Cyclic Ureate Tantalum Catalyst for Preferential Hydroaminoalkylation with Aliphatic Amines: Mechanistic Insights into Substrate Controlled Reactivity

The efficient and catalytic amination
of unactivated alkenes with
simple secondary alkyl amines is preferentially achieved. A sterically
accessible, N,O-chelated cyclic
ureate tantalum catalyst was prepared and characterized by X-ray crystallography.
This optimized catalyst can be used for the hydroaminoalkylation of
1-octene with a variety of aryl and alkyl amines, but notably enhanced
catalytic activity can be realized with challenging N-alkyl secondary amine substrates. This catalyst offers turnover
frequencies of up to 60 h–1, affording full conversion
at 5 mol% catalyst loading in approximately 20 min with these nucleophilic
amines. Mechanistic investigations, including kinetic isotope effect
(KIE) studies, reveal that catalytic turnover is limited by protonolysis
of the intermediate 5-membered azametallacycle. A Hammett kinetic
analysis shows that catalytic turnover is promoted by electron rich
amine substrates that enable catalytic turnover. This more active
catalyst is shown to be effective for late stage drug modification.