New Catalysts for Synthesis of Stereodefined and Modifiable Tetrasubstituted Alkenes

Introduction

Tetrasubstituted olefins are key to drug discovery, and the ability to synthesize such entities is a compelling goal. Pioneering studies have led to a number of 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 CF3 unit. Most protocols can only afford one of the possible isomers.

Importance of Tetrasubstituted Alkenes

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 Challenges

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).

Limited Cases

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 due to rapid decomposition.

Catalyst Development

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.

Catalyst Design

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.

New Class of Catalysts

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-