Deprotonation mesomerically stabilized

For the deprotonation of less acidic precursors, which do not lead to mesomerically stabilized anions, butyllithium/TMEDA in THF or diethyl ether, or the more reactive, but more expensive,. seobutyllithium under these conditions usually are the most promising bases. Het-eroatomic substitution on the allylic substrate, which docs not contribute to the mesomeric or inductive stabilization often facilitates lithiation dramatically 58. In lithiations, in contrast to most other metalations, the kinetic acidity, caused by complexing heteroatom substituents, may override the thermodynamic acidity, which is estimated from the stabilization of the competing anions. These directed lithiations59 should be performed in the least polar solvent possible, e.g.. diethyl ether, toluene, or even hexane. 

The effect of the ring heteroatom can be seen in the reactivity of alkylpyridines. Deprotonation from the a-carbon of a substituent at position 4 or 2 is much easier than from a similar substituent at position 3. For example, mesomeric stabilization of the negative charge in (4a) and (5a) will involve contributions from canonical forms (4b) and (5b) in which the charge is carried on ring nitrogen, but a similar contributor cannot be drawn for (6a Scheme 2). 

The ease of the halogen displacement is attributed to mesomeric stabilization of the transition state, which has some SN1 character. Neither addition of HMPT nor replacement of Li by K is necessary both could even have an adverse effect, since the chloroether could be deprotonated to the carbenoid ClCH(M)OR (the RCH2CH(Cl)OR homologues also could undergo 1,2-elimination of HC1 under more polar conditions). 

Ab initio calculations carried out by the RHF method with full geometry optimization using the 6-310 basis set have revealed the influence of CH3- and CF3-substitution on 3-propiothiolactones and their deprotonation products. Only the 2-methyl /3-lactone forms a mesomeric stabilized carbanion on a-deprotonation on deprotonation, the 3-methyl and more acidic 2- and 3-trifluoromethyl derivatives ring open to form ketene thiolate ions. 

If (10) and (12) are allowed to equilibriate under conditions where deprotonation and reprotonation can both occur, the product obtained will then be the more stable one (thermodynamic control). The sum of the bond energies of the bonds in (10) is greater than that for (12) while the enol (12) is stabilized by mesomerism, it is still less stable than the ketone (10) in ethano-lic solution. The equilibrium between (10) and (12) in ethanol therefore favors the ketone, only 5% of enol being present. 

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