Advancing Chemical Synthesis through Automation, Processes and Thinking
Beilstein Organic Chemistry Symposium 2017

26 – 28 September 2017
Potsdam, Germany

 

Scientific Organizers:

Ian Baxendale / Department of Chemistry, University of Durham, United Kingdom

Andreas Kirschning / Institute of Organic Chemistry, Leibniz Universität Hannover, Germany

Summary

Conference overview

The conference was held at the Avendi Hotel in Potsdam on the banks of the Griebnitzsee during the period of the 26th– 28th of September 2017. The gathering was designed to cover a range of topics in celebration of four assembled Thematic Series “Flow Chemistry III and III“ edited by Andreas Kirschning and “Automated chemical synthesis” edited by Ian Baxendale, Marcus Baumann and Richard Bourne which were published in the Open Access Beilstein Journal of Organic Chemistry. Participants and speakers were drawn from both industry and academia traveling from many different countries to be present and giving the conference a truly international flavour. To encourage significant time for discussions and the productive interchange of thoughts and ideas the attendance list was limited to only 55 people. A nutritious supply of food, coffee and on occasion beer (well it was in Germany) sustained the participants through a range of stimulating talks and in the further discussions and debates that followed.

 

Background

The themes of Flow Chemistry and Automated Chemical Synthesis are rapidly evolving areas influenced by many interwoven subjects including robotics, continuous processing technologies, new and improved reaction monitoring devices and aspects of software design & control. They further draw on knowledge from other core disciplines such as mathematics, biology and the computational sciences as well as bridging chemical synthesis and reaction engineering. Our vision for the conference was to bring together the leading minds from a diverse cross section of regular contributors to these scientific themes to highlight the most interesting research and discuss a vision of the future.

 

Speakers and Science

We were delighted to gather a truly inspirational group of speakers covering a broad range of topics and we were privileged to have an excellent group of interactive attendees who helped to tease out many new aspects in questioning and challenging the ideas and concepts presented.

Several overarching themes relating to automated chemical synthesis were covered during the conference with particular emphasis being placed upon data capture, including accuracy and completeness of experimental data – also pertaining to the recording and ultimate publication of procedures/protocols and evidence data. Data mining and computer aided synthetic route design/planning and how this impacts on the selection of reactors was discussed. Of increasing importance were methods of statistical analysis and evolutionary algorithms which as highlighted are expected to further facilitate complex decision making processes – including for monitoring and enabling rapid responses to changes in chemical reactions (the dedicated worker/observer concept).

These ideas were complimented by several talks which outlined new concepts and strategies in automated data capture and analysis linking with the ideals of integrated feedback and self-regulating/optimising chemical processes. These approaches were shown to be valid not only for small molecule preparation but also polymer synthesis and other large macromolecular assemblies.

Of course many speakers noted that despite all the innovations true leaps in efficiency and productivity often arose through a better fundamental understanding of the speciation and mechanistic pathways involved in the transformations. In this context it was apparent throughout the conference how many new catalyst systems have been developed to improve chemical reactions (C-C forming and C-H activation). Of note was that many of these catalysts were being prepared as heterogeneous immobilised systems for more effective use within continuous flow reactors. This was also a trend being reflected in the emergence of more biocatalyst driven processes where efficiency gains in yield and selectivity were being achieved through judicious application of chemical engineering in reactor design and improved biocatalysts production. Again, immobilisations of the enzymatic species as well as the potential co-factors were being addressed to increase efficiency and reduced downstream processing requirements.

Alternative activation processes involving photo and electrochemical transformations were also very prevalent with several demonstrations of improved reactor construction allowing access to new and complex chemical architectures in high productivity. Convincing case studies of how flow chemistry could be used to accelerate drug discovery and enable ready scale up of reactions involving traditionally ‘forbidden’ chemistries were disclosed. This also involved examples of complete ‘make and screen’ platforms to identify preliminary targets in initial hit generation. The different stages of drug discovery were expanded upon with talks regarding the future designs of small footprint chemical reactors for ‘on-demand’ drug delivery (synthesis/formulation/dispensing) and also models for larger scale plant design relating to bulk medicine manufacture. Linking to these ideas was how new thinking in reactor design such as using technologies like 3D printing could be applied to facilitate rapid prototyping and lead to new reactor formats.

Overall it was a lively and though provoking conference. The general sentiment was that innovation very is strong in the chemical sciences and that we are on the crux of a technological revolution which will significantly change but also enhance our synthetic capabilities.

Ian Baxendale and Andreas Kirschning

Program

 

I. REACTIVE INTERMEDIATES AND REAGENTS

Flash chemistry makes it possible for intermolecular reactions to outpace intramolecular reactions
Jun-ichi Yoshida, Kyoto University

Flow photochemistry in organic synthesis - generating molecular complexity on the gram and kilogram scales
Kevin Booker-Milburn, University of Bristol

II. MEDICINAL CHEMISTRY APPLICATIONS

From a priori data (mining) to automated discovery and development
Alexei Lapkin, University of Cambridge

Enabling chemistry technologies - accelerators of drug discovery
Stevan Djuric, AbbVie, North Chicago

III. PROCESSING

Process development and scale-upof multiphase reactions in micro reactors
Thorsten Röder, University of Applied Sciences Mannheim

The missing capabilities, that once addressed, will enable small, agile factories for pharmaceutical manufacture
Andrew Rutter

 

IV. ONLINE ANALYSIS

Integrating chemical synthesis and analysis at the microscale
Detlev Belder, Leipzig University

Online monitoring in continuous flow polymerizations: towards autonomous precision polymer synthesis
Tanja Junkers, Hasselt University

V. BIOCATALYSIS

Designing chemoenzymatic synthesis in flow by reaction engineering and online analytics
Andreas Liese, Hamburg University of Technology

Chances and challenges of biocatalysis in flow chemistry
Martina Pohl, Forschungszentrum Jülich

Biocatalytic esterifications and transaminations in microflow systems
Polona Žnidaršič Plazl, University of Ljubljana

Exploiting the power of flow chemistry in synthesis: enabling safe use of hazardous reagents
Anita Maguire, University College Cork

VI. NEW CONCEPTS

Accelerated C–H activation chemistry in flow microreactors
Timothy Noël, Eindhoven University of Technology

Immobilized catalytic systems for asymmetric flow processes
Miquel A. Pericàs, Institute of Chemical Research of Catalonia

 

VII. PROCESSING

Automated flow chemistry systems for screening, kinetics, and optimization
Klavs F. Jensen

From one to multiple flows and back to ONE-FLOW
Volker Hessel

VIII. NEW CHEMICAL METHODS

Advanced techniques and approaches for small molecule synthesis
Kerry Gilmore

Set-up and assessment of flow systems for streamlined synthesis and medicinal chemistry
Antimo Gioiello

Powerful organic synthesis by flow reactions with heterogeneous catalysts
Shu Kobayashi

Digitization of organic synthesis into reactionware cartridges for remote multi-step organic synthesis of pharmaceuticals on demand
Lee Cronin

Gruppenbild Symposium OC Synthesis 2017