Cu(OTf)₂-Catalyzed Isomerization of 7-Oxabicyclic Alkenes: A Practical Route to the Synthesis of 1-Naphthol Derivatives

Abstract

Lewis acid catalyzed isomerization of 7-oxabicyclic alkenes into 1-naphthol derivatives in high yields (87-98%) under mild reaction conditions has been developed. The mechanism of this reaction is briefly postulated.Brønsted acid catalyzed isomerization of 7-oxabicyclic alkenes into 1-naphthol derivatives is one of the most fundamental reactions in organic synthesis. [2][3][4] This process has proven to be effective for incorporating the naphthol fragment into complex molecules; 5-8 however, the use of strong protic acids has limited the utilization of this reaction, especially in Brønsted acid sensitive substrates. Furthermore, the use of strong protic acids leads to highly acidic waste streams, which pose an environmental problem for industrial processes. For these reasons, several alternative approaches to 1-naphthol derivatives that do not require the presence of strong protic acids have been developed. Unfortunately, these methods suffer from drawbacks such as the use of expensive palladium catalysts, high reaction temperatures and limited substrate scope. Miura et al. 9 reported a palladium-catalyzed annulation of o-bromobenzaldehydes with 2-substituted 2-alkenals, however, high temperature (120°C) is required in this reaction. Furthermore, yields are generally moderate due to the production of 1,3-disubstituted naphthalenes accompanied by decarbonylation. Recently, Martin et al. 10 reported an elegant palladium-catalyzed ring-opening of 7-oxabicyclic alkenes with aryl and vinyl halides followed by oxidation of the intermediate dihydronaphthols with 2-iodoxybenzoic acid (IBX). This protocol provides 2-substituted 1-naphthol derivatives in good yields, however, it suffers from drawbacks such as the use of expensive palladium catalyst and excess IBX (3 equiv). From a practical point of view, it is thus highly desirable to develop a novel method for the preparation of 1-naphthol derivatives.During the past decades, metal-based Lewis acids have found many applications in organic synthesis. 11 Nevertheless, they have largely been neglected as effective catalysts for the isomerization of 7-oxabicyclic alkenes into 1-naphthol derivatives, probably due to the reaction with the bridging oxygen of 7-oxabicyclic alkenes, which reduces the reactivity of Lewis acids. Metal triflates are unique Lewis acids that are currently of great research interest. 12-17 Metal triflates are generally stable and still active in the presence of many substrates containing heteroatoms such as nitrogen, oxygen and sulfur. Due to these advantages, they are widely used in organic synthesis. 18 We envisioned that metal triflates with suitable cations and anions might be effective catalysts for the isomerization of 7-oxabicyclic alkenes into 1-naphthol derivatives. In this paper, we report the first example of Cu(OTf) 2 -catalyzed isomerization of 7-oxabicyclic alkenes into 1-naphthol derivatives under mild conditions. 19This methodology has the following features: (i) it differs from the isomerization catalyzed by Brønsted acids in having a ...

Construction of Cyclopenta[b]naphthalenol Frameworks by Weinreb Amide‐Directed Umpolung Ring Opening of Methylenecyclopropanes

“…[9a] However, synthe-sizing the two motifs mainly depends on transitionmetal catalysis, and metal-free protocols deserve the further exploration. [10] Herein, we wish to report a novel synthetic protocol on the rapid construction of polycyclic cyclopenta[b]naphthalenol framework from Weinreb amide-tethered methylenecyclopropanes and alkynes without the use of transition metals through an umpolung ring opening of cyclopropane under mild conditions.…”