Over the past 20 years, thermomorphic multiphase systems (TMS) have been used as a versatile and elegant strategy for the recovery and recycling of homogeneous transition‐metal catalysts, in both batch‐scale experiments and continuously operated processes. TMS ensure a homogeneous reaction in a monophasic reaction mixture at reaction temperature and the recovery of the homogeneous transition‐metal catalyst through liquid–liquid separation at a lower separation temperature. This is achieved by using at least two solvents, which have a highly temperature‐sensitive miscibility gap. The suitability of commercially available solvents makes this approach highly interesting from an industrial point of view. For the first time, herein, all studies in the area of TMS are reviewed, with the aim of providing a concise and integral representation of this approach for homogeneous catalyst recovery. In addition to the discussion of examples from the literature, the thermodynamic fundamentals of the temperature‐dependent miscibility of solvents are also presented. This review also gives key indicators to compare different TMS approaches, for instance. In this way, new solvent combinations and in‐depth research, as well as improvements to existing approaches, can be addressed and promoted.

We present the development of catalytic autotandem reactions into continuous-flow processes on the example of homogeneously catalyzed hydroaminomethylation (consisting of hydroformylation and subsequent reductive amination) as a case study. The synthesis of higher aliphatic amines was successfully operated in a continuous-flow miniplant. Key to success was the development of an integrated catalyst recycling for the homogeneous Rhodium/SulfoXantphos catalyst. With 1-decene and diethylamine as substrates, an average yield of the linear amine of 61% over 60 h of stable process operation was achieved. The catalyst recycling has been accomplished by using a thermomorphic multiphase system (TMS) consisting of methanol and ndodecane, which was rationally established in batch experiments with a methodical approach. This TMS ensured high catalytic activities and facilitated an efficient catalyst separation and recycling. Before application in a continuous process, catalyst recyclability was proven, showing high catalyst activity over six runs with turnover frequencies up to 2400 h −1 .

For the first time, the successful application of the homogeneously catalyzed reductive amination in a thermomorphic multiphase system (TMS) and the first reported scale-up of this reaction into a continuous process, which recovers and recycles the homogeneous catalyst in flow, is presented. Herein, the model substrate 1-decanal reacts with the secondary amine diethylamine to form the corresponding product N,N-diethyldecylamine. A thermomorphic multiphase system (TMS) is established as a recycling strategy to recover and reuse the catalyst for the continuous process. After screening different solvents for the TMS and optimizing the reaction conditions in batch mode, the recycling of the rhodium catalyst was realized in a fully automated miniplant. Parameters influencing the stability of the process were identified and optimized to develop the continuous process. The process was operated in a steady state over 90 h with yields >90% of the desired product and low catalyst leaching <1%/h.

Solvents have an enormous impact on yield and turnover of chemical reactions in complex media. There is, however, a lack of consistent model-based tools to a priori identify the appropriate solvent for homogeneously catalyzed reactions. Here, a thermodynamically consistent approach for a reductive amination reaction is presented. It combines solvent screening using a thermodynamic-activity model and quantum chemical calculations. The optimization of activity coefficient-based predicted kinetics gives a suitable list of candidate solvents. The results were confirmed by batch experiments in selected solvents. This approach allows reducing time and lab resources for solvent selection to a minimum.

Herein, we report about the development of an isomerization/hydroformylation tandem reaction to selectively convert fatty acid methyl esters into asymmetric α,ω-functionalized aldehyde esters. An orthogonal tandem catalytic system consisting of a palladium-based isomerization catalyst and a rhodium-based hydroformylation catalyst was developed, using methyl 3-hexenoate as a model substrate. Using this catalyst, high yields (81% at 99% conversion) and regioselectivities (l/b-ratio of 98/2) toward the desired terminal hydroformylation product are obtained in the conversion of methyl 3-hexenoate under mild conditions. Ethyl 4-decenoate was subsequently applied as a second model substrate to identify challenges associated with the longer chain length of the unsaturated ester. Finally, methyl oleate was converted using the developed catalyst system. High aldehyde yields of 74% (at 99% conversion) with an l/b-ratio of 91/9 are obtained.