Enolates torsional effect

Houk and co-workers examined the role of torsional effects in the stereoselectivity of enolate alkylation in five-membered rings, and their interpretation can explain the preference for C(5) alkylation syn to the 2-methyl group in trans-2,3-dimethylcyclopentanone.59... 

There is one report that showed how torsional, involving allylic CH bonds and steric effects but not orbital distortions, provide an explanation for the stereoselectivity of pyrrolidinone enolate alkylations. A prediction was... 

The chemical shifts of a-protons in some conformationally rigid enol ethers, e.g., 1, have been studied. It was found that they depend not only on their relative position with respect to the alkoxy group, but also on the torsional angle between the C —H and the C—C bonds it is claimed that electric-field effects of the alkoxy groups are responsible267. H Chemical shifts have also been used for the stereochemical assignment of eyclohexylidenecyanoacetates 2. 

Acid-catalysed hydrogen-deuterium exchange in norcamphor has also been investigated by Werstiuk and Banerjee (1977) (DOAc—D20—DC1 medium). It was observed that exo-deuteron addition to the enol is also preferred, but with a slightly smaller selectivity (x 190). This would mean that, if torsional factors cause preferential base-catalysed exo-exchange, they also occur for acid-catalysed keto-enol tautomerism. However, the absence of important torsional strain effects on the rate constants of acid-catalysed enolisation of cyclic and bicyclic ketones contradicts this assumption. 

Recent studies have suggested that coordination with a lithium cation may be responsible for the stereochemical outcome in Meyers-type enolate alkylations . In fact, the hypothesis that the diastereofacial selectivity observed in these reactions might result from specific interactions with a solvated lithium cation was already proposed in 1990 . Nevertheless, the potential influence exerted by solvation and lithium cation coordination was not supported by a series of experimental results reported by Romo and Meyers , who stated that it would appear that neither the aggregation state of the enolate nor the coordination sphere about lithium plays a major role in the observed selectivity. This contention is further supported by recent theoretical studies of Ando , who carried out a detailed analysis of the potential influence of solvated lithium cation on the stereoselective alkylation of enolates of y-butyrolactones. The results showed conclusively that complexation with lithium cation had a negligible effect on the relative stability of the transition states leading to exo and endo addition. The stereochemical outcome in the alkylation of y -butyrolactones is determined by the different torsional strain in the endo and exo TSs. 

Other problems dealt with by the Hehre-Pople method are internal rotation in vinylcyclopropane and vinylcyclobutane 153>, the structure of homoallyl cation 154> and ethylenebenzenium cation 155>, torsional barriers in -substituted phenols 156), inversion barriers in -substituted anilines 157>, the effects of a-substitution in keto-enol tautomerism 158> and the circumambulatory rearrangement in bicyclo [3.1.0] hex-3-en-2-yl cation 159> ... 

For esters, thermodynamic equilibration of enolates is less likely, but additives can still affect the selectivity. Using LDA in THF for example, deprotonation of ethyl propionate is 94% fO)-selective, but in THF containing 45% DMPU, deprotonation is 93-98% ZfO)-selective [36]. Ireland rationalizes this observation in terms of the transition states in Scheme 3.4 as follows in the absence of additives, there is a close interaction between the metal, the carbonyl oxygen and the base which leads to a tight transition structure and E(0)i is favored. In the presence of coordinating additives, there is more effective solvation for the lithium, and therefore weakened interaction between the lithium and the carbonyl oxygen. The cyclic transition structures will be expanded, and may even open to an acyclic transition structure. When the association between the base and the ester is diminished, the 1,3-diaxial strain in Z(0) is reduced, whereas E(O) (and acyclic structures with similar torsion angles) are still destabilized by AL3 strain [36]. 

It is also important to note that several factors influence both the stereoselectivity of hydrogen exchange and enolate formation in base-promoted reactions. Houk, Ando and co-workers found that differing conju-gative stabilization by CH p-orbital overlap does not directly influence stereoselectivity.205 Steric effects only dominate is exceptionally crowded transition structures, but torsional strain involving vicinal bonds contributes significantly to the stereoselectivity of all cases studied. 

When enolates are allowed to reach equilibrium, the composition of the mixture is usually more closely balanced than under kinetically controlled conditions. In general, the more highly substituted enolate is the preferred isomer, but if the alkyl groups are sufficiently branched as to interfere with the solvation of the enolate, there can be exceptions. Torsional and ring strain effects also come into play with cyclic ketones. The identity of the metal cation and the solvent, which are the major factors in determining the extent of ion pairing, also affect the position of the equilibrium. 

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