Ti-catalyzed cascading hydroaminoalkylation as a route to complex functionalized amines

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Project Summary/Abstract Central to the development of medicine is organic chemistry and catalysis as it has permitted the discovery of new reactions and methods for the synthesis of key pharmaceutical components that will play a critical role in continuing the advancement of modern medicine. With the high presence of nitrogen atoms in drug candidates due to their high biological activity, it is crucial to develop new and innovative methods to synthesize and functionalize nitrogen-containing molecules. Recently, reactive titanium intermediates were used to explore second insertions of unsaturated species yielding useful nitrogen heterocycles. This proposal will focus on developing an efficient and one-step atom- economical Ti-catalyzed multicomponent, cascading hydroaminoalkylation reaction to produce β- cycloalkyl amines from dienes and amine/aniline substrates. This methodology has potential to be a valuable synthetic tool because β-cycloalkyl amines products are scaffolds present in pharmaceutical compounds such as cyclopentamine and propylhexedrine and in M3 muscarinic antagonist. Additionally, this method will provide a fundamental understanding of this new reaction class that can be extended into other cascading reactions to rapidly build molecule complexity.