Continuous-flow systems have recently emerged as a powerful tool for performing chemical transformations, since they ensure some advantages over traditional batch procedures, such as faster reactions, safer reactions, quick reaction optimization and easy scale-up. However, the application of continuous-flow systems to the stereoselective synthesis of chiral multifunctional molecules is still underdeveloped. In this context, we explored the use of different micro- and mesoreactors to perform stereoselective organocatalyzed reactions under continuous flow conditions. These studies were performed employing commercial traditional glass microreactors but also with PEEK (Polyetheretherketone) and PTFE (Polytetrafluoroethylene) HPLC tubing-based mesoreactors. Different in continuo organocatalytic synthesis of Active Pharmaceutical Ingredients (APIs) have been developed. The synthesis of a direct precursor of (S)-Baclofen in flow was realized by performing a metal-free stereoselective addition of activated nucleophiles to β-nitrostyrenes promoted by a bifunctional Takemoto type catalyst. Optimization of the experimental setup gave excellent enantioselectivities (up to 85% ee) and higher productivities if compared to the flask syntheses. The potential of this flow chemistry approach was demonstrated by the successful synthesis of other APIs such as (S)-Pregabalin intermediate and (S)-Warfarin . Moreover, continuous flow synthetic methodologies can also be easily combined to other enabling technologies, such as 3D-printing. This technology allows chemists to build devices with high precision and well-defined architecture. The combination of these two technologies in organic synthesis opens new and intriguing possibilities such as the fabrication of ad hoc designed-reactors. In this context, an in-house designed and 3D-printed reactionware device was realized and employed for the catalytic in flow synthesis of a Metaraminol, with good diastereo- and enantioselectivities.
Continuous-flow catalytic, stereoselective synthesis in micro- and meso- reactors / S. Rossi, A. Puglisi, M. Benaglia. ((Intervento presentato al 6. convegno EuCheMS Chemistry Congress tenutosi a Siviglia nel 2016.
|Titolo:||Continuous-flow catalytic, stereoselective synthesis in micro- and meso- reactors|
ROSSI, SERGIO (Corresponding)
|Data di pubblicazione:||set-2016|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Citazione:||Continuous-flow catalytic, stereoselective synthesis in micro- and meso- reactors / S. Rossi, A. Puglisi, M. Benaglia. ((Intervento presentato al 6. convegno EuCheMS Chemistry Congress tenutosi a Siviglia nel 2016.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|