title: A direct retro-Reformatsky fragmentation: formal ring enlargement of cyclic ketones for novel and practical synthesis of heterocyclic enamines.
abstract: 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 alpha,alpha-dibromination, to produce alpha,alpha,omega-tribromo-beta-ketoester compounds in a one-pot reaction. Highly regioselective reduction of alpha,alpha,omega-tribromo-beta-ketoesters with Cu-Zn alloy under mild conditions afforded omega-bromo-beta-ketoesters in good to excellent yields. Treatment of omega-bromo-beta-ketoesters with sodium azide followed by intramolecular aza-Wittig reaction or catalytic hydrogenation furnished heterocyclic secondary enamines, while a straightforward cyclocondensation of omega-bromo-beta-ketoesters with amines led to the formation of heterocyclic tertiary enamines.
authors.affiliation: Laboratory of Chemical Biology, Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Mei-Xin
authors.initials: MX
authors.lastname: Zhao
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Wang
authors.forename: Chu-Yi
authors.initials: CY
authors.lastname: Yu
authors.forename: Zhi-Tang
authors.initials: ZT
authors.lastname: Huang
authors.forename: George W J
authors.initials: GW
authors.lastname: Fleet