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Masterarbeit Universität Innsbruck 2024

Herein, we report the first total synthesis of (±)-marilines B and C, as well as a failed approach to (±)-mariline A, by using our recently developed multicomponent reaction method, which involves the interception of ortho-quinone methides with various nitrogen nucleophiles to allow easy assembly of various benzylic amine cores with diverse substituents.

Mechanically interlocked molecules have found extensive applications in areas all across the physical sciences, from materials to catalysis and sensing. However, introducing mechanical bonds and entanglements at the molecular level is still a significant challenge due to the inherent restriction in entropy needed to preorganize strands before interlocking. Over the last decade, dynamic covalent chemistry has emerged as one of the most efficient methods of forming rotaxanes, catenanes and molecular knots. By using reversible bonds such as imines, disulfides and boronate esters, one can use the inherent error-correction in these linkages to form interlocked architectures with high fidelity and often in excellent yields. This review reports on recent advances in the use of dynamic covalent chemistry to make mechanically interlocked molecules, systematically surveying clipping, capping and templating approaches with dynamic bonds. Furthermore, it is also discussed how dynamic bonds can be used to control motion, co-conformational expression and catalytic activity in mechanically interlocked molecular machinery., QC 20231122

Covalent adaptable networks (CANs) can replace classical thermosets, as their unique dynamic covalent bonds enable recyclable crosslinked polymers. Their creep susceptibility, however, hampers their application. Herein, an efficient strategy to enhance creep resistance of CANs via metal coordination to dynamic covalentimines is demonstrated. Crucially, the coordination bonds not only form additional crosslinks, but also affect the imine exchange. This dual effect results in enhanced glass transition temperature (Tg), elasticmodulus (G′) and creep resistance. The robustness of metal coordination is demonstrated by varying metal ion, counter anion, and coordinating imine ligand. All variations in metal or anion significantly enhance the material properties. The Tg and G′ of the CANs are correlated to the coordination bond strength, offering a tunable handle by which choice of metal can steer material properties. Additionally, large differences in Tg and G′ are observed for materials with different anions, which are mostly linked to the anion size. This serves as a reminder that for coordination chemistry in the bulk, not onlythe metal ion is to be considered, but also the accompanying anion. Finally, the reinforcing effect of metal coordination is proved insensitive to the metal–ligand ratio, emphasizing the robustness of the applied method.

Piperazine rings are essential motifs frequently found in commercial drugs. However, synthetic methodologies are mainly limited to N-substituted piperazines, preventing structural diversity. Disclosed herein is a straightforward catalytic method for the synthesis of complex C-substituted piperazines based on an uncommon head-to-head coupling of easily prepared imines. This 100% atom-economic process allows the selective formation of a sole diastereoisomer, a broad substrate scope, and a good functional group tolerance employing a bench-stable iridium catalyst under mild reaction conditions. Key to the success is the addition of N-oxides to the reaction mixture, as they notably enhance the catalytic activity and selectivity.

2 + 2 Photocycloadditions are idealized, convergent construction approaches of 4-membered heterocyclic rings, including azetidines. However, methods of direct excitation are limited by the unfavorable photophysical properties of imines and electronically unbiased alkenes. Here, we report copper-catalyzed photocycloadditions of non-conjugated imines and alkenes to produce a variety of substituted azetidines. Design principles allow this base metal-catalyzed method to achieve 2 + 2 imine-olefin photocycloaddition via selective alkene activation through a coordination-MLCT pathway supported by combined experimental and computational mechanistic studies.

2 + 2 Photocycloadditions are idealized, convergent construction approaches of 4-membered heterocyclic rings, including azetidines. However, methods of direct excitation are limited by the unfavorable photophysical properties of imines and electronically unbiased alkenes. Here, we report copper-catalyzed photocycloadditions of non-conjugated imines and alkenes to produce a variety of substituted azetidines. Design principles allow this base metal-catalyzed method to achieve 2 + 2 imine-olefin photocycloaddition via selective alkene activation through a coordination-MLCT pathway supported by combined experimental and computational mechanistic studies.

Growing interest in sustainable sources of chemicals and energy from renewable and reliable sources has stimulated the design and synthesis of renewable Schiff-base (iminium) ionic liquids (ILs) to replace fossil-derived ILs. In this study, we report on the synthesis of three unique iminium-acetate ILs from lignin-derived aldehyde for a sustainable "future" lignocellulosic biorefinery. The synthesized ILs contained only imines or imines along with amines in their structure; the ILs with only imines group exhibited better pretreatment efficacy, achieving >89% sugar release. Various analytical and computational tools were employed to understand the pretreatment efficacy of these ILs. This is the first study to demonstrate the ease of synthesis of these renewable ILs, and therefore, opens the door for a new class of "Schiff-base ILs" for further investigation that could also be designed to be task specific.

Turning thermosets into fully sustainable materials requires utilization of biobased raw materials and design for easy recyclability. Here, dynamic covalent chemistry for fabrication of covalent adaptable networks (CANs) could be an enabling tool. CAN thermosets ideally combine the positive material properties of thermosets with thermal recyclability of linear thermoplastics. Among the dynamic covalent bonds, imine bond, also called Schiff base, can participate in both dissociative and associative pathways. This induces potential for chemical recyclability, thermal reprocessability and self-healing. This review presents an overview of the current research front of biobased thermosets fabricated by Schiff base chemistry. The discussed materials are categorized on the basis of the employed biobased components. The chemical approaches for the synthesis and curing of the resins, as well as the resulting properties and recyclability of the obtained thermosets are described and discussed. Finally, challenges and future perspectives are briefly summarized., QC 20230612

The metalcycles are compounds that are contained within organometallic chemistry and that can have a very different nature depending on the metal as well as on the ligands attached to it; Due to this, their properties and reactivity cover a large field of research. In this work, the study of this type of compounds using nitrogen and phosphorus ligands, which may have very different characteristics, will be addressed. This allows the design of the synthesis of families of compounds that have the usual properties and applications of the metalcycles, such as their use as catalysts in industrial processes, the evaluation of their potential cytotoxicity or luminescent properties related mainly to metal.

Closed-loop recycling of polymers represents the key technology to convert plastic waste in a sustainable fashion. Efficient chemical recycling and upcycling strategies are thus highly sought-after to establish a circular plastic economy. Here, we present the selective chemical depolymerization of polycarbonate by employing a vanillin derivative as bio-based feedstock. The resulting di-vanillin carbonate monomer was used in combination with various amines to construct a library of reprocessable poly(imine-carbonate)s, which show tailor-made thermal and mechanical properties. These novel poly(iminecarbonate) s exhibit excellent recyclability under acidic and energy-efficient conditions. This allows the recovery of monomers in high yields and purity for immediate reuse, even when mixed with various commodity plastics. This work provides exciting new insights in the design of bio-based circular polymers produced by upcycling of plastic waste with minimal environmental impact., Closed-loop recycling of polymers represents the key technology to convert plastic waste in a sustainable fashion. Efficient chemical recycling and upcycling strategies are thus highly sought-after to establish a circular plastic economy. Here, we present the selective chemical depolymerization of polycarbonate by employing a vanillin derivative as bio-based feedstock. The resulting di-vanillin carbonate monomer was used in combination with various amines to construct a library of reprocessable poly(imine-carbonate)s, which show tailor-made thermal and mechanical properties. These novel poly(imine-carbonate)s exhibit excellent recyclability under acidic and energy-efficient conditions. This allows the recovery of monomers in high yields and purity for immediate reuse, even when mixed with various commodity plastics. This work provides exciting new insights in the design of bio-based circular polymers produced by upcycling of plastic waste with minimal environmental impact.

Density functional theory computations have elucidated the mechanism and origins of stereoselectivity in McGlacken's aldol-Tishchenko reaction for the diastereoselective synthesis of 1,3-amino alcohols using Ellman's t-butylsulfinimines as chiral auxiliaries. Variations of stereochemical outcome are dependent on the nature of the ketone starting materials used, and the aspects leading to these differences have been rationalized. The intramolecular hydride transfer step is the rate- and stereochemistry-determining step, and all prior steps are reversible.

[Resumen] En la actualidad, el autoensamblaje de moléculas a través de interacciones covalentes se ha postulado como una herramienta de gran utilidad para la síntesis de nuevos receptores moleculares, que son de gran interés en biomedicina por su versatilidad y múltiples aplicaciones. Específicamente, los complejos host-guest resultan especialmente interesantes, ya que pueden responder a estímulos externos como cambios en el medio celular externo y ser modulados para su utilización como sistemas de liberación controlada de fármacos. Entre estos compuestos, destaca el macrociclo red box cuya capacidad aceptora puede ser modulada mediante reacciones redox y cambios de pH, con el fin de maximizar su potencial como vehículo de liberación controlada de fármacos en aplicaciones biomédicas. Como primer paso para evaluar el potencial de la red box como sistema de liberación de fármacos, en el presente estudio se evaluó su biocompatibilidad mediante la realización de ensayos biológicos basados en medidas de la viabilidad celular y citotoxicidad en una línea celular normal (HFF-1) y otra tumoral (HeLa). Además, para confirmar que el macrociclo es capaz de atravesar la membrana plasmática, se llevó a cabo un estudio de internalización celular. Los resultados mostraron que la red box afectó en mayor medida a la viabilidad y proliferación celular de la línea no tumoral, lo cual podría estar relacionado con la mayor velocidad de división de las células cancerosas y/o una mayor permeabilidad al compuesto de la línea no tumoral. Asimismo, el estudio preliminar de internalización celular en células HeLa reveló la entrada de un pequeño porcentaje de red box en el interior de las células siendo mayor a las 24 h de exposición., [Resumo] Na actualidade, a autoensamblaxe de moléculas a través de interaccións covalentes postulouse como unha ferramenta de gran utilidade para a síntese de novos receptores moleculares, que son de gran interese en biomedicina pola súa versatilidade e múltiples aplicacións. Especificamente, os complexos host-guest resultan especialmente interesantes, xa que poden responder a estímulos externos, coma cambios no medio celular externo e ser modulados para a súa utilización como sistemas de liberación controlada de fármacos. Entre estes compostos, destaca o macrociclo red box cuxa capacidade aceptora pode ser modulada mediante reaccións redox e cambios de pH, co fin de maximizar o seu potencial como vehículo de liberación controlada de fármacos en aplicacións biomédicas. Como primeiro paso para avaliar o potencial da red box como sistema de liberación de fármacos, no presente estudo avaliouse a súa biocompatibilidade mediante a realización de ensaios biolóxicos baseados en medidas da viabilidade celular e citotoxicidade nunha liña celular normal (HFF-1) e outra tumoral (HeLa). Ademais, para confirmar que o macrociclo é capaz de atravesar a membrana plasmática, levouse a cabo un estudo de internalización celular. Os resultados mostraron que a red box afectou en maior medida á viabilidade e proliferación celular da liña non tumoral, o cal podería estar relacionado coa maior velocidade de división das células cancerosas e/ou unha maior permeabilidade ao composto da liña non tumoral. Así mesmo, o estudo preliminar de internalización celular en células HeLa revelou a entrada dun pequeno porcentaxe de red box no interior das células sendo maior ás 24 h de exposición., [Abstract] Nowadays, self-assembly of molecules through covalent interactions has been postulated as a very useful tool for the synthesis of new molecular receptors, being of great interest in biomedicine due to their versatility and multiple applications. Specifically, hostguest complexes are especially interesting, since they can respond to external stimuli as those from the external cellular environment and be modulated for their use as controlled drug delivery systems. Among these compounds, the macrocycle red box, whose acceptor capacity can be modulated by redox reactions and changes in pH to maximize its potential as a vehicle for controlled drug delivery in biomedical applications, is of great interest. As a first step to evaluate its potential as a drug delivery system, in the present study the biocompatibility of red box was evaluated by conducting biological assays based on measurements of cell viability and cytotoxicity in a normal cell (HFF-1) and in a tumor cell (HeLa) lines. Furthermore, to confirm the macrocycle capability to cross the cell membrane, a cell internalization study was carried out. The results showed that the red box affected the cell viability and proliferation of the non-tumor line to a greater extent, which could be related to the higher division rate of cancer cells and/or the major permeability to the compound of the non-tumor line. Likewise, the preliminary study of cellular internalization in HeLa cells revealed the entry of a small percentage of red box inside the cells, being higher after 24 h of exposure.

The stabilisation of metal nanoparticles and control of their oxidation state are crucial factors in nanocatalysis. Elemental sulfur has been found to be a cheap and effective stabilising agent for copper nanoparticles in the form of copper(I) oxide. The Cu2ONPs/S8 system has been characterised by ICP-OES, EDX, XRD, XPS, FE-SEM, SEM, TEM and Cryo-EM. Astonishingly, in organic medium, the copper nanoparticles are organised as concentric rings within nanodroplets of sulfur of ca. 20–70 nm. In synthetic organic chemistry, imines can be directly obtained by the less studied and practiced oxidation of primary amines; however, the reaction conditions utilised are usually harsh and far from meeting the principles of Green Chemistry. Cu2ONPs/S8 has been successfully applied to the solvent-free aerobic oxidation of primary amines to imines under ambient conditions, using air as a terminal oxidant. The catalyst is effective in the homo- and heterocoupling of benzylic amines at very low copper loading (0.3 mol%), being catalytically superior to a range of commercial copper catalysts. A reaction mechanism has been proposed based on experimental evidence, which clarifies the major uncertainty regarding the key intermediate. The results of this study suggest a number of new avenues for research in nanocatalysis.

Palladium-metalated PCN-222 enables the aerobic photo-oxidative cross-condensation of anilines with benzylic amines yielding a series of linear and cyclic imines. The reaction is very efficient under mild conditions, which allows the isolation of simple, yet elusive, intermediates such as 2-(benzylideneamino)-aniline and 2-(benzylideneamino)phenols. Recyclability studies show excellent activity and selectivity after five runs. The methodology was successfully applied for the synthesis of an antitumor agent (PMX-610).

Nonheme iron oxygenases utilize dioxygen to accomplish challenging chemical oxidations. A further understanding of the Fe-O2 intermediates implicated in these processes is challenged by their highly transient nature. To that end, we have developed a ligand platform featuring phosphinimide donors intended to stabilize oxidized, high-spin iron complexes. O2 exposure of single crystals of a three-coordinate Fe(II) complex of this framework allowed for in crystallo trapping of a terminally bound Fe-O2 complex suitable for XRD characterization. Spectroscopic and computational studies of this species support a high-spin Fe(III) center antiferromagnetically coupled to a superoxide ligand, similar to that proposed for numerous nonheme iron oxygenases. In addition to the apparent stability of this synthetic Fe-O2 complex, its ability to engage in a range of stoichiometric and catalytic oxidation processes demonstrates that this iron-phosphinimide system is primed for development in modeling oxidizing bioinorganic intermediates and green oxidation chemistry.

Density functional theory computations have elucidated the mechanism and origins of stereoselectivity in McGlacken's aldol-Tishchenko reaction for the diastereoselective synthesis of 1,3-amino alcohols using Ellman's t-butylsulfinimines as chiral auxiliaries. Variations of stereochemical outcome are dependent on the nature of the ketone starting materials used, and the aspects leading to these differences have been rationalized. The intramolecular hydride transfer step is the rate- and stereochemistry-determining step, and all prior steps are reversible.

The stabilisation of metal nanoparticles and control of their oxidation state are crucial factors in nanocatalysis. Elemental sulfur has been found to be a cheap and effective stabilising agent for copper nanoparticles in the form of copper(I) oxide. The Cu2ONPs/S8 system has been characterised by ICP-OES, EDX, XRD, XPS, FE-SEM, SEM, TEM and Cryo-EM. Astonishingly, in organic medium, the copper nanoparticles are organised as concentric rings within nanodroplets of sulfur of ca. 20–70 nm. In synthetic organic chemistry, imines can be directly obtained by the less studied and practiced oxidation of primary amines; however, the reaction conditions utilised are usually harsh and far from meeting the principles of Green Chemistry. Cu2ONPs/S8 has been successfully applied to the solvent-free aerobic oxidation of primary amines to imines under ambient conditions, using air as a terminal oxidant. The catalyst is effective in the homo- and heterocoupling of benzylic amines at very low copper loading (0.3 mol%), being catalytically superior to a range of commercial copper catalysts. A reaction mechanism has been proposed based on experimental evidence, which clarifies the major uncertainty regarding the key intermediate. The results of this study suggest a number of new avenues for research in nanocatalysis.

[Resumen] En la actualidad, el autoensamblaje de moléculas a través de interacciones covalentes se ha postulado como una herramienta de gran utilidad para la síntesis de nuevos receptores moleculares, que son de gran interés en biomedicina por su versatilidad y múltiples aplicaciones. Específicamente, los complejos host-guest resultan especialmente interesantes, ya que pueden responder a estímulos externos como cambios en el medio celular externo y ser modulados para su utilización como sistemas de liberación controlada de fármacos. Entre estos compuestos, destaca el macrociclo red box cuya capacidad aceptora puede ser modulada mediante reacciones redox y cambios de pH, con el fin de maximizar su potencial como vehículo de liberación controlada de fármacos en aplicaciones biomédicas. Como primer paso para evaluar el potencial de la red box como sistema de liberación de fármacos, en el presente estudio se evaluó su biocompatibilidad mediante la realización de ensayos biológicos basados en medidas de la viabilidad celular y citotoxicidad en una línea celular normal (HFF-1) y otra tumoral (HeLa). Además, para confirmar que el macrociclo es capaz de atravesar la membrana plasmática, se llevó a cabo un estudio de internalización celular. Los resultados mostraron que la red box afectó en mayor medida a la viabilidad y proliferación celular de la línea no tumoral, lo cual podría estar relacionado con la mayor velocidad de división de las células cancerosas y/o una mayor permeabilidad al compuesto de la línea no tumoral. Asimismo, el estudio preliminar de internalización celular en células HeLa reveló la entrada de un pequeño porcentaje de red box en el interior de las células siendo mayor a las 24 h de exposición., [Resumo] Na actualidade, a autoensamblaxe de moléculas a través de interaccións covalentes postulouse como unha ferramenta de gran utilidade para a síntese de novos receptores moleculares, que son de gran interese en biomedicina pola súa versatilidade e múltiples aplicacións. Especificamente, os complexos host-guest resultan especialmente interesantes, xa que poden responder a estímulos externos, coma cambios no medio celular externo e ser modulados para a súa utilización como sistemas de liberación controlada de fármacos. Entre estes compostos, destaca o macrociclo red box cuxa capacidade aceptora pode ser modulada mediante reaccións redox e cambios de pH, co fin de maximizar o seu potencial como vehículo de liberación controlada de fármacos en aplicacións biomédicas. Como primeiro paso para avaliar o potencial da red box como sistema de liberación de fármacos, no presente estudo avaliouse a súa biocompatibilidade mediante a realización de ensaios biolóxicos baseados en medidas da viabilidade celular e citotoxicidade nunha liña celular normal (HFF-1) e outra tumoral (HeLa). Ademais, para confirmar que o macrociclo é capaz de atravesar a membrana plasmática, levouse a cabo un estudo de internalización celular. Os resultados mostraron que a red box afectou en maior medida á viabilidade e proliferación celular da liña non tumoral, o cal podería estar relacionado coa maior velocidade de división das células cancerosas e/ou unha maior permeabilidade ao composto da liña non tumoral. Así mesmo, o estudo preliminar de internalización celular en células HeLa revelou a entrada dun pequeno porcentaxe de red box no interior das células sendo maior ás 24 h de exposición., [Abstract] Nowadays, self-assembly of molecules through covalent interactions has been postulated as a very useful tool for the synthesis of new molecular receptors, being of great interest in biomedicine due to their versatility and multiple applications. Specifically, hostguest complexes are especially interesting, since they can respond to external stimuli as those from the external cellular environment and be modulated for their use as controlled drug delivery systems. Among these compounds, the macrocycle red box, whose acceptor capacity can be modulated by redox reactions and changes in pH to maximize its potential as a vehicle for controlled drug delivery in biomedical applications, is of great interest. As a first step to evaluate its potential as a drug delivery system, in the present study the biocompatibility of red box was evaluated by conducting biological assays based on measurements of cell viability and cytotoxicity in a normal cell (HFF-1) and in a tumor cell (HeLa) lines. Furthermore, to confirm the macrocycle capability to cross the cell membrane, a cell internalization study was carried out. The results showed that the red box affected the cell viability and proliferation of the non-tumor line to a greater extent, which could be related to the higher division rate of cancer cells and/or the major permeability to the compound of the non-tumor line. Likewise, the preliminary study of cellular internalization in HeLa cells revealed the entry of a small percentage of red box inside the cells, being higher after 24 h of exposure.

Tato bakalářská práce se zabývá způsoby syntézy azo látek, iminů a jejich fotochemických vlastností. V rešeršní části práce jsou popsány možné syntézy azo látek a iminů a jejich fotochemické vlastnosti. V experimentální části je popsána syntéza 1-(4-methoxyfenyl)-N-fenyl-1-[4-(trifluormethyl)fenyl]methaniminu a 1-([1,1´-bifenyl]-2-yl)-2-(2,6-difluorfenyl)diazenu. Následně jsou zkoumány jejich fotochemické vlastnosti a reaktivita s palladnatými solemi., This bachelor thesis is focused on the methods of synthesis of azo compounds, imines and their photochemical properties. The theoretical part of the thesis describes possible syntheses of azo compounds and imines and their photochemical properties. The experimental part describes the synthesis of 1-(4-methoxyphenyl)-N-phenyl-1-[4-(trifluoromethyl)phenyl]methanimine and 1-([1,1´-biphenyl]-2-yl)-2-(2,6-difluorophenyl)diazene. Subsequently, their photochemical properties and reactivity with palladium salts are investigated., Fakulta chemicko-technologická, Studentka prezentovala svoji bakalářskou práci a vyjádřila se k připomínkám., Dokončená práce s úspěšnou obhajobou

In this chapter, we describe the development in homogeneous Ir-catalyzed asymmetric hydrogenation with particular emphasis on the achievements made during the last 10 years. We also present their application to the synthesis of complex molecules. The first section deals with the hydrogenation of unfunctionalized olefins or with poorly coordinative groups. The second section includes the advances made in the hydrogenation of functionalized olefins. The last two sections cover the hydrogenation of imines and ketones, respectively.

[Abstract] Graphene-based materials are particularly suitable platforms for the development of new systems able to release drugs upon the application of controlled electrochemical stimuli. Herein, we report a new electro-responsive graphene carrier functionalised with aldehydes (as drug models) through imine-based linkers. We explore a new type of drug loading/release combination based on the formation of a covalent bond and its cleavage upon electrolysis. The new graphene–drug model hybrid is stable under physiological conditions and displays a fast drug release upon the application of low voltages.

The straightforward synthesis of N,N-disubstituted formamides using a combination of 1,1,1,3,3,3-hexafluoroispropanol (HFIP) and H2O2 is described. The unique features of HFIP allowed the utilization of a green oxidant such as H2O2, and the products, arising from an oxidation–rearrangement sequence, were obtained in good to high yields under smooth reaction conditions.

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.

The straightforward synthesis of N,N-disubstituted formamides using a combination of 1,1,1,3,3,3-hexafluoroispropanol (HFIP) and H2O2 is described. The unique features of HFIP allowed the utilization of a green oxidant such as H2O2, and the products, arising from an oxidation–rearrangement sequence, were obtained in good to high yields under smooth reaction conditions.

In recent years, five-membered ring cyclic sulfamidate imines (5H-1,2,3-oxathiazole 2,2-dioxides) have received increasing attention as useful precursors for the stereoselective synthesis of many valuable heterocycles. Bearing a reactive N-sulfonyl imine moiety as part of the stereodefined skeleton, this sulfamidate imine platform has been utilised as a substrate in many reactions, including nucleophilic additions and reductions, to prepare highly functionalised cyclic sulfamidates. In addition, cyclic sulfamidate imines can also readily participate as nucleophiles in many chemical transformations, owing to the reactivity of the acidic proton(s) adjacent to the imine moiety. This short review highlights recent developments involving cyclic sulfamidate imines, including their synthesis and their diastereoselective and enantioselective chemical reactions.

Herein, we demonstrate the first example of a multistep solid-state organic synthesis, in which a new imine-linked two-dimensional covalent organic framework (COF-170, 1) was transformed through three consecutive postsynthetic modifications into porous, crystalline cyclic carbamate and thiocarbamate-linked frameworks. These linkages are previously unreported and inaccessible through de novo synthesis. While not altering the overall connectivity of the framework, these chemical transformations induce significant conformational and structural changes at each step, highlighting the key importance of noncovalent interactions and conformational flexibility to COF crystallinity and porosity. These transformations were assessed using 15N multiCP-MAS NMR spectroscopy, providing the first quantitation of yields in COF postsynthetic modification reactions, as well as of amine defect sites in imine-linked COFs. This multistep COF linkage postsynthetic modification represents a significant step toward bringing the precision of organic solution-phase synthesis to extended solid-state compounds.

The Davis-Beirut reaction provides access to 2H-indazoles from aromatic nitro compounds. However, N-aryl targets have been traditionally challenging to access due to competitive alternate reaction pathways. Previously, the key nitroso imine intermediate was generated under alkaline conditions, but as reported here, the photochemistry of o-nitrobenzyl alcohols empowered Brønsted acid catalyzed conditions for accessing N-aryl targets. Anilines and alkyl amines give different outcomes under optimized conditions; the proposed mechanism was studied using quantum chemical calculations.

Primary amines have been subjected to an acceptorless dehydrogenative homo‐ and heterocoupling into imines with a cobalt catalyst. The catalytically active species are composed of cobalt nanoparticles, which are generated in situ by heating Co2(CO)8 in the presence of trioctylphosphine oxide as a surfactant. The nanoparticles have been characterized by transmission electron microscopy where the image showed spherical and small particles with a narrow size distribution. The catalyst can be recovered and used again with essentially no effect on the yield. The catalyst can also be used for the dehydrogenative coupling of alcohols and amines into imines.

An in situ formed cobalt catalyst is developed from cobalt(II)bromide, bis[2-(diisopropylphosphino)-4-methylphenyl]amine and zinc metal. The catalyst mediates the acceptorless dehydrogenative coupling of alcohols and amines into imines with the release of hydrogen gas and the transformation is applied to the synthesis of a variety of imines from different alcohols and amines. The mechanism is investigated with labelled substrates and based on the results a cobalt(I) PNP complex is believed to be the catalytically active species which abstracts hydrogen gas from the alcohol through a metal ligand bifunctional pathway.

A simple methodology for the synthesis of enynes by indium mediated diastereoselective allylation of aromatic N-tert-butanesulfinylimines bearing alkenyl groups at ortho-position with allyl bromide has been developed. The addition of the allyl indium intermediate to the chiral imine took place with excellent diastereoselectivity. Ruthenium-catalyzed ring-closing metathesis of the resulting enynes provided the expected cyclic 1,3-dienes in good to moderate yields. These chiral dienes are potential precursors of biologically and pharmacologically active morphane derivatives.

A new catalytic method for separating enantiomers of racemic compounds is proposed. Catalytic asymmetric addition of chiral trans-2-substituted cyclohexanols to imines provided diastereomeric mixtures of aminals, and the subsequent separation of the enantiomers by silicagel column chromatography and the hydrolysis of the aminals produced the alcohols in an optically active form.

A green method for epoxidation of imines using an environmentally benign oxidant system, H2O2/dimethyl carbonate, was developed. N-Alkyloxaziridines were prepared in high yields from N-alkylamines and (hetero)aromatic aldehydes in one-pot fashion, whereas N-sulfonyloxaziridines have been prepared by using the same oxidant system and 5 mol% of Zn(OAc)2·2H2O as catalyst.

Reaction options, alkoxide vs hydroxide vs amine addition to the key intermediate (o-nitrosoimine) generated in the Davis-Beirut reaction of an o-nitrobenzylamine substrate, are reported to explain the nucleophilic addition selectivity of this one-pot indazole-forming process. The hydroxide addition/deprotection pathway as well as the fate of the resulting o-nitrosobenzaldehyde were both uncovered with several o-nitrobenzylamine substrates, and design elements required for an efficient double Davis-Beirut reaction, inspired by new mechanistic insights, were defined.

A simple methodology for the synthesis of enynes by indium mediated diastereoselective allylation of aromatic N-tert-butanesulfinylimines bearing alkenyl groups at ortho-position with allyl bromide has been developed. The addition of the allyl indium intermediate to the chiral imine took place with excellent diastereoselectivity. Ruthenium-catalyzed ring-closing metathesis of the resulting enynes provided the expected cyclic 1,3-dienes in good to moderate yields. These chiral dienes are potential precursors of biologically and pharmacologically active morphane derivatives.

Direct hydroxymethylation of C=N double bonds including imines, nitrones, oximes, hydrazones and iminium salts is a less explored synthetic approach to 1,2-amino alcohols that provides good alternatives to the classical methods. The review deals with nucleophilic additions of organometallic hydroxymethyl reagents and lithiated alkoxyallenes to C=N double bonds. Reductive cross couplings between C=N double bonds and aldehydes or ketones are also discussed.

An efficient procedure for the direct arylation of pyrrolidine with phenols and naphtols is reported. Upon reaction with catalytic amounts of a binuclear copper(II)-7-azaindole complex under an atmosphere of oxygen, pyrrolidine is smoothly oxidized to the corresponding imine which can be trapped in situ by a series of phenols and naphtols in fair to good yields. This copper-catalyzed direct oxidative arylation of pyrrolidine offers an efficient entry to alpha-aryl-pyrrolidines in a single step and without the need for protecting or directing groups., SCOPUS: le.j, info:eu-repo/semantics/published

The geometries, stabilities, and 1,3-dipolar cycloaddition reactivities of 24 mesoionic azomethine ylides and imines were investigated using density functional theory calculations at the M06-2X/6-311+G-(d,p)/M06-2X/6-31G-(d) level. The computed structures highlight how the commonly used "aromatic" resonance form should be replaced by two more accurate resonance structures. Stabilities of the dipoles were assessed by various homodesmotic schemes and are consistent with these compounds being nonaromatic. The activation free energies with ethylene or acetylene range from 11.8 to 36.6 kcal/mol. Within each dipole type, the predicted cycloaddition reactivities correlate with the reaction energies and the resonance stabilization energies provided by the various substituents. Endocyclic (X) heteroatoms increase the reactivity of the 1,3-dipoles in the order of O > NH ≅ S, whereas exocyclic (Y) substituents increase it in the order of CH2 > NH > O > S. Distortion/interaction analysis indicated that the difference in reactivity between differently substituted 1,3-dipoles is driven by distortion, whereas the difference between azomethine ylides and imines is related to lower interaction energies of imines with the dipolarophiles.

We present an overview of the toxicological profile of the fast-acting, lipophilic macrocyclic imine toxins, an emerging family of organic compounds associated with algal blooms, shellfish contamination and neurotoxicity. Worldwide, shellfish contamination incidents are expanding; therefore, the significance of these toxins for the shellfish food industry deserves further study. Emphasis is directed to the dinoflagellate species involved in their production, their chemical structures, and their specific mode of interaction with their principal natural molecular targets, the nicotinic acetylcholine receptors, or with the soluble acetylcholine-binding protein, used as a surrogate receptor model. The dinoflagellates Karenia selliformis and Alexandrium ostenfeldii / A. peruvianum have been implicated in the biosynthesis of gymnodimines and spirolides, while Vulcanodinium rugosum is the producer of pinnatoxins and portimine. The cyclic imine toxins are characterized by a macrocyclic skeleton comprising 14-27 carbon atoms, flanked by two conserved moieties, the cyclic imine and the spiroketal ring system. These phycotoxins generally display high affinity and broad specificity for the muscle type and neuronal nicotinic acetylcholine receptors, a feature consistent with their binding site at the receptor subunit interfaces, composed of residues highly conserved among all nAChRs, and explaining the diverse toxicity among animal species. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

Allenyl- and propargylboronates have emerged as versatile reagents to effect regioselective propargylation or allenylation reactions of aldehydes, ketones, imines, and iminium ions. These boron-­derived reagents have the ability to undergo transmetalation reactions with other metals (Ag, Cu, In, and Zn), often using only catalytic amounts of these metals, leading to more facile and highly regioselective reactions. Enantioselective organocatalyzed reactions have also been developed using, chiral diols, aminophenols, and phosphoric ­acids. This short review highlights recent developments in this area.

Allenyl- and propargylboronates have emerged as versatile reagents to effect regioselective propargylation or allenylation reactions of aldehydes, ketones, imines, and iminium ions. These boron-­derived reagents have the ability to undergo transmetalation reactions with other metals (Ag, Cu, In, and Zn), often using only catalytic amounts of these metals, leading to more facile and highly regioselective reactions. Enantioselective organocatalyzed reactions have also been developed using, chiral diols, aminophenols, and phosphoric ­acids. This short review highlights recent developments in this area.

Allenyl- and propargylboronates have emerged as versatile reagents to effect regioselective propargylation or allenylation reactions of aldehydes, ketones, imines, and iminium ions. These boron-­derived reagents have the ability to undergo transmetalation reactions with other metals (Ag, Cu, In, and Zn), often using only catalytic amounts of these metals, leading to more facile and highly regioselective reactions. Enantioselective organocatalyzed reactions have also been developed using, chiral diols, aminophenols, and phosphoric ­acids. This short review highlights recent developments in this area.

The copper-catalyzed intermolecular enantioselective addition of styrenes to imines has been achieved under mild conditions at ambient temperature. This process features the use of styrenes as latent carbanion equivalents via the intermediacy of catalytically generated benzylcopper derivatives, providing an effective means for accessing highly enantiomerically enriched amines bearing contiguous stereocenters. Mechanistic studies shed light on the origin of the preferential styrene hydrocupration in the presence of an imine with the Ph-BPE-derived copper catalyst.

Synthetic elicitors are drug-like compounds that are structurally distinct from natural defense elicitors. They can protect plants from diseases by activating host immune responses and can serve as tools for the dissection of the plant immune system as well as leads for the development of environmentally-safe pesticide alternatives. By high-throughput screening, we previously identified 114 synthetic elicitors that activate expression of the pathogen-responsive CaBP22(-333)::GUS reporter gene in Arabidopsis thaliana (Arabidopsis), 33 of which are [(phenylimino)methyl]phenol (PMP) derivatives or PMP-related compounds. Here we report on the characterization of one of these compounds, 2,4-dichloro-6-{(E)-[(3-methoxyphenyl)imino]methyl}phenol (DPMP). DPMP strongly triggers disease resistance of Arabidopsis against bacterial and oomycete pathogens. By mRNA-seq analysis we found transcriptional profiles triggered by DPMP to resemble typical defense-related responses.

The following herein introduces a Ni(0) catalyst that effectively does hydrosilylation of imines to form the corresponding aminosilanes which are of interest in the electronics industry. Preliminary studies of bis-1,5-cyclooctadienyl nickel(0), Ni(COD)2, showed it to be an effective catalyst with relatively good conversion at room temperature and low catalyst loadings (~3%). However, selectively for the aminosilane was limited since there was a significant amount of conversion to the corresponding amine. To circumvent amine production, a combination of using a reengineered Ni(0) catalyst and a new silane was used. Ni(COD)2 was reacted with two equivalents of the sterically encumbering m-terphenyl isocyanide CNArMes2 (ArMes2 = 2,6-(2,4,6-Me3C6H2)2C6H3) to form Ni(COD)(CNArMes2)2. In turn, it was used in the catalyst studies showing less propensity to dehydrocouple and a better selectively for the desired aminosilane. Using hexylsilane in place of phenylsilane led to further improvement, showing complete selectivity for the aminosilane. A scope of imines was explored and showed rather consistent reaction rates (t = 2hr) at room temperature at low catalyst loading (3-2.5%). Studies were carried out to try and isolate an intermediate in the catalytic cycle where oxidative addition occurs of Ni(COD)(CNArMes2)2 with the silane. Insight is given into the possible mechanism.

The copper-catalyzed intermolecular enantioselective addition of styrenes to imines has been achieved under mild conditions at ambient temperature. This process features the use of styrenes as latent carbanion equivalents via the intermediacy of catalytically generated benzylcopper derivatives, providing an effective means for accessing highly enantiomerically enriched amines bearing contiguous stereocenters. Mechanistic studies shed light on the origin of the preferential styrene hydrocupration in the presence of an imine with the Ph-BPE-derived copper catalyst.

A green method for epoxidation of imines using an environmentally benign oxidant system, H2O2/dimethyl carbonate, was developed. N-Alkyloxaziridines were prepared in high yields from N-alkylamines and (hetero)aromatic aldehydes in one-pot fashion, whereas N-sulfonyloxaziridines have been prepared by using the same oxidant system and 5 mol% of Zn(OAc)2·2H2O as catalyst.

The reaction of epoxides with tert-butanesulfinamide in the presence of a Lewis acid, such as erbium triflate or boron trifluoride–diethyl ether, in THF as solvent, under microwave or thermal activation, produces N-tert-butylsulfinylimines in reasonable yields. Aromatic and gem-disubstituted and trisubstituted alkyl epoxides performed better than mono-alkyl-substituted compounds. After imine formation, a subsequent indium-promoted allylation can be carried out in the same reaction flask in a single synthetic operation leading to homoallylamine derivatives with generally high yields.

The following herein introduces a Ni(0) catalyst that effectively does hydrosilylation of imines to form the corresponding aminosilanes which are of interest in the electronics industry. Preliminary studies of bis-1,5-cyclooctadienyl nickel(0), Ni(COD)2, showed it to be an effective catalyst with relatively good conversion at room temperature and low catalyst loadings (~3%). However, selectively for the aminosilane was limited since there was a significant amount of conversion to the corresponding amine. To circumvent amine production, a combination of using a reengineered Ni(0) catalyst and a new silane was used. Ni(COD)2 was reacted with two equivalents of the sterically encumbering m-terphenyl isocyanide CNArMes2 (ArMes2 = 2,6-(2,4,6-Me3C6H2)2C6H3) to form Ni(COD)(CNArMes2)2. In turn, it was used in the catalyst studies showing less propensity to dehydrocouple and a better selectively for the desired aminosilane. Using hexylsilane in place of phenylsilane led to further improvement, showing complete selectivity for the aminosilane. A scope of imines was explored and showed rather consistent reaction rates (t = 2hr) at room temperature at low catalyst loading (3-2.5%). Studies were carried out to try and isolate an intermediate in the catalytic cycle where oxidative addition occurs of Ni(COD)(CNArMes2)2 with the silane. Insight is given into the possible mechanism.