Iridium/Zinc-Co-Catalyzed Ring-Opening Reactions of Oxabicyclic Alkenes with Indole Nucleophiles: A Combined Experimental and Theoretical Study

An experimental and theoretical investigation on the
iridium/zinc-co-catalyzed
ring-opening reactions of oxabicyclic alkenes with indole nucleophiles
is reported. The reaction affords trans-3-indolyl-1,2-dihydronaphthalen-1-ol
products in good yield with no N-alkylated products
observed. The C–C bond-forming reaction does not require prior
functionalization and is entirely atom-economic. The mechanism and
origins of selectivity in the iridium-catalyzed ring-opening reaction
have been examined at the M06-D3/Def2TZVPP level of theory. Orbital
analysis and natural population analysis charges demonstrate that
the Cα site of the π-allyliridium intermediate
is the most electrophilic site of attack. Distortion/interaction analysis
reveals that the chemoselectivity likely originates from an earlier-stage
transition state between Cα and C3, which
requires less distortion energy compared to Cα–N1 during the rate-determining intermolecular nucleophilic attack.
Moreover, conceptual density functional theory was used to conceptualize
the preferential reactive sites of the nucleophiles probed. The C–C
bond-forming step is speculated to proceed through a Friedel–Crafts-type
reaction.