Photo-Flow Processes for the Synthesis of Drug-Like Entities

The scientific progress that has characterised the last 20 years has allowed for reaching achievements that at the beginning of this century were probably only imaginable. For example, today it is possible to have robotic surgery to perform incredibly precise procedures, smart tools to control the energy footprint, the Cloud for data sharing together with ultra-fast internet connection, augmented reality (AR) applied to entertainment, medicine, education, and business. As a matter of fact, the chemistry community enjoyed the benefits of technology too. The advent of flow technology, that is the possibility to perform chemical reactions in small tubes in a continuous fashion, has revolutionised the way of doing chemistry. With this technology, many transformations are performed safer than traditional methods, leading to a renaissance of forgotten reactions that were considered too unsafe or not inefficient. Many other transformations performed in flow mode are more energetically convenient, reducing the cost and the energetic impact of a process. Moreover, some transformations have been discovered because of the application of flow chemistry, due to the unique features that this technology offers. Since the general awareness for topics such as sustainability, data sharing, workplace safety and productivity is undeniably increased over the last decade, the scientific community and industries have happily welcomed this technology. In fact, FDA and EMA have also expressed their support for the application of continuous manufacturing in industry, which would lead to safer, more efficient, and less environmentally detrimental processes. Despite this, flow chemistry still needs to expand its horizons and the technology transfer that comes from academia and research institutes is essential. As the inventor of the post-it, Geoffrey Nicholson, stated “Research transforms money into knowledge … technology transfer transforms knowledge into money.” Therefore, the work described in this thesis aims to contribute to the knowledge related to photochemical reactions performed in flow. Photochemistry has in fact an enormous potential in the development of new synthetic processes for the generation of complex structures, typically present in pharmacophores. Flow technology deeply enhances the capabilities of photochemistry, thanks to the possibility to perform photochemical reactions in a milder way due to the efficient irradiation and the possibility to use new light sources that ensure selective and efficient irradiation without being energetically onerous. This thesis will highlight a selection of photo-flow chemistry applications showcasing the synthesis of compounds relevant in medicinal chemistry programs.