Mapping the Interactions of I2, I., I-, and I+ with Alkynes and Their Roles in Iodocyclizations

A combination of experiment and theory has been used to explore the mechanisms by which molecular iodine (I-2) and iodonium ions (I+) activate alkynes towards iodocyclization. Also included in the analysis are the roles of atomic iodine (I-.) and iodide ion (I-) in mediating the competing addition of I-2 to the alkyne. These studies show that I-2 forms a bridged I-2-alkyne complex, in which both alkyne carbons are activated towards nucleophilic attack, even for quite polarized alkynes. By contrast, I+ gives unsymmetrical, open iodovinyl cations, in which only one carbon is activated toward nucleophilic attack, especially for polarized alkynes. Addition of I-2 to alkynes competes with iodocyclization, but is reversible. This fact, together with the capacity of I-2 to activate both alkyne carbons towards nucleophilic attack, makes I-2 the reagent of choice (superior to iodonium reagents) for iodocyclizations of resistant substrates. The differences in the nature of the activated intermediate formed with I-2 versus I+ can also be exploited to accomplish reagent-controlled 5-exo/6-endo-divergent iodocyclizations.