PHOTO ORGANO-Ir CAT · Photochemical cascade reactions by merging organo- and iridium catalysis: A stereocontrolled entry to molecular complexity.

Photochemical cascade reactions by merging organo- and iridium catalysis: A stereocontrolled entry to molecular complexity.

The requirement for drug discovery to facilitate the identification of successful lead candidates has challenged synthetic chemists to develop innovative strategies to rapidly generate screening collections of chiral molecules. Recently, the application of asymmetric aminocatalysis to cascade reactions has addressed this target enabling extraordinary levels of sophistication and stereocontrol, while fulfilling the requirements for both atom and step economy. Because of the rapid progress achieved, the general perception is that it would be difficult to further expand the synthetic potential of the aminocatalytic cascade approach. However, recent works from the host’s laboratories demonstrate that, by exploiting the photochemical activity of organocatalytic intermediates, light irradiation unlocks reaction pathways unavailable in the ground-state domain. In particular, by bringing a catalytically generated iminium ion to an electronically excited state, it is possible to perform β-functionalisations of enals not achievable under thermal control. This project seeks to capitalise upon this novel reactivity to further expand the synthetic potential of the organocatalytic cascade technique, by providing new opportunities for reaction invention. We planned to accomplish this by exploiting the photochemistry of iminium ions in processes that synergistically combine enamine chemistry with transition metal catalysis, thus merging, for the first time, tandem organo-metal catalysis with asymmetric photoreactions. The specific objectives were the following: 1. Design and optimise cascade reactions that take advantage of the unprecedented reactivity enabled by the photo-activation of iminium ions and exploit it in synergistic enamine/transition metal catalytic processes. 2. Functionalize and modify the compounds obtained using the above methodologies to access previously elusive natural-product-inspired architectures. 3. Evaluate the biological activity of the analogue libraries generated through bioassays and, eventually, modify and improve the most promising leads via fine modification of the previous structures Research endeavours that the project have produced: 1. A novel photochemical asymmetric protocol that converts raw materials into value-added synthetic building blocks, by exploiting the reactivity of chiral organocatalytic intermediates (iminium ions) under visible-light irradiation. 2. A further unprecedented asymmetric photochemical protocol, which is currently under investigation. 3. Five written contributions, including scientific papers and outreach publications.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз