Synthesis of medium ring azacycles via allene-based cyclisations: evaluation of possible mechanistic pathways

Abstract

Two pathways have been evaluated to account for the l₂-mediated cyclisation of the allenic sulfonamides 1a–e based on (i) the steric demands of the allenic unit and (ii) the ambident reactivity of the sulfonamide anion. The 1, 3-disubstituted allenic sulfonamides 6 and 7 have been prepared and both undergo a facile cyclisation, without the need of an external base, to give the smaller of the two possible ring sizes 8 and 11, respectively. In the case of 7, the intermediate allylic iodides 9 and 10 have been observed and steric factors appear to play a decisive role in determining the preference for ring size in this cyclisation sequence. A possible role for the sulfonamide unit acting as an ambident nucleophile by undergoing initial O-alkylation has also been examined. The sulfonimidates 15a–c undergo thermal [3,3]-rearrangement to give the corresponding sulfonamides 16a–c but the conditions required to achieve this O- to N-migration step would preclude involvement of this pathway in the l₂-mediated cyclisation of allenic sulfonamides.