Electrophile-mediated cyclisations: regioselective synthesis of substituted cyclic nitrones and crystal structures of the nitrone cycloadducts

Abstract

A series of allenic oximes (2a,b) and (3a,b) have been prepared and shown to undergo AgI catalysed cyclization via nitrogen to give the isomerically defined heterocyclic nitrones (4), (5), (7), and (9). In the case of the (E)-γ-allenic oximes cyclisation via oxygen was observed leading to the corresponding dihydro-oxazines, e.g.(6). The ketoxime-derived nitrones (4) and (5) were relatively unreactive but the less hindered aldoxime derivatives (7) and (9) were readily trapped by a range of 1,3-dipolarophiles providing access to derivatives of trans-2,6-disubstituted piperidines and trans-2,5-disubstituted pyrrolidines. Crystallographic analysis of the methiodide derivatives of the cycloadducts (8d) and (8e) served to confirm these stereochemical assignments and the application of this methodology to the synthesis of the unusual pyrrolizidine alkaloid (±)-(18) is described. Attempts to trigger the cyclisation of allenic oximes (2a,b) and (3a,b) with mercury(II) and palladium(II) electrophiles failed. No reaction was observed between the corresponding olefinic oximes (22a,b) and AgI and although the acetylenic derivatives (23a,b) did react with AgI all attempts to trap a nitrone or otherwise characterise this reaction pathway failed.