ENANTIOMERICALLY PURE CHIRAL AUXILIARIES

In asymmetric synthesis, the use of enantiomerically pure chiral auxiliaries involves the temporary introduction of a chiral group G onto an achiral substrate R-Y. This modified substrate R-Y-G is subsequently transformed, ideally through a highly diastereoselective process, into a new product R-Z -G. After cleavage of the chiral auxiliary, the final product R-Z, bearing a new stereocenter, is formed. 

The requirements for methods based on chiral auxiliaries follow  

In general, the recycling is desirable, so the chiral auxiliary should be easy to recover without any loss of enantiomeric purity. However, if the auxiliary is inexpensive, it need not be recycled. In some cases, the chiral auxiliary is actually destroyed during the cleavage reaction to produce the final product. Such transformations are called immolative processes. 

Each pure enantiomer of the chiral auxiliary should be readily available so that it is possible to prepare at will both enantiomers of the target molecules. Most chiral auxiliaries are therefore either natural product, or compounds derived from natural products by classical high yielding transformations. 

In the present chapter, the most frequently used enantiomerically pure chiral auxiliaries will be described, along with some new and efficient auxiliaries. These 

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Asymmetric amplification in reactions involving partially resolved chiral auxiliaries is now a well-established phenomenon that is very attractive since it gives improved enantioselectivities witb respect to expectations based upon the ee of the auxiliary. It may have practical application in that enantiomerically pure chiral auxiliaries are not always required for highly selective asymmetric synthesis. Asymmetric amplification is also of fundamental importance in order to achieve efficient asymmetric autocatalysis. Finally, evidence of an asymmetric amplification is a very useful piece of information in mechanistic studies. 

To complete the reaction sequence of Figure 13.35, the desired alkylated ketone needs to be released from the kethydrazone. Ozonolysis cannot be used in the present case. Ozonoly-sis would cleave not only the C=N double bond but also the C=C double bond. Another method must therefore be chosen. The kethydrazone is alkylated to give an iminium ion. The iminium ion is much more easily hydrolyzed than the hydrazone itself, and mild hydrolysis yields the deshed -enantiomer of 6-methyl-2-cyclohexenone. The other product of hydrolysis is a RAMP derivative. This RAMP derivative carries a methyl group at the N atom and cannot be recycled to the enantiomerically pure chiral auxiliary A that was employed initially. 

There are many examples in the literature where partially resolved chiral auxiliaries or chiral ligands were used for asymmetric synthesis. A correction was usually made by dividing the ee (%) of the product (EE pro by the ee (%) of the auxiliary (ee aux) multiplying by 1(X). The value thus obtained (EE ) is the ee (%) predicted for the produa prepared with enantiomerically pure chiral auxiliary or ligand. This calculation corresponds to equation [1] where all the enantiomeric excesses are taken with absolute values <1. 

Secondly, radical polymerization of monomers possessing a chiral auxiliary can also afford highly isotactic rich polymer. In such monomer systems, tacticity is not determined by relative 1,3-interactions between the stereo-genic center of the penultimate unit and the prochiral radical center. Instead, the (enantiomerically pure) chiral auxiliary imposes a preference for the formation of either (R) or (S) absolute stereogenic centers at the prochiral... 

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