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 γ-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 γ-position can be generated efficiently.

Asymmetric Inverse-Electron-Demand Diels–Alder Reactions of 2-Pyrones by Lewis Acid Catalysis

Diels–Alder reactions of 2-pyrones with alkenes can provide highly functionalized [2,2,2]-bicyclic lactones under mild reaction conditions. Synthetic utilizations of these reactions have been well demonstrated in natural-product synthesis. Although several catalytic asymmetric strategies have been realized, current research in this area is still largely underdeveloped. Recent advances in enantioselective inverse-electron-demand Diels–Alder reactions with Lewis acid catalysis are reviewed.1 Introduction2 State of the Art of Enantioselective Diels–Alder Reactions of 2-Pyrones by Lewis Acid Catalysis3 Enantioselective Synthesis of Arene cis-Dihydrodiols by Diels–­Alder/Retro-Diels–Alder Reactions of 2-Pyrones4 Enantioselective Synthesis of cis-Decalin Derivatives by Diels–­Alder Reactions of 2-Pyrones5 Conclusions

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

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.

Photoredox-Catalyzed Hydroxymethylation of -Ketoesters: Application to the Synthesis of [3.3.3] Propellane Lactones

Photoredox-catalysed hydroxymethylation of -ketoesters substituted by an allyl subunit on the -position afforded directly the corresponding bicyclic lactones possessing both a hydroxy group and an unsaturation. A subsequent regioselective iodoetherification...