Chiral Phosphoric Acid Catalyzed Enantioselective Synthesis of α‑Tertiary Amino Ketones from Sulfonium Ylides

Herein we disclose
a new catalytic asymmetric approach for the
synthesis of chiral α-amino ketones, which is particularly useful
for the less accessible acyclic α-tertiary cases. By a protonation–amination
sequence, our approach represents a rare asymmetric H–heteroatom
bond insertion by α-carbonyl sulfonium ylides, an attractive
surrogate of diazocarbonyls. The mild intermolecular C–N bond
formation was catalyzed by chiral phosphoric acids with excellent
efficiency and enantioselectivity. The products are precursors to
other important chiral amine derivatives, including drug molecules
and chiral ligands. The enantioselectivity was controlled by dynamic
kinetic resolution in the amination step, rather than the initial
protonation. This process opens up a new platform for the development
of other related insertion reactions.