Catalytic Asymmetric Synthesis of α‑Allyl α‑Tertiary Aminoesters from α‑Iminoesters and “Umpoled” π-Allyl Co Nucleophiles

Chiral α-tertiary aminoesters bearing an α-allyl
substitution
are highly sought after molecules in biochemistry and medicinal chemistry
studies. Herein, we describe a catalytic asymmetric synthetic method
to acquire these functional molecules from α-iminoesters and
allylic carbonates. Under the catalysis of cobalt and spiropyrrolidine-derived
amino-oxazoline ligands, the electrophilic allyl-Co(III) complex was
umpoled to a nucleophilic allyl-Co(II) complex in reductive conditions,
enabling a highly enantioselective nucleophilic addition. This approach
provides a novel entry to α-tertiary aminoesters with versatile
α-substituents with respect to either benzyl, alkyl, or allyl
groups. Preliminary mechanistic investigations and density functional
theory (DFT) studies suggest an allyl transfer process with initial
chelation of the Co(II) complex with the α-iminoester, which
might account for the regio- and enantioselectivity of this reaction.