Rules for ring closure.

Abstract

The ease of formation of cyclic structures shows some regularity which can be described by a set of 'rules' for ring closure. The restrictions on the endocyclic transfer of groups due to SN2 displacements having linear transition states are exemplified by studied on a biogenetic type synthesis of penicillin and, more generally, on the endocyclic attack of a nucleophile attached by a linking chain to an enone or polarized double bond. The formation of five-memebered rings is considered. In base, enones such as 4-hydroxy- and 4-amino-2-methylenebutanoates close exocyclically to give the corresponding five-membered lactones and lactams, respectively. Hydroxymethyl vinyl ketones, however, do not cyclize in base. In strong acid, hydroxy-enones close endocyclically to five-membered ring, as in the formation of cyclic ethylene ketals from acetone and ethanediol. The endocyclic closure of nucleophilic centres to polarized double bonds to give five-membered rings is impeded by restrictions of geometry; these restrictions can be overcome in acid through the generation of oxonium or protonated forms.