Asymmetric Counter-Anion-Directed Aminomethylation: Synthesis of Chiral β‑Amino Acids via Trapping of an Enol Intermediate

A novel
enantioselective aminomethylation reaction of diazo compound,
alcohol and α-aminomethyl ether enabled by asymmetric counteranion-directed
catalysis is disclosed that offers an efficient and convenient access
to furnish optically active α-hydroxyl-β-amino acids in
high yield with high to excellent enantioselectivities. Control experiments
and DFT calculations indicate that the transformation proceeds through
trapping the in situ generated enol intermediate with methylene iminium
ion, and the asymmetric induction was enabled by chiral pentacarboxycyclopentadiene
anion via H-bonding and electrostatic interaction.