Synthesis, 15N NMR spectroscopy and cycloaddition reactions of some azabicycles.

The synthesis of 15N-enriched samples of derivatives of the 7-azabicyclo[2.2.1]heptyl system was achieved and 15N n.m.r, spectra were recorded both on enriched samples and, in some cases, at natural abundance. Signals corresponding to the two slowly-inverting isomers were seen in the N-methyl-7-azabicyclo[2.2.1]heptyl systems at low temperatures (-20 C). For the N-chloro-analogues, the nitrogen inversion was slower and the two invertomers could be seen at ambient temperature. The influence of substitution at the nitrogen atom, the effects of unsaturation and the presence of substituted aryl rings were assessed. The work was extended to include a wide range of amines where no 15N n.m.r. studies had been reported including bicyclic systems in which nitrogen is part of a less-strained two atom bridge e.g. 2-methyl-2-azabicyclo[2.2.1]heptyl and -[2.2.2]-octyl systems. Direct measurement of invertomer ratios was not possible using low temperature n.m.r. methods due to the low inversion barriers and therefore kinetic protonation was used as an alternative approach to investigate the invertomer ratios and preferences. The facial selectivity of different nitrogen-containing dienophiles was investigated. The addition of cyclopentadiene, cyclohexadiene and phenyl azide to strained 7-aza- and 2-aza-bicycle[2.2.1]heptene derivatives was shown to take place on the exo- face of these dienophiles, while the addition of the same dienes to the less-strained lactam (28), based on the 2-methyl-2-azabicyclo[2.2.2] oct-5-ene-3-one system, took place on both the exo- and the endo-faces of the alkene, The structures of the cycloadducts obtained were determined by 1H n.m.r. spectroscopy and confirmed by X-ray crystallography in two cases.