5-exo versus 6-endo Thiyl-Radical Cyclizations in Organic Synthesis

Since the discovery of the radical mediated thiol-ene and thiol-yne reactions, these reactions have been employed in an intramolecular manner for the synthesis of sulfur-containing heterocycles. Although closely related on a mechanistic basis, the thiol-ene and thiol-yne cyclization can differ greatly in regioselectivity and product distribution, with the thiol-ene process being more predictable and thus attracting greater utilization. Herein, we review intramolecular thiyl-radical addition reactions and the factors leading to the observed regioselectivity in examples in which both the 5-exo and 6-endo mode of cyclization are feasible. We highlight the applications of these important reactions for organic synthesis in the recent literature.