N-Heterocyclization in Electrophilic Haloamidation Reactions of 1,5-Cyclooctadiene. Synthesis and Rearrangements of the Granatanine and Homonortropane Skeletons

Article abstract of DOI:10.1021/jo00077a031

The transannular N-heterocyclization of 1,5-cyclooctadiene using either N-bromo- or N-iodosuccinimide and cyanamide is a preparatively useful method for the synthesis of 9-azabicyclononanes 2 and 3.This reaction failed when N-chlorosuccinimide was employed.The chloro-substituted derivative 2c was prepared, with retention of configuration, from both pure 2a and from an equimolar mixture of 2a and 3a by nucleophilic displacement with chlorine, followed by dehydration of the resulting carboxamide 4c.Acidic hydrolysis of the cyanamide group in 2a and 3a gave the ureas 4a and 5a.Reaction of 2a and 3a with tributyltin hydride gave the debrominated derivatives 8 and 9, while treatment of the same compounds with LiAlH4 afforded a single air-sensitive product which was trapped as the urea 7.Substitution of the halogens in 2a and 3a (or 2b and 3b) by acetoxy groups using silver acetate in acetic anhydride gave 12 and 13 as a result of inversion at one side and retention of the configuration on the other side of the starting materials which was accompanied by transamidation at the nitrogen bridge.Treatment of 2a with dicyclohexylethylamine led to complete dehydrobromination and the formation of 14.