Synthesis of 2-hydroxy-3-indolinones and 3-hydroxy-2-indolinones by anionic cyclization, in situ oxidation and rearrangement

Lithiation with butyllithium of 2-(benzylamino)benzamides (N-benzyl anthranilamides) occurs at the benzylic position to give an α-amino-organolithium that cyclizes to the 3-indolinone (indoxyl) ring (similar to a Parham cyclization). Autoxidation in air gives 2-hydroxy-3-indolinones. In the absence of a proton source, rearrangement of the aryl group from C-2 to C-3 occurs to give the 3-hydroxy-2-indolinone (oxindole) ring.

Graphical abstractLithiation of 2-(benzylamino)benzamides promotes cyclization to give 3-indolinones which undergo in situ oxidation and either protonation to 2-hydroxy-3-indolinones or rearrangement to 3-hydroxy-2-indolinones.Figure optionsDownload full-size imageDownload as PowerPoint slide