(2S,3aR,7aS)-Perhydroindolic acid, the key intermediate in the synthesis of trandolapril, and its trans-isomers, were readily prepared. These prolinelike molecules are unique in that they contain a rigid bicyclic structure, with two hydrogen atoms trans to each other at the bridgehead carbon atoms. These molecules were used successfully as chiral organocatalysts in asymmetric domino Michael addition/cyclization reactions of aldehyde esters with b,g-unsaturated a-keto esters. They proved to have excellent catalytic behavior, allowing for the synthesis of multi-substituted, enantiomerically enriched hemiacetal esters. Under optimal conditions (using 10 mol% catalyst loading), a series of b,g-unsaturated a-keto esters was examined with up to 99% de, ee and yield, respectively. Additionally, the enantiomerically enriched hemiacetal esters could be readily transformed into their corresponding bioactive pyranoA C H T U N G T R E N N U N G [2,3-b]pyrans (possessing a multi-substituted bicyclic backbone).