Dearomatization and domino reactions as tools for the synthesis of functionalized polycyclic molecules

The aim of this project is to develop transition-metal catalyzed domino reactions involving functionalized chiral dienes, obtained via enzymatic dearomatization of arenes.

We have earlier seen that subjecting such dienes to Pd-catalysis triggers a reaction cascade, resulting in a highly functionalized tricyclic system in a single step.

Our aim is now to develop more complex cascades, by involving additional reaction steps or using multicatalyst systems, to see if new types of polycyclic scaffolds can be attained.

Potential applications include the synthesis of pharmaceuticals and natural products, where one molecule we are targeting is kinamycin F, with anticancer activity.A second aim is to use naturally occurring azulenes to construct chemosensors for detecting trimethylamine-N-oxide (TMAO). TMAO is important for many biological processes, including as an indicator of heart disease.

The common denominator linking the two parts is the use of transition metals, in conjunction with enzymatic dearomatization.

Additional tools are DFT-methods for mechanistic studies, as well as 2D NMR and x-ray diffraction.The importance here lies in advancing the field of transition metal catalysis, not only in terms of reaction parameters, but also in the molecular complexity that can be attained. The targeted azulene-based chemosensors are novel and could also be used to detect other chemical species.

The readout will be colorimetric, allowing applications in inexpensive portable devices.