Multifaceted use of mass spectrometry in asymmetric synthesis: from selection of organocatalyst, to the screening of immobilized organocatalyst in flow mode.
|Marco Pierini||Componenti strutturati del gruppo di ricerca / Structured participants in the research project|
|Giulia Mazzoccanti||Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group|
|Claudio Villani||Componenti strutturati del gruppo di ricerca / Structured participants in the research project|
|Ilaria D'Acquarica||Componenti strutturati del gruppo di ricerca / Structured participants in the research project|
|Deborah Quaglio||Componenti strutturati del gruppo di ricerca / Structured participants in the research project|
The project targets the design and preparation of immobilized organocatalysts to be employed in batch and flow modes. The selection of the more efficient catalytic system and the control of its activity after the immobilization procedure will be obtained by mass spectrometry experiments. As a starting point, the ESI-MS off-line reaction monitoring of catalytic systems allows the evaluation of catalytic efficiency (in terms of yield and reaction rate) and the identification of the involved intermediates. Once the most interesting system has been identified, the project involves the preparation of its heterogeneous version (with a supported catalyst) to be used in continuous flow reactions. Smaller equipments for flow reactions are very attractive at lab-scale, because they allow a fast screening and an easy on-line monitoring of processes to optimize their productivity. Meso-reactors (like a small HPLC column) and micro-reactors (like 3-D printed channels) are built and connected to the mass spectrometer to control the progress of catalytic reactions. Chiral organocatalysts bearing primary amino groups (such as 9-amino-9-epi-cinchona alkaloids and vicinal chiral diamines) or thiourea and amide functions (such as 9-amino-9-epi-cinchona alkaloid derivatives) will be exploited as privileged structures in the activation of carbonyl compounds providing new carbon-carbon bonds. These catalysts, their intrinsically charged intermediates (enamine or iminium ion), the active catalyst-substrate complexes (via noncovalent bonding) and products are easy ionizable and suitable to be explored by mass spectrometry. The project aims at creating a useful platform enabling catalyst selection and an early stage of process intensification (immobilized organocatalysts, flow mode reactions) with low material consumption.