Santiago V. Luis

Supported chiral catalysts: the role of the polymeric network

In the preparation of chiral-supported catalysts, the immobilization process can produce changes in the behavior of the resulting resin-supported species. The polymeric matrix plays important roles that affect the activity, selectivity and stability of the final catalysts. Pseudodilution effects very often favor the activity of the supported species, and the presence of the hydrophobic matrix increases the stability of the water-sensitive active sites. The steric interaction between the polymeric backbone and the groups in the chiral auxiliary can modify, even dramatically, the stereochemical outcome of the reaction.

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.

Chemical reactions and processes under flow conditions

Chapter 1: Engineering Factors for Efficient Flow Processes in Chemical Industries Chapter 2: Flow Processes Using Polymer-supported Reagents, Scavengers and Catalysts Chapter 3: Zeolites and related Materials for Developing Continuous Flow Systems Chapter 4: Microfluidic Devices for Organic Processes Chapter 5: Flow Processes in non-Conventional Media

Functional monolithic resins for the development of enantioselective versatile catalytic minireactors with long-term stability: TADDOL supported systems

Polymeric monoliths containing TADDOL subunits have been prepared by polymerization of the corresponding functional monomers. Treatment with TiX4 species affords Ti-TADDOLates, which can be used sequentially for two different reactions, namely the Diels–Alder reaction and the ZnEt2 addition to benzaldehyde. These monolithic materials allow working either in batch or under flow conditions. The Diels–Alder reaction is carried out more efficiently in batch that under flow conditions, but the opposite is found for the ZnEt2 addition. Enantioselectivities obtained compare well with those for other related supported systems. In some cases ee values found for the polymer-bound system are higher than those for the homogeneous analogue. The supported Ti-catalysts show an extraordinary long-term stability, being active for at least one year.

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.

Crystal structures of the HCl salts of pseudopeptidic macrocycles display “knobs into holes” hydrophobic interactions between aliphatic side chains

The crystal structures of three HCl salts of pseudopeptidic macrocycles show a H-bonding tubular stack of the rings, where the amino acidic side chains (Val, Leu, Ile) display an inter-columnar “knobs into holes” hydrophobic interaction pattern.

Oxaaza cyclophanes in the recognition of nucleotides. The role of oxygen and electron-rich aromatic rings

Dioxapolyaza cyclophanes derived from resorcinol and different polyamine chains have been studied in aqueous solution as abiotic receptors for nucleotides. The presence of the additional ethyleneoxy subunits is reflected in a higher basicity and in a significant increase in the log K values for the interaction with nucleotides relative to that of related polyazacyclophanes.

Residence time distribution, a simple tool to understand the behaviour of polymeric mini-flow reactors

A simple method for the determination of the residence time distribution (RTD) of different polymer-based mini-flow reactors has been developed. The flow patterns have been adjusted employing the axial dispersion model, allowing a quantitative comparison of the flow patterns of the different structures. The use of different pulse tracer experiments highlights the differences in reactor behaviour depending on the nature (gel vs. macroporous) and shape (beads vs. monoliths) of the polymeric materials used in the reactor preparation. Thus, reactors based on monolithic columns showed a superior performance in terms of flow distribution when compared to commercial bead-shaped packed polymers of different sizes and backbone structure, confirming previous experimental results. These differences can help to understand the different catalytic efficiency detected for these mini-flow fixed-bed reactors. The model presented can help to properly design new processes based on the use of continuous flow reactors facilitated by functional materials, which is becoming an essential goal nowadays, in particular in the context of developing new efficient and clean technologies.

Development of efficient processes under flow conditions based on catalysts immobilized onto monolithic supported ionic liquid-like phases*

The introduction of imidazolium subunits into polystyrene-divinylbenzene (PS-DVB) polymers enables the preparation of a variety of catalytic systems. Those include the stabilization of catalytically active Pd nanoparticles (PdNPs), immobilized enzymes, and basic catalysts. The use of monolithic supports having the appropriate morphological properties is greatly advantageous for the development of efficient catalytic processes under flow conditions based on those systems. On the other hand, the combination of those supported catalytic systems and flow conditions can be further implemented, in terms of green chemistry, by the substitution of the use of traditional solvents by environmentally friendly conditions such as the use of supercritical fluids (SCFs).

A novel method for the functionalization of polystyrene resins through long aliphatic spacers

Abstract The preparation of functionalized polystyrene-divinylbenzene resins containing functional groups bonded to the polymeric matrix by a long alkyl chain has been accomplished in a two-step procedure from unfunctionalized resins and the acid chloride of a monoalkyl ester of an alkanedioic acid. The procedure is useful for the preparation of spacer-modified polymers of variable crosslinking degrees, including highly crosslinked macroreticular resins such as XAD-4. The high mobility of the chains is revealed by the easy analysis of the polymers by gel-phase 13 C-NMR spectroscopy.