Activated complexes in the epoxide deprotonations

Kinetics is capable of giving information about activated complexes (transition states (TSs)). In particular, reaction orders with respect to 

In the activated complexes shown, an electron lone pair on the amide nitrogen of the lithium amide is abstracting a (3-proton from the epoxide, while the lithium is coordinating the other lone pair on the amide nitrogen and the pyrrolidine nitrogen besides the epoxide oxygen. Such TSs have previously been proposed by Asami [4,32]. 

The activated complexes are not enantiomers but rather diastereoisomers and therefore differ in free energy. It is this energy difference between activated complexes that yields the stereoselectivity of the deprotonation reaction. In Fig. 2, we illustrate how the free energy difference (AG) between the activated complexes affect the product composition, as given by percent (5 )-product (%(5 )-3). 

A detailed computational study of possible activated complexes involved in the cyclohexene oxide deprotonations has been carried out [17,29,33]. Geometry optimizations of both specifically solvated and unsolvated activated complexes at various levels of theory ranging from PM3 to mPWlK/6-31 + G(d) have been carried out. In Figs 3 and 4 the optimized structures of the activated complexes with the latter theory are shown. 

From the experimentally obtained product composition in THF 90% of (5)-3 and 10% of (R)-3, a free energy difference (AG) between the two rate-limiting diastereoisomeric activated complexes of 1.33 kcal moP is calculated. In Table 1, energy differences and product compositions obtained by computational chemistry at various levels of theory are presented for activated complexes built from one molecule of epoxide 2, monomeric or dimeric lithium amide 4 and no or one specifically solvating THF or DEE molecule. 

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