Heterogeneous Catalysis for Tandem Reactions

As long as the molecular complexity increases, the number of chemical transformations will increase in parallel, becoming a highly demanding synthetic process in terms of time and resources. Since the loss of material after each purification step will also dramatically reduce the overall efficiency of a synthetic process, the conversion of such transformation into a practical and efficient process will be a great challenge for synthetic chemists. Recent examples have shown that multifunctional catalytic systems can reduce the number of synthetic steps by leading sequential catalytic processes into one-synthetic operation. These one-pot processes allow for different reactions to be carried out in a single vessel without purification between steps, hence avoiding stop-and-go syntheses and therefore producing an economical and environmental benefit. Multienzymatic systems that perform multistep reactions in nature have been a model for the development of artificial systems in an attempt to mimic different aspects of synthetic strategies that operate in biological systems. However, there has been significant progress in this direction over past decades, one-pot catalytic reactions are still not of general application. A primary reason is that controlling one-pot multistep reactions is rather difficult because, unlike for biocatalysts, the interactions arising between different active species and components involved in the global synthetic sequence can cause deactivation. In fact, an active center should be compatible with residual material (substrates, intermediates, solvents, additives) that coexists from preceding steps and should also exhibit reaction sequence selectivity. It is thus necessary to find a common operational window for connecting each individual reaction into a global process, hence creating difficulties that will increase gradually with the number of combined catalytic cycles. One way to approach the problem relies on the preparation of multisite solid catalysts in which a series of well-optimized isolated active sites able to catalyze the different reactions are immobilized on a support. For instance, if one considers a bifunctional catalyst, this can be designed in such a way that the two different catalytic functions (say, for example, an acidic and a basic site) act in a collaborative way in the transition state, or each one catalyzes a different reaction in a multistep catalytic process. It becomes apparent that the design of an ideal multifunctional solid catalyst should involve generating the actives sites on a unique support; however, the material synthesis procedure to achieve this objective can sometimes be difficult. Then composite solids can be prepared in which a different catalytically active site is located in each component of the composite. Although the conceptual methodology for using multifunctional catalysts to catalyze multistep reactions looks straightforward, this is not so straightforward in practice. Indeed, a common reaction window should be found in which the different reactions can operate on the different catalytic sites in a one-pot process. This involves searching for compatible reaction temperatures, pressures, solvents, etc. Therefore, the first step in the design of a one-pot multistep catalytic process is to perform a thermodynamic study to establish the thermodynamic compatibility of the different reactions. This study has to be made with an open mind since, in some cases, the use of multifunctional catalysts can help to perform in a one-pot sequential way reactions in which one of them is not occurring under optimal thermodynamic conditions to achieve maximum product yield. Consider, for instance, the well-known bifunctional alkane hydroisomerization on hydrocracking solid catalysts, formed by a metal function (for instance, Pt) supported on an acid carrier (for instance, amorphous silica− alumina or zeolites). In this case, the first reaction step is the dehydrogenation of an alkane on the metallic function to give the corresponding olefin plus hydrogen. Then, when the olefin is formed, it adsorbs onto the acidic function to give a carbenium ion that undergoes branching isomerization (or cracking, or both), desorbing as an olefin that becomes hydrogenated on the metallic function (see Scheme 1). The reactions are carried out under high H2 pressure (P ≥ 30 bar) and relatively low temperatures (180−400 °C), which are thermodynamically unfavorable for performing the first reaction