Electrochemically assisted deprotection of acetals, ketals, and dithioacetals under neutral conditions†

Abstract

Electroorganic synthesis (EOS) enables unattainable molecular transformations that cannot be achieved through conventional acid/base or thermal reactions to be realized by exploiting molecular redox capabilities. The use of acetals as protecting groups for the carbonyl functionality is a pivotal component of natural product synthesis and drug discovery. Acetal deprotection typically requires aqueous acid hydrolysis. Herein, we present the development of an electrochemical deprotection reaction for cyclic acetal, ketal, and dithioacetal derivatives, with a diverse range of such aromatic and aliphatic substrates deprotected in yields of between 55% and quantitative. Mechanistic investigations provided insight into the electro-deprotection process involving acetals. Lithium perchlorate (LiClO₄) plays a dual role, functioning as both the electrolyte and the oxygen source for the carbonyl moiety, with the electro-deprotection reaction proceeding to afford carbonyl products. Moreover, reaction efficiency was markedly enhanced by the addition of 1,3,5-trioxane, which acts as a Li activator.