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Baumann, Marcus
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Baumann, Marcus
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Baumann, Marcus
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Now showing 1 - 10 of 11
- PublicationA Perspective on Continuous Flow Chemistry in the Pharmaceutical Industry(American Chemical Society, 2020-01-10)
; ; ; Continuous flow manufacture is an innovative technology platform, which is gaining momentum within the pharmaceutical industry. The key advantages of continuous flow include faster and safer reactions, which can be more environmentally friendly, smaller footprint, better quality product, and critically, the ability to perform chemistry that is difficult or impossible to do in batch mode. Globally, significant efforts have been made to develop the manufacturing flexibility and robustness of processes used to produce chemicals in a continuous way, yet despite these scientific developments, a major challenge for industry is the established application of flow technology to commercially relevant examples. The identification of opportunities to apply flow solutions to current processes is also critical to the success of this new technology for pharmaceutical and fine chemical companies. This review highlights industrial hurdles and the importance of education and showcases recent (2018-2019) and relevant industrial examples where utilization of flow technology has been successfully performed.713Scopus© Citations 186 - PublicationDiastereoselective Synthesis and Diversification of Highly Functionalized CyclopentanonesAn efficient entry into highly substituted cyclopentanones is presented based on functionalizing cyclopentenones by means of an aza-Michael reaction with different aniline nucleophiles. The excellent diastereoselectivity of this process is ascribed to H-bonding between a tertiary alcohol and the incoming nucleophiles. Additionally, the functionalization of the parent cyclopentenones via the Baylis-Hillman reaction is demonstrated. Together, these transformations showcase the elaboration of a simple precursor by installation of versatile functionalities at either the α- or β-position of the embedded enone and thus represent valuable methods for the construction of diversely functionalized cyclopentanones.
119Scopus© Citations 1 - PublicationA Scalable Continuous Photochemical Process for the Generation of AminopropylsulfonesAn efficient continuous photochemical process is presented that delivers a series of novel γ-aminopropylsulfones via a tetrabutylammonium decatungstate (TBADT) catalysed HAT-process. Crucial to this success is the exploitation of a new high-power LED emitting at 365 nm that was found to be superior to an alternative medium-pressure Hg lamp. The resulting flow process enabled the scale-up of this transformation reaching throughputs of 20 mmol h−1 at substrate concentrations up to 500 mM. Additionally, the substrate scope of this transformation was evaluated demonstrating the straightforward incorporation of different amine substituents as well as alkyl appendages next to the sulfone moiety. It is anticipated that this methodology will allow for further exploitations of these underrepresented γ-aminopropylsulfone scaffolds in the future.
108Scopus© Citations 12 - PublicationDevelopment of a Telescoped Flow Process for the Safe and Effective Generation of Propargylic AminesPropargylic amines are important multifunctional building blocks that are frequently exploited in the synthesis of privileged heterocyclic entities. Herein we report on a novel flow process that achieves the safe and effective on-demand synthesis of propargylic amines in a telescoped manner. This process minimizes exposure to hazardous azide intermediates and renders a streamlined route into these building blocks. The value of this approach is demonstrated by the rapid generation of a small selection of drug-like thiazolines that result from a high-yielding reaction cascade between propargylic amines with different aryl isothiocyanates.
72Scopus© Citations 5 - PublicationA concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimicAn assembled suite of flow-based transformations have been used to rapidly scale-up the production of a novel auxin mimic-based herbicide which was required for preliminary field trials. The overall synthetic approach and optimisation studies are described along with a full description of the final reactor configurations employed for the synthesis as well as the downstream processing of the reaction streams.
60Scopus© Citations 15 - PublicationContinuous flow photochemistry for the preparation of bioactive moleculesThe last decade has witnessed a remarkable development towards improved and new photochemical transformations in response to greener and more sustainable chemical synthesis needs. Additionally, the availability of modern continuous flow reactors has enabled widespread applications in view of more streamlined and custom designed flow processes. In this focused review article, we wish to evaluate the standing of the field of continuous flow photochemistry with a specific emphasis on the generation of bioactive entities, including natural products, drugs and their precursors. To this end we highlight key developments in this field that have contributed to the progress achieved to date. Dedicated sections present the variety of suitable reactor designs and set-ups available; a short discussion on the relevance of greener and more sustainable approaches; and selected key applications in the area of bioactive structures. A final section outlines remaining challenges and areas that will benefit from further developments in this fast-moving area. It is hoped that this report provides a valuable update on this important field of synthetic chemistry which may fuel developments in the future.
58Scopus© Citations 57 - PublicationIntegrating continuous flow synthesis with in-line analysis and data generationContinuous flow synthesis of fine chemicals has successfully advanced from an academic niche area to a rapidly growing field of its own that directly impacts developments and applications in industrial settings. Whilst the numerous advantages of flow over batch processing are widely recognised and have led to a wider uptake of continuous flow synthesis within the community, we have reached a point where continuous flow synthesis has to transition from a stand-alone enabling technology to a readily integrated synthesis concept. Thus it is paramount to embrace a multitude of in-line analysis and purification techniques to not only allow for efficiently telescoped multi-step sequences but ultimately generate bioactivity data concomitantly on newly synthesised entities. This short review summarises the state of the art in this field and presents both challenges and opportunities that arise from this ambitious endeavour.
93Scopus© Citations 26 - PublicationContinuous Flow Synthesis of Quinolines via a Scalable Tandem Photoisomerization-Cyclization ProcessA continuous photochemical process is presented that renders a series of quinoline products via an alkene isomerization and cyclocondensation cascade. It is demonstrated that a high-power LED lamp generates the desired targets with higher productivity and efficiency than a medium-pressure Hg-lamp. The scope of this tandem process is established and allows for the generation of various substituted quinolines in high yields and with throughputs of greater than one gram per hour. Finally, this effective flow process is coupled with a telescoped hydrogenation reaction to render a series of tetrahydroquinolines including the antimalarial natural product galipinine.
120Scopus© Citations 19 - PublicationSynthesis of Bioderived Cinnolines and Their Flow-Based Conversion into 1,4-Dihydrocinnoline DerivativesStarting from phenylhydrazine and glucose, a versatile cinnoline scaffold was obtained on a multigram scale and further derivatized. A simple continuous-flow hydrogenation process permits the conversion of selected cinnolines into their 1,4-dihydrocinnoline counterparts. These products are generated in high yields and high purities with residence times of less than one minute and, along with their cinnoline precursors, are expected to serve as valuable heterocyclic building blocks for future medicinal chemistry programs.
105Scopus© Citations 4 - PublicationDevelopment of a Continuous Flow Photoisomerization Reaction Converting Isoxazoles into Diverse Oxazole ProductsA continuous flow process is presented, which directly converts isoxazoles into their oxazole counterparts via a photochemical transposition reaction. This results in the first reported exploitation of this transformation to establish its scope and synthetic utility. A series of various di- and trisubstituted oxazole products bearing different appendages including different heterocyclic moieties were realized through this rapid and mild flow process. Furthermore, the robustness of this approach was demonstrated by generating gram quantities of selected products while also providing insights into likely intermediates.
137Scopus© Citations 13