Design Of Phase-separated L-proline For The Direct Asymmetric Aldol Reactions In Aqueous Phase

The direct asymmetric aldol reaction is one of the most important C-C bond-forming reactions in organic synthesis. The obtained β-hydroxy ketone is the important intermediates in synthesis of natural products. L-proline is an excellent catalyst for the direct asymmetric aldol reaction, due to the mild reaction conditions, as well as the process without prior stoichiometric formation of the nucleophile. However, the L-proline is insoluble in organic solvents, which results in the high catalyst loading and lower catalytic efficiency for the reaction. Furthermore, high polar organic solvent often requires to stabilize the catalytical active intermediate. The recovery and reuse of L-proline is troublesome. To address the issue, novel serial L-proline with high efficiency and controllable separation has been developed for the direct asymmetric aldol reaction in water.A novel L-proline possessing a thermoregulated phase-transfer function was prepared by introducting the "smart" poly (N-isopropylacrylamide)(PNIPAAm) group to the framework of the L-proline. FT-IR, UV-vis and1H-NMR spectroscopy shows the covalent linkage of the PNIPAAm mioiety with L-proline through the terminal NH2-group of PNIPAAM and the-COOH of L-proline. The PNIPAAm functionalized L-proline exhibits reversible switching between hydrophobicity and hydrophilicity at the CST in the direct asymmetric aldol reaction between cyclohexanone/cyclopentanone and aromatic aldehydes in water. The temperature dependent water-solubility allows the L-proline catalyst to perform thermoregulated phase-separable catalysis (TPSC) in the direct asymmetric aldol reaction in water.99%conversion to aldol product was obtained within6h. Furthermore, the catalyst can be precipitated out from the reaction system for efficient reuse by enhancing reaction temperature after the reaction.A series of polyisopropoxy functionalized ionic liquid (IL) with different unit number of isopropoxy has been introduced into the framework of L-proline through covalent bond. The obtained catalysts were employed in the direct asymmetric aldol reaction between cyclohexanone/acetone and aromatic aldehydes in water. It is found that the polyisopropoxy imidazolium IL endows the novel catalysts with a phase transfer function. The catalysts show excellent catalytic performance between cyclohexanone and aromatic aldehydes of direct asymmetric aldol reaction. After the reaction, the catalyst can be effectively recovered by solvent extraction, and was reused more than four times without loss of activity.Based on the phase transfer function, as well as the unique solubility, of the polyethylene glycol (PEG), a PEG functionalized IL has been introduced into the structure of L-proline by covalent linkage. The rasulted catalyst was employed in the direct asymmetric aldol reaction between various aldehydes and cyclohexanone in water. Moderate catalytic activity with high selectiviy is observed over the novel catalyst. This part of research work is still in continue.