Isocyanide-Based One-Pot Cascade Synthesis of 3-Acyl Isoindolinones

A series of 3-acyl-substituted isoindolinone derivatives were synthesized in a one-pot manner via the reaction of o-bromobenzaldehydes, isocyanides, and carboxylic acids in the presence of palladium catalyst and base. The reaction employing easily available starting materials features simple operation and high efficiency. The mechanistic study showed that the reaction might undergo 1) Pd-catalyzed [3+2] cyclization of o-bromobenzaldehyde with isocyanide and the re-insertion of another molecule of isocyanide, 2) addition of carboxylic acid to in situ formed ketenimine followed by a rearrangement relay to give 3,3-diacyl-substituted isoindolinone derivative. Further transformations of the obtained products through decarbonylation could also be realized.

Automated summary

A series of 3-acyl-substituted isoindolinone derivatives were synthesized in a one-pot manner, using easily available starting materials and featuring simple operation and high efficiency.