Size‐Tunable Micron‐Bubbles Based on Fluorous–Fluorous Interactions of Perfluorinated Dendritic Polyglycerols

This paper describes the behavior of various generations of polyglycerol dendrimers that contain a perfluorinated shell. The aggregation in organic solvents is based on supramolecular fluorous–fluorous interactions, which can be described by means of ¹⁹F NMR spectroscopy. In order to study the interaction and aggregation phenomena of dendrimers with perfluorinated shell and perfluoro‐tagged guest molecules we investigated [G3.5]‐dendrimer with a perfluorinated shell in the presence of perfluoro‐tagged disperse red. Noteworthy, the interaction intensities varied in an unexpected manner depending on the equivalents of perfluoro‐tagged guest molecules added to the dendrimers in solution which then formed supramolecular complexes based on fluorous–fluorous interactions. We found that these complexes aggregated around residual air in the solvent to form stable micron‐sized bubbles. Their sizes correlated with the interaction intensities measured for certain dendrimer–guest molecule ratios. Degassing of the solutions led to a quasi phase separation between organic and fluorous phase, whereby the dendrimers formed the fluorous phases. Regassing the sample with air afforded bubbles of the initial size again.     

Heterogenization of a Modified Grubbs–Hoveyda Catalyst on a ROMP‐Derived Monolithic Support

A ring‐opening metathesis polymerization‐ (ROMP‐) based monolith was synthesized using a Grubbs' first generation catalyst. The living termini were used for surface grafting of norborn‐5‐ene‐2‐ylmethyl hexafluoroglutarate. The free carboxylic acid groups of the graft polymer were converted into the corresponding silver salt and reacted with the Grubbs–Hoveyda catalyst [RuCl₂(CH (2‐iPrO )C₆H₄)(IMesH₂)] (IMesH₂ = 1,3‐bis(2,4,6‐trimethylphenyl)‐4,5‐dihydroimidazol‐2‐ylidene) to yield a stable heterogeneous version of this catalyst for use in ring‐closing metathesis (RCM) under continuous flow conditions.

The monolith‐supported Grubbs–Hoveyda catalyst.     

Total Synthesis of (+)‐Cryptocaryalactone and of a Diastereoisomer of (+)‐Strictifolione via Ring‐Closing Metathesis (RCM) and Olefin Cross‐Metathesis (CM)

Ring‐closing metathesis (RCM) and olefin cross‐metathesis (CM) reactions were used as the key steps for the synthesis of (+)‐cryptocaryalactone ( 1 ) and the first synthesis of the diastereoisomer 3 of (+)‐strictifolione, starting from the commercially available L ‐malic acid (=(2S)‐2‐hydroxybutanedioic acid).     

A New Synthesis of Benzofurans from Phenols via Claisen Rearrangement and Ring‐Closing Metathesis

Based on Claisen rearrangement, the double bond isomerization of O‐allyl function together with the formation of O‐vinyl function in one pot, and ring‐closing metathesis (RCM), various phenols were transformed into various benzofurans in good yields.     

DFT Mechanistic Study on Diene Metathesis Catalyzed by Ru‐Based Grubbs–Hoveyda‐Type Carbenes: The Key Role of π‐Electron Density Delocalization in the Hoveyda Ligand

The catalytic activity and catalyst recovery of two heterogenized ruthenium‐based precatalysts ( H and NO₂(4) ) in diene ring‐closing metathesis have been studied by means of density functional calculations at the B3LYP level of theory. For comparison and rationalization of the key factors that lead to higher activities and higher catalyst recoveries, four other Grubbs–Hoveyda complexes have also been investigated. The full catalytic cycle (catalyst formation, propagation, and precatalyst regeneration) has been considered. DFT calculations suggest that either for the homogeneous and heterogenized systems the activity of the catalysts mainly depends on the ability of the precursor to generate the propagating carbene. This ability does not correlate with the traditionally identified key factor, the Ru???O interaction strength. In contrast, precatalysts with lower alkoxy‐dissociation energy barriers and lower stabilities compared with the propagating carbene also present larger C1? C2 bond length (i.e., lower π character of the C? C bond that exists between the metal–carbene (Ru?C) and the phenyl ring of the Hoveyda ligand). Catalyst recovery, regardless of whether a release–return mechanism occurs or not, is also mainly determined by the π delocalization. Therefore, future Grubbs–Hoveyda‐type catalyst development should be based on fine‐tuning the π‐electron density of the phenyl moiety, with the subsequent effect on the metalloaromaticity of the ruthenafurane ring, rather than considering the modification of the Ru???O interaction.     

Synthesis and Catalytic Activity of a Two-core Ruthenium Carbene Complex: a Unique Catalyst for Ring Closing Metathesis Reaction

The reaction of a ruthenium carbide complex RuCl2(C:)(PCy3)2 with [H(Et2O)x]+[BF4]– at a molar ratio of 1:2 produced a two-core ruthenium carbene complex, {[RuCl(=CHPCy3)(PCy3)]2(μ-Cl)3}+·[BF4]–, in the form of a yellow-green crystalline solid in a yield of 94%. This two-core ruthenium complex is a selective catalyst for ring closing metathesis of unsubstituted terminal dienes. More importantly, no isomerized byproduct was observed for N-substrates when the two-core ruthenium complex was used as the catalyst at an elevated temperature(137 °C), indicating that the complex is a chemo-selective catalyst for ring closing metathesis reactions.     

Synthesis of Diverse Oxa‐Carbocycle‐Annulated Flavones Using the Combined Claisen Rearrangement and Ring‐Closing Metathesis

A simple and efficient route for the synthesis of oxepine‐, oxocine‐, oxepinone‐, and dioxocine‐angularly annulated flavone skeletons has been developed. The combined Claisen rearrangement and the ring‐closing metathesis are used as key steps for the construction of C₇/C₈–C₆–C₆ tricyclic core structures.     

A Retrospective on the Design and Synthesis of Novel Molecules through a Strategic Consideration of Metathesis and Suzuki–Miyaura Cross‐Coupling

Synergy in synthesis : Strategic consideration of metathesis and Suzuki–Miyaura (SM) cross‐coupling for C? C bond‐formation processes has opened up new and “green” synthetic routes to various complex targets. The use of this synergistic combination for the synthesis of supramolecular ligands, polyaromatic compounds, and complex natural products is covered in this Focus Review.

     

Synthesis of Carbazole Alkaloids by Ring‐Closing Metathesis and Ring Rearrangement–Aromatization

Aprocess for the assembly of carbazole alkaloids has been developed on the basis of ring‐closing metathesis (RCM) and ringrearrangement–aromatization (RRA) as the key steps. This method is based on allyl Grignard addition to isatin derivatives to provide smooth access to 2,2‐diallyl 3‐oxindole derivatives through a 1,2‐allyl shift. The diallyl derivatives were used as RCM precursors to afford a novel class of spirocyclopentene‐3‐oxindole derivatives, which underwent a novel RRA reaction to afford carbazole derivatives. The synthetic sequence to carbazoles was shortened by combining the RCM and RRA steps in an orthogonal tandem catalytic process. The utility of this methodology was further demonstrated by the straightforward synthesis of carbazole alkaloids, including amukonal derivative, girinimbilol, heptaphylline, and bis(2‐hydroxy‐3‐methylcarbazole).     

Constrained Peptides with Target‐Adapted Cross‐Links as Inhibitors of a Pathogenic Protein–Protein Interaction

Bioactive conformations of peptides can be stabilized by macrocyclization, resulting in increased target affinity and activity. Such macrocyclic peptides proved useful as modulators of biological functions, in particular as inhibitors of protein–protein interactions (PPI). However, most peptide‐derived PPI inhibitors involve stabilized α‐helices, leaving a large number of secondary structures unaddressed. Herein, we present a rational approach towards stabilization of an irregular peptide structure, using hydrophobic cross‐links that replace residues crucially involved in target binding. The molecular basis of this interaction was elucidated by X‐ray crystallography and isothermal titration calorimetry. The resulting cross‐linked peptides inhibit the interaction between human adaptor protein 14‐3‐3 and virulence factor exoenzyme S. Taking into consideration that irregular peptide structures participate widely in PPIs, this approach provides access to novel peptide‐derived inhibitors.     

Modular Total Synthesis of (–)‐Palmyrolide A and (+)‐(5S,7S)‐Palmyrolide A via Ring‐Closing Metathesis and Alkene Isomerization†

A pentamodule assembly approach has been established for total synthesis of the naturally occurring (–)‐palmyrolide A and (+)‐5,7‐epi‐palmyrolide A. By using the racemic tert‐butyl carbinol‐containing alkyl iodide, the two diastereoisomeric macrolides could be obtained from the same sequence of reactions, demonstrating the flexibility of the multimodule assembly strategy for diverted total synthesis.     

Mechanochemical Immobilisation of Metathesis Catalysts in a Metal–Organic Framework

A simple, one‐step mechanochemical procedure for immobilisation of homogeneous metathesis catalysts in metal–organic frameworks was developed. Grinding MIL‐101‐NH₂(Al) with a Hoveyda–Grubbs second‐generation catalyst resulted in a heterogeneous catalyst that is active for metathesis and one of the most stable immobilised metathesis catalysts. During the mechanochemical immobilisation the MIL‐101‐NH₂(Al) structure was partially converted to MIL‐53‐NH₂(Al). The Hoveyda–Grubbs catalyst entrapped in MIL‐101‐NH₂(Al) is responsible for the observed catalytic activity. The developed synthetic procedure was also successful for the immobilisation of a Zhan catalyst.     

Drug–Membrane Interaction on Immobilized Liposome Chromatography Compared to Immobilized Artificial Membrane (IAM), Liposome/Water,and Octan‐1‐ol/Water Systems

The objective of this study was to investigate drug–membrane interaction by immobilized liposome chromatography (ILC; expressed as lipophilicity index log K_s) and the comparison with lipophilicity indices obtained by liposome/H₂O, octan‐1‐ol/H₂O, and immobilized artificial membrane (IAM) systems. A set of structurally diverse monofunctional compounds and drugs (nonsteroidal anti‐inflammatory drugs and β‐blockers) were selected in this study. This set of solutes consists of basic or acidic functionalities which are positively or negatively charged at physiological pH 7.4. No correlation was found between log K_s from ILC and lipophilicity indices from any of the other membrane model systems for the whole set of compounds. For structurally related compounds, significant correlations could be established between log K_s from ILC and lipophilicity indices from IAM chromatography and octan‐1‐ol/H₂O. However, ILC and liposome/H₂O systems only yield parallel partitioning information for structurally related large molecules. For hydrophilic compounds, the balance between electrostatic and hydrophobic interactions dominating drug partitioning is different in these two systems.     

Formal Synthesis of (−)‐Cyclaradine Using Ring Closing Metathesis

The stereoselective formal synthesis of (?)‐cyclaradine from the inexpensively available starting material L ‐glutamic acid is described, using Eschenmoser's reagent, and applying Luche reduction, Grignard reaction, and ring closing metathesis (RCM) as the key steps.     

Metal‐Ion Metathesis in Metal–Organic Frameworks: A Synthetic Route to New Metal–Organic Frameworks

A porous metal–organic framework, Mn(H₃O)[(Mn₄Cl)₃(hmtt)₈] (POST‐65), was prepared by the reaction of 5,5′,10,10′,15,15′‐hexamethyltruxene‐2,7,12‐tricarboxylic acid (H₃hmtt) with MnCl₂ under solvothermal conditions. POST‐65(Mn) was subjected to post‐synthetic modification with Fe, Co, Ni, and Cu according to an ion‐exchange method that resulted in the formation of three isomorphous frameworks, POST‐65(Co/Ni/Cu), as well as a new framework, POST‐65(Fe). The ion‐exchanged samples could not be prepared by regular solvothermal reactions. The complete exchange of the metal ions and retention of the framework structure were verified by inductively coupled plasma–atomic emission spectrometry (ICP‐AES), powder X‐ray diffraction (PXRD), and Brunauer–Emmett–Teller (BET) surface‐area analysis. Single‐crystal X‐ray diffractions studies revealed a single‐crystal‐to‐single‐crystal (SCSC)‐transformation nature of the ion‐exchange process. Hydrogen‐sorption and magnetization measurements showed metal‐specific properties of POST‐65.     

Grubbs Catalysts Immobilized on Merrifield Resin for Metathesis of Leaf Alcohols by using a Convenient Recycling Approach

Three new types of heterogeneous catalysts were prepared using a facile approach by the immobilization of Grubbs catalysts on PEGylated Merrifield resin. One of the immobilized catalysts was more efficient than the free catalyst for the metathesis of leaf alcohols in conversion and selectivity and was reused repeatedly (up to 5 cycles) with only a slight loss of activity (10.5 %). The long-chain PEGylated linker provided an appropriate distance between the resin and the catalytic center so that the ruthenium catalysts acted as the free catalyst.