Synthesis of (−)-Centrolobine by Prins Cyclizations that Avoid Racemization

The segment-coupling Prins cyclization avoids two of the problems common to other Prins cyclization protocols: side-chain exchange and partial racemization by reversible 2-oxonia Cope rearrangement. Model studies demonstrate the stereochemical fidelity of Prins cyclizations using α-acetoxy ethers compared with direct aldehyde−alcohol Prins reactions. Furthermore, we propose a mechanism for the racemization observed in some intermolecular Prins cyclizations. Two straightforward syntheses of optically pure (−)-centrolobine highlight the utility of Prins cyclizations.