Configurational stability, of organolithium

Brandt, P. Haeffner, F. A DFT-derived model predicts solvation-dependent configurational stability of organolithium compounds a case study of a chiral a-thioallyllithium compound. /. Am. Chem. Soc. 2003, 325, 48-A9. 

Benzylsulfides may be lithiated with PhLi,83 and the acetal group of 111 both assists lithiation and imparts stereoselectivity on the reaction (the configurational stability of organolithiums such as 112 is discussed in section 5.1).84... 

Besides changing the configurational stability of organolithiums, solvent modification can affect the reaction path. Although benzyl chloride reacts with butyllithium in ether to give the Wurtz coupling products, bibenzyl and amylbenzene, tranr-stilbene is also a product (26). Isolation of the chlorobibenzyl was possible. 

Figure 13.2 Hoffmann s test for determining the configurational stability of organolithium species [35],...

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... 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

Some heteroatom-substituted or chelate-stabilized organolithium compounds, on the other hand, can be sufficiently stable toward racemization to enable their use in stereoselective reactions with electrophiles [223, 225, 271, 531, 543, 552-554] (Scheme 5.75). This increased configurational stability of a-heteroatom-substituted carbanions might be due to the stronger pyramidalization of such carbanions [261,555] and fixation of the metal by chelate formation. 

The Hoffmann test. The Hoffmann test,4 while not quantitative, gives a qualitative guide to the configurational stability of an organolithium on the timescale of its addition to an electrophile. 

The configurational stability of primary organolithiums, while of no synthetic consequence, has been determined by NMR methods. Analysis of the line shape of the AA BB system of 1713 or of the ABX system of 1814 gave half-lives for inversion of about 0.01 s for 17 or 18 in ether at 30 °C, increasing (for 17) to about 0.1 s at 0 °C and 1 s at -18 °C. The rate of inversion was decreased by a factor of 8 in pentane or 10 in toluene, but the addition of 1 equiv. TMEDA to pentane restored a rate of inversion more or less equal to that in pentane. 

Corey exploited the remarkable configurational stability of cyclopropyllithiums in his synthesis of hybridalactone. The stannane 28 was made by Simmons-Smith cyclopropanation of the allylic alcohol 27 and resolved by formation of an O-methyl mandelate ester. Transmetallation of 29 with 2 equiv. BuLi gave an organolithium which retained its stereochemistry even in THF over a period of 3 h at 0 °C, finally adding to 31 to give 32. 

It has already been noted that the presence of a small ring favours configurational stability in organolithiums. The first organolithium a to nitrogen of proven configurational stability was the isonitrile-substituted cyclopropyllithium 114. Treatment of the enantiomerically pure isonitrile 113 with LDA for 30 min at -72 °C followed by methylation returned the product cyclopropane 115 in 98% ee.25 114 maintained its configuration up to -52 °C (the ee was eroded to 93% after 30 min at this temperature) but racemised within 30 min at -5 °C. 

The limited configurational stability of a-alkylthio organolithiums does not extend to those with benzylic lithium-bearing carbon atoms.112 A Hoffmann test reaction of 233 with 6, for example, gives a 40 60 ratio of stereoisomers 234 whether enantiomerically pure or racemic 6 is used.6 Dynamic NMR experiments2 quantified the barrier to racemisation in 233 as 9.95 kcal mol-1 at 213 K, the temperature at which the diastereotopic CH2 group coalesces. 

Since the thermodynamic acidity of C-H bonds and the configurational stability of the resulting organolithium tend to be opposed to one another, relatively few examples of provable stereospecific deprotonation are known. Those that are known, such as... 

In the case of a dianionic species 49, the s)mthesis of racemic a-amino acid 50 by carboxylation may be achieved (eq 63). The lack of enantionselectivity may be due to the presence of a negative charge on the iminoacetal, which decreases the configurational stability of the benzylic organolithium species. In contrast, carboxylation of the monoanionic species 51, formed in the presence of (—)-sparteine, leads to a highly enantioselective result as shown in (eq 64). 

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