Recently, imido zirconium and titanium complexes have been shown to react with allenes and alkynes in a cycloaddition reaction. For the titanium complexes, these reactions are catalytic and serve to generate products with primary amines bound to secondary carbons. This process works intramolecularly to produce 2-substituted 2,3,4,5-tetrahydropyridines, valuable intermediates in the synthesis of natural products and pharmaceutical candidates, especially if generated asymmetrically. In this proposal, we design chiral catalysts for this reaction such that one enantiomer of the starting alpha-chiral amine reacts preferentially to the other enantiomer. This methodology is developed as a dynamic kinetic resolution (DKR) by the design and employment of electron-withdrawing ligands on titanium and use of appropriate base to epimerize the alpha-N-imido proton by pushing electron density onto the titanium center. Under these conditions, the less reactive enantiomer of starting material may be converted to a racemic mixture, which will again have one preferentially reactive enantiomer. This cycling will ultimately generate the tetrahydropyridines in high yield and enantioselectivity. In so doing, we will provide simple and convenient access to these chiral heterocycles.
