FLACH · C-H activation and carbonylation in continuous-microflow

The aim of this research proposal is to employ microreactor technology in order to boost the palladium(II)-catalyzed C–H carbonylation reaction. In this way, the approach described in this proposal is conceptually different from the traditional batch strategies, which are currently published in the scientific literature. The ability to use elevated temperatures in a safe and reliable way may assist the deprotonation step, which is required to enable C–H functionalization. In addition, excellent interfacial contact between gaseous CO and the liquid phase can be expected in micro flow. This feature of microreactor technology allows for an enhancement of the mass-transfer from the gas to the liquid phase. Different flow regimes will be evaluated during this project in order to facilitate CO transfer. In addition, increasing the CO gas pressure leads to a further increase of the concentration of gaseous components in the liquid phase. Such reaction conditions need specialized equipment in batch processes, such as Parr bombs or autoclaves, but can be easily achieved in micro flow through combination of back pressure regulators and high pressure pumps. Consequently, by employing elevated temperatures and pressures, the applicant foresees that C–H carbonylation reactions can be accelerated significantly.Key objectives in this research proposal:1.Development of a microfluidic setup for the C–H carbonylation chemistry.2.Providing a comprehensive study on the influence of temperature and pressure on the C–H carbonylation reaction.3.Investigating the influence of the flow regime on the C–H carbonylation reaction.4.Exploiting the insights gained in objectives 1-3, the applicant expects to understand the key factors affecting the reactivity of the C–H carbonylation systems and this will allow us to broaden the reaction scope, leading to a myriad of novel compounds relevant for drug discovery and material science.