A novel and practical synthesis of heterocyclic enamines has been developed from the formal ring enlargement of cyclic ketones, which comprised the retro-Reformatsky fragmentation reaction as a key step. Under alkaline bromination conditions, the Reformatsky adducts derived from five- to seven-membered cyclic ketones underwent efficiently a direct retro-Reformatsky fragmentation, followed by spontaneous α,α-dibromination, to produce α,α,ω-tribromo-β-ketoester compounds in a one-pot reaction. Highly regioselective reduction of α,α,ω -tribromo-β-ketoesters with Cu-Zn alloy under mild conditions afforded ω-bromo-β-ketoesters in good to excellent yields. Treatment of ω-bromo-β-ketoesters with sodium azide followed by intramolecular aza-Wittig reaction or catalytic hydrogenation furnished heterocyclic secondary enamines, while a straightforward cyclocondensation of ω-bromo-β -ketoesters with amines led to the formation of heterocyclic tertiary enamines.
