3.5 - Reactivity of Small and Large Rings

Abstract

This chapter provides an overview of the reactivity of small and large ring systems. The reactivity of small (three- and four-membered) heterocyclic rings is dominated by the effects of ring strain, which facilitates various modes of ring opening. Aromaticity is seldom observed; antiaromaticity is present in only a few isolated examples and thus does not play a general role. Many reactions are initiated by unimolecular ring opening, to give diradicals or ylides, from which the reaction products are derived. Four-membered systems often cleave into two two-membered fragments (each consisting of two former ring atoms and their ligands). Attack on ring carbons concomitant with ring opening is very common and is usually subject to electrophilic catalysis. Large heterocycles, i.e., those with more than six ring members, often show little effect of ring strain on the reactivities of the neutral molecules. Factors important for large ring reactivity are unsaturation, especially of polyenic and aromatic character, and the steric accessibility of heteroatoms and functional groups, as well as the possibility of transannular reactions. However, the majority of unsaturated large rings are not aromatic, even where the Hückel rule is obeyed formally. Onium ions of small and large heterocyclic compounds are usually produced by electrophilic attack on a heteroatom. In most three- and four-membered rings, nucleophilic attack on an adjacent carbon and ring opening follow immediately, stabilizing the system. In large rings the onium ion behaves as would an acyclic analogue, except where aromaticity or transannular reactions come into play. Anions of small-ring heterocycles can be generated in certain circumstances, but anions from large heterocycles often resemble their acyclic counterparts. Small-ring radicals with the unpaired electron at the heteroatom or at a carbon adjacent to a heteroatom undergo ring cleavage as the predominant mode of stabilization, as known for oxaziranes, aziridines, diaziridines, diazirines, oxaziridines, and thietanes.