New Catalysts for Synthesis of Stereodefined and Modifiable Tetrasubstituted Alkenes
Tetrasubstituted olefins are key to drug discovery, and the ability to access such entities is crucial. Pioneering studies have led to noteworthy advances but significant shortcomings remain. For example, it is especially challenging to access tetrasubstituted alkenes that contain four sizeable substituents or a fluorine atom and/or a trifluoromethyl group. The limited number of available protocols only afford one of the two possible isomers.
Tetrasubstituted alkenes that containmultiple modifiable substituentsare particularly attractive, because they can serve as diversification points that lead to a large assortment of desirable compounds. Olefin metathesis offers a strategically distinct, efficient, and stereodivergent route to such entities. Yet, olefin metathesis catalysts that can be used to generate a wide range of tetrasubstituted olefins are yet to be introduced.
We will use the new ERC Advanced Grant to design a new class of pivoting molybdenum and tungsten catalysts that can be used to promote ring-closing metathesis and cross-metathesis reactions that efficiently generate readily modifiable tetrasubstituted olefins. The unique design feature in these catalysts is that rotation of the ligands is synchronized, allowing a suitable binding pocket to become available that accommodates a highly substituted metallacyclobutane.
We will also design an entirely new class of cyclic molybdenum and tungsten catalysts for cross-metathesis between easily accessible trisubstituted alkenes and polyhalogenated alkenes. A distinguishing feature of these catalysts is that intramolecularity plays a key role within the catalytic cycle. Stereodivergency will be achieved by stereoretentive processes with commercially available tetrasubstituted polyhalo olefins. The new complexes will represent another exciting new chapter in catalyst design, expanding the range of accessible tetrasubstituted alkenes.