A 12-membered pyridinophane scaffold containing two pyridine and two tertiary amine residues is examined as a prototype ligand (tBuN4) for supporting nitrene transfer to olefins. The known [(tBuN4)MII(MeCN)2]2+ (M = Mn, Fe, Co, and Ni) and [(tBuN4)CuI(MeCN)]+ cations are synthesized with the hexafluorophosphate counteranion. The aziridination of para-substituted styrenes with PhI=NTs (Ts = tosyl) in various solvents proved to be high yielding for the Cu(I) and Cu(II) reagents, in contrast to the modest efficacy of all other metals. For α-substituted styrenes, aziridination is accompanied by products of aziridine ring opening, especially in chlorinated solvents. Bulkier β-substituted styrenes reduce product yields, largely for the Cu(II) reagent. Aromatic olefins are more reactive than aliphatic congeners by a significant margin. Mechanistic studies (Hammett plots, KIE, and stereochemical scrambling) suggest that both copper reagents operate via sequential formation of two N–C bonds during the aziridination of styrene, but with differential mechanistic parameters, pointing towards two distinct catalytic manifolds. Computational studies indicate that the putative copper nitrenes derived from Cu(I) and Cu(II) are each associated with closely spaced dual spin states, featuring high spin densities on the nitrene N atom. The computed electrophilicity of the Cu(I)-derived nitrene reflects the faster operation of the Cu(I) manifold.

In the field of chiral recognition, chiral cyclic organic compounds, especially heterocyclic organic compounds, have attracted little attention and have been rarely studied as chiral substrates by means of 1H NMR spectroscopy. In this paper, enantiomers of thiohydantoin derivatives, representing typical five-membered N,N-heterocycles, have been synthesized and utilized for assignment of absolute configuration and analysis of enantiomeric excess. All enantiomers have been successfully differentiated with the assistance of novel tetraaza macrocyclic chiral solvating agents (TAMCSAs) by 1H NMR spectroscopy. Surprisingly, unprecedented nonequivalent chemical shift values (up to 2.052 ppm) of the NH proton of substrates have been observed, a new milestone in the evaluation of enantiomers. To better understand the intermolecular interactions between host and guest, Job plots and theoretical calculations of (S)-G1 and (R)-G1 with TAMCSA 1a were investigated and revealed significant geometric differentiation between the diastereomers. In order to evaluate practical applications of the present systems in analyzing optical purity of chiral substrates, enantiomeric excesses of a typical substrate (G1) with different optical compositions in the presence of a representative TAMCSA (1a) can be accurately calculated based on the integration of the NH proton's signal peaks. Importantly, this work provides a significant breakthrough in exploring and developing the chiral recognition of chiral heterocyclic organic compounds by 1H NMR spectroscopy.

Tripodal ligands (TMG(3)trphen-E) that feature heavy pnictogen elements (E = Sb(III), Bi(III)) and tetramethylguanidinyl (TMG) arms have been explored in stabilizing Cu(I) and Ag(I) sites and facilitating nitrene-transfer chemistry. Compounds [(TMG(3)trphen-E)M-3(mu-X)(3)] (M = Cu(I), Ag(I); X = Cl, Br, I) have been generated upon extraction of M-3(mu-X)(3) units from MX sources, exhibiting support of the crown-shaped M-3(mu-X)(3) fragment by M-N-TMG bonds and triply bridging E -> M-3 interactions. Orbital interactions between Cu(I) sites and N-TMG residues are more dominant than Sb/Bi -> Cu-3 donor interactions between the Sb 5s or Bi 6s orbitals and admixed Cu 4s/3d orbitals, with larger interaction energies computed for Sb -> Cu-3. Nonhalogenated copper compounds [(TMG(3)trphen-E)(2)Cu-2](2+)2Y(-) (Y = PF6, B(C6F5)(4)) have been synthesized via dechlorination by TlPF6 or by application of halide-free Cu(I) sources with TMG(3)trphen-E ligands. Nitrene-transfer to olefins mediated by [(TMG(3)trphen-E)Cu-3(mu-Cl)(3)] (E = Sb and Bi) affords aziridines in good yields, primarily for unencumbered styrenes and with the more robust Sb catalyst. Amination of C-H bonds is most effective with sec-benzylic substrates and requires a more electrophilic nitrene (NTces) to achieve practicable yields with halogenated or nonhalogenated copper precursors. Hammett plots indicate that the competitive amination of para-substituted ethylbenzenes enabled by [(TMG(3)trphen-Sb)Cu-3(mu-Cl)(3)] involves stepwise C-H functionalization.

The bipodal compounds [(TMG(2)biphen(N-R))Cu-I-NCMe](PF6) (R = Me, Ar (4-CF3Ph-)) and [(TMG(2)biphen(N-Me))Cu-I-I] have been synthesized with ligands that feature a diarylmethyl- and triaryl-amine framework and superbasic tetramethylguanidinyl residues (TMG). The cationic Cu(I) sites mediate catalytic nitrene-transfer reactions between the imidoiodinane PhI = NTs (Ts = tosyl) and a panel of styrenes in MeCN, to afford aziridines, demonstrating comparable reactivity profiles. The copper reagents have been further explored to execute C-H amination reactions with a variety of aliphatic and aromatic hydrocarbons and two distinct nitrene sources PhI = NTs and PhI = NTces (Tces = 2,2,2-trichloroethylsulfamate) in benzene/HFIP (10:2 v/v). Good yields have been obtained for sec-benzylic and tert-C-H bonds of various substrates, especially with the more electron-deficient catalyst [(TMG(2)biphen(N-Ar))Cu-I-NCMe](PF6). In conjunction with earlier studies, the order of reactivity of these bipodal cationic reagents as a function of the metal employed is established as Cu > Fe > Co >= Mn. However, as opposed to the base-metal analogues, the bipodal Cu reagents are less reactive than a similar tripodal Cu catalyst. The observed fluorophilicity of the bipodal Cu compounds may provide a deactivation pathway.

Tripodal ligands that can encapsulate single or multiple metal sites in C-3-symmetric geometric configurations constitute valuable targets for novel catalysts. Of particular interest in ligand development are efforts toward incorporating apical elements that exhibit little if any electron donicity, to enhance the electrophilic nature of a trans positioned active oxidant (e.g., metal-oxo, -nitrene). The tripodal ligand TMG(3)trphen-Arene has been synthesized, featuring an arene platform 1,3,5-substituted with phenylene arms possessing tetramethylguanidinyl (TMG) residues. Compound [(TMG(3)trphen-Arene)Cu-3(mu-Cl)(3)] has been subsequently synthesized by extracting a Cu-3(mu-Cl)(3) cluster from anhydrous CuCl and shown to encapsulate a crown-shaped Cu-3(mu-Cl)(3) fragment, supported by Cu-N-TMG bonds and modest Cu-3 & ctdot;arene long-range contacts. Energy decomposition analysis (EDA) indicates that electrostatic contributions to the total interaction energy far exceed those due to orbital interactions. The latter involve orbital pairings largely associated with the N-TMG stabilization of the Cu-3(mu-Cl)(3) cluster. The independent gradient model based on the Hirshfeld partition (IGMH) corroborates that contacts between the arene platform and the Cu-3 triangle are noncovalent in nature. Catalyst [(TMG(3)trphen-Arene)Cu-3(mu-Cl)(3)] enables amination of sec-benzylic and tert-C-H bonds of a panel of substrates by pre-synthesized PhINTces in solvent matrices that incorporate small amounts of HFIP. The involvement of an electrophilic aminating agent is evidenced by the better yields obtained for electron-rich benzylic sites and is further supported by Hammett analysis that reveals the development of a small positive charge during C-H bond activation. A rather modest KIE effect (2.1) is obtained from intramolecular H(D) competition in the amination of ethylbenzene, at the borderline of reported values for concerted and stepwise C-H amination systems. DFT analysis of the putative copper-nitrene oxidant indicates that the nitrene N atom is bridging between two copper sites in closely spaced triplet (ground state) and broken-symmetry singlet electronic configurations.

Enantiomers of chiral ester derivatives containing an amide group, and possessing one or two stereogenic centers were prepared from L- and D-alpha-amino acids, and glycine with (S)- and (R)-mandelic acid for probing their chiral recognition as a new class of chiral guests by H-1 NMR spectroscopy, since chiral ester derivatives have been rarely used as chiral substrates for chiral recognition by H-1 NMR technology. The results indicated that these chiral ester derivatives have been successfully differentiated in the presence of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1 a-1 c. In order to better understand their chiral discriminating behavior, Job plots, association constants (K-a), and theoretical calculations of (S,S)-G1 and (R,R)-G1, as a representative example, were performed, respectively. In order to evaluate their practical application, the H-1 NMR spectra of G1 and G9 with various optical purities were measured (up to 98 % ee). In this work, a practical strategy has been effectively established for chiral recognition of chiral ester derivatives containing an amide group and possessing one or two chiral centers in the presence of tetraaza macrocyclic chiral solvating agents 1 a-1 c by means of H-1 NMR spectroscopy.

The tripodal compounds [(TMG3trphen)MII-solv](PF6)2 (M = Mn, Fe, Co; solv = MeCN, DMF) and bipodal analogues [(TMG2biphen)MII(NCMe)x](PF6)2 (x = 3 for Mn, Fe; x = 2 for Co) and [(TMG2biphen)MIICl2] have been synthesized with ligands that feature a triaryl- or diarylmethyl-amine framework and superbasic tetramethylguanidinyl residues (TMG). The dicationic M(II) sites mediate catalytic nitrene-transfer reactions between the imidoiodinane PhI═NTs (Ts = tosyl) and a panel of styrenes in MeCN to afford aziridines and low yields of imidazolines (upon MeCN insertion) with an order of productivity that favors the bipodal over the tripodal reagents and a metal preference of Fe > Co ≥ Mn. In CH2Cl2, the more acidic Fe(II) sites favor formation of 2,4-diaryl-N-tosylpyrrolidines by means of an in situ (3 + 2) cycloaddition of the initially generated 2-aryl-N-tosylaziridine with residual styrene. In the presence of ketone, 1,3-oxazolidines can be formed in practicable yields, involving a single-pot cycloaddition reaction of alkene, nitrene, and ketone (2 + 1 + 2). Mechanistic studies indicate that the most productive bipodal Fe(II) site mediates stepwise addition of nitrene to olefins to generate aziridines with good retention of stereochemistry and further enables aziridine ring opening to unmask a 1,3-zwitterion that can undergo cycloaddition with dipolarophiles (MeCN, alkene, ketone) to afford five-membered N-heterocycles.

Enantiomers of a series of hydantoin derivatives were prepared from d- and l-amino acids with p-tolyl isocyanate and 3,5-bis(trifluoromethyl)phenyl isocyanate as guests for chiral recognition by 1H NMR spectroscopy. Meanwhile, several tetraaza macrocyclic compounds were synthesized as chiral solvating agents from d-phenylalanine and (1S,2S)-(+)-1,2-diaminocyclohexane. An uncommon enantiomeric discrimination has been successfully established for hydantoin derivatives, representatives of five-membered N,N-heterocycles, in the presence of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1c by means of 1H NMR spectroscopy. Several unprecedented nonequivalent chemical shifts (up to 1.309 ppm) were observed in the split 1H NMR spectra. To evaluate practical applications in the determination of enantiomeric excess (ee), the ee values of samples with different optical purities (up to 95% ee) were accurately calculated by the integration of relevant proton peaks. To better understand the chiral discriminating behavior, Job plots of (±)-G1 with TAMCSA 1a were investigated. Furthermore, in order to further explore any underlying intermolecular hydrogen bonding interactions, theoretical calculations of the enantiomers of (S)-G1 and (R)-G1 with TAMCSA 1a were performed by means of the hybrid density functional theory (B3LYP/6-31G*) of the Gaussian 16 program.

Recent research has highlighted the key role played by the electron affinity of the active metal-nitrene/imido oxidant as the driving force in nitrene additions to olefins to afford valuable aziridines. The present work showcases a library of Co(II) reagents that, unlike the previously examined Mn(II) and Fe(II) analogues, demonstrate reactivity trends in olefin aziridinations that cannot be solely explained by the electron affinity criterion. A family of Co(II) catalysts (17 members) has been synthesized with the assistance of a trisphenylamido-amine scaffold decorated by various alkyl, aryl, and acyl groups attached to the equatorial amidos. Single-crystal X-ray diffraction analysis, cyclic voltammetry and EPR data reveal that the high-spin Co(II) sites (S = 3/2) feature a minimal [N3N] coordination and span a range of 1.4 V in redox potentials. Surprisingly, the Co(II)-mediated aziridination of styrene demonstrates reactivity patterns that deviate from those anticipated by the relevant electrophilicities of the putative metal nitrenes. The representative L4Co catalyst (-COCMe3 arm) is operating faster than the L8Co analogue (-COCF3 arm), in spite of diminished metal-nitrene electrophilicity. Mechanistic data (Hammett plots, KIE, stereocontrol studies) reveal that although both reagents follow a two-step reactivity path (turnover-limiting metal-nitrene addition to the C b atom of styrene, followed by product-determining ring-closure), the L4Co catalyst is associated with lower energy barriers in both steps. DFT calculations indicate that the putative [L4Co]NTs and [L8Co]NTs species are electronically distinct, inasmuch as the former exhibits a single-electron oxidized ligand arm. In addition, DFT calculations suggest that including London dispersion corrections for L4Co (due to the polarizability of the tert-Bu substituent) can provide significant stabilization of the turnover-limiting transition state. This study highlights how small ligand modifications can generate stereoelectronic variants that in certain cases are even capable of overriding the preponderance of the metal-nitrene electrophilicity as a driving force.

Enantiomers of a few new amides containing two stereogenic centers have been derived from d- and l-α-amino acids as guests for chiral recognition by 1H NMR spectroscopy. A variety of chiral amides with two or more stereogenic centers often exist in the products of catalytic asymmetric synthesis, natural products or their total synthetic products, and chiral drugs. It would be a challenging and meaningful work to explore their chiral recognition. For this purpose, a class of novel chiral bisthiourea derivatives 1-9 has been synthesized from (1S,2S)-(+)-1,2-diaminocyclohexane, d-α-amino acids, and isothiocyanates as chiral solvating agents (CSAs). CSAs 1-9 proved to afford better chiral discriminating results towards most amides with two stereogenic centers, which have been rarely studied as chiral substrates by 1H NMR spectroscopy. In particular, CSAs 7, 8 and 9, featuring 3,5-bis(trifluoromethyl)benzene residues, exhibit outstanding chiral discriminating capabilities towards all amides, providing well-separated 1H NMR signals and sufficiently large nonequivalent chemical shifts. To test their practical application in the determination of enantiomeric excess, 1H NMR spectra of chiral amides (G16) with different optical purities were measured in the presence of CSAs 7 and 8, respectively. Their ee values (up to 90%) were accurately calculated by the integration of the NH proton of the CONHPh group of G16. To better understand the chiral discriminating behavior, Job plots of (±)-G16 with CSA 7 and (±)-G17 with CSA 8 and the association constants (Ka) of (S,R)-G16 and (R,S)-G16 with CSA 7 were evaluated, respectively. In order to further reveal any underlying intermolecular hydrogen bonding interactions, theoretical calculations of the enantiomers of (S,R)-G16 and (R,S)-G16 with CSA 7 were performed by means of the hybrid density functional theory (B3LYP) with the standard basis sets of 3-21G of the Gaussian 03 program, respectively.

In this study, we aimed to clone brain-derived Cyp19b and ovary-derived Cyp19a the P450 aromatase gene isoforms and to indicate the expression levels of these genes in the hypothalamus and ovary tissues from reproductively arrested ovarian development (RA) and non-arrested ovarian development (RN) Alburnus tarichi from Lake Van, Turkey. The expression levels of Cyp19b and Cyp19a genes were predominant in the hypothalamus and ovary, respectively. The level of Cyp19b mRNA was significantly lower in the hypothalamus and ovary from RA fish than in the hypothalamus and ovary from RN fish (P<0.05). The expression level of Cyp19a was significantly lower in the ovary of RA fish (P<0.05) than RN fish while no difference was found in the hypothalamus of both RA and RN fish (P<0.05). According to these findings, we suggest that the RA fish represent a segment of the population and these fish may be more sensitive to endocrine disruption compound/s than others.

Selective amination of sigma and pi entities such as C-H and C=C bonds of substrates remains a challenging endeavor for current catalytic methodologies devoted to the synthesis of abundant nitrogen-containing chemicals. The present work addresses an approach toward discriminating aromatic over aliphatic alkenes in aziridination reactions, relying on the use of anionic metal reagents (M = Mn, Fe, Co, Ni) to attenuate reactivity in a metal-dependent manner. A family of Mn-II reagents bearing a triphenylamido-amine scaffold and various pendant arms has been synthesized and characterized by various techniques, including cyclic voltammetry. Aziridination of styrene by PhI=NTs in the presence of each Mn-II catalyst establishes a trend of increasing yield with increasing Mn-II/III anodic potential. The Fe-II, Co-II, and Ni-II congeners of the highest-yielding Mn-II catalyst have been synthesized and explored in the aziridination of aromatic and aliphatic alkenes, exhibiting good to high yields with para-substituted styrenes, low to modest yields with sterically congested styrenes, and invariably low yields with aliphatic olefins. Co-II aziridination in comparison to Mn-II but is less selective than Mn-II in competitive aziridinations of nonconjugated olefins. Indeed, Mn-II proved to be highly selective even versus well-established copper and rhodium aziridination reagents. Mechanistic investigations and computational studies indicate that all metals follow a two-step styrene aziridination pathway (successive formation of two N-C bonds), featuring a turnover-limiting metal-nitrene addition to an olefinic carbon, followed by product-determining ring closure. Both steps exhibit activation barriers in the order Fe > Mn > Co, most likely stemming from relevant metal-nitrene electrophilicities and M-II/III redox potentials. The aziridination of aliphatic olefins follows the same stepwise path, albeit with a considerably higher activation barrier and a weaker driving force for the formation of the initial N-C bond, succeeded by ring closure with a miniscule barrier.

Enantiomers of a series of tripeptide derivatives with three stereogenic centers (±)-G1-G9 have been prepared from d- and l-α-amino acids as guests for chiral recognition by 1H NMR spectroscopy. In the meantime, a family of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d has been synthesized from d-phenylalanine and (1 S,2 S)-(+)-1,2-diaminocyclohexane. Discrimination of enantiomers of (±)-G1-G9 was carried out in the presence of TAMCSAs 1a-1d by 1H NMR spectroscopy. The results indicate that enantiomers of (±)-G1-G9 can be effectively discriminated in the presence of TAMCSAs 1a-1d by 1H NMR signals of multiple protons exhibiting nonequivalent chemical shifts (ΔΔδ) up to 0.616 ppm. Furthermore, enantiomers of (±)-G1-G9 were easily assigned by comparing 1H NMR signals of the split corresponding protons with those attributed to a single enantiomer. Different optical purities (ee up to 90%) of G1 were clearly observed and calculated in the presence of TAMCSAs 1a-1d, respectively. Intermolecular hydrogen bonding interactions were demonstrated through theoretical calculations of enantiomers of (±)-G1 with TAMCSA 1a by means of the hybrid functional theory with the standard basis sets of 3-21G of the Gaussian 03 program.

In the field of chiral recognition, reported chiral discrimination by H-1 NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate the chiral discriminating abilities of a chiral auxiliary. Among them, chiral alpha-hydroxy acids, a-amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes, and also play an important role in the area of preparation of pharmaceuticals, as they are part of the synthetic process in the production of chiral drug intermediates and protein-based drugs. In this paper, several alpha-hydroxy acids and N-Ts-alpha-amino acids were used to evaluate the chiral discriminating abilities of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d by 1H NMR spectroscopy. The results indicate that alpha-hydroxy acids and N-Ts-alpha-amino acids were successfully discriminated in the presence of TAMCSAs 1a-1d by H-1 NMR spectroscopy in most cases. The enantiomers of the alpha-hydroxy acids and N-Ts-alpha-amino acids were assigned based on the change of integration of the H-1 NMR signals of the corresponding protons. The enantiomeric excesses (ee) of N-Ts-alpha-amino acids 11 with different optical compositions were calculated based on the integration of the H-1 NMR signals of the CH3 protons (Ts group) of the enantiomers of (R)- and (S)-11 in the presence of TAMCSA 1b. At the same time, the possible chiral discriminating behaviors have been discussed by means of the Job plots of (+/-)-2 with TAMCSAs 1b and proposed theoretical models of the enantiomers of 2 and 6 with TAMCSA 1a, respectively.

In the field of chiral recognition, reported chiral discrimination by 1H NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate the chiral discriminating abilities of a chiral auxiliary. Among them, chiral α-hydroxy acids, α-amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes, and also play an important role in the area of preparation of pharmaceuticals, as they are part of the synthetic process in the production of chiral drug intermediates and protein-based drugs. In this paper, several α-hydroxy acids and N-Ts-α-amino acids were used to evaluate the chiral discriminating abilities of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d by 1H NMR spectroscopy. The results indicate that α-hydroxy acids and N-Ts-α-amino acids were successfully discriminated in the presence of TAMCSAs 1a-1d by 1H NMR spectroscopy in most cases. The enantiomers of the α-hydroxy acids and N-Ts-α-amino acids were assigned based on the change of integration of the 1H NMR signals of the corresponding protons. The enantiomeric excesses (ee) of N-Ts-α-amino acids 11 with different optical compositions were calculated based on the integration of the 1H NMR signals of the CH3 protons (Ts group) of the enantiomers of (R)- and (S)-11 in the presence of TAMCSA 1b. At the same time, the possible chiral discriminating behaviors have been discussed by means of the Job plots of (±)-2 with TAMCSAs 1b and proposed theoretical models of the enantiomers of 2 and 6 with TAMCSA 1a, respectively.

Light alkanes (C-1-C-10) and simple aromatics are derived from desirable crude energy feedstock but present challenging cases for C-H functionalization purposes. This article reviews efforts to mediate C-N bond construction from these abundant sources to generate commodity chemicals of high industrial value. The nitrogen-group donors considered are largely limited to metal-bound or diffusively free nitrenes, nitrenoids, and amides/imides engaged in catalytic or stoichiometric intermolecular reactions. Both synthetic protocols and mechanistic studies are discussed to illustrate the current status of a rapidly developing field that is still in need of significant improvements to effect reactive and selective processes.

The anionic L = [(EPiPr2)2N]– (E = S, Se) form of the dichalcogenidoimidodiphosphinato‐type ligands containing iPr peripheral groups has been shown previously to afford tetrahedral [MIIL2] complexes (E = S, M = Mn, Co, Ni, Zn; E = Se, M = Co, Ni, Zn). The syntheses of the analogous [FeL2] complexes [E = S (1), Se (2)] were performed in this work through metathesis reactions between FeCl2 and the corresponding KL salts. For both 1 and 2, X‐ray crystallography revealed two distinct molecules in the asymmetric unit. Complexes 1 and 2 are isostructural and exhibit P–E and P–N bond‐length differences compared with those of the free ligands, and these differences are translated into shifts of the corresponding IR bands. Cyclic voltammetry studies showed that the FeII → FeIII oxidation in 2 occurs at a lower potential than that of 1. The zero‐field Mössbauer spectra of the two complexes are quite similar and provide evidence of similar S = 2 electronic structures. The observation of crystallographically distinct FeIIE4 sites for both 1 and 2 is also revealed in the corresponding Mössbauer spectra. Complex 2 was employed as a single‐source precursor in catalyst‐aided chemical vapor deposition experiments, which afforded the iron selenides FeSe and Fe3Se4.