Automation and microfluidic tools potentially enable efficient, fast, and focused reaction development of complex chemistries, while minimizing resource- and material consumption. The introduction of automation-assisted workflows will contribute to the more sustainable development and scale-up of new and improved catalytic technologies. Herein, the application of automation and microfluidics to the development of a complex asymmetric hydrogenation reaction is described. Screening and optimization experiments were performed using an automated microfluidic platform, which enabled a drastic reduction in the material consumption compared to conventional laboratory practices. A suitable catalytic system was identified from a library of Ru^II-diamino precatalysts. In situ precatalyst activation was studied with ¹H/³¹P nuclear magnetic resonance (NMR), and the reaction was scaled up to multigram quantities in a batch autoclave. These reactions were monitored using an automated liquid-phase sampling system. Ultimately, in less than a week of total experimental time, multigram quantities of the target enantiopure alcohol product were provided by this automation-assisted approach.

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This invention describes an apparatus that enables the automated removal of small samples from fluids such as those encountered in (bio-)chemical reactors. These samples can then be used for, e.g., kinetic analysis and quality control applications. The system was explicitly designed to be compatible with harsh and aggressive reaction conditions and can be used up to 250°C and 345 bar. The system was incorporated into a high-pressure capable operando reaction analysis platform that enabled simultaneous sampling of the reaction mixture and operando monitoring of the reaction using multiple channels of spectroscopy, thereby offering accessible and convenient data-rich experimentation. We have started a company to further develop the technology and bring it to market. We are actively looking for early adopters, collaborators, joint-venturing, and investors.@en

Alkoxycarbonylations are important and versatile reactions that result in the formation of a new C-C bond. Herein, we report on a new and halide-free alkoxycarbonylation reaction that does not require the application of an external carbon monoxide atmosphere. Instead, manganese carbonyl complexes and organo(alkoxy)borate salts react to form an ester product containing the target C-C bond. The required organo(alkoxy)borate salts are conveniently generated from the stoichiometric reaction of an organoborane and an alkoxide salt and can be telescoped without purification. The protocol leads to the formation of both aromatic and aliphatic esters and gives complete control over the ester's substitution (e.g., OMe, OtBu, OPh). A reaction mechanism was proposed on the basis of stoichiometric reactivity studies, spectroscopy, and DFT calculations. The new chemistry is particularly relevant for the field of Mn(I) catalysis and clearly points to a potential pathway toward irreversible catalyst deactivation.

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Catalysis is a critical enabling technology that directly contributes to higher standards of living. This is a remarkable feat for a technology that most consumers have no direct contact with and perhaps only vaguely know from their car’s catalytic converter. Even many technical users regard catalysts as ideal substances that promote a target transformation without being consumed in the reaction. Reality, however, is much more complex because catalysts can also produce undesirable side-products or stop working before the target reaction is complete. This dissertation explores such complexity. The aim of this work was to study real catalytic systems under relevant reaction conditions. This challenge was approached from two different directions, and the dissertation is therefore divided into two parts. Part I describes our study of non-noble Mn complexes as catalysts for a variety of reduction chemistries. Particular attention was given to the study of deactivation phenomena to understand why some catalysts stop operating early in their lifetime. This work led to catalytic methods that enable improved operation at significantly lower catalyst loading. The second part of this dissertation focuses on the development and application of automation and data-rich experimentation methods for catalysis R&D. An automated reaction analysis platform was developed that simultaneously produces kinetic data and several representative data streams of operando spectroscopy. These tools were used to study and optimise the performance of a variety of chemistries, and are expected to provide the required dense data for contemporary data-driven methods.@en

Transitioning from fossil fuels to sustainable and green energy sources in mobile applications is a difficult challenge and demands sustained and highly multidisciplinary efforts in R&D. Liquid organic hydrogen carriers (LOHC) offer several advantages over more conventional energy storage solutions, but have not been yet demonstrated at scale. Herein we describe the development of an integrated and compact 25 kW formic acid-to-power system by a team of BSc and MSc students. We highlight a number of key engineering challenges encountered during scale-up of the technology and discuss several aspects commonly overlooked by academic researchers. Conclusively, we provide a critical outlook and suggest a number of developmental areas currently inhibiting further implementation of the technology.

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Catalytic reductions of carbonyl-containing compounds are highly important for the safe, sustainable, and economical production of alcohols. Herein, we report on the efficient transfer hydrogenation of ketones catalyzed by a highly potent Mn(I)−NHC complex. Mn−NHC 1 is practical at metal concentrations as low as 75 ppm, thus approaching loadings more conventionally reserved for noble metal based systems. With these low Mn concentrations, catalyst deactivation is found to be highly temperature dependent and becomes especially prominent at increased reaction temperature. Ultimately, understanding of deactivation pathways could help close the activity/stability-gap with Ru and Ir catalysts towards the practical implementation of sustainable earth-abundant Mn-complexes.

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The catalytic asymmetric transfer hydrogenation (ATH) of ketones is a powerful methodology for the practical and efficient installation of chiral centers. Herein, we describe the synthesis, characterization, and catalytic application of a series of manganese complexes bearing simple chiral diamine ligands. We performed an extensive experimental and computational mechanistic study and present the first detailed experimental kinetic study of Mn-catalyzed ATH. We demonstrate that conventional mechanistic approaches toward catalyst optimization fail and how apparently different precatalysts lead to identical intermediates and thus catalytic performance. Ultimately, the Mn-N,N complexes under study enable quantitative ATH of acetophenones to the corresponding chiral alcohols with 75-87% ee.

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The original Fig. 6 presented incorrect thermodynamic data for the conversion 4c + KOtBu → 2 + KOMe. A revised Fig. 6 is now provided. These changes do not affect the article text and its conclusions.

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Catalytic hydrogenation and dehydrogenation reactions form the core of the modern chemical industry. This vast class of reactions is found in any part of chemical synthesis starting from the milligram-scale exploratory organic chemistry to the multi-ton base chemicals production. Noble metal catalysis has long been the key driving force in enabling these transformations with carbonyl substrates and their nitrogen-containing counterparts. This review is aimed at introducing the reader to the remarkable progress made in the last three years in the development of base metal catalysts for hydrogenations and dehydrogenative transformations.

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The reaction mechanism of ester hydrogenation catalyzed by a bidentate aminophosphine ligated manganese catalyst was studied by DFT calculations. Particular emphasize was placed on the role of the alkoxide base additives. The presence of such basic promoters as KO^tBu can improve the catalyst activity by lowering the activation barriers of H₂ dissociation as well as the hydrogenation step. The promoting effect of KO^tBu on H₂ activation is much stronger than that of tert-butoxides with other alkali metals, which is crucial for the catalyst regeneration from the deactivated Mn-alkoxide species in the resting state.

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