Electronic Nature of Ketone Directing Group as a Key To Control C‑2 vs C‑4 Alkenylation of Indoles

A novel mode of achieving
site selectivity between C-2 and C-4
positions in the indole framework by altering the property of the
ketone directing group is disclosed. Methyl ketone, as directing group,
furnishes exclusively C-2 alkenylated product, whereas trifluoromethyl
ketone changes the selectivity to C-4, indicating that the electronic
nature of the directing group controls the unusual choice between
a 5-membered and a 6-membered metallacycle. The screening of other
carbonyl-derived directing groups reveals that strong and weak directing
groups exhibit opposite selectivity. Experimental controls and deuteration
experiments lend support to the proposed mechanism.