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 η6-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.
A site isolation-enabled organocatalytic approach to enantiopure γ-amino alcohol drugs
Tetrahedron 2018, 74 (29), 3943-3946, DOI: 10.1016/j.tet.2018.04.022.