Divergent and Enantioselective Synthesis of Three Types of Chiral Polycyclic N‑Heterocycles via Copper-Catalyzed Dearomative Cyclization

Significant advancements have been made in the catalytic
asymmetric
dearomatization of indoles for constructing valuable chiral polycyclic
N-heterocycles. However, the asymmetric dearomative cyclopropanation
of indoles continues to pose a formidable challenge. Furthermore,
the diverse transformations of indoline-fused cyclopropanes via strain
release remain largely unexplored, potentially unveiling new chemistry.
Here, we disclose a Cu-catalyzed asymmetric dearomative cyclopropanation
of indole-diynes and subsequent [3 + 2] cycloaddition with oxygen,
facilitating the divergent and atom-economical synthesis of enantioenriched
cyclopropane- and 1,2-dioxolane-fused indolines with moderate to excellent
yields and generally outstanding diastereo- and enantioselectivities
with broad substrate scope. Importantly, this protocol not only represents
the first asymmetric dearomative cyclopropanation of indoles utilizing
alkynes as carbene precursors but also constitutes the first catalytic
asymmetric construction of chiral 1,2-dioxolanes with high stereoselectivity.
Interestingly, Brønsted acid-promoted ring-opening and rearrangement
of cyclopropane-fused indolines display distinctive chemoselectivity
to afford enantioenriched cyclohepta­[b]­indoles in
good to excellent efficiency and enantiocontrol. In addition, both
potential reaction pathways and the origins of chiral control within
this Cu-catalyzed asymmetric tandem sequence are robustly supported
by control experiments and theoretical calculations.