Allene-based electrophile-mediated cyclisations: efficient synthesis of medium ring azacycles

Abstract

While Ag^I- and Pd^II-based electrophiles have limited application in cyclisations of allenic amines leading to 7-membered and larger azacycles, these rings may be obtained using iodine as the electrophilic trigger. Iodination of the N-benzyl derivative 5 gives hexahydroazepine 9 either directly or via the isolable allylic iodide 10. The sulfonamide-based allylic iodides 11a–e, produced by direct iodination of allenic sulfonamides 4a–e, cyclise in the presence of NaH, and the product distribution–12vs.13–which depends on the size of rings involved, shows a preference towards formation of the larger ring 13. This chemistry provides a relatively efficient synthesis of 8-, 9-, 10- and 11-membered azacycles 13a–e and ¹³C and ¹H NMR correlations have been applied to assign the (E)/(Z)-alkene geometry of both 13 and related macrocycles 14.