A site isolation-enabled organocatalytic approach to enantiopure γ-amino alcohol drugs

Abstract Solid support-enabled site isolation has previously allowed to use paraldehyde as an acetaldehyde surrogate in aldol reactions. However, only electron-poor aldehydes were tolerated by the system. Herein, we show that the temporary conversion of benzaldehyde into η 6 -benzaldehyde Cr(CO) 3 circumvents this limitation. Asymmetric synthesis of ( R )-Phenoperidine, as well as formal syntheses of ( R )-Fluoxetine and ( R )-Atomoxetine, illustrate the benefits of this strategy.