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 (I2) 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 I2 to the alkyne. These studies show that I2 forms a bridged I2-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 I2 to alkynes competes with iodocyclization, but is reversible. This fact, together with the capacity of I2 to activate both alkyne carbons towards nucleophilic attack, makes I2 the reagent of choice (superior to iodonium reagents) for iodocyclizations of resistant substrates. The differences in the nature of the activated intermediate formed with I2 versus I+ can also be exploited to accomplish reagent-controlled 5-exo/6-endo-divergent iodocyclizations. Exploiting differences in I2 and I+: Experiment and theory explore mechanistic differences in I2 and I+-mediated iodocyclizations of alkynes, including the roles of I. and I- (see scheme). These studies provide guidance on how to achieve iodocyclizations of resistant substrates, control competing addition, and tune exo/endo-selectivity