Organolithium reagents stability

Organolithium reagents stabilized by ct-silyl groups have been recently used for the synthesis of mononuclear derivatives such as compounds 8, 9 which the bulky (PhMe2Si>3C and (Me3Si>3C as ligands directly attached to the mercury center.30 Other examples include the dialkylmercury products shown in Equations (2) and (3).31 32... 

Whereas the reactions of sulfones with nucleophiles via pathways A and B of equation 1 are most frequently observed, the nucleophilic substitution reaction by pathway D has been observed only in the cases where the leaving carbanion can be stabilized, or in the highly strained molecules. Chou and Chang3 has found recently that an organolithium reagent attacks the sulfur atom of the strained four-membered sulfone in 34. When this sulfone is treated with 1 equivalent methyllithium, followed by workup with water or Mel, 38 or 39 are formed in high yield. 

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. 

Alternatively, organolithium reagents of the type (CH3)3SiCH(Li)Z, where Z is a carbanion-stabilizing substituent, can be prepared by deprotonation of (CH3)3SiCH2Z with -butyllithium. 

An extensive review appeared on the configurational stability of enantiomeric organolithium reagents and the transfer of the steric information in their reactions. From the point of view of the present chapter an important factor that can be evaluated is the ease by which an inversion of configuration takes place at the metallation site. It happens that H, Li, C and P NMR spectra of diastereotopic species have been central to our understanding of the epimerization mechanism depicted in equation 26, where C and epi-C represent the solvated complex of one chiral species and its epimer, respectively. It has been postulated that inversion of configuration at the Li attachment site takes place when a solvent-separated ion pair is formed. This leads to planarization of the carbanion, its rotation and recombination to form the C—Li bond, as shown in equation 27, where Li+-L is the solvated lithium cation. An alternative route for epimerization is a series of... 

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. 

Some reports concerning the reaction of lithiated thioallylethers with oxiranes have been published. A slow reaction was observed with a terminal oxirane. However, with cyclopentadiene oxide, the reaction occured smoothly with an excellent regioselectivity in favor of the Sjv2 displacement in the ally lie position. Other examples involving sulfur, selenium and silicon stabilized organolithium reagents have been reported . 

Dimethylpyrimido[4,5-f]pyridazine-5,7-dione 23 and its derivatives undergo attack at both C-3 and C-4. Under conditions of kinetic control, addition occurs preferentially at the more electron-deficient C, whereas thermodynamic control conditions, or the use of bulkier nucleophiles, favor addition at the less hindered position 3. This duality is illustrated by the addition of Grignard and organolithium reagents to C of 3-chloro analogue 24 (Equation 9), whereas stabilized nucleophiles such as the anion of nitromethane add at C-3 (Scheme 10) <2000CHE975>. Displacement of the 3-chloride occurs also upon treatment of 24 with amines (Equation 10) <2000CHE1213>. 

In cases where an alkyl has no (5 hydrogens (or no accessible ]8 hydrogen), an important alternative process, a elimination, can occur. M. L. H. Green40 has proposed the process shown in Scheme 3 to explain the formation of the ylide complex shown. Another interesting example (Scheme 4) is due to Shaw.6 It is not known whether Schrock s62 remarkable chemistry (equation 45), which led to the first examples of carbenes not stabilized by heteroatoms, also goes via a elimination or, perhaps more likely, by deprotonation of an alkyl at the a position by an organolithium reagent or other base. 

Basu, A. Thayumanavan, S. Configurational stability and transfer of stereochemical information in the reactions of enantioenriched organolithium reagents. Angeur. Chem. Int. Ed. 

A. Basu, S. Thayumanavan, Configurational Stability and Transfer of Stereochemical Information in the Reactions of Enantioenriched Organolithium Reagents, Angew. Chem. Int. Ed. Engl. 2002, 41, 716— 738. 

Section I)13. In the case of the carboxylic anion, the lithiation of acyclic and cyclic orthoth-ioesters allows the preparation of intermediates XII12. All these stabilized organolithium reagents have been widely used in organic synthesis and in this section their application as acylating agents by this defensive strategy will be mainly considered. 

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