| The first part of this thesis is about the study of achiral additives enhancing enantioselectivities on the (S)-BINOL/Ti(IV) complex catalyzed aldol condensation of aldehydes with Chan’s Diene. Chan’s Diene, named 1,3-bis(trimethylsilyloxy) -1-methoxy-1,3 -butadiene, has been used as nucleophilic reagent to formδ-hydroxy-β-ketoesters by reacting with aldehydes. If catalyzed by (S)-BINOL/Ti(IV) complex, the reaction. can form different chiral substances. We examined the effect of various achiral additives on the aldol reaction of aldehydes with Chan’s diene catalyzed by (S)-BINOL/Ti(IV). The reactions were carried out at room temperature and the most outstanding result was achieved using LiCl as achiral additive, giving up to 99%e.e.. The late literatures reported the reactions must be carried out at -78°C using molecular sieves as achiral additive to achieve similar values of e.e. . Optically activeδ-hydroxy-β-ketoesters are key intermediates of drugs of hyperlipidemia and arteriosclerosis, so the better condition of this catalytic system is beneficial for application.The second part of this thesis is about the asymmetric synthesis of Orlistat. Orlistat is an anti-obesity drug acting on the peripheral system, marketed in several countries under the name Xenical by the Hoffman La Roche company. There are four chiral centers in the Orlistat molecular, so it is hard to asymmetric synthesis of Orlistat. We designed a new and practical process for the preparation of Orlistat. Orlistat was synthesized from lauraldehyde and Chan’s Diene by Mukaiyama-aldol reaction, followed by protection of the hydroxyl group, reduction of the carbonyl group, alkylation, lactonization and Mitsunobu reaction. There are six new compounds, including 98, 99,100,101,102 and 103. |
