Rearrangement or gem-difluorination of quinine and 9-epiquinine and their acetates in superacid

In HF-SbF5, quinine 1or 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 alpha-chloronium ion. This one is trapped by a fluoride ion and leads to the product by halogen exchange. (C) 2005 Elsevier Ltd. All rights reserved.