One‐Step Chemo‐, Regio‐ and Stereoselective Reduction of Ketosteroids to Hydroxysteroids over Zr‐Containing MOF‐808 Metal‐Organic Frameworks

Zr‐containing MOF‐808 is a very promising heterogeneous catalyst for the selective reduction of ketosteroids to the corresponding hydroxysteroids through a Meerwein‐Ponndorf‐Verley (MPV) reaction. Interestingly, the process leads to the diastereoselective synthesis of elusive 17α‐hydroxy derivatives in one step, whereas most chemical and biological transformations produce the 17β‐OH compounds, or they require several additional steps to convert 17β‐OH into 17α‐OH by inverting the configuration of the 17 center. Moreover, MOF‐808 is found to be stable and reusable; it is also chemoselective (only keto groups are reduced, even in the presence of other reducible groups such as C=C bonds) and regioselective (in 3,17‐diketosteroids only the keto group in position 17 is reduced, while the 3‐keto group remains almost intact). The kinetic rate constant and thermodynamic parameters of estrone reduction to estradiol have been obtained by a detailed temperature‐dependent kinetic analysis. The results evidence a major contribution of the entropic term, thus suggesting that the diastereoselectivity of the process is controlled by the confinement of the reaction inside the MOF cavities, where the Zr(4+) active sites are located.