Bis-Lewis Acid and Chloride Anion Cooperatively Catalyzed One-Pot Five-Step Cascade toward N‑Fused 5/7/6 and 5/6/6 Tricycles

N-Fused 5/7/6 tricyclic scaffold is
the core structure
of tetrapetalone family alkaloids. Herein, we disclose a strategy
for the atom- and step-economic synthesis of N-fused
5/7/6 tricyclic scaffolds via a bis-Lewis acid and chloride cooperatively
catalyzed one-pot five-step cascade reaction of o-alkenylaryl isocyanides with α,β-unsaturated carbonyls.
The reaction is initiated by a [4 + 1] cycloaddition to form a furan
intermediate, which is followed by furan-based [4 + 2] cycloaddition,
C–O scission, C–C cleavage, and finally C–N formation.
Notably, instead of the conventional [4 + 2] cycloaddition of furan
to form a benzene ring, in this domino process, the in situ generated six-membered ring is reopened to create a N-fused 5/7/6 tricyclic framework. Based on the results of control
experiments and DFT calculations, both the bis-Lewis acid and the
nucleophilic chloride participated in reactivity regulation. Furthermore,
this efficient domino transformation could be applied to assemble N-fused 5/6/6 tricycles and the amino analog of (±)-tetrapetalone
G.