Novel O-ferrocenoyl hydroxyproline conjugates: Synthesis, characterization and catalytic properties

A series of mono- and disubstituted O-ferrocenoyl conjugates of 3-trans- and 4-trans-hydroxy-L-proline amino acids are synthesized. These conjugates are protected by tert-butloxycarbonyl (Boc) group at the N-terminus. The Boc removal of the ferrocene (Fc) hydroxy-L-proline conjugates affords a series of mono- and disubstituted Fc conjugates containing free amine at the N-terminus. These conjugates are characterized by NMR and IR spectroscopies as well as mass (MS) spectrometry. The catalytic properties of the free amine Fc conjugates toward aldol addition reaction are studied. The enantioselectivity of the aldol reaction products in acetone solvent is determined by the position of the N-atom in the proline residue with respect to the proline point of attachment to the Fc scaffold. The 4-trans-hydroxy-L-proline containing Fc catalyst favors the production of the R-isomer, while Fc catalysts containing 3-trans-hydroxy-L-proline favors the production of the S-isomer.

Graphical abstractThe synthesis and characterization of mono- and disubstituted O-ferrocenoyl hydroxyproline conjugates is described. The Fc conjugates have been investigated as homogenous catalysts in aldol coupling reaction. The catalyst structure–selectivity relationship in O-ferrocenoyl hydroxyproline catalysts has been addressed. The disubstituted O-ferrocenoyl hydroxyproline catalysts exhibits a higher conversion compared to the monosubstituted O-ferrocenoyl hydroxyproline catalysts with an acceptable ee values.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The first synthesis and characterization of O-ferrocenoyl hydroxyproline conjugates are described. ► The O-ferrocenoyl hydroxyproline conjugates exhibits a catalytic properties toward aldol reaction. ► The structure–enantioselectivity relationship in Fc-hydroxyproline cataylsts is being studied for the first time.