Carbonylative lactonization via carbonyl oxygen attack: a short and selective total synthesis of uncinine and its analogues

A novel cytotoxic butenolide alkaloid, uncinine, has been synthesized for the first time in 8 steps from propargyl alcohol. The sequence features a mild and efficient tandem carbonylative lactonization of a β-iodoenone precursor using an inorganic base at 1 atm CO, and an indirect attachment of the pyrrolidinone ring via nucleophilic substitution with methyl γ-aminobutyrate.