Catalytic Enantioselective Addition of Aromatic, Heteroaryl, and Alkenyl Halides to N -Boc and N -Cbz Aldimines: Entatic States in Transition Metal Catalysis

Nickel complexes of chiral bis(oxazoline)s efficiently catalyze highly enantioselective asymmetric reductive arylation, heteroarylation, and alkenylation of N-Boc- and N-Cbz-aldimines. The protocol employs readily available organic halides and triflates and operates under neutral conditions. The reactions tolerate nitrogen-containing heterocycles, alkylamines, alcohols, and other sensitive functional groups. Mechanistic studies using an isolated arylnickel bromide complex showed that insertion proceeds through a neutral aryl nickel species. DFT calculations implicate a low-barrier insertion step of “elementary 1,4-addition” in which the carbamoyl oxygen coordinates to nickel and stabilizes the six-membered cyclic transition state. Interestingly, one bis(oxazoline) complex of nickel undergoes almost no structural reorganization during aryl transfer to an imine going from the ground state to transition state, mimicking “entatic states” in active sites of some metalloenzymes.