Rearrangement or gem-difluorination of quinine and 9-epiquinine and their acetates in superacid
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- 作者：Debarge ; Sé ; bastien ; Thibaudeau ; Sé ; bastien ; Violeau ; Bruno ; Martin-Mingot ; Agnè ; s ; et. al.
- 关键词：Cinchona alkaloids ; Superacid ; Gem-difluorination ; Rearrangement
- 刊名：Tetrahedron
- 出版年：2005
- 出版时间：February 21, 2005
- 年：2005
- 卷：61
- 期：8
- 页码：2065-2073
- 全文大小：366 K
文摘
In HF-SbF5, quinine 1a or its dihydrochloride rearranges into compound 3 (89 % ), the preferred conformation of the substrate favouring the observed cyclization. Under similar conditions epiquinine 2a dihydrochloride yields in equal amounts two 10,10-difluoro derivatives, epimeric at C-3. In this case, the more stable conformation of the substrate in which the benzylic hydroxyl group is ‘exo’ to the quinuclidyl moiety, prevents the cyclisation. Similarly acetates 1b and 2b give the corresponding 10,10-difluoro derivatives epimeric at C-3. Formation of gem-difluoro compounds implies the formation of chloro intermediates at C-10 followed by an hydride abstraction, yielding an α-chloronium ion. This one is trapped by a fluoride ion and leads to the product by halogen exchange.