Kinetic, ESI–CID–MS, and Computational Studies of π‑Allyliridium C,O-Benzoate-Catalyzed Allylic Amination: Understanding the Effect of Cesium Ion

The mechanism of π-allyliridium C,O-benzoate-catalyzed allylic amination was studied by (a) reaction progress kinetic analysis (RPKA), (b) tandem electrospray ionization–mass spectrometry (ESI–MS) analysis, and (c) computational studies involving density functional theory calculations. RPKA reveals a zero-order dependence on allyl acetate, first-order dependence on catalysts, and fractional-order dependence on amines. These data corroborate rapid ionization of the allylic acetate, followed by turnover limiting C–N bond formation. To illuminate the origins of the 0.4 kinetic order dependence on amine, ESI–MS analyses of quaternary ammonium-labeled piperazine with multistage collision-induced dissociation (CID) were conducted that corroborate intervention of cesium-bridged amine dimers that dissociate to form monomeric cesium amide nucleophiles. Computational data align with RPKA and ESI–CID–MS analyses and suggest that early transition states mitigate the impact of steric factors, thus enabling the formation of highly substituted C–N bonds with complete levels of branched regioselectivity. Specifically, trans effects of the iridium complex facilitate nucleophilic attack at the more substituted allyl terminus trans to phosphorus with enantioselectivity governed by steric repulsions between the chiral bisphosphine ligand and the π-allyl of a dominant diastereomer of the stereogenic-at-metal complex. Beyond defining the aspects of the mechanism of π-allyliridium C,O-benzoate-catalyzed allylic amination, these data reveal that a key feature of cesium carbonate lies not only in its enhanced basicity but also in its capacity for Lewis acid enhanced Brønsted acidification of amines.