Kinetics Stereoisomerizations

When the aldol reaction is carried Wt under thermodynamic conditions, the product selectivity is often not as high as under kinetic conditions. All the regioisomeric and stereoisomeric enolates may participate as nucleophiles. The adducts can return to reactants, and so the difference in stability of the stereoisomeric anti and syn products will determine the product composition. 

Some Formal Properties of the Kinetics of Pentacoordinate Stereoisomerizations... 

The pentacoordinate molecules of trigonal bipyramidal form, like PF5, are a very nice example for the study of the formal properties of stereoisomerizations. They are characterized by an appreciable nonrigidity and they permit the description of kinetics among a reasonable number of isomers, at least in particular cases (see below). Therefore the physical and chemical properties of these molecules have been thoroughly investigated in relation to stereoisomerization. Recent reviews may be found in the literature on some aspects of this problem. Mislow has described the role of Berry pseudorotation on nucleophilic addition-elimination reactions and Muetterties has reviewed the stereochemical consequences of non-rigidity, especially for five- and six-atom families as far as their nmr spectra are concerned. 

The constraint matrices for typical ligand partitions may be found elsewhere . We have investigated some of their formal properties, in relation to stereoisomerization kinetics. We give an account of the main results. Details and demonstration have been worked out in reference. ... 

The stereoisomerization kinetics of the various processes and for particular ligand partitions may be described in two essentially different ways ... 

To close the list of formal properties of the kinetic equations for stereoisomerizations with particular ligand partitions, let us simply recall that the solution of process P ... 

The effect of HMPA on the reactivity of cyclopentanone enolate has been examined.44 This enolate is primarily a dimer, even in the presence of excess HMPA, but the reactivity increases by a factor of 7500 for a tenfold excess of HMPA at -50° C. The kinetics of the reaction with CH3I are consistent with the dimer being the active nucleophile. It should be kept in mind that the reactivity of regio- and stereoisomeric enolates may be different and the alkylation product ratio may not reflect the enolate composition. This issue was studied with 2-heptanone.45 Although kinetic deprotonation in THF favors the 1-enolate, a nearly equal mixture of C(l) and C(3) alkylation was observed. The inclusion of HMPA improved the C(l) selectivity to 11 1 and also markedly accelerated the rate of the reaction. These results are presumably due to increased reactivity and less competition from enolate isomerization in the presence of HMPA. 

The cation-radicals of stilbene have been detected by ESR spectroscopy. These cation-radicals are accumulated and then consumed in the course of consecutive reactions. The stereoisomeric composition of the final products occurs to be constant and does not depend on the configuration of the initial substrate. Acetoxylation of the olefinic bond in cix-stilbene is almost one order of magni-tnde slower than in trany-stilbene. This kinetic feature deserves a special explanation, because cis-stilbene is less stable thermodynamically than irani-stilbene and should react faster. The products obtained are depicted in Scheme 2.29. 

For many ketones, stereoisomeric as well as regioisomeric enolates can be formed, as is illustrated by entries 6, 7, and 8 of Scheme 1.3. The stereoselectivity of enolate formation, under conditions of either kinetic or thermodynamic control, can also be controlled to some extent. We will return to this topic in more detail in Chapter 2. 

The enolates derived from cyclic ketones are necessarily. E-isomers. The enolate of cyclohexanone reacts with benzaldehyde to give both possible stereoisomeric products under kinetically controlled conditions. The stereochemistry can be raised to about 6 1 in favor of the anti isomer under optimum conditions.7 8... 

Both type A and B transformations are kinetically controlled and, therefore, the stereochemical result is based on an energetic comparison of transition states. By contrast, there is a large group of reactions where stereoselective bond formation occurs under thermodynamic control, and the stereoselectivity stems from the energy difference of the stereoisomeric products. Section 2.3.6. describes some pertinent examples. 

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