Cyclometallated ruthenium catalyst enables late-stage directed arylation of pharmaceuticals
Authors: Marco Simonetti, Diego M Cannas, Xavier Just-Baringo, Iñigo J Vitorica-Yrezabal, Igor Larrosa
Journal: Nature Chemistry
Publication Date: 21 June, 2018
Department of: Chemistry
New class of ruthenium catalysts allows late-stage arylation of drugs
Most drugs and other biologically active compounds incorporate a large number of polar functional groups, which are responsible for the observed activity. However, the presence of these polar groups increase difficulty for chemists to modify these compounds as often transition metal catalyst will be incompatible with those functionalities.
Chemists at the University of Manchester have uncovered new mechanistic insights on the workings of ruthenium-catalysed C‒H arylations. This discovery has led to the design of a new class of ruthenium catalysts that present extremely high reactivity, when compared to current state-of-the-art catalysts, on C‒H arylation. These catalysts maintain their high reactivity under very mild conditions (e.g. room temperature), while displaying exquisite selectivity and efficiency, making them particularly suitable for the modification of highly functionalized delicate molecules such as drugs compounds. These ruthenium catalysts provide chemists with a tool to install aromatic groups at desired positions of complex molecules, opening the door to the exploration of new chemical space that would otherwise be impractical to access.
- Drug molecules generally contain several polar groups, often nitrogen- and oxygen-based. These can potentially coordinate catalysts and lead to catalyst poisoning or suffer reactions that decompose the molecules.
- C‒H arylation is a type of reaction that allows selecting one of the multiple C‒H bonds found in an organic molecule and replacing it with an aromatic ring through a C‒C bond formation.
- Late stage arylation is a specific type of C‒H arylation that is applicable to complex molecules, rather than just to simple ones.
- The picture shows the transformation of drugs into arylated versions upon reaction with the ruthenium “gate” catalysts.