Dipole-stabilized carbanions

Dimethylpropanoyl)-l, 2,3,4-tetrahydroisoquinolincs 16 form dipole-stabilized lithium carbanions on deprotonation, but their addition to aldehydes or methyl ketones proceeds nevertheless with low simple diastereoselectivity22 23. However, a high preference for the formation of the w-diastereomer is observed after transmetalation with magnesium bromide22"24. 

Deprotonation is the most convenient manner for the generation of alkyllithium derivatives. However, most of the potential precursors have insufficient acidity. Notable exceptions are those substrates which lead to dipole-stabilized carbanions , among them O-alkyl iV,A-dialkylcarbamates 15 ° and A-Boc-(cyclo)alkylamines 18 ° (equation 5). A... 

However, dipole stabilization is less significant as an aid to carbanion formation with unsaturated azaheterocycles, since the nitrogen lone-pair electrons are normally incorporated into the 77-electron system of the heterocycle, and are therefore less readily available for donation to the substituent group. In fact, dipole-stabilization can even be a hindrance in some systems where exocyclic ip -carbanion formation is competitive with internal ip -carbanion formation. In these cases it is the heterocycle itself that is responsible for the dipole-stabilization of the external carbanion. 

Attempts to extend this process to the related 2-pyridone system have been less successful, with only a small proportion of C-6 lithiation being observed with l-methyl-2-pyridone [85CC1021 88JCS(P1)1]. In fact, the major mode of reaction involves lithiation of the exocyclic methyl group, to give a carbanionic species that is dipole-stabilized by the heterocyclic amide group (Scheme 120) (83MI1). 

Interestingly, the protected pyrroline starting material is obtained from the analogous pyrrolidine via the intermediacy of the dipole-stabilized sp3-carbanion and diphenylselenide derivatives (85JOC1019) (Scheme 135). 

A study of gas-phase negative-ion chemistry of Lewis acid-base complexes of BH3 with Me2S, Me3N, Me3P, and Et3N has shown that the a-CH acidities in the complexes (to form dipole-stabilized carbanions) are up to 20 kcal mol-1 higher than in the uncomplexed molecules.150... 

Hay, D. R. Song, Z. Smith, S. G. Beak, P. Complex-induced proximity effects and dipole-stabilized carbanions kinetic evidence for the role of complexes in the a -lithiations of carboxamides./. Am. Chem. Soc. 1988, 110, 8145-8153. 

Beak, P. Reitz, D. B. Dipole-stabilized carbanions novel and useful intermediates. Chem. Rev. 1978, 78, 275-316. 

L. B. Dipole stabilized carbanions in series of cyclic aldonitrones. Aldonitrone metalation and dimerization in LDA and BuLi solutions. Heterocyclic Comm. 1998, 4, 261-270. 

Carbanions which bear an a-heteroatom, which is bonded to a functional group capable of inducing a partial positive charge on that heteroatom (64), are both of theoretical interest and of synthetic importance (Seebach et al., 1983). Such have been termed dipole stabilized carbanions (Beak and Reitz,... 

Dipole-Stabilization is a term coined by Beak to describe the situation that results when a carbanion is stabilized by an adjacent dipole. Such a situation arises when, for example, an amide is deprotonated a to nitrogen. The chemistry of these systems has been reviewed, - so only a few pertinent points will be made here. Firstly, metalation occurs syn to the carbonyl oxygen, and when the system is cyclic, the equatorial proton is removed selectively, and the electrophile attacks equatorially, as shown in equation (5), 24, 25 Thus, in contrast to nitrosamines, amide anions give the less stable equatorial product. 4,i25... 

Other dipole-stabilized carbanions are obtained from succinimides, amine oxides , nitroalkanes thioimidates dithiocarbonates, formamides " and thiofoilnamides,e.g. ... 

Alkyl arenecarbothioates (42), on the other hand, undergo deprotonation at the 5-alkyl group. The resulting dipole-stabilized carbanions may be acylated by the starting compound (42) to form 5-(2-oxoal-kyl) arenethioates (equation 37). ... 

Thus the nitrosamine anion is a resonance-stabilized species in which the carbanionic lone pair overlaps the TT-system of the nitrosamine. By contrast, the amide anion is a dipole-stabilized species in which the lone pair remains in or near the nodal plane of the amide n -system. Given the similarity of the two systems, this difference in behavior is striking. Although the geometry observed in nitrosamine anion alkylations is similar to that of their isoelectronic counterparts, oxime dianions,it is puzzling that amide anions differ, since they are also isoelectronic, as shown in Figure 1. 

Reaction with benzoate esters. The reaction of benzyl benzoate (1) with LiTMP in THF at -78° gives benzoin benzoate (2) in 65% yield. The reaction is considered to involve abstraction of a proton to form a dipole-stabilized carbanion (a) followed by reaction of this with the starting ester. 

Most a-thio carbanions are configmationally labile and racemize rapidly even at low temperature as shown in the preceding section. This may be the reason why the asymmetric reaction of a-lithiated thiocarbamates reported by Hoppe and coworkers does not show such high enantioselectivity [34] as attained in the reaction of similar dipole-stabilized a-oxy organolithium compounds [Eq. (4)] [2, 39]. Note that the stereochemistry of the products obtained from a-lithiated thiocarbamates is different from that obtained in the a-lithiated carbamate [Eq.(5)]. 

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