Divergent Reactivity of gem-Difluoro-enolates toward Nitrogen Electrophiles: Unorthodox Nitroso Aldol Reaction for Rapid Synthesis of α-Ketoamides.

An amination reaction of in situ generated gem-difluoro-enolates has been explored with electrophilic nitrogen sources. While their exposure to azodicarboxylates smoothly produced fluorinated α-amino ketones, reaction with nitrosoarenes (nitroso aldol reaction) furnished α-ketoamides in very high yields (up to 94%). The reaction is very fast (typically completed within 5 min) and scalable and tolerates various sensitive functional groups. Synthetic utility of this process was highlighted through the production of diverse nitrogen heterocycles and an orexin receptor antagonist.