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A combination of Ga(I) centers as important building blocks and scaffolds containing N-heterocyclic imines gives new insights into low-valent Ga chemistry. In this study, a mixture of LDipNLi (LDip = 1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene), tBuOK, and Cp*Ga (Cp* = pentamethylcyclopentadienyl) in toluene afforded [LDipN-Ga]2 (1) via salt metathesis. X-ray structure analysis of 1 revealed a four-membered Ga2N2 ring, and DFT studies indicated the presence of a lone pair at each Ga center. In addition, compound 1 demonstrated diverse reactivities towards methyl trifluoromethanesulfonate, diphenyl disulfide, 9,10-phenanthrenequinone, and ECl2 (E = Ge or Sn). [ABSTRACT FROM AUTHOR]

Direct enantioselective synthesis of 2‐substituted chromen‐4‐ones, bearing the amino group at α‐stereogenic center with respect to the heterocycle is developed. It is based on Mannich‐type asymmetric addition of 3‐hydroxychromen‐4‐one and its analogues to N‐protected imines in the presence of available alkaloid dihydrocuprein. α‐Stereogenic chromenone amino derivatives were formed in this reactions in 81–95% yield with up to 98% ee. The chiral adducts were transformed to diverse enantiomerically enriched chromen‐4‐one functional derivatives. [ABSTRACT FROM AUTHOR]

A facile enantioselective alkynylation of cyclic ketimines attached to a neutral functional group utilizing the dual Cu(I)‐CPA catalysis is described. The strategy of the alkynylation of 2‐aryl‐3H‐indol‐3‐one directly to chiral propargylic amines containing indolin‐3‐one moiety in good yields and enantioselectivities. Moreover, gram‐scale synthesis of chiral propargylamines based C2‐quaternary indolin‐3‐ones was performed. The synthetic applications were confirmed by transformations of the products with no decrease in the yield and enantioselectivity. [ABSTRACT FROM AUTHOR]

Application of bioisostere plays an important role in drug discovery. α‐Aminoboronic acid is the familiar bioisostere of α‐amino acid. Developing reactions for the synthesis of a wide variety of α‐aminoboronic acid is one important task for synthetic chemistry. Herein, we report the development of nucleophilic C‐borylation chemistry for N‐arylimines catalyzed by nickel. The reaction proceeds through the insertion of a borylnickel species into the C=N bond to afford the corresponding α‐aminoboronate, which was isolated as acetamide after trapping with acetic anhydride. N‐Benzyl imine is also tolerated by the developed reaction. [ABSTRACT FROM AUTHOR]

α-Amino ketones are important motifs in synthetic and medicinal chemistry. Efficient methods to directly access these motifs from feasible precursors are, however, limited. Herein, a visible-light mediated reductive cross-electrophile coupling of readily available imines and anhydrides was developed. Under mild reaction conditions, the umpolung reactivity of diverse imines engaged with anhydrides gives a variety of α-amino ketones with good yields and a broad functional group compatibility. Primary mechanistic studies revealed that this transformation might proceed through a radical–radical cross coupling pathway dominantly. [ABSTRACT FROM AUTHOR]

A cross‐1,3‐dipolar cycloaddition reaction of α‐halohydroxamates (in situ generated azaoxyallyl cations) with N,N′‐cyclic azomethine imines was developed. The synthetic protocol provided facile and rapid access to pyrazolo[1,2‐a][1,2,4]triazine derivatives in good yields and excellent diastereoselectivities under mild metal‐free conditions. [ABSTRACT FROM AUTHOR]

Miscellaneous imines and acyl hydrazones were prepared from 5-nitrofuraldehyde and 5-nitrothiophene-2-carboxaldehyde. Their activities against Toxoplasma gondii and Leishmania major parasites were evaluated. Promising antiparasitic effects and selectivities were observed for certain acyl hydrazones and imines. Cobalt(II) and copper(II) complexes conserved the high anti-Toxoplasma activities of 3-hydroxy-2-naphthoic carboxyl hydrazone (2a). In addition, sound activities against L. major promastigotes were observed for various analogs of 2a (2b and 2i) and pyrid-2-ylpyrazole-based imines (3g and 3h). Relatively low toxicities to kidney cells and macrophages indicate promising selectivity profiles for these compounds. [ABSTRACT FROM AUTHOR]

Dehydrogenation of saturated N‐heterocycles and hydrocarbons provides an important route to corresponding aromatic compounds. Herein, an efficient and selective MnAlO‐catalyzed aerobic oxidative dehydrogenation of five‐ and six‐membered N‐heterocycles, imines and hydrocarbons is presented. The reaction features excellent yields of the products, mild reaction conditions, readily available and reusable catalyst. Various N‐heterocycles and hydrocarbons can be tolerated by the reaction system and transformed to the corresponding aromatic counterparts. Mechanistic studies revealed that the reaction proceeds mainly through an electron transfer mechanism. [ABSTRACT FROM AUTHOR]

An efficient sequential one‐pot, two‐step pseudo‐four‐component reaction between 3/4‐methyl N‐sulfonyl ketimines with 3‐chloropropiophenones triggered by DIPEA/NaHCO3 as a cooperative base and subsequent aza‐cyclization using NH4OAc is reported. This transition‐metal‐oxidant‐free technique concocts new C−C/C=C/C=N−C bonds selectively, guaranteeing acceptable yields of 2,3,6‐trisubstituted pyridines possessing ortho‐hydroxyaryl/benzenesulfonamide and propiophenone moieties at C2 and C3 positions, respectively. Interestingly, while replacing methyl‐substituents with straight alkyl chains of N‐sulfonyl ketimines, only a monoalkylation reaction happened with in situ‐generated vinyl ketones to deliver promising yields of 3‐picoline derivatives. Moreover, the synthetic transmutation of prepared pyridine derivative led to several important classes of pyridocoumarin, 5H‐chromenopyridine, and di(pyridin‐3‐yl) methane derivatives. [ABSTRACT FROM AUTHOR]

[40] Recently, pyrazolone-based MBH carbonates have emerged as versatile precursors to access spiropyrazolone scaffolds. Keywords: annulation; spiropyrazolones; diastereoselectivity; Morita-Baylis-Hillman carbonates; spirooxindoles EN annulation spiropyrazolones diastereoselectivity Morita-Baylis-Hillman carbonates spirooxindoles 1732 1738 7 08/18/23 20230901 NES 230901 Graph The construction of spiro carbocyclic/heterocyclic structures has received enormous attention from synthetic and medicinal-chemistry researchers in recent decades. Under the optimized reaction conditions, the pyrazolone MBH carbonates B 1a b - B c b reacted efficiently with the 3-methyleneoxindoles B 2a b - B v b to afford the corresponding spiropyrazolone oxindole derivatives B 3a b - B x b in good to excellent yields (up to 98%) and with very high diastereoselectivities (dr 99:1) (Scheme 1). [36] Despite these recent advances in synthesizing spiropyrazolone-fused oxindole derivatives, few methods have been described for the synthesis of a spirocyclic molecule bearing three different scaffolds, such as pyrazolone, oxindole, and cyclopentene, in a diastereoselective manner. [Extracted from the article]

A new class of spirocyclic imines (SCIs) has been theoretically investigated by applying a variety of quantum chemical methods and basis sets. The uniqueness of these compounds is depicted by various peculiarities, e.g., the incidence of planar six-membered rings each with two imine groups (two π bonds) and the incorporation of the isosteres carbon, silicon, or germanium spiro centers. Additional peculiarities of these novel SCIs are mirrored by their three-dimensionality, the simultaneous occurrence of nucleophilic and electrophilic centers, and the cross-hyperconjugative (spiro-conjugation) interactions, which provoke charge mobility along the spirocyclic scaffold. Substitution of SCIs with strong electron-withdrawing substituents, like the cyano group or fluorine, enhances their docking capability and impacts their reactivity and charge mobility. To gain thorough knowledge about the molecular properties of these SCIs, their structures have been optimized and various quantum chemical concepts and models were applied, e.g., full NBO analysis and the frontier molecular orbitals (FMOs) theory (HOMO-LUMO energy gap) and the chemical reactivity descriptors derived from them. For the assessment of the charge density distribution along the SCI framework, additional complementary quantum chemical methods were used, e.g., molecular electrostatic potential (MESP) and Bader's QTAIM. Additionally, using the aromaticity index NICS (nuclear independent chemical shift) and other criteria, it could be shown that the investigated cross-hyperconjugated sila and germa SCIs are spiro-aromatics of the Heilbronner Craig-type Möbius aromaticity. [ABSTRACT FROM AUTHOR]

The chemistry of fluorinated compounds has experienced extraordinary growth in recent decades due to the many and varied properties which many of the compounds that contain fluorinated groups possess. Among all of them, fluorinated chiral imines, in particular the Ellman's imines, are of great importance since they are some of the most interesting building blocks for the synthesis of a large number of enantioenriched carbocycles and heterocycles with extraordinary biological and synthetic properties. This personal account covers the most significant results obtained in our research group in the last two decades concerning asymmetric tandem reactions, paying special attention to the intramolecular aza‐Michael reaction (IMAMR), diversity oriented synthesis (DOS), asymmetric tandem reactions involving a p‐tolylsulfinyl group as chiral inducer and cycloaddition processes, in particular, the Pauson‐Khand reaction, [2+2+2]‐cycloadditions and metathesis reactions, starting mainly from enyne compounds and through the use of fluorinated chiral N‐sulfinyl imines and their derivatives as starting materials. [ABSTRACT FROM AUTHOR]

A chemoselective dehydrogenation protocol for benzylic amines catalyzed by the TEtraQuinoline (TEQ)/FeCl2 complex is described. In combination with 2 equiv of tert‐butyl hydroperoxide, as little as 0.1 mol% of catalyst loading was sufficient to convert primary and secondary benzylic amines to the corresponding imines and dimerized imines, respectively. Subsequent hydrolysis of the imines allowed for removal of the benzyl group on the nitrogen atom. Nonaromatic carbon‐carbon multiple bonds and the O‐Bn group remained intact in the present protocol, providing a complementary deprotection procedure to reductive removal conditions exerted by Pd catalysis. [ABSTRACT FROM AUTHOR]

In this work, the synthesis and structure of an antimony complex with an aromatic, asymmetric tridentate ligand without an Sb-C bond were studied. Ethoxy(2-salicylidenaminophenolato)antimony(III) was studied with NMR, UV-Vis, and IR spectroscopy and the molecular structure was determined by single crystal X-ray diffraction. The antimony atom is formally tetracoordinate in this molecule. Coordinative unsaturation becomes visible in the solid-state structure where intermolecular Sb...O interactions supplement the coordination sphere of the antimony atom to be hexacoordinated. Quantum chemical calculations were performed in order to obtain a better understanding of the bond properties in the antimony complex. These show a spherical distribution of the lone pair at antimony and polar shared bonds from antimony to the heteroatoms of the tridentate ligand. [ABSTRACT FROM AUTHOR]

The first examples of regioselective aryl ortho-C–H functionalization with diphenyldiazomethane for the construction of Caryl–Nhydrazinato bonds were accomplished via the activation of C–H bonds and the subsequent reaction of diphenyldiazomethane with the RE–Caryl bond. The reactions of rare-earth metal monoalkyl complexes LRE(CH2SiMe3)(THF)2 (L = 2,5-[(2-pyrrolyl)CPh2]2(N-Me-pyrrole)) supported by a neutral N-methylpyrrole anchored dipyrrolyl ligand with 2 equiv. of Ph2CN2 gave irreversibly unprecedented hydrazonato-functionalized imino rare-earth metal complexes LRE(Ph2C＝NNC6H4-(o-C＝NHPh) (RE = Y (2a), Lu (2a′)) in good yields involving a rather complex process including the interaction of a diazo unit with a RE–Calkyl bond, a β-H elimination, a N–N cleavage, 1,4-hydrogen transfer and the subsequent C–N coupling with another diphenyldiazomethane. More important is that regioselective aryl C–H bond functionalization with diphenyldiazomethane to construct the Caryl–Nhydrazinato bonds can be easily achieved by three-component reactions of rare-earth metal monoalkyl complexes, a wide range of substituted imines (including aldimines, ketimines or analogous 2-phenylpyridine) and diphenyldiazomethane, affording various hydrazonato-functionalized phenyl, thienyl imino or pyridyl rare-earth metal complexes 2b–2j at room temperature. A further study indicated that the substituents on the phenyl ring have a great effect on the reaction pathway and governed the Caryl–Nhydrazinato bond construction. Moreover, the experimental studies show that the formation of the Caryl–Nhydrazinato bonds is thermodynamically facile, which could be realized at room temperature easily. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers. The catalytic asymmetric dearomatization (CADA) reaction is a powerful protocol for the assembly of three-dimensional cyclic compounds but phenols have been considered challenging substrates. Here, the authors report the chiral phosphoric acidcatalyzed divergent intermolecular CADA reactions of phenols with azoalkenes to obtain tetrahydroindolone and cyclohexadienone products in good yields with excellent ee values. [ABSTRACT FROM AUTHOR]

Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold‐catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin‐derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram‐scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones. [ABSTRACT FROM AUTHOR]

Mannich‐type reactions involving alkylzinc reagents have been developed using different strategies. We show that the addition of these organometallic species to sulfonyl imines occurs upon simple heating and affords Mannich products in moderate to excellent yields (14 examples, 30–99 %). Interestingly, N‐alkyl imines were also found to be suitable partners after activation as an acyliminium by acetyl chloride (12 examples, 49–86 %) or, more originally, by TMSCl (14 examples, 26–87 %). These methods proved complementary, leading to the preparation of both N‐protected secondary or tertiary amines and N‐unprotected secondary amines in good yields, with an increased eco‐compatibility, and under simple conditions. [ABSTRACT FROM AUTHOR]

Here described an acid‐controlled regional diverse synthesized process of CF3‐containing ketoimines by the condensation of benzo[b]thiophene‐2,3‐dione and 2,2,2‐trifluoroethlamine. The imines obtained at either the 2‐position or 3‐position can be further used as substrates in asymmetric organocatalyzed [3+2]‐cycloaddition reactions, leading to a library of regiodiverse bispiro‐compounds with 85–96 % yield and 65–99 % ee. [ABSTRACT FROM AUTHOR]

α-Aminophosphonates and related compounds are important due to their real and potential biological activity. α-Aminophosphonates may be prepared by the Kabachnik–Fields condensation of oxo compounds, amines and dialkyl phosphites, or by the aza-Pudovik addition of the same P-reagents to imines. In this review, the methods that allow for the synthesis of α-aminophosphonates with optical activity are surveyed. On the one hand, optically active catalysts or ligands may induce enantioselectivity during the Kabachnik–Fields reaction. On the other hand, asymmetric catalysis during the aza-Pudovik reaction, or hydrogenations of iminophosphonates, may prove to be a useful tool. Lastly yet importantly, it is possible to start from optically active reagents that may be associated with diastereoselectivity. The "green" aspects of the different syntheses are also considered. [ABSTRACT FROM AUTHOR]

A highly efficient protocol for stereoselective synthesis of novel polycyclic benzo[b]thiophene derivatives was developed. Using quinine-derived bifunctional thiourea (5 mol%) as a catalyst, asymmetric [3+3] annulation of N-(benzo[b]thiophen-2-yl)-sulfonamide with 2-alkynyl cycloenone could provide dihydrobenzo[4,5]thieno[2,3-b]pyridine derivatives in moderate to good yields (up to 93%) with mostly excellent enantioselectivities (up to 97% ee) under mild conditions. In addition, large-scale experiments and derivatizations were explored. In particular, the target product in large-scale experiments could be easily purified by filtration and the filtrated product showed >99% ee. [ABSTRACT FROM AUTHOR]

A photoredox‐catalyzed umpolung strategy for the synthesis of homoallylamines from unactivated imines and allyl bromides is described. This strategy exploited N,N‐diisopropylethylamine (DIPEA) as an auxiliary agent to indirectly realize the cross‐coupling of imines and allyl bromides. Various sterically hindered homoallylamines were synthesized by combining photocatalysis with halogen atom transfer (XAT). Notable characteristics of this approach include water‐insensitive reaction conditions, high yield (up to 99%), wide substrate scope (suitable for N‐aryl/alkyl and C‐aryl ketimines and aldimines, 39 examples), and high tolerance of functional groups (such as cyano, ester, amide, and thioamide). [ABSTRACT FROM AUTHOR]

An efficient copper‐catalyzed oxidative dehydrogenation of tetrahydroisoquinolines has been developed, giving a general and convenient strategy from amines toward imines in excellent yields. A series of tetrahydroisoquinolines bearing electron‐donating/withdrawing groups proceeded smoothly with air (O2) as oxidant. The oxidative dehydrogenation proved to be an atom‐economical and environmentally friendly strategy, which could effectively avoid generating stoichiometric hazardous wastes. In addition, this methodology provides a convenient and effective approach to the reutilization of amines, especially for the synthesis of enantiomerically pure substances, such as (+)‐Solifenacin, in industrial process. Preliminary experimental results revealed that the reaction was carried out via a process of oxidative dehydrogenation. [ABSTRACT FROM AUTHOR]

The commercially available 4,4ʹ-trimethylenedipiperidine (TMDP) was used in the solid state to activate various aldehydes and controlled the libration of methyl amine for preparing the corresponding N-methyl imines. It was indicated that TMDP could play multiple roles simultaneously in this reaction, including (a) a bifunctional base with a predicted pKa ~ 11 and a good scavenger of acid, (b) a catalyst able to form strong hydrogen bonding and chemical interactions with aldehyde functional group through hemiaminal and/or iminium intermediate, and (c) liberating methyl amine from its salt viz. methylammonium chloride. TMDP could be regenerated by neutralization. It was also regenerated by heating at 70 °C, which is reported for the first time according to the best of our knowledge. The regenerated reagent was stable regarding its chemical structure, and there was no significant loss in the catalytic efficiency even after several runs. The mechanism was investigated by performing several control reactions and studying the FTIR and NMR spectra in the solid-state synthesis. The current work demonstrated TMDP as a safe and greener promoter-acid scavenger for organic transformations compared with toxic, flammable, volatile liquid secondary amines such as piperidine. [ABSTRACT FROM AUTHOR]

Complexes of Schiff bases (SBs) with metals are promising compounds exhibiting a broad range of applications, such as catalysts, polymers, dyes, and several biological activities, including antimicrobial, anticancer, antioxidant, antimalarial, analgesic, antiviral, antipyretic, and antidiabetic actions. Considering the crisis that the whole world is now facing against antimicrobial-resistant bacteria, in the present review, we chose to focus on the activity of SBs as antimicrobials, particularly underlying the most recent studies in this field. Finally, some interesting catalytic applications recently described for metal complexes with SBs have also been discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] The exploration of emerging photocatalysts like covalent organic frameworks (COFs) is an essential but challenging endeavor to find sustainable solutions for selective organic transformations. Anthraquinones are envisaged to construct COFs for visible light photocatalysis because their derivatives are employed industrially as oxidation catalysts or organic dyes. Herein, an anthraquinone COF, TpAQ-COF, is successfully constructed with 1,3,5-triformylphloroglucinol (Tp) and 2,6-diaminoanthraquinone (AQ). Then, the selective oxidation of amines over TpAQ-COF is implemented. Amines can be effectively converted into corresponding imines over TpAQ-COF powered with green light and oxygen, during which superoxide radical anion is discerned as the pivotal reactive oxygen species. This work suggests that COFs could inherit the advantages of molecular building blocks for selective reactions powered with broad visible light. [ABSTRACT FROM AUTHOR]

Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr). Once a sulfilimine cross-link is created, bromide is released into the extracellular space and becomes available for reutilization. Whether the HOBr generated by peroxidasin is used very selectively for creating sulfilimine cross-links or whether it also causes oxidative damage to bystander molecules (e.g., generating bromotyrosine residues in basement membrane proteins) is unclear. To examine this issue, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to define the distribution of bromine in mammalian tissues. We observed striking enrichment of bromine (79Br, 81Br) in basement membranes of normal human and mouse kidneys. In peroxidasin knockout mice, bromine enrichment of basement membranes of kidneys was reduced by ∼85%. Proteomic studies revealed bromination of tyrosine-1485 in the NC1 domain of α2 collagen IV from kidneys of wild-type mice; the same tyrosine was brominated in collagen IV from human kidney. Bromination of tyrosine-1485 was reduced by >90% in kidneys of peroxidasin knockout mice. Thus, in addition to promoting sulfilimine cross-links in collagen IV, peroxidasin can also brominate a bystander tyrosine. Also, the fact that bromine enrichment is largely confined to basement membranes implies that peroxidasin activity is largely restricted to basement membranes in mammalian tissues.

ObjectiveIntravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation.ConclusionsDirect and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.

Abstract Organic imine cage compounds have found a variety of different applications in several fields in materials science. To design tailor-made cages for corresponding applications, synthetic approaches to cages with tunable functionalities, sizes and shapes have to be found. Here we report a series of cages with truncated cubic shape and tetrahedral geometry possessing nitrogen-rich cavities.

Personal care products (PCPs) inevitably come into contact with the skin in people’s daily life, potentially causing adverse effects on human health. The adverse effects can be exacerbated under UV irradiation but are rarely studied. In this study, to clearly understand the damage of representative PCPs to human skin and their photochemical transformation behaviors, fragrance tonalide (AHTN) was measured in the presence of amino acids as a basic building block of human tissue. The results showed that amino acids could decelerate the photochemical transformation rate of AHTN, increasing the likelihood of AHNT persisting on the skin surface and the health risk to the human being. Further, the interaction between amino acids and AHTN was investigated. AHTN could play bidirectional roles in damaging amino acids: the photosensitizer and reactive activator. As a photosensitizer, the 1O2 generated from the AHTN photosensitization was partly employed to oxidative damage amino acids. Furthermore, by combining experiments with quantum chemical computation, the carbonyl group of the activator AHTN was found to be the active site to activate the N-containing group of amino acids. The activation mechanism was the electron transfer between AHTN and amino acids. Imines formed during the photochemical transformation of AHTN with histidine/glycine were the molecular initiating event for potential skin sensitization. This study reported for the first time that skin photosensitizer formation threatens human health during the photochemical transformation of AHTN.

Dynamic covalent chemistry (DCC) has, in recent years, provided valuable tools to synthesize molecular architectures of increasing complexity. We have also taken advantage of imine DCC chemistry to prepare TPMA‐based supramolecular cages for molecular recognition applications. However, the versatility of this approach has as a major drawback the intrinsic hydrolytic lability of imines, which hampers some applications. We present herein a synthetic strategy that combines the advantages of a thermodynamic‐driven formation of a supramolecular structure using imine chemistry, together with the possibility to synthetize chiral hydrolytically stable structures through a [3,3]‐sigmatropic rearrangement. A preliminary mechanistic analysis of this one‐pot synthesis and the scope of the reaction are also discussed. [ABSTRACT FROM AUTHOR]

[21][24] We wish to report herein our synthetic approach toward -hydroxyamino ketones, which involves the radical acylation of nitrone with 2-acylbenzothiazolene under organophotoredox catalysis (route C). Metal- and Additive-Free Synthesis of -Hydroxyamino Ketones Enabled by Organophotocatalyst Hydroxyamino ketone, hydroxylamine, nitrone, benzothiazoline, metal-free, organophotocatalyst Keywords: hydroxyamino ketone; hydroxylamine; nitrone; benzothiazoline; organophotocatalyst; metal-free EN hydroxyamino ketone hydroxylamine nitrone benzothiazoline organophotocatalyst metal-free 1391 1394 4 07/11/23 20230725 NES 230725 Graph Nitrogen-containing compounds are prevalent in organic compounds, and a range of novel catalytic approaches have been extensively explored. [Extracted from the article]

The reaction of [Ru(PPh3)3Cl2] with a group of four 1,4-diazabutadiene ligands (p-RC6H4N＝C(H)–C(H)＝NC6H4R-p; R = OCH3, CH3, H and Cl; abbreviated as L-R) in an equimolar ratio afforded chloro-bridged di-ruthenium complexes (1–4) of the general type [Ru2(PPh3)2(L-R)2Cl3]Cl. The crystal structures of complexes 1 (R = OCH3), 2 (R = CH3) and 4 (R = Cl) were determined and the molecular structure of complex 3 (R = H) was optimized using the DFT method. Each complex showed four intense absorptions in the visible and ultraviolet regions, the origin of which was probed employing TDDFT calculations. The complexes were found to serve as efficient catalyst precursors for the oxidative and deaminative C–N coupling of a series of primary amines, producing corresponding imines in good yields. Homo-coupling of benzylamines and cross-coupling of two differently substituted benzylamines or benzylamine with anilines and other aryl/alkyl amines could be realized using this catalytic protocol with aerial oxygen as the oxidant. [ABSTRACT FROM AUTHOR]

With formaldehyde as an atom-economical carbonyl synthon, the EtOH-catalyzed electrochemical multicomponent synthesis of various imidazolidine-fused sulfamidates was developed. A wide range of products were obtained in good to excellent yields under organic oxidant-free, energy-saving and mild conditions. The mechanistic study revealed that the in situ generated ethoxide played a crucial role in producing aminomethylene radicals at a lower voltage. [ABSTRACT FROM AUTHOR]

The electro‐reductive coupling of nitro and carbonyl compounds enables a facile, environmentally friendly and energy benign transformation toward value‐added nitrones or imines, but the selectivity is still challenging. Here, the surface roughness of Cu electrodes is introduced for the first time as the determinant to switch products from nitrones to imines owing to the controllable reduction of nitroarenes to hydroxylamines or amines on tailored CuI/Cu0 interfaces. The roughness‐dependent selectivity, that is the decrease of nitrones and the increase of imines with enhanced roughness, is visible in the electro‐reductive coupling of nitrobenzene and furfural. Thus, the high selectivity of nitrone (98 %) and imine (80 %) can be achieved on a surface smooth Cu foil and the one electrochemically roughened in the presence of I−, respectively. Such roughness‐dependence of nitrone/imine selectivity on Cu electrodes is further verified in a wide substrate scope, highlighting the promise of surface/interfacial engineering for electrochemical synthesis. [ABSTRACT FROM AUTHOR]

A synthetic method to prepare 1,2‐diamines efficiently that relies on the 4CzPN‐catalysed α‐aminoalkylation of azomethine imines by secondary and tertiary α‐silylamines under blue light emitting diode (LED) light (456 nm) is described. Achieved under metal‐ and additive‐free reaction conditions at room temperature, the synthetic protocol was shown to afford product yields up to 99% and applicable to the late‐stage functionalisation of three drug molecules and the gramme‐scale preparation of one example. [ABSTRACT FROM AUTHOR]

The efficient one-pot halofluorination of a β-enaminophosphonate/β-iminophosphonate tautomeric mixture resulting in α,α-halofluorinated β-iminophosphonates is reported. Subsequent imine reduction gave the corresponding β-aminophosphonates as a racemic mixture or with high diastereoselectivity. The proposed protocol is the first example of a synthesis of N-inactivated aziridines substituted by a fluorine and phosphonate moiety on the same carbon atom. Based on spectroscopic and theoretical studies, we determined the cis/trans geometry of the resulting fluorinated aziridine-2-phosphonate. Our procedure, involving the reduction of cis/trans-fluoroaziridine mixture 24, allows us to isolate chiral trans-aziridines 24 as well as cis-aziridines 27 that do not contain a fluorine atom. We also investigated the influence of the fluorine atom on the reactivity of aziridine through an acid-catalyzed regioselective ring-opening reaction. The results of DFT calculations, at the PCM/ωB97x-D/def2-TZVPD level of theory, are in good agreement with the experiments. The transition states of the SN2 intramolecular cyclization of vicinal haloamines have been modeled. [ABSTRACT FROM AUTHOR]

In this research, a metal-free diastereoselective formal 1,3-dipolar cycloaddition of N-2,2,2-trifluoroethylisatin ketimines and cyclopentene-1,3-diones which can efficiently lead to the desymmetrization of cyclopentene-1,3-diones is developed. With the developed protocol, a series of tetracyclic spirooxindoles containing pyrrolidine and cyclopentane subunits can be smoothly obtained with good results (up to 99% yield and 91:9 dr). Furthermore, the methodology can be extended to trifluoromethyl-substituted iminomalonate, and the corresponding formal [3+2] cycloaddition reaction affords bicyclic heterocycles containing fused pyrrolidine and cyclopentane moieties in moderate yields with >20:1 dr. The synthetic potential of the methodology is demonstrated by the scale-up experiment and by versatile transformations of the products. [ABSTRACT FROM AUTHOR]

An organocatalytic asymmetric synthesis of directly linked benzothiazole‐dihydroimidazoles with two adjacent tertiary‐quaternary stereocenters through a Mannich‐type reaction of isocyanoacetates with N‐(2‐benzothiazolyl)imines is disclosed. When employing bifunctional dihydroquinine‐derived squaramide as catalyst, moderate to excellent yields (up to 97 % yield), moderate diastereoselectivities and excellent enantioselectivities (up to >99 % ee) were obtained for a variety of substrates. In addition, the transformation of the resulted directly linked benzothiazole‐dihydroimidazole into highly functionalized α,β‐diamino esters was also demonstrated. [ABSTRACT FROM AUTHOR]

Catalytic reduction of a representative set of imines, both aldimines and ketimines, to amines has been studied using transfer hydrogenation from 1,4‐dicyclohexadiene. Unusually, this has been achieved using s‐block pre‐catalysts, namely 1‐metallo‐2‐tert‐butyl‐1,2‐dihydropyridines, 2‐tBuC5H5NM, M(tBuDHP), where M=Li–Cs. Reactions have been monitored in C6D6 and tetrahydrofuran‐d8 (THF‐d8). A definite trend is observed in catalyst efficiency with the heavier alkali metal tBuDHPs outperforming the lighter congeners. In general, Cs(tBuDHP) is the optimal pre‐catalyst with, in the best cases, reactions producing quantitative yields of amines in minutes at room temperature using 5 mol % catalyst. Supporting the experimental study, Density Functional Theory (DFT) calculations have also been carried out which reveal that Cs has a pathway with a significantly lower rate determining step than the Li congener. In the postulated initiation pathways DHP can act as either a base or as a surrogate hydride. [ABSTRACT FROM AUTHOR]

For the first time, condensations of amines with carbonyl compounds have been performed in supercritical carbon dioxide (sc‐CO2). The reactions with aldehydes or active ketones proceed at moderate temperatures (35–55 °C) without use of external catalysts. The process is autocatalytic: it is accelerated by the carbonic acid generated in situ by interaction between the released water and the CO2 medium. The imine products were obtained in high yields in a crystalline form and did not require further purification. The one‐pot transfer hydrogenation and [4+2] cycloaddition reactions performed in the CO2 medium have uncovered attractive prospects for facile green synthesis of more complex and valuable compounds from the generated in situ imine products. [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]

Keywords: chiral phosphoric acid; organocatalysis; cycloaddition; alkenes; alkynes EN chiral phosphoric acid organocatalysis cycloaddition alkenes alkynes 1200 1214 15 06/19/23 20230704 NES 230704 1 Introduction Asymmetric cycloaddition reaction is the most powerful strategy for the construction of various enantioenriched carbocycles and heterocycles, [1] because it provides an efficient and completely atom-economical route from simple precursors. In order to achieve this goal, we needed to overcome the following issues: (1) realization of efficient cycloaddition of alkynes with appropriate partners; (2) the installation of suitable groups onto alkynes to avoid free rotation around the potential C-C axes; (3) the choice of a competent chiral catalyst to promote the designed cycloaddition reactions and to control the stereoselectivity. 3 CPA-Catalyzed Cycloaddition of Alkynes Although the CPA-catalyzed cycloaddition of alkenes have been well documented, the CPA-catalyzed asymmetric cycloaddition reaction of alkynes is still lacking. On the other hand, the cycloaddition of alkynylnaphthols with imines proceeded via a sequential [4+2] cycloaddition, an alkyne-type Povarov cycloaddition, and an auto-oxidation reaction. [Extracted from the article]

Substituted piperidine rings are a common motif in natural products and pharmaceutical drugs. The asymmetric synthesis of piperidines bearing multiple stereocentres remains a challenge, and current approaches often rely on lengthy reaction sequences and 'chiral pool' strategies. Herein, we report multi‐enzymatic and chemo‐enzymatic methods that allow the preparation of piperidines with three chirality centres in only two steps from achiral diketoester precursors. Stereocontrol is achieved by a highly enantioselective transamination leading to optically pure (ee >99%) enamine or imine intermediates, followed by diastereoselective reduction of these unsaturated N‐heterocycles using either platinum(0)‐catalysed flow hydrogenation or enzymatic imine reduction. In the latter case, coupling of the two biocatalytic reactions in a concurrent one‐pot process is possible, thus reducing the synthetic sequence to a single biotransformation. In total, nine trisubstituted piperidines were prepared in high stereoisomeric purities (dr ≥98:2) and isolated yields of up to 73%. Lead‐likeness analysis of five representative products using an open‐source webtool suggests that these compounds possess considerable application potential as building blocks in drug discovery. [ABSTRACT FROM AUTHOR]

The Castagnoli–Cushman reaction was carried out with various fused and bridged bicyclic anhydrides. The influence of the anhydride nature and, specifically, the size of fused anhydride rings on the reaction pathway were investigated. The negative outcome of the reaction in the case of small rings and bridged systems was mechanistically described. The scope and limitations of the procedure involving anhydrides and imines were discussed. The high diastereoselectivity of the method was proved and showed its correlation with the previous results. The reaction was optimized and scaled up to afford multigram amounts of products in a single run (up to 50 g). [ABSTRACT FROM AUTHOR]

First representatives of ferrocenyl-containing mesoionic heterocyclic compounds were synthesized by the reaction of 4-lithium derivatives of sydnones and sydnone imines with ferrocenecarboxaldehyde. A series of 4-(α-hydroxy)- and 4-(α-methoxy)ferrocenyl-methyl derivatives of sydnones and sydnone imines, which were found in vegetation tests using seeds of corn cv. Krasnodarskaya 291 AMB, exhibit growth-regulating and antidote activity against the herbicide metsulfuron-methyl. [ABSTRACT FROM AUTHOR]

A crucial step in the formation of mono-aminoboranes (R2N–BH2) from the corresponding imine–BH3 adducts, under mild reaction conditions, is the 1,3-hydride shift. We offer experimental and theoretical insights into this molecular rearrangement according to two mechanistic pathways: intra-molecular (unimolecular) and inter-molecular (bimolecular). Even though a few experimental observations were inconclusive, an isotope-based experiment suggested that the 1,3-hydride shift occurs bimolecularly. In addition, the shape of the potential energy landscape, generated via the computational means, strongly suggests that these reactions are bimolecular. Relative energy gradient analysis enabled to identify the driving forces according to both scenarios and to explain the unusual shape of the minimum energy path in a unimolecular process. Our results imply that elevated temperature (60 °C) supplies the reactants with sufficient energy to cross the barrier, whereby each collision with properly oriented reactants results in mono-aminoborane formation. [ABSTRACT FROM AUTHOR]

The cycloaddition reactions of eleven substituted anthracenes with nosylated quinone imines provides a convenient route to the respective triptycenes. Following re‐aromatization, selective O‐butylation and cleavage of the nosyl‐group the respective triptycene anilines are obtained, which are converted into the respective imidazolium salts according to established procedures. Deprotonation of the imidazolium salts provide new triptycene‐NHC‐metal complexes (M=AuCl, RhCl(cod), IrCl(cod), RhCl(CO)2, IrCl(CO)2, PdI2(py), PtCl2(py), Pd(allyl)Cl) with unusual ligand sterics. [ABSTRACT FROM AUTHOR]