Preparation of 2-Substituted 3-Methoxycarbonyl-4-methoxyfurans that Allow Access to Highly Functionalized Naphthalenes via Regioselective Cycloaddition with Alkoxybenzyne

Abstract

A facile synthetic method of 2-substituted 3-methoxycarbonyl-4-methoxyfurans has been developed, allowing construction of highly functionalized naphthalene derivatives via (1) regioselective benzyne [4+2] cycloaddition with α-alkoxybenzyne and (2) reductive aromatization.

First Total Syntheses of Tetracenomycins C and X

“…Further disconnection of 9 , via the key tricycle 10 , suggested a three‐component assembly by exploiting dual cycloadditions of 1,4‐benzdiyne equivalent B . Two relevant benzyne species would be sequentially generated from bis(tosyloxy)diiodobenzene C , and go on to react with two different arynophiles; that is, [2+2] cycloaddition with ketene silyl acetal (KSA) 11 and [4+2] cycloaddition with trisubstituted furan 12 . Based on this analysis, we started the synthetic venture, and its successful implementation is described in the following text.…”

“…The synthesis started with the generation of a benzyne species from bis‐tosylate 13 ( n BuLi, tetrahydrofuran, −95 °C, 10 min), which underwent regioselective [2+2] cycloaddition to premixed KSA 11 (−95→−20 °C, 1 h), giving benzocyclobutene 14 in 73 % yield (Scheme ) . The next step was the [4+2] cycloaddition of iodo‐tosylate 14 with furan 12 ( n BuLi, THF, −78 °C, 4 h), which gave two products. Pleasingly, careful structural analysis revealed these products to be stereoisomeric bis‐cycloadducts 15 (d.r.=1:1) because of the lack of facial selectivity relative to the stereogenic centers in 14 , but both were composed of single regioisomers, as later determined by single‐crystal X‐ray diffraction analysis (see 16 , Scheme ).…”

Valorization of 2,5-furandicarboxylic acid. Diels–Alder reactions with benzyne

“…In contrast, there are only a few examples of reactions between benzyne and heavily oxidized furans. 43,44 In this work we detail for the first time the Diels-Alder reaction of 5 with benzyne and selective conversion of the adduct to either 1,4-naphthalenedicarboxylic acid 10 (Fig. 2) or its dimethyl ester 9.…”

Directed Ortho and Remote Metalation of Naphthalene 1,8-Diamide: Complementing SEAr Reactivity for the Synthesis of Substituted Naphthalenes

“…To organic chemists, the naphthalene ring, initially part of isolates obtained from coal tar distillates, , has attained considerable representation as a substructure in natural products, , bioactive molecules and drugs, nanomaterials, transition metal coordinated ligands, and other materials with useful properties. , The 1,8-disubstituted naphthalenes are of special and long-standing interest due to their properties of atropisomerism, as structural components in natural products, use as proton sponges, nerve growth factor (NGF) inhibitors, models of biological receptors, light-energized compounds, and ligands for catalysis. The synthesis of substituted naphthalenes encompasses a vast number of methods. , However, as a cursory perusal of the literature will indicate, a need exists for systematic, wide-ranging methodologies for the regioselective construction of naphthalenes with three or more substituents …”