Base-Promoted Cascade Reactions for the Synthesis of 3,3-Dialkylated Isoindolin-1-ones and 3-Methyleneisoindolin-1-ones

Abstract

Cascade reactions of <i>ortho</i>-carbonyl-substituted benzonitriles with ((chloromethyl)sulfonyl)benzenes as pronucleophiles led to new isoindolin-1-ones with a tetrasubstituted C-3 position or to (<i>Z</i>)-3-(sulfonyl-methylene)isoindolin-1-ones. The reactions start from readily available materials, are carried out under mild conditions, and do not require metal catalysis. Promoted only by the cheap and environmentally benign K₂CO₃ as the base, up to six elemental steps can be combined in a single pot. Hence, a sequential one-pot cascade/β-elimination/alkylation furnished useful intermediates for the synthesis of aristolactam natural products. The observed selectivity and the mechanism were investigated by DFT studies.