Stereocontrolled Construction of Spirooxindole-Containing 5,6,7,8-Tetrahydropyrrolo[1,2-]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.

Diastereoselective construction of tetracyclic chromanes a triply annulative strategy.

A triple Michael/aldol cascade reaction has been established to construct tetracyclic chromanes in a diastereoselective fashion (≥5 : 1 dr). The polycyclic products were generated in 50-78% isolated yields under mild and metal-free conditions. Five reactive sites of enolate-tethered divinyl ketones were sequentially utilized to form four C-C bonds in a one-pot operation, leading to a construction of three new rings.