Pyramidal racemization process

Both thermal- and acid-induced equilibrations of 3,3-disubstituted thietane oxides were very slow (K 10-5 s-1)194. The results suggest that thietane oxides are similar to the various acyclic sulfoxides with respect to the rates of thermally induced pyramidal inversion at sulfur238, and that this inversion process, therefore, does not interfere significantly in the above exchange/racemization studies. 

Pyramidal inversion is perhaps the simplest way to cause racemization. In this process the conversion of one enantiomer into another... 

Kinetic studies on the thermal racemization of the sulfonium salt 211 revealed that the process requires much lower activation energies when compared with thermal racemization of sulfoxides. Comparison of the relative rates for racemization of sulfonium salts 211, 212, and 213 was taken (151) as evidence that racemization of 211 is the result of pyramidal inversion, not of an alternative dissociation mechanism. On the other hand, Brower and Wu (249) concluded that the volume of activation for the racemization of sulfonium ion 211, AF = +6.4 ml/mol, is more compatible with a transition state in which partial dissociation has occurred. 

Oae (251,252) as well as Darwish and Datta (253) investigated the process of thermal racemization of chiral alkylarylsulfimides and diarylsulfimides. It was found to proceed at temperatures as low as 65 to 100°C with a rate constant of the order 1 to 10 X 10" sec" , which corresponds to an activation energy of about 23 to 30 kcal/mol. These data indicate that the thermal racemization of sulfimides is much faster than that of analogous sulfoxide systems. The racemization of sulfimides is a unimolecular reaction practically independent of the polarity of the solvent this property, coupled with the absence of decomposition products, supports the view that racemization of sulfimides occurs by pyramidal inversion. 

Mislow and co-workers (258) and Hammond (259) have shown that optically active diaryl sulfoxides, which are configurationally stable in the dark at 200°C, lose their optical activity after 1 hr at room temperature on irradiation with ultraviolet light. Similarly, an easy conversion of the trans isomer of thianthrene-5,10-oxide 206a into the thermodynamically more stable cis isomer takes place upon irradiation in dioxane for 2 hr. However, the behavior of a-naphthylethyl p-tolyl sulfoxide under comparable irradiation conditions is different, namely, it is completely decomposed after 4 min. These differences are not surprising because the photochemical racemization of diaryl sulfoxides occurs by way of the pyramidal inversion mechanism whereas decomposition of the latter sulfoxide occurs via a radical mechanism with the cleavage of the sulfur-carbon bond. It is interesting to note that photoracemization may be a zero-order process in which the rate depends only on the intensity of the radiation and on the quantum yield. 

It is important that this process results in the preferential formation of a thermodynamically stable alcohol diastereomer. The anion-radicals contain an almost undoubtedly planar C-0 and give rise to pyramidal hydroxy carboradicals. The hydroxy carboradicals form pyramidal hydroxy carbanions, which cannot exist in the presence of ammonium cation for a long time. Therefore, the equilibrium including pyramidal inversion, probably, takes place at the step of carboradical formation, rather than carbanion formation. Transformation of a carboradical into a carbanion obviously proceeds faster than its dimerization or disproportionation. As a consequence, the reduction of an optically active ketone into an alcohol goes without racemization (Rautenstrauch et al. 1981). 

Enantiomerically pure sulfonium salts can undergo racemization, though the process is not usually rapid. Three processes have been implicated in racemization these are (1) reversible dissociation (Scheme 5.3a), similar to that suggested for the racemization of tetraalkylammonium salts (Section 5.6) (2) pyramidal inversion at sulfur, analogous to nitrogen inversion in amines and (3) reversible dissociation into a carboca-tion and a sulfide (Scheme 5.3b) (see Andersen10). 

As a result of pyramidal inversion, a chiral amine quite literally turns itself inside out, like an umbrella in a strong wind, and in the process becomes a racemic mixture. The activation energy for pyramidal inversion of simple amines is about 25 kj (6 kcal)/mol. For ammonia at room temperature, the rate of nitrogen inversion is approximately 2 X 10" s. For simple amines, the rate is less rapid but nonetheless sufficient to make resolution impossible. 

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