Synthesis of Highly Enantioenriched Bis-spirooxindole Pyrrolizidine/Pyrrolidines through Asymmetric [3+2] Cycloaddition Reaction

Synthesis of highly enantioenriched bis-spirooxindole pyrrolizidine scaffold was established using 1,3-dipolar cycloaddition of isatin-derived azomethine ylides by (E)-2-oxoindolin-3-ylidene acetyl sultam with four contiguous and two quaternary stereogenic centers in generally high yields (up to 96%) and diastereoselectivities (up to 99 : 1). In addition, highly enantioenriched bis-spirooxindole pyrrolidines were generated in high yields and highly regio- and -diastereoselectivities (up to 99 : 1) by utilizing this chiral auxiliary controlled method. The obtained cycloadducts underwent retro-Mannich ring-opening cyclization and produced new diastereoisomers of bis-spirooxindole pyrrolizidine/pyrrolidines skeleton that could not be accessed by direct 1,3-dipolar cycloaddition.