Benzyllithium compounds

The carbolithiation of styiyl carbamates such as 486 by alkyllithium/(—)-sparteine (11) leads to configurationally stable benzyllithium compounds 487, which have been further substituted by electrophiles (equation 133) °. However, only low enantioselectivities could be achieved with (—)-sparteine (11) (e.r. = 70 30) or (—)-o -isosparteine (14) (e.r. ... 

A number of cycloalkyl-, vinyl-, aryl-, and benzyllithium compounds (predominantly benzyl-lithiums) are converted into fluoro derivatives in good to excellent yields, e.g. formation of 4, 5, and 6 19 however, when this method was applied to the synthesisof 3-fluorobenzocyclobutene from the lithium salt a violent explosion occurred when the reaction mixture was warmed from — 70 C to room temperature.20 Various fluoro-substituted thiophenes 7 are obtained when the starting compounds (thiophene, 2-methylthiophene, etc.) arc transformed with al-kyllithium compounds to the corresponding lithium derivatives then fluorinated with perchloryl fluoride at 0 C.21 Potassium tricyanomethanidc is converted at —15 C in triglyme into tricyanofluoromethane in 81 % yield.22... 

Ahlbrecht, H. Harbach, J. Hoffmann, R. W. Ruhland, T. On the racemization of a-hetero-substituted benzyllithium compounds. Liebigs Ann. Chem. 1995, 211-216. 

Compounds 39-42 display an array of aryl 13C chemical shifts together with one bond 13C—6Li coupling constants seen at low temperature of 3 to 4 Hz, which is suggestive of more localized benzyllithium compounds compared to the clearly delocalized f-benzyllithiums described above. The 1 1 1 multiplicity of the 6Li bonded 13C NMR... 

Fig. 1. Molecular structure of tetiameric benzyllithium compound 1 [Ig] in the erystsd SCHAKAL plot [2].

After treating mc-2 with tert-butyllithium, both benzyllithium compounds (1-3)2 and m-3-TMEDA could be crystalhzed at -30 °C and subjected to X-ray structure analysis (Scheme 1). 

The HOMO of -3 TMEDA, showing a pyramidalized carbanionic unit, was visualized (Fig. 5) and compared with the HOMO of the benzyllithium compound (I ,S)-8, which displays a planar carbanionic unit. Whereas the planar system (R,S)-S reacts under inversion, in the case of the pyramidal system m-3-TMEDA retention of configuration should be expected. 

Since the stannylation proceeds with inversion and the Hthio-destannylation is a stereoretentative reaction, for the first time, the clean inversion of an enan-tioenriched benzyllithium compound could be accompHshed with a chirafity transmission of greater than 95% [Eq. (61)] [131,133]. 

Taking an example of a sulfur-stabilized benzyllithium compound, Hoffmann and coworkers performed two reactions of the racemic a-thio carbanion with a racemic or a chiral aldehyde [Eq. (3)] [17-19], and found that both reactions afford an identical diastereomeric ratio of the product. From these results, they have concluded that the sulfur-stabilized benzyllithium compound epimerizes faster than it reacts with the aldehyde, i.e., it is configurationally labile in THF at -78°C. 

Enantioselective Reactions of Benzyllithium Compounds without an Adjacent Heteroatom... 

The chiral benzyllithium compound generated by the reaction of the enan-tioenriched stannyl precursor with s-BuLi-(-)-sparteine was reacted with cyclohexanone to give the product with good enantioselectivity. Interestingly, this reaction proceeds with inversion of the configuration of the stannylated carbon [Eq.(43)j. 

Two different reaction conditions for the synthesis of the diastereomerically enriched benzyllithium compounds have been used in the study a kinetically controlled route, diastereotopos-differentiating deprotonation at low temperatures, mostly observed in nonpolar solvents (e.g. in toluene, n-pentane) or a thermodynamically controlled route, epimerization between two diastereomeric lithium alkyls at higher temperatures, mostly observed in polar solvents (e.g. in THF) (Scheme 1). 

All our calculations are in agreement with the results of dynamic C NMR studies by Fraenkel and co-workers. That group was able to show that the benzyllithium compound (R,5)-2 exists as a monomeric single diasteieomer in THF solution between -93 and +27 °C [5]. This again fits with the results of the trapping reactions at variable temperatures performed by Chan and our research group which prove a stability of configuration on at least the time scale of the reaction. 

Chiral benzyllithium compounds (90), generated by stereospecific deprotonation of the corresponding carbamate (89) with j-BuLi(TMEDA), maintain configurative... 

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