Hard carbanion

Prior to our work, Helling had reacted a series of hard carbanions with [Fe(mesitylene)2]++ (PFg )2 to obtain an attack on each ring giving the bis(cy-clohexadienyl)Fe" complex [31], Eq. (1). Stabilized carbanions reacted only once [31, 32] first step of Eq. (1) ... 

Metallated azoles frequently show expected properties, especially if not too many heteroatoms are present. Thus, Grignard reagents prepared from halogeno-azoles (see Section 3.4.3.9.3) show normal reactions, as in Scheme 154. 2-Lithioimidazoles react normally, e.g., with benzophenone (Scheme 155). Lithiated imidazoles are not always particularly reactive toward electrophiles and yields may be low. The nature of the quenching electrophile is the critical factor. Hard reagents like benzophenone tend to give better yields than the softer methyl iodide heteroaryl lithiums have hard carbanion centers. 

In view of the observations of the ionic dissociation of nitro-cyano compounds, it is hardly surprising that even a hydrocarbon could dissociate ionically into a stable carbocation and carbanion, provided that the medium is polar enough to prevent the recombination reaction and to ensure equilibration. 

Hardly surprisingly the tendency of alkanes to lose proton and form carbanions is not marked, as they possess no structural features that either promote acidity in their H atoms, or are calculated to stabilise the carbanion with respect to the undissociated alkane (cf. carboxylic acids, p. 55). Thus CH4 has been estimated to have a pKa value of 43, compared with 4.76 for MeC02H. The usual methods for determining pKa do not, of course, work so far down the acidity scale as this, and these estimates have been obtained from measurements on the iodide/organo-metallic equilibria ... 

The H atom flanked by the two 0=0 groups in (22) exhibits hardly any more acidic character than the analogous one in the corresponding hydrocarbon. The different behaviour of (22) stems from the fact that after proton removal, the carbanion s lone pair would be in an sp3 orbital more or less at right angles to the p orbitals on each of the adjacent carbonyl carbon atoms (cf. p. 259) no sp3/p overlap could thus take place, consequently there would be no stabilisation of the -ve charge through delocalisation, and the (unstabilised) carbanion does not, therefore, form. 

The interfacial mechanism provides an acceptable explanation for the effect of the more lipophilic quaternary ammonium salts, such as tetra-n-butylammonium salts, Aliquat 336 and Adogen 464, on the majority of base-initiated nucleophilic substitution reactions which require the initial deprotonation of the substrate. Subsequent to the interfacial deprotonation of the methylene system, for example the soft quaternary ammonium cation preferentially forms a stable ion-pair with the soft carbanion, rather than with the hard hydroxide anion (Scheme 1.8). Strong evidence for the competing interface mechanism comes from the observation that, even in the absence of a catalyst, phenylacetonitrile is alkylated under two-phase conditions using concentrated sodium hydroxide [51],... 

The radical anion pathway (e-c-P-d-p Scheme 2) requires a rate-determining protonation after cyclization, i.e., a slow protonation of a hard oxyanion. However, such proton transfer rates are usually diffusion controlled, so this seems unlikely [32,33], On the other hand, the carbanion closure (e-P-d-c-p) portrayed in Scheme 4 requires a very reasonable suggestion that the ratedetermining step corresponds to protonation of the soft, weakly basic radical anion 42, prior to cyclization [32-35] this is the preferred mechanism. One must use caution, however, realizing that these conclusions are drawn for the particular set of substrates which were examined. In some cases, radical anion cyclization remains a viable option. 

Mixed bonding is possible with the metal ion coordinated by hard atoms and neutralised by a carbanion. One example is the compound containing infinite chains of. [.Li+...N(CH2CH2)3N...]. neutralised by... 

Backwall and coworkers have extensively studied the stereochemistry of nucleophilic additions on 7r-alkenic and ir-allylic palladium(II) complexes. They concluded that nucleophiles which preferentially undergo a trans external attack are hard bases such as amines, water, alcohols, acetate and stabilized carbanions such as /3-diketonates. In contrast, soft bases are nonstabilized carbanions such as methyl or phenyl groups and undergo a cis internal nucleophilic attack at the coordinated substrate.398,399 The pseudocyclic alkylperoxypalladation procedure occurring in the ketonization of terminal alkenes by [RCC PdOOBu1], complexes (see Section 61.3.2.2.2)42 belongs to internal cis addition processes, as well as the oxidation of complexed alkenes by coordinated nitro ligands (vide in/ra).396,397... 

Chemoselectivity can also be partially explained by a hard and soft acid and base (HSAB) theory.11 From HSAB theory, the lithium cation is a harder acid than the magnesium cation and, with a, 3-unsatu-rated ketones, C-l (carbonyl carbon) is a harder base than C-3 thus reactions of organolithiums are preferred at the the hard site, C-l, affording 1,2-addition products. The structure of the carbanion is also... 

It should be noted with (3), (4), (13) and (14) only hard lithium nucleophiles are tolerated, while for (5), (6), (7) and (15) the range of useful lithium nucleophiles, e.g. including lithio-l,3-dithianes and lithium enolates, is broader. In addition, none of these Michael acceptors react with organocuprates, Grig-nard reagents or stabilized carbanions. 

Many carbanionic nucleophiles that would be considered too hard to react as Michael donors can be made into effective reagents for conjugate addition reactions by appending resonance or inductively stabilizing groups to soften their intrinsic Lewis basicity. Such stabilized anionic Michael donors include enolates, alkylthio-substituted carbanions, ylides and nitro-substituted carbanions. 

Steric effects provide examples of hard cases with respect to predicting reactivities. The same might be said to be true of solvent effects for reactions of n-nucleophiles or carbanions. However, while values of N may vary with solvent the differences can be exploited, for example, in promoting a desired reaction in synthesis. Moreover, in attempting to interpret solvent effects, it is possible that comparing measurements of reaction rates and (preferably)... 

Clearly, the area of the interface and the basicity of the inorganic salt affect the amount of available onium carbanion. It should be also noted that an excessively lipophilic phase-transfer catalyst would hardly access the interface, and consequently the use of such a catalyst would result in an insufficient reaction. 

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