Stereospecific Hydroformylation of 1-Substituted Cyclopent-3-en-1-ols: A Concise Access to Bridged [2, 2, 1] Bicyclic Lactones With A Quaternary Stereocenter

Abstract

\n An efficient method for enantioselective construction of bridged [2, 2, 1] bicyclic lactones bearing a quaternary stereocenter was achieved by Rh-catalyzed asymmetric hydroformylation /intramolecular cyclization/PCC oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols were transformed into their corresponding y-hydroxyl aldehydes with specific syn-selectivity, then hemiacetal formed in situ and oxidized by PCC in one-pot, affording 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 γ-position can be generated efficiently. Gram-scale reaction and several transformations to corresponding amide, alcohol and acid demonstrated the practical value of this methodology.