The oxidative, intermolecular homo- and cross-coupling of phenols has been an area of intense interest over the last decade. Despite this, the intramolecular coupling of unactivated C-H and C-C positions in tethered bisphenols to form complex molecular architectures remains a challenge to synthetic organic chemists. Inspired by prior work within our group, a simple, bench-stable vanadium(V)-oxo catalyst was developed for the intramolecular oxidative coupling of simple tethered phenols to form phenol-dienone products with a newly generated quaternary center. This mild reaction is catalytic in vanadium, utilizing oxygen as a co-oxidant, and demonstrates broad scope in substitution type and pattern on the tethered phenol rings. Given the prevalence of the phenol-dienone motif in natural products and related compounds, this method was applied to the syntheses of three biologically relevant molecules. Most notably, <i>N</i>-(ethoxycarbonyl)-5'-hydroxynorreticuline was oxidized catalytically to its corresponding salutaridine derivative, a chemical transformation which is biomimetic to the key oxidative coupling step in the biosynthesis of morphine. This newly developed intramolecular coupling reaction proceeds in good yield with catalytic quantities of vanadium and may offer a mild, operationally simple alternative to similar reported transformations.

Vanadium-catalyzed intramolecular oxidative coupling of tethered phenols to generate phenol-dienone products

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.