Novel annulation catalysts via direct C-H bond amination

Introducing functionality into unactivated C-H bonds, a ubiquitous group in organic molecules, remains a significant challenge due to the inertness of the substrate. Traditional synthesis strategies involve functional group exchange, an inefficient process that generates significant waste and often requires strong chemical oxidants. This invention describes two novel iron-based catalysts used for direct functionalization of a broad range of C-H bonds.

The method described in US Pat. No. 9487472 uses an iron-based catalyst to synthesize acyclic and cyclic amines of various chain lengths, ring sizes, and architectures on C-H bonds. A related method (patent pending) uses another novel iron-based catalyst to aminate C-H bonds without activating or protecting groups to produce substituted bicyclic, spiro, and fused heterocycles. Additionally, with this method the catalyst can be easily separated from the product and recycled to improve overall performance.

This invention significantly improves a synthesis process that has historically been fraught with multiple steps, reagents, and waste generation, facilitating facile synthesis of acyclic and cyclic amines. These compounds are common in commodity chemicals as well as bioactive (e.g. nucleobases, B vitamins) and pharmaceutical (e.g. antibiotics, anti-histamines, anti-diabetics, NSAIDs, chemotherapies) molecules. This offers the potential to synthesize a broader library of active compounds for drug development and drug screening, or to improve synthesis processes for existing active compounds.

U.S. Patent(s) Issued: US 9,487,472 , US 9,724,682