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Asymmetric reactions that convert racemic mixtures into enantioenriched amines are of significant importance due to the prevalence of amines in pharmaceuticals, with about 60% of drug candidates containing tertiary amines. Although transition metal catalyzed allylic substitution processes have been developed to provide access to enantioenriched α-disubstituted allylic amines, enantioselective synthesis of sterically demanding α-tertiary amines with a tetrasubstituted carbon stereocenter remains a major challenge. Herein, we report a chiral diene-ligated rhodium catalyzed asymmetric substitution of racemic tertiary allylic trichloroacetimidates with aliphatic secondary amines to afford α-trisubstituted-α-tertiary amines. Mechanistic investigation is conducted using synergistic experimental and computational studies. Density functional theory calculations show that the chiral diene-ligated rhodium promotes the ionization of tertiary allylic substrates to form both anti and syn π-allyl intermediates. The anti π-allyl pathway proceeds through a higher energy than the syn π-allyl pathway. The rate of conversion of the less reactive π-allyl intermediate to the more reactive isomer via π−σ−π interconversion was faster than the rate of nucleophilic attack onto the more reactive intermediate. These data imply that the Curtin−Hammett conditions are met in the amination reaction, leading to dynamic kinetic asymmetric transformation. Computational studies also show that hydrogen bonding interactions between β-oxygen of allylic substrate and amine-NH greatly assist the delivery of amine nucleophile onto more hindered internal carbon of the π-allyl intermediate. The synthetic utility of the current methodology is showcased by efficient preparation of α-trisubstituted-α-tertiary amines featuring pharmaceutically relevant secondary amine cores with good yields and excellent selectivities (branched−linear >99:1, up to 99% enantiomeric excess). 

Abstract Three binuclear species [LCo^III₂(μ‐Pz)₂](ClO₄)₃(1), [LNi^II₂(CH₃OH)₂Cl₂]ClO₄(2), and [LZn^II₂Cl₂]PF₆(3) supported by the deprotonated form of the ligand 2,6‐bis[bis(2‐pyridylmethyl) amino‐methyl]‐4‐methylphenol were synthesized, structurally characterized as solids and in solution, and had their electrochemical and spectroscopic behavior established. Species1–3had their water reduction ability studied aiming to interrogate the possible cooperative catalytic activity between two neighboring metal centers. Species1and2reduced H₂O to H₂effectively at an applied potential of −1.6 V_Ag/AgCl, yielding turnover numbers of 2,820 and 2,290, respectively, after 30 minutes. Species3lacked activity and was used as a negative control to eliminate the possibility of ligand‐based catalysis. Pre‐ and post‐catalytic data gave evidence of the molecular nature of the process within the timeframe of the experiments. Species1showed structural, rather than electronic cooperativity, while species2displayed no obvious cooperativity. DFT methods complemented the experimental results determining plausible mechanisms.