (dmap) to form Lewis base adducts (2,6-iPr2C6H3O)3Ta(bipy)(L) (L = py (3), dmap (4)), and it exhibits rich redox reactivity toward small molecules: (a) single electron transfer (SET) occurs upon exposure of 2 to phenyl sulfide or selenide dimer, giving the open-shell, bipy-centered radical complexes (2,6-iPr2C6H3O)3Ta(bipy•)(PhE) (E = S (5), Se (6)). (b) Regioselective C-C σ-bond formation via radical coupling is observed in the SET reaction of 2 and aldehydes, ketones, or imines to furnish insertion products 7-13, namely, sterically more crowded benzophenone, acetophenone, 2,6-dichlorobenzaldehyde, and benzophenone imine couple with C6 or C6' of bipy in 2, respectively, whereas sterically less hindered benzaldehyde, cyclohexanone, and benzylideneaniline couple with C2 or C2' of bipy, respectively.

Synthesis of an Unsymmetrical Dialumane and Kinetic Analysis of its Alkene Insertion.

An unsymmetrical dialumane was synthesized by the reaction of a nucleophilic alumanyl anion with a bromoalumane and it was structurally characterized to show the existence of the Et2O-coordination to the Al atom. The reactivity of the obtained Al-Al bond toward ethylene and styrene was examined, and the resulting insertion products underwent subsequent reactions. The reaction of the dialumane with styrene was decelerated by an addition of Et2O, suggesting that an Et2O dissociation occurred before the alkene insertion, which can be distinguished from an associative mechanism involving a five-coordinated Al intermediate.

In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China.

To date, the global prevalence of New Delhi metallo-β-lactamase (NDM) in carbapenem-resistant Enterobacterales (CRE) has been of concern, which is not inhibited by classical β-lactamase inhibitors (BLIs). In this study, we investigated the newly developed antimicrobial agents or inhibitors against NDM-producing Enterobacterales (NPEs). The in vitro activities of cefiderocol, cefepime/taniborbactam, meropenem/taniborbactam, cefepime/zidebactam, meropenem/nacubactam, aztreonam/nacubactam and aztreonam/avibactam were analyzed in 204 NPE strains collected in China. The potential resistance mechanisms were identified by whole genome sequencing. Of 204 NPE strains, 18.1% (37/204) were resistant to cefiderocol, in which cirA deleterious alteration, PBP3 insertion and NDM production were taken as potential resistance mechanisms; 28.9% (59/204) were resistant to cefepime/zidebactam, involving K. pneumoniae with ompK35 deleterious alteration; 22.5% (46/204) were resistant to cefepime/taniborbactam, in which YRIN or YRIK inserted in PBP3 and altered ompC are more frequently detected in the resistant E. coli isolates; 27.9% (57/204) were resistant to meropenem/taniborbactam. Aztreonam/avibactam and aztreonam/nacubactam exhibited excellent activity against NPE. However, meropenem/nacubactam had the lowest activity, with only 49.0% (100/204) of all isolates having MICs of <4/4 mg/L. Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance.

Access to Syn α‐Amino‐β‐Hydroxyesters by N−H Insertion on O‐Protected α‐Diazo‐β‐Hydroxyesters

AbstractThe N−H insertion reaction is a versatile method for creating C−N bonds under mild conditions, providing in particular an efficient access to both natural and non‐natural α‐amino acid derivatives. In this field, the direct N−H insertion on α‐diazo‐β‐hydroxyesters has not yet been investigated and constitutes a significant challenge, due to competitive migration processes. We report herein the first N−H insertions on O‐protected α‐diazo‐β‐aryl‐β‐hydroxyesters, enabling to synthesize a wide range of α‐amino‐β‐hydroxyesters by tuning the nature of the amine and the aryl substituent. Overall, 28 N−H insertion products have been isolated, with moderate to good yields in most cases, and diastereoisomeric ratios up to 8.0 : 1 in favor of the syn diastereoisomer.

Molecular Dynamics of the Davies Ambimodal C-H Functionalization/Cope Rearrangement Reaction.

The mechanism of the dirhodium-catalyzed combined C-H functionalization/Cope rearrangement (CH/Cope) reaction discovered by the Davies group has been investigated with density functional theory (DFT) calculations and quasi-classical molecular dynamics (MD) simulations. Computations from the Davies group previously showed that there is a post-transition state bifurcation leading to a direct CH reaction and also to the CH/Cope product. While this work was in preparation, the Tantillo group and the Ess group independently reported quantum mechanical and molecular dynamics studies on the dirhodium-tetracarboxylate-catalyzed diazoester CH/Cope and CH insertion reactions with 1,3-cyclohexadiene and 1,4-cyclohexadiene, respectively. The Tantillo group cited "dynamic mismatching" to explain the origins of the low yield of CH/Cope products in some experiments; the Ess group explained the origins of product selectivity from the perspective of TS vibrational modes and their synchronization that occurs at the entropic intermediates. We report quasi-classical trajectories for the reaction of the carbene with 1-methylcyclohexene that afford both the CH/Cope and C-H insertion products. After passing through the transition state that involves mostly hydrogen transfer, momentum drives the reaction trajectories toward the CH/Cope products.

Halogencarbene-free Ciamician-Dennstedt single-atom skeletal editing

Single-atom skeletal editing is an increasingly powerful tool for scaffold hopping-based drug discovery. However, the insertion of a functionalized carbon atom into heteroarenes remains rare, especially when performed in complex chemical settings. Despite more than a century of research, Ciamician-Dennstedt (C-D) rearrangement remains limited to halocarbene precursors. Herein, we report a general methodology for the Ciamician-Dennstedt reaction using α-halogen-free carbenes generated in situ from N-triftosylhydrazones. This one-pot, two-step protocol enables the insertion of various carbenes, including those previously unexplored in C-D skeletal editing chemistry, into indoles/pyrroles scaffolds to access 3-functionalized quinolines/pyridines. Mechanistic studies reveal a pathway involving the intermediacy of a 1,4-dihydroquinoline intermediate, which could undergo oxidative aromatization or defluorinative aromatization to form different carbon-atom insertion products.

Biochemical, structural, and single-molecule characterization of LIG1 active site mutants demonstrate role of F635 and F872 residues for faithful ligation.

Human DNA ligase 1 (LIG1) finalizes DNA repair pathways by an ultimate ligation step and discriminates against nicks containing unusual ends, yet the contribution of the conserved active site residues for faithful end joining remains unknown. Here, using biochemistry, X-ray crystallography, and single-molecule approaches, we comprehensively characterized LIG1 mutants carrying Ala(A) and Leu(L) substitutions at the active site residues Phe(F)635 and Phe(F)872. Our results showed an abolished ligation of nick DNA substrates with all 12 non-canonical mismatches, while the mutagenic nick sealing of oxidatively damaged ends by wild-type enzyme is significantly reduced by F635A/L and F872A/L substitutions. Furthermore, sugar discrimination against a single ribonucleotide at 3'- or 5'-end of nick DNA is distinctly affected depending on architecture of 3'-terminus:template base pairing. Finally, our LIG1 structures demonstrated the importance of DNA end alignment governed by the distance to nick site through F635 and F872 residues, and single-molecule measurements showed similar nick DNA binding modes for LIG1 wild-type and active site mutants in real-time. Overall, our study provides a mechanistic insight into the mechanism by which conserved F635 and F872 residues contribute to ligation efficiency of nick repair intermediates that mimic DNA polymerase-mediated mismatch, damaged, or ribonucleotide insertion products and how LIG1 ensures faithful end joining at the final step of DNA repair to maintain genome integrity.

Mutagenic ligation of polβ mismatch insertion products during 8-oxoG bypass by LIG1 and LIG3α at the downstream steps of base excision repair pathway.

Base excision repair (BER) maintains genome integrity by fixing oxidized bases that could be formed when reactive oxygen species attack directly on the DNA. We previously reported the importance of a proper coordination at the downstream steps involving gap filling by DNA polymerase (pol) β and subsequent nick sealing by DNA ligase (LIG) 1 or 3α. Yet, how the fidelity of 8-oxoG bypass by polβ affects the efficiency of ligation remains unclear. Here, we show that LIG1 can seal nick products of polβ after both dATP and dCTP insertions during 8- oxoG bypass, while ribonucleotide insertions completely diminish the repair coordination with both ligases, highlighting a critical role for nucleotide selectivity in maintaining BER accuracy. Furthermore, our results demonstrate that LIG3α exhibits an inability to ligate nicks of polβ dCTP:8-oxoG insertion or with preinserted 3'-dC:8-oxoG. Finally, AP-Endonuclease 1 (APE1) proofreads nick repair intermediates containing 3'-dA/rA and 3'-dC/rC mismatches templating 8-oxoG. Overall, our findings provide a mechanistic insight into how the dual coding potential of the oxidative lesion and identity of BER ligase govern mutagenic versus error-free repair outcomes at the final steps and how the ribonucleotide challenge compromises the BER coordination leading to the formation of deleterious repair intermediates.

Chemoselective and Triggered Decomposition of Diazo Esters by the [(IMes)Rh2(OAc)4] Complex: En Route to Assisted Tandem Catalysis from Mixtures of Diazo Compounds

AbstractDecomposition of aryl and unsubstituted diazo ester into Rh(II)‐carbenes by the [(IMes)Rh2(OAc)4] complex is shown to be slower than with Rh2(OAc)4. Diazo esters substituted by a second electron‐withdrawing group do not suffer nitrogen extrusion when exposed for several hours to this (NHC)Rh(II) complex at room temperature. This chemoselective decomposition of diazo esters depending on their substituent (Ar, H, EWG) can furthermore be achieved on a mixture of substrates. The catalytic activity of [(IMes)Rh2(OAc)4] towards electron‐poor diazo compounds is also restored by heating to reflux in chloroform, or after decomplexation of the NHC by addition of GaCl3. The [(IMes)Rh2(OAc)4] complex was then used to induce a fully selective reaction cascade from a mixture of two diazo esters. First, a donor/acceptor diazo compound was decomposed selectively at room temperature to give an intermolecular O−H insertion product without any decomposition of the electron poor diazo compound. Addition of GaGl3 then triggered nitrogen extrusion from the diazo malonate to give a 1,5‐C−H insertion product. This transformation, where decomposition of diazo compounds catalyzed by Rh(II) complexes can be externally controlled, represents the first example of assisted tandem catalysis with two metal carbene precursors.

Synthesis and Reactivity of the Rare-Earth Metal Complexes Bearing the Indol-2-yl-Based NCN Pincer Ligand.

The pincer rare-earth dialkyl complexes [κ3-LRE(CH2SiMe3)2 (RE = Lu(1a), Yb(1b), Er(1c), Y(1d), Dy(1e))] with the indol-2-yl-based NCN pincer ligand were synthesized by the reactions of the proligand HL (L = 1-Me2NCH2CH2-3-(2-iPrC6H5N═CH)C8H4N) with RE(CH2SiMe3)3(THF)2. These complexes exhibited a variety of reactivities toward organic compounds such as amines, triphenylphosphine ylide, N-phenylimidazole, pyridine derivatives, and o-carborane leading to σ-bond metathesis, migration insertion, and redox reaction products. The reactions of the dialkyl rare-earth metal complexes with o-carborane afforded the novel NCN pincer-ligated carboryne-based metallacyclopropanes which reacted with diphenyl ketone to give insertion products of the RE-C2-ind and one of the RE-Ccage bonds, while the reaction of the carboryne-based metallacyclopropanes with diphenyldiazomethane produced the di-aza-metallacyclopentanes via the insertions of the N═N bond of the diphenyldiazomethane into two RE-Ccage bonds and the RE-C2-ind bond. The reactions of the dialkyl complexes with 2 equiv of 2,2'-bipyridine afforded the pincer-ligated bis(2,2'-bipyridyl monoanionic radical) complexes via the homolytic redox reaction.

Electrophilic Behavior of the "Nucleophilic" Pyramidane: Reactivity of Ge-Pyramidane towards Organolithium Reagents.

The particular reactivity of the recently discovered class of the main group element polyhedral clusters, pyramidanes, remains largely unexplored. In this communication, we report the reaction of the germapyramidane with tert-butyllithium leading to the rather unusual organogermanium compound [Li+(thf)2]⋅2-, as the product of the formal insertion of a Ge-apex into the C-Li bond. This reactivity mode exemplifies unusual electrophilic behaviour of a pyramidane, which is a priori considered as a nucleophilic reagent. Being highly reactive, [Li+(thf)2]⋅2- readily undergoes reactions with electrophiles (MeI, EtBr), initially forming intermediate germahousenes, which isomerize to the thermodynamically more favourable germoles.

Organomagnesia: Reversibly High Carbon Dioxide Uptake by Magnesium Pyrazolates.

A series of new pyrazolate and mixed pyrazolate/pyrazole magnesium complexes is described and their reactivity toward carbon dioxide is examined. The dimeric complex [Mg(pzt Bu, t Bu)2]2 inserts CO2 instantly and quantitatively forming the tetrameric complex [Mg(CO2·pzt Bu, t Bu)2]4 and monomeric donor-stabilized [Mg(CO2·pzt Bu, t Bu)2(thf)2]. Complexes of the type [Mgx(pzR,R)2 x(HpzR,R)y]n (R = iPr, tBu) engage in similar insertion reactions involving dissociation of the carbamic acid HOOCpzR,R. Even solid polymeric derivatives [Mg(pzR,R)2]n (R = Me, H) react instantaneously and exhaustively with CO2, the resulting [Mg(CO2·pz)2]m featuring a CO2 capacity of 35.7wt% (8.2mmol g-1). All described magnesium pyrazolates display completely reversible CO2 uptake in solution and in the solid state, respectively, as monitored via VT 1H NMR and in situ FTIR spectroscopy as well as thermogravimetric analysis. Fluorinated [Mg2(pzCF3,CF3)4(thf)3] does not yield any isolable CO2 insertion product but exhibits the highest activity in the catalytic transformation of epoxides and CO2 to cyclic carbonates.

Iron(II) Phthalocyanine-Catalyzed Homodimerization and Tandem Diamination of Diazo Compounds with Primary Amines: Access to Construct Substituted 2,3-Diaminosuccinonitriles in One-Pot.

We herein first report the homodimerization and tandem diamination of diazo compounds with primary amines catalyzed by the iron(II) phthalocyanine (PcFe(II)), which can construct one C-C bond and two C-N bonds within 20 min in one-pot. Compared to the traditional metal-catalyzed N-H insertion reaction between amines with diazo reagents, the developed reaction almost does not generate the N-H insertion product, but the homodimerization/tandem diamination product. The proposed mechanism studies indicate that primary amines play a crucial role in the homocoupling of diazo compounds via dimerization of iron(III)-acetonitrile radical generated from the reaction between diazoacetonitrile with PcFe(II) coordinated by bis(amines); the β-hydride elimination is involved, and then, the attack of primary amines toward the carbon atoms on the formed C-C bond is followed. Moreover, this novel reaction can be used to effectively prepare substituted 2,3-diaminosuccinonitriles with high yields and even up to >99:1 d.r., encouragingly these products contain both 1,2-diamines and succinonitrile motifs, which are two classes of important organic compounds with significant applications in many yields. This reaction is also suitable for the gram-scale preparation of 2,3-bis(phenylamino)succinonitrile (2a) with a yield of 84%. Therefore, the developed reaction represents a new type of transformation.

Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway.

DNA ligase (LIG) I and IIIα finalize base excision repair (BER) by sealing a nick product after nucleotide insertion by DNA polymerase (pol) β at the downstream steps. We previously demonstrated that a functional interplay between polβ and BER ligases is critical for efficient repair, and polβ mismatch or oxidized nucleotide insertions confound the final ligation step. Yet, how targeting downstream enzymes with small molecule inhibitors could affect this coordination remains unknown. Here, we report that DNA ligase inhibitors, L67 and L82-G17, slightly enhance hypersensitivity to oxidative stress-inducing agent, KBrO3, in polβ+/+ cells more than polβ-/- null cells. We showed less efficient ligation after polβ nucleotide insertions in the presence of the DNA ligase inhibitors. Furthermore, the mutations at the ligase inhibitor binding sites (G448, R451, A455) of LIG1 significantly affect nick DNA binding affinity and nick sealing efficiency. Finally, our results demonstrated that the BER ligases seal a gap repair intermediate by the effect of polβ inhibitor that diminishes gap filling activity. Overall, our results contribute to understand how the BER inhibitors against downstream enzymes, polβ, LIG1, and LIGIIIα, could impact the efficiency of gap filling and subsequent nick sealing at the final steps leading to the formation of deleterious repair intermediates.

Impact of DNA ligase 1 and IIIα interactions with APE1 and polβ on the efficiency of base excision repair pathway at the downstream steps

Base excision repair (BER) requires a tight coordination between the repair enzymes through protein-protein interactions and involves gap filling by DNA polymerase (pol) β and subsequent nick sealing by DNA ligase (LIG) 1 or LIGIIIα at the downstream steps. AP-Endonuclease 1 (APE1), by its exonuclease activity, proofreads 3'-mismatches incorporated by polβ during BER. We previously reported that the interruptions in the functional interplay between polβ and the BER ligases result in faulty repair events. Yet, how the protein interactions of LIG1 and LIGIIIα could affect the repair pathway coordination during nick sealing at the final steps remains unknown. Here, we demonstrate that LIGIIIα interacts more tightly with polβ and APE1 than LIG1, and the N-terminal non-catalytic region of LIG1 as well as the catalytic core and BRCT domain of LIGIIIα mediate interactions with both proteins. Our results demonstrated less efficient nick sealing of polβ nucleotide insertion products in the absence of LIGIIIα ZnF domain and LIG1 N-terminal region. Furthermore, we showed a coordination between APE1 and LIG1/LIGIIIα during the removal of 3'-mismatches from the nick repair intermediate on which both BER ligases can seal non-canonical ends or gap repair intermediate leading to products of single deletion mutagenesis. Overall results demonstrate the importance of functional coordination from gap filling by polβ coupled to nick sealing by LIG1/LIGIIIα in the presence of proofreading by APE1, which is mainly governed by protein-protein interactions and protein-DNA intermediate communications, to maintain repair efficiency at the downstream steps of the BER pathway.

Diborane Reductions of CO2 and CS2 Mediated by Dicopper μ-Boryl Complexes of a Robust Bis(phosphino)-1,8-naphthyridine Ligand.

A dinucleating 1,8-naphthyridine ligand featuring fluorene-9,9-diyl-linked phosphino side arms (PNNPFlu) was synthesized and used to obtain the cationic dicopper complexes 2, [(PNNPFlu)Cu2(μ-Ph)][NTf2]; [NTf2] = bis(trifluoromethane)sulfonimide, 6, [(PNNPFlu)Cu2(μ-CCPh)][NTf2], and 3, [(PNNPFlu)Cu2(μ-OtBu)][NTf2]. Complex 3 reacted with diboranes to afford dicopper μ-boryl species (4, with μ-Bcat; cat = catecholate and 5, with μ-Bpin; pin = pinacolate) that are more reactive in C(sp)-H bond activations and toward activations of CO2 and CS2, compared to dicopper μ-boryl complexes supported by a 1,8-naphthyridine-based ligand with di(pyridyl) side arms. The solid-state structures and DFT analysis indicate that the higher reactivities of 4 and 5 relate to changes in the coordination sphere of copper, rather than to perturbations on the Cu-B bonding interactions. Addition of xylyl isocyanide (CNXyl) to 4 gave 7, [(PNNPFlu)Cu2(μ-Bcat)(CNXyl)][NTf2], demonstrating that the lower coordination number at copper is chemically significant. Reactions of 4 and 5 with CO2 yielded the corresponding dicopper borate complexes (8, [(PNNPFlu)Cu2(μ-OBcat)][NTf2]; 9, [(PNNPFlu)Cu2(μ-OBpin)][NTf2]), with 4 demonstrating catalytic reduction in the presence of excess diborane. Related reactions of 4 and 5 with CS2 provided insertion products 10, {[(PNNPFlu)Cu2]2[μ-S2C(Bcat)2]}[NTf2]2, and 11, [(PNNPFlu)Cu2(μ,κ2-S2CBpin)][NTf2], respectively. These products feature Cu-S-C-B linkages analogous to those of proposed CO2 insertion intermediate.

Fused granulate fabrication of injection molding inserts from high-performance ULTEM 9085™ thermoplastic for cosmetic packaging industry

RTIM refers to the integration of rapid tooling (RT) using additive manufacturing (AM) with injection molding (IM). Due to the use of raw material (pellet), screw extrusion, fused granulate fabrication (FGF) allows for a cost-effective and versatile production of RTIM inserts especially compared to other material extrusion (MEX) AM processes, such as fused filament fabrication (FFF). This study 3D printed RTIM inserts out of high-performance thermoplastic polyetherimide (PEI) (ULTEM 9085) in granular form, using an in-house developed FGF system. A cosmetic compact was used as a case study part with a simplified design. A dynamic mechanical analysis (DMA) conducted on FGF ULTEM 9085 demonstrated that the strength of the inserts is sustained up to 140 °C, which suits injection molding using polypropylene (PP). Optical profilometry of the FGF 3D printed RTIM inserts demonstrated that when using a 0.4 mm nozzle, the flat surfaces produced had microscopic gaps larger than 10–1 mm. These gaps are sufficiently large so that melt of low viscosity polymer is able to flow through, which leads to undesired part flash. The IM experiments confirmed that the inserts were capable of producing PP parts but with the predicted flash. Simulated part deflection differed both on geometry and magnitude from the actual deflection measured by optical profilometry. A total of 36 prototype parts were produced before the inserts failed due to poor inter-layer bond strength. FGF RTIM using ULTEM 9085 is deemed suitable for prototype part production. Improving the inter-layer bond strength and decreasing part complexity could increase the number of parts produced.

P(III)-Mediated Formal Reductive N-H Bond Insertion Reaction of Hydrazones to α-Keto Esters.

A diazo-, metal-, and base-free multi-substituted hydrazone synthesis via a formal reductive N-H bond insertion reactions of hydrazones to α-keto esters has been developed. The protocol features a broad substrate scope and good functional group tolerance, providing N-H bond insertion products in moderate to excellent yields. Moreover, P(III)-mediated N-H functionalization of pharmaceutical containing hydrazone moiety was also successfully achieved.

Amino- and Alkoxybenziodoxoles: Facile Preparation and Use as Arynophiles.

We report here on the facile synthesis of amino- and alkoxy-λ3-iodanes supported by a benziodoxole (BX) template and their use as arynophiles. The amino- and alkoxy-BX derivatives can be readily synthesized by reacting the respective amines or alcohols with chlorobenziodoxole in the presence of a suitable base. Unlike previously known nitrogen- and oxygen-bound iodane compounds, which have primarily been employed as electrophilic group transfer agents or oxidants, the present amino- and alkoxy-BX reagents manifest themselves as nucleophilic amino and alkoxy transfer agents toward arynes. This reactivity leads to the aryne insertion into the N-I(III) or O-I(III) bond to afford ortho-amino- and ortho-alkoxy-arylbenziodoxoles, iodane compounds nontrivial to procure by existing methods. The BX group in these insertion products exhibits excellent leaving group ability, enabling diverse downstream transformations.

Aziridination via Nitrogen-Atom Transfer to Olefins from Photoexcited Azoxy-Triazenes.

Herein, we report that readily accessible azoxy-triazenes can serve as nitrogen atom sources under visible light excitation for the phthalimido-protected aziridination of alkenes. This approach eliminates the need for external oxidants, precious transition metals, and photocatalysts, marking a departure from conventional methods. The versatility of this transformation extends to the selective aziridination of both activated and unactivated multisubstituted alkenes of varying electronic profiles. Notably, this process avoids the formation of competing C-H insertion products. The described protocol is operationally simple, scalable, and adaptable to photoflow conditions. Mechanistic studies support the idea that the photofragmentation of azoxy-triazenes results in the generation of a free singlet nitrene. Furthermore, a mild photoredox-catalyzed N-N cleavage of the protecting group to furnish the free aziridines is reported. Our findings contribute to the advancement of sustainable and practical methodologies for the synthesis of nitrogen-containing compounds, showcasing the potential for broader applications in synthetic chemistry.