A direct retro-Reformatsky fragmentation: formal ring enlargement of cyclic ketones for novel and practical synthesis of heterocyclic enamines.

Journal article

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: Zhao, M; Wang, M; Yu, C; Huang, Z; Fleet, G

• Publication status: Published
• Journal: Journal of organic chemistry
• Volume: 69
• Issue: 3
• Pages: 997-1000
• Publication date: 2004-02-01
• DOI: 10.1021/jo0351320
• EISSN: 1520-6904
• ISSN: 0022-3263
• Language: English