Unlocking the Aromatic\nCope Rearrangement with Gold(I)\nCatalysis

Aromatic Cope Rearrangement (ArCopeR) is a highly challenging\nchemical\nreaction under thermal conditions, primarily attributed to the loss\nof aromaticity during the initial [3,3]-sigmatropic step of the process.\nSuch a rare transformation typically requires high temperatures and\nspecially engineered 1,5-hexadiene scaffolds, making it impractical\nfor the straightforward synthesis of molecules. Here, we demonstrated\nthat gold(I) catalysts significantly lower the energetic barriers\nassociated with ArCopeR, enabling the reaction to be carried out at\nlow temperatures (rt to 70 °C) in dichloroethane or hexafluoroisopropanol\nwith high yields. Specifically, phosphine gold(I) complex ((<i>p</i>-CF<sub>3</sub>Ph)<sub>3</sub>PAuOTf) permits for the diastereoselective\nand divergent aromatic Cope rearrangement from various α-allyl-α′-heteroaromatic\nγ-lactone or malonate derivatives, while <i>N</i>-heterocyclic\ncarbene gold(I) (IPrAuNTf<sub>2</sub>) allows the selective dearomatization\nreaction. Extended quantum-mechanics calculations, consistent with\nexperimental observations, reveal that (i) an interweaved transformation\noccurs instead of the expected ArCope cascade made of formal [3,3]-sigmatropic\nrearrangement and [1,3]H-shift steps and that (ii) van der Waals interactions\nbetween the catalyst and substrate contribute to the interrupted ArCope\nprocess leading to dearomatize products. This study presents the first\ncatalytic and synthetically useful protocol to promote ArCopeR under\nmild conditions.