羰基的立体选择性还原.docVIP

实验十 羰基的立体选择性还原（~30学时） 原版实验教材实验（选自DYSON PERRINS LAB, UNIVERSITY OF OXFORD 2nd YEAR ORGANIC PRACTICAL COURSE） STEREOSELECTIVITY IN REDUCTION AIMS OF THIS PRACTICAL To demonstrate the use of stereoselective reagents in organic synthesis. To show that optical rotation can be used to demonstrate the presence of stereoisomers. THEORY One of the most important phenomena in organic chemistry is chirality. As proteins (enzymes, receptors, etc) are derived from L-amino acids, the protein will interact preferentially with a specific enantiomer of an added molecule. If the wrong enantiomer is present then the effect of the correct one can be reduced or a completely different, and most likely undesired, effect can be seen. Nowadays, all drugs have to pass stringent tests if racemic mixture is to be prescribed instead of the pure enantiomer. Asymmetric synthesis is a subdivision of chemistry that deals with the synthesis of pure chiral compounds and is of extreme importance since a lot of organic chemistry is based on the synthesis of biologically active and/or natural compounds. In this experiment you are going to investigate the reduction of a prochiral ketone, which in this case is ethyl acetoactate. In part A, the reduction is carried out using sodium borohydride. The mechanism goes through a tetrahedral intermediate, which is chiral. The achiral nucleophilic hydride source is free to attack from either above or below the plane of the ketone, and therefore will produce two different enantiomeric intermediates. Since enantiomers have the same physical and chemical properties, both are equally likely to form and therefore the reaction should give the racemic mixture. In Pert B, the sodium borohydride is first converted into a chiral reagent. As the reagent it now chiral, the transition states that arise from the attack being either above or below the plane of the ketone will be diastereomeric. This means that they will have different rates of formation and, therefore, one shou