Tetrahedron 2018-04-11

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

Shoulei Wang, Carles Rodríguez-Escrich, Xinyuan Fan, Miquel A. Pericàs

Index: 10.1016/j.tet.2018.04.022

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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 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.