New Catalysts for Synthesis of Stereodefined and Modifiable Tetrasubstituted Alkenes

Tetrasubstituted olefins are key to drug discovery, and the ability to such entities is a compelling goal. Pioneering studies have led to a number of noteworthy advances by significant shortcomings remain.

For example, it is especially challenging to access tetrasubstituted alkenes that contain four sizeable substituents or a F atom and/or a CF3 unit. Most protocols can only afford one of the possible isomers.

Tetrasubstituted alkenes that contain multiple modifiable substituents are 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, there are only a few reported olefin metathesis reactions that generate a cyclic tetrasubstituted olefin that does not contain two methyl substituents at each carbon (i.e., no stereochemistry).

A much smaller number (four cases) are RCM reactions that afford cyclic tetrasubstituted olefins with one modifiable C–Cl bond. All involve a Ru catalyst.

However, olefin metathesis reactions that can generate poly-halogenated olefins cannot be effected with a Ru catalyst (rapid decomposition).

Only a Mo or a W catalyst must be used, but such complexes do not exist.We will design a new class of pivoting Mo and W catalysts that can be used to promote efficient RCM and cross-metathesis (CM) reactions that generate a wide range of readily modifiable tetrasubstituted olefins.

We will accomplish this by designing catalysts wherein the rotation of the imido and aryloxide ligands is synchronized, so that a proper binding pocket is made available. The expected products, which can serve as versatile diversification points, will contain 2-3 easily modifiable units.

We will also design an entirely new class of cyclic Mo and W catalysts for CM between easily accessible trisubstituted alkenes and polyhalogenated alkenes. A unique feature of these catalysts is that intra