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Abstract

The catalytic functionalization of the α C(sp³)–H bond of amines has become a powerful approach for synthesizing nitrogen-containing compounds. In recent years, the use of inexpensive and earth-abundant early transition metals has proven valuable for selectively assembling substituted amines and N-heterocycles. Herein, we examine the use of zirconium as a platform for accessing several types of nitrogenous compounds through catalytic α C–H functionalization of amines. A zirconium complex supported by a bis(ureate) ligand can be employed for promoting a variety of element−element bond-forming catalytic processes as discussed in Chapter 1. Mechanistic insights, gained from a combination of kinetic analysis, isolation of reaction intermediates and stoichiometric reactivity, have revealed a series of features that are essential to this zirconium system for enabling catalytic E−E’ bond formation. Using this zirconium system, the catalytic synthesis of allylic amines via hydroaminoalkylation of alkynes was accomplished. In these reactions, the α C–H bond of an amine is added across an unsaturated π-bond of an alkyne in a 100% atom-economic fashion. Mechanistic insights have revealed the importance of ligand design in the generation of a sterically accessible metal center for enabling catalytic turnover through protic amine coordination. The reactivity of zirconium-based catalysts was explored for the regioselective 4,1-hydroaminoalkylation of conjugated dienes to access homoallylic amines. Reactivity assessment of stoichiometrically prepared reaction intermediates has revealed the mechanistic nature of the change on the mode of addition of these reactions with respect to the 1,2 mode of addition of traditional early transition-metal-catalyzed hydroaminoalkylation reactions. Finally, the new understanding of the reactivity of the bis(ureate) zirconium complex was leveraged for promoting dehydrogenative C(sp³)–C(sp²) coupling between amines and nitrogen-containing heterocycles to yield C2 aminoalkylated N-heterocycles. In this transformation, the expanded coordination number at zirconium coupled with the highly flexible ancillary ligand was crucial for mediating challenging reaction steps as supported experimentally and by DFT calculations. These results highlight the expanding potential of early transition metals for catalyzing various types of C–C bond forming reactions that provide access to value-added nitrogen-containing products.