Copper(II)-catalyzed oxidation of N-substituted isoindolinones to the corresponding phthalimides

A series of N-substituted isoindolinones were treated with an oxidation system comprised of catalytic copper(II) acetate monohydrate and tert-butylhydroperoxide (TBHP) in a non-chlorinated solvent (acetonitrile).As a result of benzylic methylene oxidation, the oxidation system afforded the corresponding phthalimides in isolated yields of 50-98%.Simple isoindolinones responded quite well to the oxidation system and gave the products after a reaction period of 24-48 hours at room temperature.The oxidation was selective for the benzylic (C3) carbon of the isolindolinone as opposed to isolated methylene groups and benzylic methyl groups.Using selected substrates, an analogous oxidation method mediated by Cu(II) oxinate is also detailed.N O R Cu(II) acetate TBHP/MeCN 48 h/rt N O R O 13 Examples 50-98%