Approaches to asymmetric catalysis with polymer-supported pyrrolidines

Abstract

El presente proyecto de investigación se centra en la inmovilización de sistemas catalíticos derivados de pirrolidinas sobre polímeros entrecruzados de PS que permiten realizar enantioselectivamente la formación de enlaces carbono-carbono y carbono-heteroátomo a través de procedimientos con las características de mejora de la sostenibilidad en procesos organocatalíticos altamente eficientes vía mecanismos tipo enamina e ión iminio así como reacciones en cascada así como su aplicación en condiciones de flujo continuo. También se describen ligandos quirales para la reducción asimétrica de cetonas mediante complejos de rutenio en medio orgánico y acuoso y de boro, donde la enantioselectividad depende de cómo se haya anclado la unidad catalítica sobre el polímero.

The present research project developed is focused in the immobilization of catalytic systems allowing the formation of carbon-carbon and carbonheteroatom bonds through enantioselective procedures with improved sustainability characteristics (suppression of catalyst separation steps, preferential use of water as a solvent under aerobic conditions, avoidance of protecting groups and, hence, of protection and deprotection steps). In particular, the study is directed towards the organocatalysis field, although also asymmetric catalytic processes mediated by metal complexes have been developed. The approach introduced by our group combines the optimization of the catalytic properties of the ligands, which is greatly facilitated by their modular nature, with a design principle consisting in performing the anchoring to the polymer through auxiliary functional groups, positioned on the ligand molecule for minimal perturbation of the catalytic site. In this manner, we have been able to develop polymersupported ligands that do not show any decrease in catalytic activity or in enantioselectivity with respect to their homogeneous counterparts. The usual anchoring strategy used is the Cu-catalyzed azide/alkyne 1,3 dipolar cycloaddition. In this manner, in this work proline and pyrrolidine derivatives have been synthesized to catalyze organic transformations via enamine and iminium ion mechanisms as Mannich or Michael reactions. Organocatalytic cascade process has also been reported as useful method for the preparation of highly functionalized cyclohexane derivatives in a straightforward and efficient manner and the use of supported organocatalysts has allowed us to implement this reactions not only in batch processes but also in continuous flow conditions obtaining large amount of desired product with high enantiopurity. As have been mentioned, asymmetric catalysis mediated by metal complexes has been investigated. One project collect the study of the asymmetric reduction of ketones with borane and oxazaborolidine type catalysts as aminoalcohols in homogeneous phase and the application of diphenylprolinol derivatives supported on polymers by click-chemistry or by direct nucleophilic substitution to the Merrifield resin. It is verified experimentally that the triazole ring formed by anchoring the monomer to the polymer matrix by click reaction has an important role in the selectivity of the catalyst because leads to a not enantioselective path due to the boron coordination to the triazole. When triazole ring is not present, aromatic ketones are reduced with high enantioselectivities (90-99%) and complete conversion after 30 minutes of reaction with qualitative yield because the easy removing of the catalyst from the product by filtration. Also a series of new modular Ru/aminoalcohol systems has been developed and used as enantioselective catalysts in the asymmetric transfer hydrogenation reaction of ketones in both water and 2-propanol. The catalytic behaviour exhibited in these two media follows different tendencies regarding the tuneable ligand structure. While the bulkiness of the R1 group has a positive effect on the activity for reactions in 2-propanol, ligands with bulky R1 groups are generally less active in water. Additionally, cationic, anionic, and neutral surfactants do not improve the catalytic behaviour in water.