Stereocontrolled Construction of Spirooxindole-Containing 5,6,7,8-Tetrahydropyrrolo[1,2‑a]pyridine via Michael/Friedel–Crafts Domino Reaction Promoted by Secondary Amine-Squaramide

An asymmetric Michael/Friedel–Crafts cascade reaction with Morita–Baylis–Hillman (MBH) nitroallylic esters and 3-pyrrolyloxindoles has been developed for the stereoselective construction of spirooxindole-containing tetrahydroindolizines. A range of tetracyclic scaffolds possessing three consecutive chiral centers, including an all-carbon quaternary stereocenter, were generated in 53–85% isolated yields with high diastereoselectivities and enantiopurities (≥3:1 dr, 50–98% ee). A newly synthesized bifunctional secondary amine/squaramide organocatalyst was demonstrated to exhibit better stereochemical control than their tertiary analogues.