Iodocarbocyclization and iodoaminocyclization reactions mediated by a metallic reagent

We have developed new iodine-mediated carbocyclization and aminocyclization reactions through activation of intramolecular carbon or amide nucleophiles by metallic reagents. In the presence of 12 and Ti(OR)₄ or TiCl₄-Et₃N, iodocarbocyclization of various active methine compounds having alkenyl or alkynyl groups proceeded in a highly stereospecific manner to give iodocyclo-alkanes or -alkenes in good yields. The present reaction can be also applied to asymmetric catalytic reaction; that is, the reaction of 4-alkenylmalonate derivatives with Ti(TADDOLate)₂ catalyst gave iodoalkylcyclopentanes with excellent enantioselectivity (> 95%ee). Furthermore, iodoaminocyclization of unsaturated amide derivatives with an ambident nucleophilic center and iodoaziridination of N-allylic tosylamides, featuring regiocontrol and an activation of an amide nucleophile by a basic metallic reagent, were also established.