Synthetically useful noncatalytic strategy: a stereocontrolled rapid cyclization of a three component system to afford hexahydropyrrolizines.

We demonstrate a highly regio- and stereoselective annulation strategy involving unprecedented C2-H and N-H of proline esters, α,β-unsaturated aromatic aldehydes and deactivated olefins without a catalytic aid to afford medicinally important pyrrolo[3,4-a]pyrrolizines and hexahydropyrrolizines under benign reaction conditions.

FeCl3⋅6H2O-catalyzed intermolecular-cascade cyclization of acetoacetanilide: aldehyde-tuned synthesis to valuable 2-pyridone analogues.

The first ever breakthrough toward activation of β-ketoacetanilide and subsequent C-C and C-N bond-forming intermolecular-cascade cyclization processes is demonstrated by development of the unprecedented Lewis acid property of non-toxic FeCl(3)⋅6H(2)O. Aromatic, aliphatic, α,β-unsaturated, chiral sugar-based and chromone aldehydes were regio- and stereoselectively cyclized with acetoacetanilides toward construction of valuable N-containing highly functionalized 2-pyridones (see scheme for an example).