Organolithium reagents, addition deprotonation

The enantioselective addition of the amino organolithium reagents consists of two stereo-controlled reactions, the asymmetric deprotonation (equation 14) and the following addition to electrophiles. The stereochemical course of the addition depends on the electrophile E. In the cases where heterocyclic enone or a,-unsaturated lactones are the electrophiles (entries 5-7), the addition proceeds with retention of configuration. In contrast, with the other electrophiles in Table 10 and trimethyltin chloride in equation 15, the addition proceeds with inversion of configuration. In the addition which proceeds with retention of configuration, a pre-complexation between the electrophiles and lithium may be involved (equation 16). 

From the practical piont of view however, due to other favorable possible pathways a- or -deprotonation) as depicted above, it is interesting to differentiate between simple organolithium reagents, which show a high basicity, and stabilized organolithium reagents, with a lower basicity, but also a moderate nucleophihcity. In many cases, activation of the reaction can be obtained by the addition of a strong Lewis acid. 

The high propensity of organolithium compounds to form mixed complexes with other organolithium species in solution has been utilized successfully in synthesis using chiral lithium amides. Either the chiral lithium amides have been added to organolithium reagents in an effort to achieve asymmetry in addition reactions, or various additives have been introduced to alter the reactivity or selectivity of the chiral lithium amides themselves, e.g. in deprotonation reactions. 

Deprotonation of the hydroxyalkylpolysilanes la-lc with two or more equivalents methyllithium, rbutyllithium, or phenyllithium, respectively, leads to the trisilanes 6a-6e, which are formed by addition of the excess organolithium reagent to the polar Si=C-bond (Eq. 4). 

The reaction of alkyllithium reagents with acyclic and cyclic tosylhydrazones can lead to mixtures of elimination (route A) and addition (route B) products (Scheme 22). The predominant formation of the less-substituted alkene product in the former reaction (Shapiro Reaction) is a result of the strong preference for deprotonation syn to the N-tosyl group. Nucleophilic addition to the carbon-nitrogen tosyl-hydrazone double bond competes effectively wiA a-deprotonation (and alkene formation) if abstraction of the a-hydrogens is slow and excess organolithium reagent is employed. Nucleophilic substitution is consistent with an Su2 addition of alkyllithium followed by electrophilic capture of the resultant carbanion. 

Metallated imines can be formed from imines derived from enolizable carbonyl compounds by deprotonation with Grignard reagents or organolithium reagents, but more recent studies have generally involved the use of lithium dialkylamides, e.g. LDA, as the base. Alternative methods of producing metallated imines, e.g. addition of r-butyllithium to the imine double bond of 2-azadienes, are known. 

The addition of organolithium compounds to simple imines is less satisfactory as a general synthetic method, particularly when a-hydrogens are present, as alread described in the a-deprotonation of imines with organolithium reagents. 

Organolithium reagents are oligomers (i.e., dimers, trimers, and higher species) in nondonor solvents such as alkanes LiMe is a tetramer with a cubane structure 14.1, for example. RLi forms solvates with THE Addition of the chelating ligand Me2NCH2CH2NMe2 (TMEDA) leads to formation of a monomer, and this increases the reactivity. n-BuLi can deprotonate toluene... 

A full paper on the conjugate addition of organolithium reagents to free a, -unsaturated carboxylic acids (rather than esters) has now appeared. Methyl groups at the a- and /3-carbon of the alk-2-enoic acid decrease reactivity as acceptors, and foster deprotonation, respectively. The lithium enediolate resulting from the conjugate addition can be intercepted by electrophiles. PM3 calculations are in agreement with the substituent effects. 

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