Synthesis of phenol derivatives from cyclopentenones with arynes as key intermediates

Abstract

Phenols are frequent motifs in drug discovery and material sciences, thus their synthesis continue to attract attention. Herein we present a five-step cascade reaction for the synthesis of phenol derivatives from their corresponding 2-trimethylsilylcyclopentenone and arynophile precursors, and iodoform. The methodology builds on previously reported anion-accelerated electrocyclic ring-opening which provides the corresponding 3-iodo-2-trimethylsilylphenoxy anion. A Brook-like rearrangement provides the key benzyne intermediate, which reacts in situ with the arynophile. The reactivity of different classes of arynophiles were investigated, and it was shown that under the optimized conditions [4 + 2] and [2 + 2] cycloadditions as well as nucleophilic addition were productive, while [3 + 2] was not. Isolated yields were up to 40%.

Keywords

• Electrocyclic Ring-opening
• Phenols
• Aryne
• Brook-like rearrangement