Brønsted Acid Mediated Cascade Reaction To Access 3-(2-Bromoethyl)benzofurans

Abstract

A unified protocol for the construction of 3-(2bromoethyl)benzofurans and 2-(benzofuran-3-yl)ethylamines from bis[(trimethylsilyl)oxy]cyclobutene has been developed. This mild and facile strategy was applied for the synthesis of a series of 5-HT serotonin receptor agonists, underlining its potential for the syntheses of bioactive compounds and natural products.

Last Decade of Unconventional Methodologies for the Synthesis of Substituted Benzofurans

“…This mild and facile strategy was applied for the synthesis of a series of 5-HT serotonin receptor agonists, underlining its potential for the syntheses of bioactive compounds and natural products. Seggi and co-workers reported that 3-(2-bromoethyl)benzofurans were readily obtained from commercially available bis[(trimethylsilyl)oxy]cyclobutene and various phenols via a Brønsted acidmediated nucleophilic addition−carbocyclic rearrangement cascade reaction; this is a one-pot, metalfree process that operates in mild conditions [184]. In the presence of a Brønsted acid, 2hydroxycyclobutanone and its precursor bis[(trimethylsilyl)oxy]cyclobutene behaved as electrophilic acceptors for intermolecular nucleophilic addition, followed by a ring closure−ring fission process.…”

Metal-free [2 + 2] and [4 + 2] cycloadditions ofN-aryl-substituted ynamides to construct functionalized aminocyclobutenes and 4-aminoquinolines

“…1,2 In addition, cyclobutenes have also been used as versatile synthons to construct a diverse array of valuable skeletons due to their inherent ring strain. 3,4 Of particular interest are the aminocyclobutenes. 5 Although many impressive synthetic routes to aminocyclobutenes and 4-aminoquinolines have been explored in the past decades, 6–10 accessing these important structures by convenient and atom-economical methods remains an intriguing objective, especially in synthesizing them under transition-metal-free reaction conditions.…”

Insights into the Reactivity of 2-Hydroxycyclobutanones with Thiols Corroborated by Quantum Chemical DFT Investigations and NMR and Raman Analysis

“…Due to the ease of preparation 1 and extensive chemical reactivity, 2 2-hydroxycyclobutanones 1 constitute a powerful building block for organic synthesis. These cyclic ketones have recently been used for the preparation of benzofuran 3 and tryptamine derivatives 4 and the synthesis of cyclopropane and cyclobutane adducts via the addition of different nucleophiles such as phosphonium ylides, 5 indoles, 6 or aromatic thiols. 7 Furthermore, acid-catalyzed re-actions of 2-hydroxycyclobutanones with benzylic alcohols allow access to bis(cyclobutyl)dioxin derivatives.…”