Organocatalysis
- Non enantioselective version
We have developed a general and efficient biomimetic method for the synthesis of aldimines from aldehydes and compounds bearing the NH2 group in the presence of pyrrolidine as catalyst. These organocatalytic reactions, based on the application of the concept of nucleophilic catalysis, proceed with outstanding yields in the absence of acids and metals under simple and environmentally friendly conditions and minimum experimental manipulation. The method has been mainly applied to the synthesis of N-sulfinyl and N-sulfonyl imines, but its general validity has been proven with the preparation of representative N-phosphinoyl, N-alkyl and N-aryl imines. These unprecedented reactions, presumably occurring via iminium activation without requiring acidic conditions, are an interesting and competitive alternative to the classical methods for preparing aldimines.
The formation of nitrones by direct condensation between equimolecular amounts of N-substituted hydroxylamine hydrochlorides and aromatic or aliphatic aldehydes is efficiently promoted by pyrrolidine in a matter of minutes under very mild conditions in almost quantitative yields after a simple filtration through a short pad of silica gel. According to theoretical, spectroscopic and experimental studies, this success is due to the ability of pyrrolidine to liberate the hydrochloride of the hydroxylamine and catalyze the reaction via iminium activation ion. Moreover, a cooperative pyrrolidine/pyrrolidinium chloride effect facilitates several steps of the catalytic cycle through proton transfer without hampering the nucleophilicity of the hydroxylamine by protonation.
Pyrrolidine catalyzes very efficiently, presumably via iminium activation, the formation of acyloximes, acylhydrazones and thiosemicarbazones derived from aromatic and aliphatic aldehydes using equimolar amounts of reagents and green solvents. Experimental simplicity and excellent yields after a simple filtration are the main advantages of the method, being an alternative to those currently available especially for the acyl derivatives, which do not work under uncatalyzed conditions. Its application to the synthesis of acyloximes by direct condensation between aldehydes and acylhydroxylamines is unprecedented.
Goldsmith, D., Belenń Cid de la Plata, M. and Morales, S. 2016. Pyrrolidine. e-EROS Encyclopedia of Reagents for Organic Synthesis. 1–10.
- Enantioselective version.
· Development of new nucleophiles in iminium activation
We have demonstrated that a nitro group attached to an aromatic ring can be used as a temporary activating group of benzylic nucleophiles increasing their acidity and allowing their participation in organocatalytic processes. Sevaral cheap and commercially or easily available nucleophiles are able to react with β-alkyl and aryl substituted acroleines in a highly enantioselective manner to afford interesting and versatilie building blocks.
·Development of new additives in iminium activation
We have discovered that quaternary ammonium salts can be employed as efficient additives in organocatalyzed Michael additions via iminium intermediates. In a sequential way, they first favour the formation and stabilization of the iminium intermediate and then activate the nucleophile as an enolate by the action of ammonium hydroxide, a base generated only after iminium ion formation
·Development of new electrophiles
We are working on the development of new applications of our highly reactive sulphonyl Michael acceptor 1 and synthetic transformations of sulfones.
We have demonstrated the synthetic usefulness of 1, monoactivated in the challenging preparation of enantioenriched α-allylated aldehydes bearing quaternary centers using enantioselective enamine catalysis and Julia-Kocienski olefination. This is the first time that a monoactivated vinyl sulfone is used in an organocatalytic process via enamine activation.
The utility of building block 1 has also been validated with the enantio and diastereoselective preparation of nitrocyclohexenes and cyclohexylamines. This [3 + 3] annulation strategy based on the use of pro-bis(nucleophile) 2 in an asymmetric Michael addition / intramolecular Julia - Kocienski olefination sequence is an alternative to the direct reluctant enantioselective Diels-Alder approach. The potential of the methodology has been demonstrated with a concise enantioselective formal synthesis of trandolapril.
To illustrate the great potential for new applications of the easily available vinyl sulfone 3 in several fields, such as organic synthesis and bioconjugates formation, we have performed a systematic assessment of its reactivity in Michael, radical and cycloaddition reactions. Heteroaryl vinyl sulfone 3 presented an excellent performance, overwhelmingly superior to phenyl vinyl sulfone 1 and with clear advantages over bissulfone 2 in terms of reactivity and selectivity in many reactions, which might be due to the conformational and orbital control exerted by the tetrazole unit according to DFT calculations. Moreover, some alternative transformations to the Julia-Kocienski olefination are also described over the obtained products. Paragraph. Haz clic aquí para editar.
Graphene based catalysts
We are working on carbocatalysis and on the development of organic and metallic graphene supported catalysts.
Graphene Oxide (GO) features a wide range of functional groups which may act as active sites and therefore allows the possibility to develop new sustainable catalytic systems. The aim is to take advantage of the properties of graphene looking for a synergistic interaction with metals or organocatalysts to exploit it in the catalysis of organic reactions.
Graphene Oxide (GO) features a wide range of functional groups which may act as active sites and therefore allows the possibility to develop new sustainable catalytic systems. The aim is to take advantage of the properties of graphene looking for a synergistic interaction with metals or organocatalysts to exploit it in the catalysis of organic reactions.
- Reduced Graphene Oxide Supported Piperazine in Aminocatalysis
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Used in Ullman and click reactions, ongoing in flow chemistry. 
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- Magnetic materials. Functionalized materials are transformed in magnetic materials to study catalytic properties and facilitate separation.
