Configurational Stability of Carbanions

In carbanions, for instance enolates, in which delocalization of the negative charge to a more electronegative atom (N, O, S) is possible, the cation is usually bound to this atom if the cation is hard (e.g. alkali metal cations, Mg2+ [530], Zn2+) in this case the nucleophilic carbon atom becomes a planar sp2 hybrid. If the cation is soft (e.g. the cations of late transition metals) it will often be bound to the depro-tonated carbon atom these organometallic compounds are, however, usually only weak nucleophiles and will not be treated here. 

Electrophilic substitutions at carbon, for example the reaction of an organometal-lic reagent with an electrophile, can occur either with retention [236, 238, 274, 275, 525, 529] or inversion [234, 471] at the nucleophilic carbon atom [57, 189, 522, 531, 532], 

Organometallic compounds with covalent, sparsely polarized C-M bonds do not usually epimerize readily. Thus, organoaluminum or organomercury compounds are configurationally stable up to 150 °C [540, 541] if oxidants or other radical chain 

Enantiomerically pure organolithium compounds have been prepared by tin-lithium exchange [261], mercury-lithium exchange [549], or by lithiation in the presence of a chiral, enantiomerically pure or enriched amine, for example sparteine [271] 

1 Hamell, M. Levine, R. Condensations effected by the alkali amides. IV. The reactions of esters with lithium amide and certain substituted lithium amides. J. Org. Chem. 1950, 35, 162-168. 

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A simple experimental test of the potential configurational stability of carbanions was recently published26 48 it is based on double stereodifferentiation3 and can be carried out with the racemates. 

H. Configurational stability of carbanions stabilized by d-orbitals./. Am. Chem. Soc. 1962,... 

Optically active 0-benzoylatrolactic acid and its methyl ester were reduced to 2-phenylpropionic acids with almost complete loss of optical activity [392]. On the other hand, Nonaka and coworkers [393] found that l-(2-pyridyl)alkanols were reduced to 2-alkylpyridines with configurational retention in acidic medium l-(4-pyridyl)alkanols gave racemic 4-alkylpyridines. The stereochemical course was discussed considering perpendicular adsorption of pyridylalkanol molecules on the cathode and the configurational stability of carbanion intermediates. 

One major task is the selection of the optimal cation" for a given carbanion . It determines to a great extent the mechanism of the reaction and the positional and configurational stability of the allyl moiety, and thus, the regioselectivity, EjZ selectivity, and diastereoselectivity. Some reviews cover these topics in general1 " 5. 

The inductive and electrostatic effects, steric constraints and conjugative interactions are the major factors that determine the configurational stability of a-sulfonyl carbanions. These are thought to be pyramidal with appreciable electrostatic inhibition to racemization by way of inversion. LCAO-MO-SCF calculations have indicated the conformer 195 in which the lone pair is directed along the bisector of the OSO angle to be the most stable in acyclic sulfones. ... 

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... 

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. 

Meyers, A. I. Milot, G. a-Alkylation and stereochemistry of cis- and trans-decahydroqui-nolines mediated by the formamidine and Boc activating groups. Synthesis of pumiliotoxin C.J. Am. Chem. Soc. 1993, 335, 6652-6660. Elworthy, T. R. Meyers, A. I. The configurational stability of chiral lithio a-amino carbanions. The effect of Li-O vs Li-N complexa-tion. Tetrahedron 1994, 50, 6089-6096. 

Hammerschmidt, F. Hanninger, A. Enantioselective deproto nation of benzyl phosphates by homochiral lithium amide bases. Configurational stability of benzyl carbanions with a dialkoxyphosphoryloxy substituent and their rearrangement to optically active a-hydroxy phosphonates. Chem. Ber. 1995, 328, 823-830. Avolio, S. Malan, C. Marek, I. Knochel, P. Preparation and reactions of functionalized magnesium carbenoids. Synlett 1999, 1820-1822. 

Raabe, G. Gais, H.-J. Fleischhauer, J. Ab initio study of the effect of fluorination upon the structure and configurational stability of a-sulfonyl carbanions the role of negative hyperconjugation. J. Am. Chem. Soc. 1996,... 

Most alkyl carbanions undergo facile pyramidal inversion. Cyclopropyl anions are an exception, presumably because the transition state, with a planar trigonal carbon, is more strained than the ground state. The configurational stability of cyclopropyl anions is of value in the synthesis of deuterated cyclopropanes by the Haller-Bauer reaction (see Section II.B). An interesting dilemma arises when a cyclopropyl anion is stabilized by a n-electron acceptor substituent such as a nitrile or an ester. Will the anion then retain its pyramidal equilibrium geometry for the strain reasons alluded to above, or will it become planar in order to maximize overlap of the filled orbital on carbon with the n orbital of the substituent Walborsky and coworkers addressed this question in a series of experiments in which rates of H/D exchange and racemization were compared for an optically active cyclopropane exposed to a base in a deuterated hydroxylic solvent. The outcome can be illustrated with the particular example of 1,1-diphenylcyclopropane-2-... 

The configurational stability of alkenyl anions is obviously remarkably high compared with that of alkyl anions ". The order of stability of the carbanions of the chloroethylenes , (207), reflects that a/i//-beta-elimination occurs more easily than syn-beta-elimination or alpha-elimination ". 

The enantioselective reactions of carbanions a to S, Se, P or halogens and those of benzyllith-ium compounds are reviewed, focusing on the enantiodetermining pathways in relation to the configurational stability of the lithium carbanions and the lithium carbanion-chiral ligand complexes. 

Enantioselectivity through an asynunetric deprotonation pathway is largely dependent on the configurational stability of the carbanion and the interaction between a substrate and a chiral base. On the other hand, when the enantioenriched product is formed in the reaction with an electrophile, even though the deprotonation gives the racemic carbanion, this pathway is termed asymmetric substitution [1], Enantioselection through an asymmetric substitution path-... 

Hoffmann and coworkers proposed an excellent method for evaluating the configurational stability of the lithium carbanion within the time scale of the rate of the reaction with an electrophile (Hoffmann test) [12]. The Hoffmann test is composed of two experiments. In the first experiment, a racemic organo-lithium compound is reacted with a racemic aldehyde such as 2-(Nd -diben-zylamino)-3-phenylpropanal,the relative rate of formation of the diastereomeric products (k55 kjjj) being estimated by an antUsyn ratio of the products (Fig. 5). 

Fig. 7. Configurational stability of a-thio-, a-seleno-, a-phosphono-, a-sulfonyl, a-silyl and a-bromo carbanions estimated by the Hoffinaim test...

Padwa A, Wanamaker MW (1986) Significance of the anomeric effect on the configurational stability of cyclopropyl carbanions. Tetrahedron Lett 27 2555-2558... 

The preparation, stabilization, and characterization of buckybowl anions, ranging from archetypal corannulene to large hemifullerenes, have been reviewed. The synthetic potential and configurational stability of configurationally labile chiral carbanions next to electron-withdrawing groups has been summarized. ... 

Alkenyllithium derivatives, carrying carbanion-stabilizing substituents, which facilitate the formation of solvent-separated ion pairs, can also exhibit preparatively useful configurational stability in respect to the double bond of the precursor. 

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