A concise access to bridged [2,2,1] bicyclic lactones with a quaternary stereocenter via stereospecific hydroformylation

["Chiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these compounds are rare. Here we report an efficient method for enantioselective construction of bridged [2,2,1] bicyclic lactones bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/pyridium chlorochromate (PCC) oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols are transformed into corresponding gamma-hydroxyl aldehydes with specific syn-selectivity. Then, hemiacetals form in situ and oxidation with PCC in one-pot affords bridged [2,2,1] bicyclic lactones in high yields and excellent enantiomeric excess. Replacing the hydroxyl group by an ester group, cyclopentanecarbaldehydes with a chiral all-carbon quaternary stereocenter in the gamma-position can be generated efficiently.","Enantiomeric bridged [2,2,1] bicyclic lactone skeletons and their ring-opening products are important scaffolds widely occurring in both pharmaceutics and biology active compounds. Here the authors show an efficient method for enantioselective construction of these compounds bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/ pyridinium chlorochromate oxidation."]