Synthesis of 2-bromomethyl-2,3-dihydrobenzofurans from 2-allylphenols enabled by organocatalytic activation of N-bromosuccinimide

Abstract

2-Bromomethyl-2,3-dihydrobenzofurans are valuable and highly functionalized compounds that can be obtained by an intramolecular reaction between 2-allylphenols and a bromenium ion source (Br⁺). Due to the ineffectiveness of the safe and easy-to-handle brominating agent N-bromosuccinimide (NBS) to deliver the desired products, a catalytic process using a mixture of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and acetic acid was conceived. We hypothesized that this catalytic system delivers in situ acetyl hypobromite (AcOBr) as the active brominating agent, enabling the conversion of a range of 2-allylphenols with diverse electron densities to the products. The protocol was robust enough to permit the reaction to be scaled up to 10 mmols of starting material. Besides, the functional group interconversion with a 2-bromomethyl-2,3-dihydrobenzofuran derivative was successfully demonstrated.