Acidity of a-hydrogens

The question arises whether there are any unique characteristics associated with the acidity of a-hydrogens when the sulfone or the sulfoxide group is incorporated within a three-membered ring system. 

The issue of the acidity of a-hydrogens in thiirene oxides and dioxides is dealt with only in the dioxide series, since neither the parent, nor any mono-substituted thiirene oxide, is known to date. Thus the study of the reaction of 2-methylthiirene dioxide (19c) with aqueous sodium hydroxide revealed that the hydroxide ion is presumably diverted from attack at the sulfony 1 group (which is the usual pattern for hydroxide ion attack on thiirene dioxides) by the pronounced acidity of the vinyl proton of this compound113 (see equation 14). 

To summarize under favorable conditions the acidity of a-hydrogens facilitates the generation of a-sulfoxy and a-sulfonyl carbanions in thiirane and thiirene oxides and dioxides as in acyclic sulfoxides and sulfones. However, the particular structural constraints of three-membered ring systems may lead not only to different chemical consequences following the formation of the carbanions, but may also provide alternative pathways not available in the case of the acyclic counterparts for hydrogen abstraction in the reaction of bases. 

Acidity of a-hydrogens of aldehydes and ketones The aldehydes and ketones undergo a number of reactions due to the acidic nature of a-hydrogen. 

The acidity of a-hydrogen atoms of carbonyl compounds is due to the strong electron withdrawing effect of the carbonyl group and resonance stabilisation of the conjugate base. 

The Michael addition is an enolate ion addition to an a,(3 unsaturated Ccirbonyl. This reaction takes advantage of the increased acidity of a hydrogen atom that s a to two carbonyl groups. This enolate ion is very stable, so it s less reactive than normal enolates. The more-stable enolate leads to a greater control of the reaction so that only one or two products form instead of multiple products from a less stable (and therefore more reactive) enolate. An example of this type of reaction is in Figure 11-24 with the mechanism in Figure 11-25. 

The acidity of a hydrogens is attributed partly to the electron-attracting inductive effects of the ester oxygens, and partly to resonance stabilization of the resulting anion (Section 17-1 A) ... 

When the a carbon of the ester carries a second strongly electron-attracting group, the acidity of a hydrogen is greatly enhanced. Examples of such compounds follow ... 

Imines may be activated by complexation with Lewis acids, but this also increases the acidity of a-hydrogen atoms. A combination of copper(i) halide and boron trifluoride etherate is a possible solution to the problem [6, 7]. Activation by trimethylsilyl triflate is also effective with aldimines (though not with ketimines) [7, 8]. 

Besides addition, alkynes undergo certain reactions that are due to the acidity of a hydrogen atom held by triply-bonded carbon. 

We shall discuss reactions resulting from the acidity of a-hydrogens in Secs. 21.11-21.12 and 26.1-26.3.)... 

The carbonyl group thus affects the acidity of a-hydrogens in just the way it affects the acidity of carboxylic acids by helping to accommodate the negative charge of the anion. 

Enzymes are marvelous catalysts. Yet, even with their powerful help, these biological reactions seek the easiest path. In doing this, they take advantage of the same structural effects that the organic chemist does the acidity of a-hydrogens, the leaving ability of a particular group, the ease of decarboxylation of j8-keto acids. 

In 1978, O Donnell and coworkers developed the benzophenone imines of glycine alkyl esters 4 as glycine anion equivalents, which have been found to be perfed to use in the phase-transfer catalysis [10]. An essential feature of this reaction system lies in the selective mono substitution of the starting Schiff base, the O Donnell substrate 4. This can be possible because of the significant difference in acidity of a-hydrogen between starting substrate 4 p/C,(DMSO) 18.7 (R=Et)] and a-monosubstituted produd S p/C,(DMSO) 22.8 (R=Et, E = Me), 23.2 (R=Et, E = CH2Ph)] [11]. This dramatic acidity difference makes it possible for selective formation of only monoalkylated product without concomitant production of undesired dialkylated produd or racemization. 

The inductive effect of the heteroatom, which withdraws electrons to a greater extent from an adjacent carbon atom (a-positions), allows direct a-lithiation of practically all five-membered heterocycles. The relative acidities of a-hydrogens in some different classes are illustrated in the table below. 

Why does the size of an atom have such a significant effect on the stability of the base and, therefore, on the acidity of a hydrogen attached to it The valence electrons of F are in a 2sp orbital, the valence electrons of CF are in a 3sp orbital, those of Br are in a 4sp orbital, and those of F are in a 5sp orbital. The volume of space occupied by a 3sp orbital is significantly greater than the volume of space occupied by a 2sp orbital because a 3sp orbital extends out farther from the nucleus. Because its negative charge is spread over a larger volume of space, CF is more stable than F . 

Section 6.9 Acidity of a Hydrogen Bonded to an sp Hybridized Carbon... 

The acidity of a-hydrogens bonded to carbons flanked by two carbonyl groups increases because the electrons left behind when the proton is removed can be delocalized onto two oxygen atoms. j8-Diketones have lower pK values than j8-keto esters because electrons are more readily delocalized onto ketone carbonyl groups than they are onto ester carbonyl groups. 

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