Products, molecules containing chiral centers

With a molecule such as chloromethane, however, there is no way to prove that attack by the nucleophile has involved inversion of configuration of the carbon atom because one form of methyl chloride is identical to its inverted form. With a molecule containing chirality centers such as f-Tchloro-3-methylcyclopentane, however, we can observe the results of an inversion of configuration by the change in stereochemistry that occurs. When r-l-chloro-3-methylcyclopentane reacts with hydroxide ion in an 5 2 reaction, the product is rw r-3-methylcyclopentanol. The hydroxyl group ends up bonded on the opposite side of the ring from the chlorine it replaces. ... 

Molecules Containing Chiral Centers as Reactants or Products... 

This target molecule again contains a chiral center and we inspect Table 18 for help. Table 18. Some enantioselective reactions that produce difunctional products... 

Protease inhibitors are well-characterized chiral drugs in terms of their mechanism of action. An important new class of protease inhibitors comprises molecules designed to treat HIV infection. In particular, indinavir sulfate (CRIXIVAN, Merck and Co., Inc.) contains five chiral centers that must be of a specific orientation for the molecule to have the desired therapeutic effect. Manufacturing processes for these compounds involving chemical synthesis steps can be quite inefficient, due to yield reduction caused by racemization at each step where a chiral center is formed. A key intermediate in the synthesis of CRIXIVAN is cis-(lS,2R)-l-amino-2-indanol [(-)-CAI], an indene derivative that contributes two chiral centers to indinavir sulfate (Fig. 1). To circumvent the technically demanding chemical synthesis of (-)-CAI and reduce product loss, Merck scientists conceptualized a bioconversion process in which indene is oxidized to one of three derivatives that can serve as precursors to (-)-CAI cis-(lS,2R)-indandiol, trans-(lR,2R)-indandiol, or (lS,2R)-indan oxide. Oxygenases that have been identified in isolates of the genus Pseudomonas and Rhodococcus can catalyze this transformation. 

Let us now examine what happens when a chiral molecule (containing one chirality center) reacts so as to yield a product with a second chirality center. As an example consider what happens when (5)-2-chloropentane undergoes chlorination at C3 (other products are formed, of course, by chlorination at other carbon atoms). The results of chlorination at C3 are shown in the box below. 

Preparation of optically active materials by use of chiral catalysts is also based on differences in transition state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new chiral center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

In order to explore mechanistic aspects of these reactions, in particular the stereochemistry of the reaction products, photo-addition reactions of DCA inclusion compounds containing acetophenone and m-chloroacetophenone guest molecules were studied. In both cases, photo-addition takes place at position 5 of DCA, resulting in the formation of a new chiral center with S configuration. This process involves a 180° rotation of the acetyl group of the guest molecule, the driving force for which was elucidated by... 

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