Nicolás Ríos-Lombardía

From salts to ionic liquids by systematic structural modifications: a rational approach towards the efficient modular synthesis of enantiopure imidazolium salts.

This paper reports a simple and robust modular synthetic strategy that leads to a large variety of configurationally and structurally diverse imidazole-based chiral ionic liquids (CILs) by lipase-catalyzed resolution. The intimate microscopic interactions of the supramolecular ionic network of these imidazolium chiral salts at the molecular level are investigated both spectroscopically (NMR, FT-IR-ATR) and theoretically, and a topological analysis of the experimental electron densities obtained by X-ray diffraction of single crystals is performed. Our results support the key role played by the relative configuration of the -OR group on the hydrogen-bonding pattern and its strong influence on the final physical properties of the imidazolium salt. We also obtained a reasonable correlation between the observed melting point and the non-covalent interactions. The spectroscopic data and the topological analysis reflect the key role played by hydrogen bonds between the OH and imidazolium C2H groups in both cation-anion and cation-cation interactions, with the presence of an OH group leading to an additional inter-cation interaction. This interaction significantly affects the properties of stereoisomeric salts. Even more interestingly, we also studied the effect of the chirality by comparing enantiopure CILs with their racemic mixtures and found that, with the exception of trans-Cy6-OH-Im-Bn-Br, the melting points of the racemic mixtures are higher than those of the corresponding enantiomerically pure forms. For stereoisomeric examples, we have successfully explained the differences in melting temperatures in light of the corresponding structural data. Chirality should therefore be taken into account as a highly attractive design vector in the preparation of ILs with specifically desired properties.

Polymeric imidazolium ionic liquids as valuable stationary phases in gas chromatography: chemical synthesis and full characterization.

Seven new functionalized polymerizable ionic liquids were chemically prepared, and later applied for the preparation of polymeric stationary phases in gas chromatography. These coated GC columns, which exhibited good thermal stabilities (240-300°C) and very high efficiencies (3120-4200 plates/m), have been characterized using the Abraham solvation parameter model. The chromatographic behavior of these polymeric IL columns has been deeply studied observing excellent selectivities in the separation of many organic substances such as alkanes, ketones, alcohols, amines or esters in mixtures of polar and non polar solvents or fragrances. Remarkably, the challenging separation of xylene isomers has been possible using a bis(trifluoromethylsulfonyl)amide based imidazolium IL coated column as a gas chromatography stationary phase.

Enzymatic Desymmetrization of Prochiral 2-Substituted-1,3-Diamines : Preparation of Valuable Nitrogenated Compounds

A wide range of prochiral 1,3-diamines were first efficiently synthesized and subsequently desymmetrized by using lipase from Pseudomonas cepacia as catalyst and diallyl carbonate as alkoxycarbonylating agent. In all cases, the amino carbamates of R-configuration were recovered. Final selective cleavage of the N-allyloxycarbonyl moiety was carried out under mild reaction conditions, which demonstrates the high versatility and potential of this chemoenzymatic route as a source of intermediates in the synthesis of related optically active nitrogenated derivatives.

From a Sequential to a Concurrent Reaction in Aqueous Medium: Ruthenium‐Catalyzed Allylic Alcohol Isomerization and Asymmetric Bioreduction

The ruthenium-catalyzed redox isomerization of allylic alcohols was successfully coupled with the enantioselective enzymatic ketone reduction (mediated by KREDs) in a concurrent process in aqueous medium. The overall transformation, formally the asymmetric reduction of allylic alcohols, took place with excellent conversions and enantioselectivities, under mild reaction conditions, employing commercially and readily available catalytic systems, and without external coenzymes or cofactors. Optimization resulted in a multistep approach and a genuine cascade reaction where the metal catalyst and biocatalyst coexist from the beginning.

Influence of the Nucleophile on the Candida antarctica Lipase B‐Catalysed Resolution of a Chiral Acyl Donor

The resolution of methyl (±)‐3‐hydroxypentanoate catalysed by Candida antarctica lipase B has been performed by using ammonia and benzyl amine as nucleophiles. In all cases, the lipase reacts faster with the R enantiomer of the ester, but when benzyl amine is used, the enantiomeric ratio is approximately three times as high as that measured for ammonia. The analysis of the molecular dynamics simulations carried out over the corresponding deacylation transition state analogues indicated specular binding modes between enantiomers that vary greatly upon the nucleophile used. For the case of ammonia, an intramolecular hydrogen bond between the β‐hydroxyl group and the protons of the nucleophile is established. However, the presence of the substituent in benzyl amine disrupts this interaction. Instead, the acyl chain binds to a more restrictive area of the protein where the higher number of contacts established with the side chains of Thr40, Gln157 and Ile189 have been identified as the reason for the higher enantioselectivity observed in the aminolysis reaction.

Enantiopure Triazolium Salts: Chemoenzymatic Synthesis and Applications in Organocatalysis

A novel family of triazolium salt enantiomers has been efficiently synthesized by combining chemical and biocatalytic methods. The stereoselective action shown by hydrolytic enzymes led to the design of simple and general chemoenzymatic routes in which tunable vectors, such as ring size, substituent stereochemistry, oxygen substitution, anion nature, or N4‐triazole alkylating chain, were considered to produce 30 enantiopure triazolium salts in very high overall yields. Finally, selected triazolium salts were tested as phase‐transfer catalysts in the asymmetric Michael addition of diethyl malonate to trans‐chalcone to rationalize their activity and stereopreference. Low to complete conversion values were achieved in the formation of the Michael addition adduct, which mainly gave low levels of stereoselectivity depending on the different structural patterns considered in this systematic study.

Characterization of hexacationic imidazolium ionic liquids as effective and highly stable gas chromatography stationary phases

Polycationic ionic liquids (ILs) are an attractive class of ILs with great potential applicability as gas chromatography stationary phases. A family of hexacationic imidazolium ILs derived from the cycloalkanol family was chemically first prepared in a straightforward manner and then applied for analytical separation purposes. Four tuneable engineering vectors, namely cation ring size structure, anion nature, spatial disposition of cycloalkanol substituents and O-substitution, were considered as experimental parameters for the design of the desired ionic liquids. A total number of five new phases based on a common benzene core respectively exhibited column efficiencies around to 2500 plates/m, broad operating temperature ranges and also, even more importantly, good thermal stabilities (bleeding temperature between 260 and 365°C), finding variations in the selectivity and analytes elution orders depending on the IL structures. Their solvation characteristics were evaluated using the Abraham solvation parameter model, establishing clear correlations between their cation structure and retention capability with respect to certain analytes. The study of relationships between the ILs structure and solvation parameters gives us an idea of the IL stationary phase to be used for specific separations.

Complementary lipase-mediated desymmetrization processes of 3-aryl-1,5-disubstituted fragments. Enantiopure synthetic valuable carboxylic acid derivatives.

Desymmetrizaton enzymatic processes have been extensively studied searching for optimal methods of producing enantioenriched monoacetates from prochiral diols and diesters. AK lipase has been found as an excellent biocatalyst for the desymmetriaztion of a series of previously synthesized 3-arylpentane-1,5-diols derivatives. The access to (S)- or (R)-monoacetates in high optical purity (86-99% ee) has been possible by using acetylation or hydrolysis reactions, respectively, where the reaction parameters have been optimized in terms of source and amount of biocatalyst, temperature, solvent, and reaction time. The synthetic potential of enantiopure monoesters has been demonstrated by using these interesting chiral building blocks for the preparation of novel enantiopure carboxylic acid derivatives.

Deracemisation of profenol core by combining laccase/TEMPO-mediated oxidation and alcohol dehydrogenase-catalysed dynamic kinetic resolution

A mild one-pot methodology has been developed to deracemise rac-2-phenyl-1-propanol by combining the use of non-selective laccase/TEMPO-mediated oxidation with enantioselective bioreduction of the racemic aldehyde intermediate under dynamic conditions. The process was easily scalable and stereocontrollable by selecting the suitable biocatalyst.

Chemoenzymatic Asymmetric Synthesis of Optically Active Pentane-1,5-diamine Fragments by Means of Lipase-Catalyzed Desymmetrization Transformations

A novel family of prochiral pentane-1,5-diamines has been efficiently synthesized, possessing stabilities significantly higher than those of corresponding propane-1,3-diamine analogues. Diamines have been later desymmetrized using Pseudomonas cepacia lipase as an efficient biocatalyst for the mono- but also stereoselective protection of one of their amino groups. Reaction parameters such as type and loading of enzyme, temperature, solvent, and acyl donor have been exhaustively analyzed, searching for optimal conditions for the production of interesting optically active nitrogenated compounds. Thus, acylation and alkoxycarbonylation processes have been compared in terms of conversion and enantiomeric excess values. The best results were found in the reaction of prochiral diamines with ethyl methoxyacetate as acyl donor and 1,4-dioxane as solvent, yielding (S)-monoamides in 33-59% isolated yield and 54-99% ee, depending on the aromatic pattern substitution.