Synthesis of Polysubstituted 2‐Naphthols by Palladium‐Catalyzed Intramolecular Arylation/Aromatization Cascade

Abstract

A palladium‐catalyzed intramolecular α‐arylation and defluorinative aromatization strategy for the synthesis of polysubstituted 2‐naphthols is reported. With ortho‐bromobenzyl‐substituted α‐fluoroketones as the substrates and palladium acetate/triphenylphosphine as the catalyst, this method features good functional group tolerance, readily available catalyst and starting materials, and high yields. The applications of the strategy are demonstrated by the synthesis of useful building blocks, such as naphtha[2,3‐b]furan, naphthol AS‐D, and ligands/catalysts.

Substituted Naphthols: Preparations, Applications, and Reactions

“…Branched ketones also provide a novel route towards naphthols, for example, ortho ‐bromobenzyl‐substituted α‐fluoroketones 165 were subjected to palladium‐catalyzed intramolecular α‐arylation and defluorinative aromatization conditions to access 2‐naphthols 166 (Scheme 30). [ 30 ] An oxidative addition of the aryl bromide moiety and the palladium catalyst initiates the cycle – this is followed by an α‐arylation of the ketone moiety to generate a 7‐membered palladacycle, followed by elimination of palladium(0) and C–C bond formation to yield a naphtnen‐2‐one. Substituted naphthols 166 are finally furnished after defluorinative aromatization.…”

“…There currently exists a number of methods for synthesizing varied naphthol derivatives. [ 25–28 ] Different chemical strategies have been employed for the synthesis of the naphthol skeleton, such as, C–H activation catalyzed by transition‐metals, [ 29 ] cyclizations, [ 30 ] Diels‐Alder reactions, [ 31 ] Claisen rearrangements, [ 32 ] pyrolysis reactions, [ 33 ] and chemical reductions, [ 34 ] amongst others. [ 35–38 ]…”