Carbanions configurational stability

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. 

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. 

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. 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

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... 

Opposite to that found for a-lithiated ethers, carbanionic centers in the a-position to a sulfur atom are configurationally unstable. The lifetime at 78 °C is in the order of seconds only, even shorter than with the homologous selenium compounds54. In the latter case, at — 120°C configurational stability has been observed in one case for at least some hours55. 

Let us now consider the effect on an SN2 reaction of stabilizing the car-banion configuration. If the carbanionic configuration [23] is the one that is stabilized - for example, by an a-carbonyl group - then the transition state is expected to take on carbanionic character. This is indeed what is observed for the Sn2 reaction of a family of a-carbonyl derivatives indicated in (86)... 

If the intermediate configuration that is stabilized is the carbanion configuration [35], then the pattern observed is that illustrated in Fig. 26d. A concerted E2 process with ElcB character takes place and the transition state may be described by (102). If the carbanion configuration is strongly... 

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,... 

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

T(2-Alkylcycloalk-l-enyl)methyl carbamates of type 56 are useful 1,2-dianion synthons that can be combined with two aldehydes in adjacent positions to provide a versatile synthesis of [fjannulated tetrahydrofurans (Scheme 81). At first, a carbanion of carbamate 56, which exhibits considerable configurational stability, is generated by (—)-sparteine-mediated deprotonation this is then converted to an optically active homoaldol product 57 with up to %% ee. An (it)-oxonium ion, which is subsequently formed under the influence of BF3, undergoes an intramolecular Mukaiyama-type addition of the enolic moiety onto the carbonyl group of a second aldehyde in the least-hindered conformation. Finally, the carhamoyl group is extmded, and after aqueous workup, diastereomerically pure tetrahydrofurans can be isolated <2005ASC1621>. 

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-... 

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. 

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