Synthesis of chiral spiro-indenes via Pd-catalyzed asymmetric (4 + 2) dipolar cyclization

Abstract

Chiral indene skeletons are widely found in biologically active natural products and pharmaceutical molecules, making indene synthesis an ongoing research hotspot in organic synthetic chemistry. However, the construction of chiral spiro-indenes bearing all-carbon quaternary stereocenters via catalytic asymmetric synthesis remains challenging due to their inherent rigidity and hindrance. Herein, we present a solution to this unmet challenge through palladium-catalyzed asymmetric (4 + 2) dipolar cyclization by trapping π-allyl-Pd 1,4-dipoles with indene-involved ketenes generated in situ from 1-diazonaphthalene-2(1H)-ones via visible light-induced Wolff rearrangement. This protocol features mild reaction conditions, wide substrate scope, and high enantio- and diastereoselectivities [31 examples, up to 86% yield, 97% enantiomer excess (ee) and 19:1 diastereoisomer ratio (dr)].

Keywords

Asymmetric cyclization / indene / ketene / palladium catalysis

References

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