Reactivity Towards Organolithium Compounds

It is noteworthy that in some cases the alkylphosphorane obtained by the addition of an organolithium compound to a phosphonium salt is sufficiently stabilized, owing to 

Alkaline hydrolysis of phosphonium salts is one of the oldest575 and of the best investigated reactions in organophosphorus chemistry and several excellent reviews are 

SCHEME 1. Different mechanisms in the alkaline hydrolysis of phosphonium salts 

A few examples of uncommon hydrolyses, corresponding formally to an SN(Ca) reaction should also be mentioned (reaction 176). Indeed with particularly stable carbenium ions such as diphenylcyclopropenium580 or tropylium581,582, spontaneous dissociation of the phosphonium ion into the phosphine and the carbenium ion occurs before reaction with the hydroxide anion can take place. 

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When both a-positions are blocked, the highly specific reactivity toward organolithium compounds disappears and metalation depends on the kind of a-substituents present. Thus whereas 2,5-dimethylthio-phene is not metalated at all, 2-methoxy-5-methylthiophene is metalated in the 3-position, similar to the known ortho metalation of anisole. On the other hand, 5-methyl-2-methylthiothiophene is also metalated (in low yield) in the 3-position, in contrast to thioanisole... 

Tertiary amines have been comparatively little used as solvents for organomagnesium compounds, though triethylamine shows some promise [2], TMEDA is more commonly used as an additive than as a solvent one molar equivalent is normally sufficient to exert the required activating effect. Pyridine is less reactive towards organomagnesium compounds than towards organolithium compounds (see p. 96), and has been used as an alternative to 1,4-dioxane in the preparation of dialkylmagnesium compounds (see p. 65). 

Organomagnesium compounds are less reactive than organolithium compounds [E] towards carbon monoxide and metal carbonyls. The initial reaction with carbon monoxide is similar — addition to give an acylmagnesium compound ... 

Organomagnesium compounds are much less reactive than organolithium compounds [G] towards THF, but the reaction of triphenylmethylmagnesium bromide with THF can give high yields of 5,5,5-triphenylpentan-l-ol [38]. 

As can be seen from reaction (1), these compounds can include groups that would be reactive toward organolithiums or organomagnesium halides and hence prohibit the use of such metal-Hg exchanges for their formation. Polycyclic aromatics , heteroaromatics ... 

Because the reactions of related in -cyclohexadienyl complexes are synthetically valuable, the reactions of this ligand have been studied extensively. An outline of how this chemistry can be conducted on the Fe(CO)j fragment is shown in Equation 11.51. A variety of cyclohexadienes are readily available from Birch reduction of substituted aromatics. Coordination and abstraction of a hydride, typically by trityl cation, leads to cationic cyclohexadienyl complexes. These cyclohexadienyl complexes are reactive toward organolithium, -copper, -cadmium, and -zinc reagents, ketone enolates, nitroal-kyl anions, amines, phthalimide, and even nucleophilic aromatic compounds such as indole and trimethoxybenzene. Attack occurs exclusively from the face opposite the metal, and exclusively at a terminal position of the dienyl system. This combination of hydride abstraction and nucleophilic addition has been repeated to generate cyclohexa-diene complexes containing two cis vicinal substituents. The free cyclohexadiene is ttien released from the metal by oxidation with amine oxides. ... 

Organozmc reagents are not nearly as reactive toward aldehydes and ketones as Grig nard reagents and organolithium compounds but are intermediates m certain reactions of alkyl halides... 

Organolithium and organomagnesium reagents are highly reactive toward most carbonyl compounds. With aldehydes and ketones, the tetrahedral adduct is stable, and alcohols are isolated after protonation of the adduct, which is an alkoxide ion. 

Alkyltriphenylphosphonium halides are only weakly acidic, and a strong base must be used for deprotonation. Possibilities include organolithium reagents, the anion of dimethyl sulfoxide, and amide ion or substituted amide anions, such as LDA or NaHMDS. The ylides are not normally isolated, so the reaction is carried out either with the carbonyl compound present or with it added immediately after ylide formation. Ylides with nonpolar substituents, e.g., R = H, alkyl, aryl, are quite reactive toward both ketones and aldehydes. Ylides having an a-EWG substituent, such as alkoxycarbonyl or acyl, are less reactive and are called stabilized ylides. 

Organolithium compounds can add to a, (3-unsaturated ketones by either 1,2- or 1,4-addition. The most synthetically important version of the 1,4-addition involves organocopper intermediates, and is discussed in Chap 8. However, 1,4-addition is observed under some conditions even in the absence of copper catalysts. Highly reactive organolithium reagents usually react by 1,2-addition, but the addition of small amounts of HMPA has been found to favor 1,4-addition. This is attributed to solvation of the lithium ion, which attenuates its Lewis acid character toward the carbonyl oxygen.111... 

One of the important new directions in the study of addition reactions of organozinc compounds to aldehydes is the use of ionic liquids. Usually, application of these compounds in reactions with common organometallic reagents has a serious problem ionic solvents are usually reactive toward them, particularly Grignard and organolithium derivatives. It has been recently reported that carbonyl compounds react with allylzinc bromide formed in situ from allyl bromide and zinc in the ionic liquid 3-butyl-l-methylimidazolium tetrafluoroborate, [bmim][BF4].285 Another important finding is that the more reactive ZnEt2 alkylates aldehydes in a number of ionic liquids at room temperature.286 The best yields (up to 96%) were obtained in A-butylpyridinium tetrafluoroborate, [bpy][BF4] (Scheme 107). 

This route is useful for the synthesis of organolithium compounds, but is often hindered with the more reactive and heavier alkali metals because of the tendency toward Wurtz coupling (equation 2). 

Organomagnesium compounds are kinetically less-reactive bases toward weakly acidic hydrogens than organolithium compounds. Usually, Metalation using an organomagnesium compound is practically limited to acid hydrogens with pXa of about 25 or lower. This includes aUcynes (equation 14) and derivatives of cyclopentadiene, indene, and fluorene. Even... 

There is similar controversy over whether the monomer (M-2) or open-dimer (OD-2) transition state governs the mode of addition of organolithium compounds to carbonyl compounds (Fig. 2). Although a four-center transition state M-2 involving the monomer has long been believed to participate in the alkylation [34], some ab initio calculation evidence shows that an open dimer OD-2 or related dimeric structure is more likely to be involved in the reactions, especially when (MeLi)2 participates [35, 36]. McGarrity and co-workers showed that the dimer of n-BuLi is tenfold more reactive than the tetramer toward benzaldehyde in THF. Even at high dilution there is no detectable concentration of the monomer [37],... 

A handicap of Grignard reagents in the field of anionic polymerization is certainly their low reactivity toward nonpolar double bonds. Unlike organolithium compounds, organomagnesium compounds are nornally inert toward monomers sueh as styrene or butadiene. Thus, their scope in the field of anionic block-copolymerization is quite limited. 

The reactivity of pyridine toward nucleophilic substitution is so great that even the powerfully basic hydride ion, H", can be displaced. Two important examples of this reaction are amination by sodium amide (Chichibabin reaction), and alkylation or arylation by organolithium compounds. 

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