KO <i> ^t </i> Bu‐Mediated Monoreduction and Difluoromethylation of Phthalimides to 3‐Substituted Isoindolinones

ABSTRACT A practical, transition‐metal‐free, chemoselective monoreduction of phthalimides to 3‐hydroxyisoindolinones is achieved with a KO t Bu/(EtO) 3 SiH hydrosilylation system under mild conditions. This reaction demonstrates broad functional group tolerance, and provides the corresponding 2 N ‐substituted‐3‐hydroxyisoindolinones in moderate to high yields. The monoreduction method is applicable for gram‐scale synthesis. Furthermore, a transition‐metal‐free, direct, and efficient chemoselective nucleophilic difluoromethylation of phthalimides is reported. This difluoromethylation method employs a KO t Bu/Me 3 SiCF 2 H system to afford a range of 2 N ‐substituted‐3‐(difluoromethyl)‐3‐hydroxyisoindolinones in moderate to good yields. These two KO t Bu‐mediated strategies offer a transition‐metal‐free, low‐cost, readily available, and practical process for the efficient conversion of phthalimides to the corresponding 3‐substituted isoindolinones.