To elucidate the origin of the facial selectivity (and hence the stereoinduction) of the intramolecular cycloaddition reaction, we next investigated the reaction mechanism for a model TDO 32 featuring a methyltryptamine sidechain appended to the camphorsultam-substituted TDO ring (Fig. ). The lowest energy conformer I is stabilised by a hydrogen bond between the indole NH and one of the oxygen atoms of the camphorsultam. In contrast, for the lowest energy conformer associated with reaction of the indole on the opposite face of the TDO (conformer II, DG 0 = +0.34 kcal mol -1 ) this hydrogen bond stabilisation is not possible.