Exploring the Building Block Potential of Readily Accessible Chiral Zn(salen) Complexes

The synthesis and full characterization of a series of chiral Zn(salen) complexes comprising a 1,2-diphenyl-ethane backbone is reported. The preparation method here reported simplifies the previously communicated methodology for these types of Zn complexes that utilized air-sensitive ZnEt2 (or alike) as metalating reagent. X-ray molecular structures are also reported for representative examples of this family of Zn(salen)s. A wide range of functionality is shown to be accessible via the present route, amplifying the potential use of these (Lewis acidic) Zn complexes as molecular building blocks. Examples in this work include the formation of supramolecular assemblies having built-in bifunctionality using versatile ZnN and ZnO coordination motifs as guiding tools

Organocatalyzed Domino [3+2] Cycloaddition/Payne-Type Rearrangement using Carbon Dioxide and Epoxy Alcohols

An unprecedented organocatalytic approach towards highly substituted cyclic carbonates from tri- and tetra-substituted oxiranes and carbon dioxide has been developed. The protocol involves the use of a simple and cheap superbase under mild, additive- and metal-free conditions towards the initial formation of a less substituted carbonate product that equilibrates to a tri- or even tetra-substituted cyclic carbonate under thermodynamic control. The latter are conveniently trapped in situ providing overall a new domino process for synthetically elusive heterocyclic scaffolds. Control experiments provide a rationale for the observed cascade reactions, which demonstrate high similarity with the well-known Payne rearrangement of epoxy alcohols

Multiple Halogenation of Aliphatic C-H Bonds within the Hofmann- Löffler Manifold

An innovative approach to position-selective polyhalogenation of aliphatic hydrocarbon bonds is presented. The reaction proceeds within the Hofmann-Löffler manifold with amidyl radicals as the sole mediators to induce selective 1,5- and 1,6- hydrogen atom transfer followed by halogenation. Multiple halogenation events of up to four innate C-H bond functionalizations have been accomplished. The broad applicability of this new entry into polyhalogenation and the resulting synthetic possibilities are demonstrated for a total of 27 different examples including mixed halogenations

Copolymerization of CO₂ and Cyclohexene Oxide Mediated by Yb(salen)-Based Complexes

New catalysts based on Yb­(salen) complexes active for the copolymerization of cyclohexene oxide (CHO) and CO₂ to give poly­(cyclo­hexene)­carbonate (PCHC) are reported. In combination with cocatalytic, nucleophilic chloride additives these new (binary) catalysts provided good conversion and selectivity for PCHC formation with average turnover frequencies of up to 35 h^–1 and narrow molecular weight distributions. The best results were obtained with the binary catalyst system <b>1</b> (0.1 mol %)/NBu₄Cl (0.05 mol %); at 90 °C a conversion of 57% was reached after 18 h with a TOF of 31 h^–1, and the polycarbonate had an <i>M</i>_n of 10.2 kg/mol and a PDI of 1.54. Comparative catalysis studies have also been performed with a series of literature systems based on transition metal/lanthanide salen complexes, and the newly presented catalysts show comparatively good activity as well as copolymerization selectivity. MALDI-ToF mass spectrometric analysis revealed that trace water contamination and/or traces of 1,2-cyclo­hexanediol were responsible for chain transfer effects limiting to some extent the maximum molecular weights that can be achieved in the current reactor setup

Copolymerization of CO₂ and Cyclohexene Oxide Mediated by Yb(salen)-Based Complexes

New catalysts based on Yb­(salen) complexes active for the copolymerization of cyclohexene oxide (CHO) and CO₂ to give poly­(cyclo­hexene)­carbonate (PCHC) are reported. In combination with cocatalytic, nucleophilic chloride additives these new (binary) catalysts provided good conversion and selectivity for PCHC formation with average turnover frequencies of up to 35 h^–1 and narrow molecular weight distributions. The best results were obtained with the binary catalyst system <b>1</b> (0.1 mol %)/NBu₄Cl (0.05 mol %); at 90 °C a conversion of 57% was reached after 18 h with a TOF of 31 h^–1, and the polycarbonate had an <i>M</i>_n of 10.2 kg/mol and a PDI of 1.54. Comparative catalysis studies have also been performed with a series of literature systems based on transition metal/lanthanide salen complexes, and the newly presented catalysts show comparatively good activity as well as copolymerization selectivity. MALDI-ToF mass spectrometric analysis revealed that trace water contamination and/or traces of 1,2-cyclo­hexanediol were responsible for chain transfer effects limiting to some extent the maximum molecular weights that can be achieved in the current reactor setup

Reactivity Control in Iron(III) Amino Triphenolate Complexes: Comparison of Monomeric and Dimeric Complexes

Iron­(III) amino triphenolate complexes with different substituents in the <i>ortho-</i>position of the phenolate moiety (R = H, Me, <i>t</i>Bu, or Ph) have been synthesized by the reaction of iron­(III) chloride and the sodium salt (Na₃L^R) of the requisite ligand. The complexes have been shown to be of either monomeric ([FeL^R(THF)]) or dimeric ([FeL^R]₂) nature by a combination of X-ray diffraction, ¹H NMR, solution magnetic susceptibility, and cyclic voltammetry studies. These analytical studies have shown that the monomeric and dimeric [FeL^R] complexes behave distinctively, and that the dimer stability is a function of the <i>ortho</i>-positioned groups. Both the dimeric as well as monomeric complexes were tested as catalysts for the catalytic cycloaddition of carbon dioxide to oxiranes, and the data show that the monomeric complexes are able to mediate this conversion with significantly higher activities than the dimeric complexes. This difference in reactivity is controlled by the substitution pattern on the ligand L^R, and is in line with the catalytic requisite of binding of the epoxide substrate by the iron­(III) center

G‑Quadruplex Identification in the Genome of Protozoan Parasites Points to Naphthalene Diimide Ligands as New Antiparasitic Agents

G-quadruplexes (G4) are DNA secondary structures that take part in the regulation of gene expression. Putative G4 forming sequences (PQS) have been reported in mammals, yeast, bacteria, and viruses. Here, we present PQS searches on the genomes of <i>T. brucei, L. major</i>, and <i>P. falciparum</i>. We found telomeric sequences and new PQS motifs. Biophysical experiments showed that EBR1, a 29 nucleotide long highly repeated PQS in <i>T. brucei</i>, forms a stable G4 structure. G4 ligands based on carbohydrate conjugated naphthalene diimides (carb-NDIs) that bind G4’s including hTel could bind EBR1 with selectivity versus dsDNA. These ligands showed important antiparasitic activity. IC₅₀ values were in the nanomolar range against <i>T. brucei</i> with high selectivity against MRC-5 human cells. Confocal microscopy confirmed these ligands localize in the nucleus and kinetoplast of <i>T. brucei</i> suggesting they can reach their potential G4 targets. Cytotoxicity and zebrafish toxicity studies revealed sugar conjugation reduces intrinsic toxicity of NDIs