Application of the Wittig Rearrangement of <i>N</i>-Butyl-2-benzyloxybenzamides to Synthesis of Phthalide Natural Products and 3-Aryl-3-benzyloxyisoindolinone Anticancer Agents

Abstract

Application of the [1,2]-Wittig rearrangement and cyclisation approach to 3-arylphthalides has been evaluated for the synthesis of three bioactive natural products. While this is successful in the case of crycolide, providing the second synthesis of this compound, the more sterically demanding targets isopestacin and cryphonectric acid prove not to be amenable to this approach, with the 2,6-disubstituted aryl groups causing the failure of the rearrangement and alkylation steps, respectively. Direct oxidation of the substituted benzhydrols resulting from [1,2]-Wittig rearrangement using MnO2 provides a new route to 3-aryl-3-hydroxyisoindolinones, and this method has been used in the synthesis of two 3-aryl-3-benzyloxyisoindolinone anticancer agents.

Keywords

• [1,2]-Wittig rearrangement
• 3-arylphthalides
• 3-aryl-3-hydroxyisoindolinones
• natural products
• anticancer agents