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A Direct Retro-Reformatsky Fragmentation: Formal Ring Enlargement of Cyclic Ketones for Novel and Practical Synthesis of Heterocyclic Enamines

2004; American Chemical Society; Volume: 69; Issue: 3 Linguagem: Inglês

10.1021/jo0351320

1520-6904

Mei‐Xin Zhao, Mei‐Xiang Wang, Chu‐Yi Yu, Zhi‐Tang Huang, George W. J. Fleet,

Catalytic Alkyne Reactions

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.