Synthesis of 1,2-disubstituted-3-alkylidenylpyrrolidines via a one-pot three-component reaction

Olsson’s three-component reaction of cyclopropylketones, aldehydes, and primary amines was investigated for application to parallel synthesis. Using an excess of Et2AlI at elevated temperatures, pyrrolidines 4, the initial products reported by Olsson and co-workers, could be completely converted to pyrrolium salts 5, by a reaction sequence involving a retro-aza-Michael addition followed by iminium salt formation. The pyrrolium salts 5 were then cleanly reduced in situ by NaBH(OAc)3 to give 3-alkylidenylpyrrolidines 6. In summary, this one-pot three-component reaction provided an efficient synthetic route to 3-alkylidenylpyrrolidines.