Continuous synthesis of homoallylic ketones via ketal-Claisen rearrangement using solid-acid catalysts

Abstract

Homoallylic ketones are useful intermediates for the synthesis of various compounds, such as drugs and natural products. However, the currently available fabrication methods for homoallylic ketones are environmentally unfriendly and tedious. We herein describe a continuous synthesis of homoallylic ketones from allylic alcohols and dimethyl ketals via ketal-Claisen rearrangement using a column-type flow reactor and a solid-acid catalyst. We have shown that the flow of N₂ gas accompanying the reaction solution improved the flow ketal-Claisen rearrangement. Long-term operation (150 h) of the flow ketal-Claisen rearrangement using a column packed with TMEDA-treated SO₃H–ZrO₂ has been successfully achieved with over 70% yield of homoallylic ketones. We believe that our proposed method could prove highly useful in the synthesis of homoallylic ketones.