Direct Catalytic Asymmetric Aldol Reaction of α‑Alkylamides

A catalytic asymmetric
aldol reaction directly employing amides
as latent enolates has remained elusive because of the resistance
of amides to enolization. A direct aldol reaction of α-alkylamides
without any electron-withdrawing group harnessed by specific activation
of 7-azaindoline amides under soft Lewis acid/Brønsted base cooperative
catalysis is reported. Diastereo- and enantioselective coupling with
ynals and aromatic aldehydes as well as divergent functional group
interconversion of the amide provided expeditious access to a variety
of aliphatic and aromatic chiral building blocks.