Chiral thermodynamic principle

Another approach to the construction of optically active chochins of known chirality — the so-called chiral recognition principle — involves the coupling of the optically active [2.2]paracyclophane derivative (R)-46 16) with the racemic mixture of the [3]chochm derivative 47. From the two diastereomeric [5]chochins which could be expected thereof, the one with (J )(S)(S)-chirality (see Fig. 2) because of eclipsed steric interactions is thermodynamically less stable than the (R)(R)(R)-isomer with Z)2-symmetry. The latter (44) was indeed the only product isolated from... 

The overall observed retention of the enantiomers, and thus the elution order, is based on several kinetically and thermodynamically controlled parameters concerned with stereorecognition nonstereoselective interactions of all partners SO(R), SA(R S), and particularly of the [SO(RI-SA(KI] and [SO(K)-SA(Si] complexes with the achiral stationary phase, also play a role (Figure 21). Therefore the retention order may be reversed for a specific pair of enantiomers depending on whether a covalently bound CSP or a CMPA is applied, but using the same chiral molecule (part) as chiral selector. These general principles, shown schematically for a CLEC system, are further complicated by the complexity of the entire system, hence they are difficult to anticipate and each case must be studied individually. 

Selectivity and efficiency Chiral separation selectivity may in the best case approach the thermodynamic selectivity of the chiral recognition but will never exceed it the separation efficiency sometimes is poor. Separation selectivity may easily exceed the thermodynamic selectivity of the recognition a chiral separation even in the absence of chiral recognition is, in principle, feasible high peak efficiency. 

However, if both diastereomers are in equilibrium, besides a preferred binding control"2, the higher reactivity of one of the diastereomeric primary substrate complexes (containing the chiral auxiliary ligand) might be responsible for stereocontrol of the overall reaction. According to the Curtin-Hammett principle, the more active primary complex does not necessarily have to be identical with the thermodynamically favored substrate complex in the equilibrium3. 

In the above examples, the protonation step involves the irreversible delivery of a proton to a reactive intermediate - a kinetic process. It should in principle be possible to carry out the conceptually simpler thermodynamic version whereby a compound racemizes in the presence of an excess of some chiral scalemic compound that in effect provides a chiral environment that maintains an enantiomeric ratio (without the need for a crystallization event). An example of such a thermodynamically controlled deracemization is contained in a seldom-cited paper from... 

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