Organocatalyzed Enantioselective [3+2] Cycloaddition Reactions for Synthesis of Dispiro[benzothiophenone-indandione-pyrrolidine] Derivatives

Abstract

An organocatalytic enantioselective [3+2] cycloaddition reaction involving 2-arylidene-1,3-indandiones and N-2,2-difluoroethylbenzothiophenone imines was developed. This approach efficiently afforded dispiro[benzothiophenone-indandione-pyrrolidine]s, featuring three stereocenters, in 84–98% yields with 3–93% ee and 9:1–>20:1 dr. Notably, the method maintained its yield and enantioselectivity integrity even in a gram-scale amplification experiment. For example, the product with substituents on aromatics were obtained in 90% yield with 91% ee and >20:1 dr. Its absolute configuration was established through X-ray single-crystal diffraction analysis, and a plausible reaction mechanism was proposed.

Keywords

• asymmetric catalysis
• 2-arylidene-1,3-indandione
• benzothiophenone
• thiourea
• squaramide
• spirocyclic compounds