Enantioselective Synthesis of α‑Oxy Amides via Umpolung Amide Synthesis

α-Oxy amides are prepared through enantioselective
synthesis
using a sequence beginning with a Henry addition of bromonitromethane
to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key
to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper­(II) bis­(oxazoline)
catalyst deliver both diastereomers of the Henry adduct with high
enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall,
this approach to α-oxy amides provides an innovative complement
to alternatives that focus almost entirely on the enantioselective
synthesis of α-oxy carboxylic acids.