A direct arylation-oxidation route to 3-arylisoindolinone inhibitors of MDM2-p53 interaction

作者：Dempster Richard K; Luzzio Frederick A^*

来源：Tetrahedron Letters, 2011, 52(39): 4992-4995.

DOI：10.1016/j.tetlet.2011.07.076

• MDM2-p53
• Isoindolinone
• Acyliminium
• Oxochromium (VI)
• Benzylic oxidation

A route to the MDM2-p53 inhibitor isoindolinone pharmacophore from a pre-formed phthalimide is detailed. The route involves treatment of 3-hydroxy-2-(n-propyl)isoindolinone with a substituted benzene in the presence of triflic acid. The resulting 3-aryl-2-(n-propyl)isoindolinones are then oxidized to the corresponding 3-hydroxy-3-aryl-2-(n-propyl) isoindolinones by treatment with 2,2'-bipyridinium chlorochromate. The benzylic oxidation represents a rather rare oxochromium (VI)-mediated reaction in which a selective C-H to C-OH transformation occurs.

• 出版日期2011-9-28