Five- and six-membered ring formation from the intramolecular reaction of a protonated oxirane and alkene

Computational studies of competing five- and six-membered cyclisation of alkenyloxiranes 1a-d show that intramolecular reaction of a protonated oxirane and alkene is a concerted, single-step, exothermic process. The reactions proceed via reactant-like transition states, but where the oxirane C-O bond is considerably stretched. Two factors are seen to affect the regiochemistry: (1) stabilisation of the transitory positive charge in the transition state favours cyclisation to the more highly substituted oxirane carbon; and (2) there is an inherent stereoelectronic preference for six-membered cyclisation over five-membered cyclisation. The inherent preference for six-membered cyclisation has a parallel in Baldwin's rules for six-membered ring closure of a carbocation with an alkene, rather than Baldwin's rule for intramolecular nucleophilic reaction of three-membered rings, suggesting that the protonated oxirane mimics a carbocation. The electronic and stereoelectronic effects for cyclisation are modified by steric interactions of axial methyl groups. These systems provide a model for the A-ring cyclisation of oxidosqualene.