Robby Vroemans

A synthesis route for cofacially linked homo- and heterotrimetallic trisporphyin complexes starting from pyrrole and benzaldehyde is presented in this work. Besides the novel aryl-based, trans-o-phenylene trisporphyrin, we investigated the respective cis-isomer as the first conformationally restricted planar-chiral trisporphyrin. The homotrimetallic Mn(III)-, Fe(III)-, Ni(II)-, Cu(II)-, Zn(II)- and Pd(II) complexes and the defined Ni(II)Fe(III)Ni(II) heterotrimetalic complex were synthesized, the metal ion insertion process studied and the resulting compounds investigated by e. g. UV-Vis, photoluminescence or high-resolution IMS measurements.

Abstract

We present a straightforward and generally applicable synthesis route for cofacially linked homo- and heterotrimetallic trisporphyin complexes. The protocol encompasses synthesising the first aryl-based, trans-o-phenylene trisporphyrin starting from pyrrole and benzaldehyde with an overall yield of 3.6 %. It also allows investigating the respective cis-isomer as the first conformationally restricted planar-chiral trisporphyrin. The free-base ligand was used in subsequent metalation reactions to afford the corresponding homotrimetallic Mn(III)-, Fe(III)-, Ni(II)-, Cu(II)-, Zn(II)- and Pd(II) complexes – additionally, a small adaptation of the protocol resulted in the defined Ni(II)Fe(III)Ni(II) complex in a total yield of 2.3 %. By monitoring Ni(II) insertion into the empty trimeric ligands, we affirmed that the outer porphyrin rings are filled before the internal ring. The molecular species were characterised by ¹H NMR, UV-Vis, photoluminescence, IR, MS, CID, and high-resolution IMS measurements.

A library of sixteen S-thiocarbamates was synthesized utilizing a newly discovered one-pot synthetic procedure starting from N-formamides, which omits isolation of the isocyanide intermediate. Experiments were conducted to investigate the mechanism and identify side-reactions and side-products. Finally, four norbornene-based thiocarbamates were polymerized by ring-opening metathesis polymerization (ROMP) and characterized thereafter.

Abstract

An efficient isocyanide-based synthesis of S-thiocarbamates was discovered and thoroughly investigated. The new reaction protocol is a one-pot procedure and allows the direct conversion of N-formamides into thiocarbamates by initial dehydration with p-toluene sulfonyl chloride to the respective isocyanide and subsequent addition of a sulfoxide component. Contrary to recent literature, which also uses isocyanides as starting material, but with other sulfur reagents than sulfoxides, in this protocol, no isolation and purification of the isocyanide component is necessary, thus significantly decreasing the environmental impact and increasing the efficiency of the synthesis. The new protocol was applied to synthesize a library of sixteen thiocarbamates, applying four N-formamides and four commercially available sulfoxides. Furthermore, experiments were conducted to investigate the reaction mechanism. Finally, four norbornene-based thiocarbamate monomers were prepared and applied in controlled ring-opening metathesis polymerization (ROMP) reactions. The polymers were characterized by size-exclusion chromatography (SEC) and their properties were investigated utilizing differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).

Synthesis
DOI: 10.1055/a-1547-0196

Cycloaddition reactions have emerged as rapid and powerful methods for constructing heterocycles and carbocycles. [3+2] Cyclo­additions of nitroalkenes with various 1,3-dipoles have been an interesting research area for many organic chemists. This review outlines the synthesis of N-substituted and NH-1,2,3-triazoles along with other five-membered N-heterocycles through cycloaddition reactions of nitro­alkenes.1 Introduction2 Synthesis of 1,2,3-Triazoles2.1 Synthesis of NH-1,2,3-Triazoles2.2 Synthesis of N-Substituted 1,2,3-Triazoles3 Synthesis of Pyrrolidines and Pyrroles4 Synthesis of Pyrazoles5 Conclusion
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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S,N co-doped carbon immobilized Co single atoms exhibit superior performance in amine self-coupling reaction, which can be attributed to the superiorities of such dual-site catalysts in boosting O₂ activation and amine adsorption, simultaneously.

Abstract

One of the most pressing challenges in single-atom catalysis is the manipulation of the coordination environment of central metals to maximize the catalyst performance. Herein, we fabricated a high-performance catalyst (Co-SNC) by introducing S into the neighboring position of the Co-N₄ coordination. The developed ball-milling method enabled large-scale synthesis, that over 4.7 g of Co-SNC can be produced in one pot. In benzylamine coupling reaction, Co-SNC exhibited the highest conversion of 97.5 % with 99 % selectivity toward N-benzylidenebenzylamine in 10 h among various Co catalysts. Density functional theory calculations revealed the crucial role of S atoms, which serve as the active sites for O₂ activation, leaving the Co atoms free to adsorb benzylamine. Consequently, the adsorption energies of O₂ and benzylamine were significantly increased. Our strategy suggests a feasible approach to enhance catalytic performance by delicately integrating dual active sites into a single catalyst unit.

Nature Chemistry, Published online: 13 August 2021; doi:10.1038/s41557-021-00754-7

Deracemization is an attractive approach in asymmetric synthesis, but it is challenging owing to thermodynamic and kinetic barriers. Here we describe a method for deracemization of alcohols based on tandem photochemical dehydrogenation and thermal enantioselective hydrogenation, using light as the only driving force.

Abstract

Deracemization of racemic chiral compounds is an attractive approach in asymmetric synthesis, but its development has been hindered by energetic and kinetic challenges. Here we describe a catalytic deracemization method for secondary benzylic alcohols which are important synthetic intermediates and end products for many industries. Driven by visible light only, this method is based on sequential photochemical dehydrogenation followed by enantioselective thermal hydrogenation. The combination of a heterogeneous dehydrogenation photocatalyst and a chiral molecular hydrogenation catalyst is essential to ensure two distinct pathways for the forward and reverse reactions. These reactions convert a large number of racemic aryl alkyl alcohols into their enantiomerically enriched forms in good yields and enantioselectivities.

Synthesis
DOI: 10.1055/a-1529-7678

Five-membered heterocyclic N-oxides attract special attention due to their significant potential applications in medicinal chemistry and advanced materials science. In this regard, novel methods for their synthesis and functionalization are in constant demand. In this short review, recent state-of-the-art achievements in the chemistry of isoxazoline N-oxides, 1,2,3-triazole 1-oxides and 1,2,5-oxadiazole 2-oxides are summarized. The main routes involving transition-metal-catalyzed and metal-free functionalization protocols along with mechanistic considerations are outlined. The transformations of these hetarene N-oxide rings as precursors to other nitrogen heterocyclic systems are also presented.1 Introduction2 Isoxazoline N-Oxides3 1,2,3-Triazole 1-Oxides4 1,2,5-Oxadiazole 2-Oxides5 Conclusion
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Phenols in the spotlight: Phenol and its derivatives are key moieties in organic chemistry. Conventionally, they are prepared through thermal functionalization strategies that present several drawbacks. Recently, alternative photochemical approaches have been implemented that involves phenols both as light-harvesting substrates or as photo-redox catalysts. This Minireview summarizes the most relevant examples within this field, highlighting the great versatility of simple phenolic frameworks in organic synthesis.

Abstract

Phenols (I) are extremely relevant chemical functionalities in natural, synthetic and industrial chemistry. Their corresponding electron-rich anions, namely phenolates (I), are characterized by interesting physicochemical properties that can be drastically altered upon light excitation. Specifically, phenolates (I) become strong reducing agents in the excited state and are able to generate reactive radicals from suitable precursors via single-electron transfer processes. Thus, these species can photochemically trigger strategic bond-forming reactions, including their direct aromatic C−H functionalization. Moreover, substituted phenolate anions can act as photocatalysts to enable synthetically useful organic transformations. An alternative mechanistic manifold is represented by the ability of phenolate derivatives I to form ground state electron donor-acceptor (EDA) complexes with electron-poor radical sources. These complementary scenarios have paved the way for the development of a wide range of relevant organic reactions. In this Minireview, we present the main examples of this research field, and give insight on emerging trends in phenols photocatalysis towards richer organic synthesis.

A novel method for structural modification by skeletal editing of secondary amines employs N-pivaloyloxy-N-alkoxyamide as a reagent. Single-atom N-deletion is a novel approach for constructing C−C bonds under N₂ extrusion and uses widely available secondary amines in late-stage skeletal modification enabling ring contraction and structure optimization of biologically active compounds.

Abstract

Late-stage modification is highly desirable for the diversification and modification of biologically active compounds. Peripheral editing (e.g., C−H activation) has been the predominant methodology, whereas skeletal editing is in its infancy. The single-atom N-deletion using anomeric amide reagents constitutes a powerful tool to modify the underlying molecular skeletons of secondary amines. N-pivaloyloxy-N-alkoxyamide is easily prepared on a large scale and promotes C−C bond formation in good yields under the extrusion of N₂ for a variety of (cyclic) aliphatic amines. The exploitation of widely available amines allows the use of existing amine synthesis protocols to translate into the construction of new C−C bonds, enabling ring contraction and the potential for structure optimization of biologically active compounds.

Escape from flatland. Increased saturation (fraction of sp³) is more likely to be successful when moving compounds through the drug development pipeline. Bridged nitrogen heterocycles have a huge potential in drug discovery, although long synthetic sequences are typically required. New step-economic and selective organic syntheses are therefore highly sought after. Bert U. W. Maes et al. describe in their Research Article on page 21988 the synthesis of the normorphan skeleton through challenging tandem catalysis. Cover design by Joris Snaet.

Nature Reviews Chemistry, Published online: 28 July 2021; doi:10.1038/s41570-021-00318-w

Abstract

Copper(II)-mediated unprecedented intermolecular radical [3+2] annulation of N,N-dimethyl enaminones has been developed. The protocol is promoted simply by copper(II) chloride to access 5-acyl-3-furancarboxaldehydes with acceptable to good yields and broad substrate scope. This reaction allows the formation of multiple new bonds, including C(sp ²)−O bond between two nucleophilic sites, C(sp ²)−C(sp ²) bond and C=O bond, through a radical cyclization process. Moreover, gram-synthesis and application research show the potential application value of this transformation in industry.

Abstract

A variety of chromeno[4,3-c]isoxazolidines were prepared in good yields through visible light promoted Chan-Lam reaction and [3+2] cycloaddition cascade reaction in one pot. Mechanistic studies showed that visible light promoted both Chan-Lam reaction and cycloaddition. The obtained products were converted to various useful chromenone derivatives. Moreover, the reaction was easily performed at gram scales with the purification of products without column chromatography and used to efficiently synthesize estrone-derived chromeno[4,3-c]isoxazolidine.