| The clear understanding of catalytic cycles in homogeneous catalysis is at the heart of effective catalyst design. Thus, by elucidating the reaction mechanism, the selectivity determining step within a catalytic cycle can be unravelled. In turn, this enables finetuning of the properties of the ligands surrounding the metal in order to effect a given reaction in a highly regioselective or enantioselective fashion. The most straightforward way to access reaction mechanisms is through kinetic studies. However, such kinetic studies on catalysed reactions are often impaired by two general problems: (i) rate-limiting processes lying outside the catalytic cycle (e.g. catalyst activation or deactivation) dominate the overall kinetics measured; and/or (ii) very high catalyst activity, making the reaction simply too fast to measure with conventional technology. To overcome these two problems kinetic studies are often performed under conditions which are far away from the conditions used in practice. This can lead to a very distorted view of the overall catalytic cycle. The project proposed here addresses these two longstanding problems in homogeneous catalysis by performing kinetic studies through ultrafast in situ measurements within a microreactor (microfluidic device). The approach combines (i) ultrafast mixing (s) of the reactants using hydrodynamic focusing in a microreactor, (ii) quantitative detection of the molecular component concentrations based on their intrinsic vibrational signature using multiplex coherent anti-Stokes Raman scattering (CARS) microscopy, and (iii) microsecond time resolution by detection of the reactants and product concentrations along the microfluidic flow with sub-micron spatial resolution. We propose to study in detail two catalytic reactions which exhibit the behaviours aforementioned: (i) the hydrosilylation of alkenes catalysed by Pt-based complexes; and (ii) the ultrafast palladium-catalysed cyclopropanation of alkenes by diazoalkanes. The kinetic data obtained through our approach will provide detailed insights into the mechanisms of these reactions which have been previously elusive. The use of a microreactor provides a means for fast and controlled mixing of the reactants, precise temperature control of the reaction and an inherently safe environment for highly exothermic reactions (through efficient heat dissipation) using aggressive and toxic chemicals. In addition, only very small quantities (mg) of expensive reactants are required. As such, microreactors have recently been developing into an ideal new platform for controlled chemistry. However, the broad application of microreactors in synthetic chemistry has been hampered by the lack of appropriate tools to quantitatively characterize the reactants and products on-line within the microreactor. The recent advent coherent anti-Stokes Raman scattering (CARS) microscopy technique now allows us to monitor the evolution of fast chemical reactions in real time inside the microreactor, without any labels. CARS is highly sensitive, with signals exceeding spontaneous Raman by more than 4 orders of magnitude. We have recently overcome an important drawback in CARS, enabling the use of CARS as a quantitative analytical tool: multiplex CARS micro/spectroscopy can give quantitative information on the spatial distribution of both reactants and products across the microreactor, as well as time-resolved data on the kinetics of the reaction. While hydrodynamic focusing provides ultrafast mixing times, the high spatial resolution (~300 nm) of multiplex CARS microscopy in combination with the controlled laminar flow along the microchannel yields the time resolution to observe the fast reaction kinetics as the chemical reactions progresses after the initial mixing step. For the study of the hydrosilylation reaction we propose to decouple, within the microfluidic device, the precatalyst activation step (generation of the active species) and the actual catalysed reaction. This will enable the kinetics of the active species to be studied under steady-state reaction conditions (constant concentration of active species). This will give access to the kinetic profile of the actual catalytic cycle, which is in this case obscured by the rate-limiting catalyst activation step. On the other hand, the palladium-catalysed cyclopropanation reaction is simply too fast (TOF >100000 h-1) to be measured precisely and accurately by conventional kinetic methods. The high time resolution offered by the combination of ultrafast mixing within a microreactor and high spatial (and therefore temporal) resolution of quantitative CARS microscopy will permit direct observation of the time evolution of this reaction. In addition, the microreactor approach inherently provides a safe environment for the hazardous chemicals (e.g. diazomethane), as well as optimal heat control (due to the large surface to volume ratio) for this highly exothermic reaction. |
