Breaking the Trend: Insight into Unforeseen Reactivity of Alkynes in Cobalt-Catalyzed Weak Chelation-Assisted Regioselective C(4)–H Functionalization of 3‑Pivaloyl Indole

Unique reactivity of diphenylacetylene
has been uncovered through
weak chelation-assisted cobalt-catalyzed regioselective C(4)–H
activation of 3-pivolyl indole. α-Hydroxy ketone and α,β-unsaturated
ketone derivatives have been synthesized in good yields from indole
and alkynes. Notably, the indole C(4)–H-functionalized α,β-unsaturated
ketone product was obtained with high stereo- and regioselectivity
simply by changing the coupling partner from symmetrical alkynes to
unsymmetrical aromatic-aliphatic alkynes. Most importantly, trifluoroethanol
acts as a sole source of water for this conversion. Quantitative detection
of bis­(2,2,2-trifluoroethyl) ether from dry trifluoroethanol through 19F NMR and LCMS studies indirectly confirms the in situ formation
of water. A six-membered cobaltacycle intermediate was detected in
HRMS, and also, this was further confirmed by the quantum mechanical
calculations, which accounts for the highly regioselective C(4)–H
functionalization.