Chemistry of pyrrolizinones. Part 1. Reactions of pyrrolizin-3-ones with electrophiles: synthesis of 3,8-didehydroheliotridin-5-one

Abstract

The reaction of pyrrolizin-3-one 1 with dry hydrogen chloride gives the 1-chloro-1,2-dihydro derivative 8 (93%) by electrophilic addition. The halogen of 8 is readily displaced by O-nucleophiles to give 6, 9 or 10 in 87–100% yield, and this strategy has been employed in a short synthesis of the necine base didehydroheliotridin-5-one 4. Pyrrolizinone 1 can be brominated by N-bromosuccinimide in the presence of nucleophiles to give 20 or 21, or under free radical conditions to give the 2-bromopyrrolizinone 22 (55%). Vilsmeier formylation of 1 gave a variety of products including the 5-formylpyrrolizinone 26 (16%), but azo-coupling could only be observed under basic conditions to give the coupled propenoate 31 (46%) via the anion of the ring-opened species 30.