Synthesis And Application Of Non-cross-linked Polystyrene Supported Hydantoin Chiral Auxiliaries

Polymer-supported chiral auxiliary has been widely applied in asymmetric aldol reaction, alkylation reaction, Mannich reaction, D-A reaction and obtained a good asymmetric induction and purification effect. In this thesis, we successfully synthesized soluble non-cross-linked polystyrene(NCPS) supported hydantoin chiral auxiliary and investigated its asymmetric induction effect in aldol reaction, mannich reaction.1. The synthesis of NCPS supported hydantoin chiral auxiliaryUsing L-tyrosine methyl ester hydrochloride as a chiral material, reacted with phenyl isocyanate under first pyridine as the base then reflux conditions of hydrochloric acid to give a chiral hydantoin.Chiral hydantoin monomer was obtained under K2CO3and1-(chloromethyl)-4-ethenylbenzen. Then reacted with propionyl chloride to give N-acylated hydantoin monomer.Finally, AIBN as the initiator, reacted with styrene in THF to give a NCPS supported hydantoin chiral auxiliary.The total yield was68%,and the loading capacity was1.20mmol/g.2. The solubility of NCPS supported hydantoin chiral auxiliaryNCPS supported hydantoin chiral auxiliary has a good solubility in THF, CH2Cl2and other solvents, but insoluble in methanol, ethanol. Thus the NCPS supported chiral auxiliary can be carried out equably in THF, CH2CI2and tested on line by IR,1H NMR,13C NMR during the reaction. After the reaction, the solvent was removed and precipitated in ice-methanol, filtered, washed until no small molecule impurity detected by TLC.3. NCPS supported hydantoin chiral auxiliary induced aldol reactionUsing NCPS supported hydantoin as chiral auxiliary, the asymmetric aldol reaction using different lewis acid, temperature were studied. The results showed that when using n-Bu2BOTf as lewis acid, a temperature of-78℃, the asymmetric aldol reactions displayed best stereoselectivity and chemical yield. Under the optimal conditions,the NCPS supported hydantoin was reacted with six different kind of aldehydes, and then cleave with LiOH/H2O2to give six (Syn, S, S) of β-hydroxy acids(ee>99%, yield75to86%).4. NCPS supported hydantoin chiral auxiliary induced mannich reaction NCPS supported hydantoin chiral auxiliary was reacted with sex different kind of aldimine under the condition of0℃, TiCl4as Lewis acid, DIPEA as aldimine. After cleave with CH3OH/DMAP, we got a high stereoselectivity (ee99%) and good yield (70to78%). Then we investigate the effection of different acylated group in the mannich reaction. We found that with the N-acylated groups R2increasing, steric stereoselective almost no change, but chmical yield decrease (73to52%). Only when R2is Ph, since the intermediate enol form a benzene ring and a large conjugated system, can activate methylene, and has a high yield.5. The reusability of NCPS supported hydantoin chiral auxiliaryThe recycling and reuse of the chiral auxiliary was studied. The results indicated that the stereoselectivity of the recovered chiral auxiliary remained almost intact for at least four reaction cycles, and the yield decreased slightly in each cycle.All the products and intermediates were characterized by IR,1H NMR and13C NMR, and spectra analysis results were consistent with the compound structures. The ee was determined by HPLC. The separation and purification process was monitored by TLC.