Synthesis of Four- to Seven-Membered Heterocycles by Ring Expansion: Ring Expansions of Thiiranes and Thietanes

Abstract

Thiiranes and thietanes are important intermediates in organic synthesis, just as their oxygen and nitrogen analogs (oxiranes and aziridines, and oxetanes and azetidines). They have been widely applied in the preparation of sulfur-containing compounds. Thiiranes undergo ring expansions to generate various four-, five-, six-, and seven-membered heterocyclic products, even larger heterocycles. Thietanes also undergo ring expansions to produce five-, six-, and seven-membered hetero- cyclic compounds, even larger heterocycles as well. The ring expansions include insertion, nucleophilic and electrophilic ring opening, and subsequent cyclization. The regioselectivities in nucleophilic ring-opening reactions of unsymmetrical thiiranes and thietanes are discussed. Generally, nucleophiles attack on the less substituted vicinal carbon atom to the sulfur in unsymmetrical thiiranes and thietanes, controlled by steric hindrance. In the presence of Lewis acids, the electronic effect significantly impacts the regioselectivity in ring-opening reactions. 2-Arylthiiranes and 2-alkenylthiiranes are attacked on their more substituted vicinal carbon atom with nucleophiles (the electronic effect control). For thietanes, elec- trophilic ring expansion is one of the major processes. Unsymmetrical thietanes undergo electrophilic ring expansion with carbenes and nitrenes through electro- philic attack and subsequent Stevens-type rearrangement, with the more substituted vicinal carbon shifting. Mechanisms on some of the most important ring expansions of thiiranes and thietanes are introduced.