Nickel-catalyzed direct carboxylation of olefins with CO2 : one-pot synthesis of α,ß-unsaturated carboxylic acid salts.

The nickel-catalyzed direct carboxylation of alkenes with the cheap and abundantly available C1 building block carbon dioxide (CO2 ) in the presence of a base has been achieved. The one-pot reaction allows for the direct and selective synthesis of a wide range of α,ß-unsaturated carboxylates (TON>100, TOF up to 6 h(-1) , TON=turnover number, TOF=turnover frequency). Thus, it is possible, in one step, to synthesize sodium acrylate from ethylene, CO2 , and a sodium salt. Acrylates are industrially important products, the synthesis of which has hitherto required multiple steps.

Ruthenium carbenes supported on mesoporous silicas as highly active and selective hybrid catalysts for olefin metathesis reactions under continuous flow.

In the search for a highly active and selective heterogenized metathesis catalyst, we systematically varied the pore geometry and size of various silica-based mesoporous (i.e., MCM-41, MCM-48, and SBA-15) and microporous (ZSM-5 and MWW) versus macroporous materials (D11-10 and Aerosil 200), besides other process parameters (temperature, dilution, and mean residence time). The activity and, especially, selectivity of such "linker-free" supports for ruthenium metathesis catalysts were evaluated in the cyclodimerization of cis-cyclooctene to form 1,9-cyclohexadecadiene, a valuable intermediate in the flavor and fragrance industry. The optimized material showed not only exceptionally high selectivity to the valuable product, but also turned out to be a truly heterogeneous catalyst with superior activity relative to the unsupported homogeneous complex.

Linker-free, silica-bound olefin-metathesis catalysts: applications in heterogeneous catalysis.

A set of heterogenized olefin-metathesis catalysts, which consisted of Ru complexes with the H(2)ITap ligand (1,3-bis(2',6'-dimethyl-4'dimethyl aminophenyl)-4,5-dihydroimidazol-2-ylidene) that had been adsorbed onto a silica support, has been prepared. These complexes showed strong binding to the solid support without the need for tethering groups on the complex or functionalized silica. The catalysts were tested in the ring-opening-ring-closing-metathesis (RO-RCM) of cyclooctene (COE) and the self-metathesis of methyl oleate under continuous-flow conditions. The best complexes showed a TON>4000, which surpasses the previously reported materials that were either based on the Grubbs-Hoveyda II complex on silica or on the classical heterogeneous Re(2)O(7)/B(2)O(3) catalyst.

Structurally disfavoured pseudopeptidic macrocycles through anion templation.

An anionic dicarboxylate is able to template the formation of geometrically disfavoured macrocycles from a dynamic covalent mixture of open chain oligoimines.

Molecular recognition of N-protected dipeptides by pseudopeptidic macrocycles: a comparative study of the supramolecular complexes by ESI-MS and NMR.

The molecular recognition properties of pseudopeptidic macrocycles have been studied by ESI-MS and NMR spectroscopy, as highly complementary experimental techniques in solution and in the gas phase. We used ESI-MS competition experiments for the high throughput screening of the supramolecular interaction between four macrocyclic receptors and different peptide-like substrates in solution, rendering the best-fitted host-guest pairs. Further insights on the non-covalent recognition process in the gas-phase were obtained through collision induced dissociation (CID) experiments. Solution studies using NMR spectroscopy ((1)H NMR titrations, NOESY and DOSY) were carried out to prove the validity of ESI-MS as a high-throughput screening method for studying the molecular recognition of the investigated pseudopeptidic macrocycles. A clear selectivity for N-protected dipeptides over N-protected amino acids, and a slight preference for dipeptides bearing aromatic side chains were observed. On the basis of the results obtained from this approach, a mode of binding has been proposed.

Structural diversity in the self-assembly of pseudopeptidic macrocycles.

The self-assembling abilities of several pseudopeptidic macrocycles have been thoroughly studied both in the solid (SEM, TEM, FTIR) and in solution (NMR, UV, CD, FTIR) states. Detailed microscopy revealed large differences in the morphology of the self-assembling micro/nanostructures depending on the macrocyclic chemical structures. Self-assembly was triggered by the presence of additional methylene groups or by changing from para to meta geometry of the aromatic phenylene backbone moiety. More interestingly, the nature of the side chain also plays a fundamental role in some of the obtained nanostructures, thus producing structures from long fibers to hollow spheres. These nanostructures were obtained in different solvents and on different surfaces, thus implying that the chemical information for the self-assembly is contained in the molecular structure. Dilution NMR studies (chemical shift and self-diffusion rates) suggest the formation of incipient aggregates in solution by a combination of hydrogen-bonding and pi-pi interactions, thus implicating amide and aryl groups, respectively. Electronic spectroscopy further supports the pi-pi interactions because the compounds that lead to fibers show large hypochromic shifts in the UV spectra. Moreover, the fiber-forming macrocycles also showed a more intense CD signature. The hydrogen-bonding interactions within the nanostructures were also characterized by attenuated total-reflectance FTIR spectroscopy, which allowed us to monitor the complete transition from the solution to the dried nanostructure. Overall, we concluded that the self-assembly of this family of pseudopeptidic macrocycles is dictated by a synergic action of hydrogen-bonding and pi-pi interactions. The feasibility and geometrical disposition of these interactions finally render a hierarchical organization, which has been rationalized with a proposal of a model. The understanding of the process at the molecular level has allowed us to prepare hybrid soft materials.

Designed folding of pseudopeptides: the transformation of a configurationally driven preorganization into a stereoselective multicomponent macrocyclization reaction.

The efficient synthesis of large-ring pseudopeptidic macrocycles through a multicomponent [2+2] reductive amination reaction is described. The reaction was entirely governed by the structural information contained in the corresponding open-chain pseudopeptidic bis(amidoamine) precursors, which have a rigid (R,R)-cyclohexane-1,2-diamine moiety. A remarkable match/mismatch relationship between the configurations of the chiral centers of the cyclic diamine and those of the peptidic frame was observed. The macrocyclic tetraimine intermediates have been studied in detail by NMR spectroscopy, circular dichroism (CD), and molecular modeling, and the results support the appropriate preorganization induced by the match combination of the chiral centers. We have also synthesized the corresponding open-chain bis(imine) model compounds. The structural studies (NMR spectroscopy, CD, modeling) of these systems showed an intrinsically lower reactivity of the mismatch combination, even when the product of the reaction was acyclic. In addition, a synergistic effect between the two chiral substructures for the correct folding of the molecules was observed. Finally, X-ray analysis of the HCl salt of one of the macrocycles showed an interesting pattern; the macrocyclic rings stack in columnar aggregates leaving large interstitial channels filled with water-solvated chloride anions.

Supramolecular control for the modular synthesis of pseudopeptidic macrocycles through an anion-templated reaction.

The anion-templated synthesis of different pseudopeptidic macrocycles has been studied in detail by using a multidisciplinary approach. The reaction between an open-chain pseudopeptidic diamine and the appropriate dialdehyde is highly affected by the presence of the best fitting anionic template. The formation of the corresponding macrocyclic tetraimino-template supramolecular complex is demonstrated by NMR (ROESY and PGSE) and mass spectrometry (ESI-TOF). These supramolecular complexes can be easily reduced to the corresponding more stable tetraamine macrocycles. Accordingly, we have used this reaction to efficiently synthesize a family of new pseudopeptidic macrocycles in a one-pot two-steps anion-templated reductive amination reaction, which comprises a multicomponent macrocyclization through the selective formation of four chemical bonds to yield a unique macrocyclic structure. Different variables like the aliphatic spacer between amino acidic moieties, geometry of the dialdehyde, and structure of the amino acid side chains were thoroughly studied, and their effect in the formation and stability of the supramolecular complexes discussed. The conformational preorganization induced by the template has been monitored by circular dichroism, reflecting the differences observed in the isolated yields, as well as by NMR spectroscopy. This effect has been also supported by molecular modeling. All the experimental and theoretical techniques were strongly consistent and reflected the same trends by comparing the different structural variables introduced in the system.