Carbanionic transition states

S,3S)-Dicarboxyaziridine (112) was isolated from a Streptomyces strain in 1975 and found to have moderate antibacterial activity against Aeromonas salmonecida [176]. Subsequent studies showed that 112 acts as a competitive inhibitor of fumar-ase, through mimicry of a carbanionic transition state [177]. No biosynthetic studies have been reported for 112, but it is conceivable that it may arise from cydiza-tion of (3R)-hydroxyaspartic acid (Figure 11.18). 

However, in some cases, HF is eliminated in preference to dehydrobromination, e.g. in the succinic acid series [5, 6] (Figure 6.4). In these less common processes, the transition state has significant carbanion (ElcB-like) character, and the products are probably governed by the relative stabilities of the possible carbanionic transition states, 6.5A and 6.5B (Figure 6.5), where a fluorine atom situated (3 to a developing carbanion centre, as in 6.5B, is more stabilising than when directly attached, as in 6.5A. This effect is also seen in eliminations from dihaloacenaphthenes [7]. 

Figure 35 Mechanism of the ECH reaction, (a) Concerted mechanism that proceeds via a carbanionic transition state, (b) Elcb reaction proceeding via the formation of an enoiate intermediate.

ECH or crotonase is the prototypical member of the crotonase superfamily. As noted above, sequence homology between ECH and 3,2-enoyl-CoA isomerase as well as with dibydroxynapbtboate syntbase (MenB) and 4-chlorobenzoyl-CoA dehalogenase resulted in the initial proposal for a superfamily based on the crotonase scaffold. Since then, many more members of the superfamily have been identified. Most family members utilize substrates that are CoA thioesters, and a unifying mechanistic theme throughout the superfamily concerns the use of an oxyanion hole to stabilize carbanionic transition states. Figure 40 shows the reactions catalyzed by a subset of family members. ... 

The Hofmann eliminations (19-21) give very low isotope effects, excepting the controversial intramolecular isotope effects for the 2-p-nitro-phenylethyl-trimethylammonium ion. The conditions vary widely and comparisons are thus difficult. The enhanced acidity of this substrate, however, should promote extensive proton transfer and the small tritium isotope effects would seem most plausibly interpreted as indicative of highly carbanionic transition states for these eliminations. The alkyl ammonium salts, possessing much more weakly acidic beta hydrogen, probably react via less carbanion-like E2 transition states . 

The increased strength and electron-withdrawing power of the C -N bond relative to the C - bond should cause reactions of the former to proceed via a more carbanionic transition state. Under the same reaction conditions, the sulphur isotope effect for 2-phenylethyldimethylsulphonium ion (I I, Table 6) indicates more C -X bond breaking than the nitrogen isotope effect in elimination from the corresponding ammonium salt. 

Comparison of the data for methoxide with those for t-butoxide in Table 6.4 illustrates a second general trend Stronger bases favor formation of the less substituted alkene. " A stronger base leads to an increase in the carbanion character at the transition state and thus shifts the transition state in the Elcb direction. A linear correlation between the strength of the base and the difference in AG for the formation of 1-butene versus 2-butene has been established. Some of the data are given in Table 6.5. 

Amination of the deactivated carbanion of 4-benzylpyridine formed with excess sodamide presumably proceeds because the strong indirect deactivation is overcome by electrophilic attack by Na+ at the partially anionic azine-nitrogen and by concerted nucleophilic attack by H2N at the 2-position via a 6-membered cyclic transition state (75). However, in simple nucleophilic displacement a carbanion will be more deactivating than the corresponding alkyl group, as is true in general for anionic substituents and their non-ionic counterparts. 

In reactions in which separated ion pairs are involved, e.g., R4N+, K or Na +, and as a borderline case, Li +, the cation does not contribute to the adjustment of the reaction partners in a dense, well-ordered transition state poor selcctivities arc usually the result of these carbanionic carbonyl additions. Further, the high basicity of such carbanionic species may cause decomposition or racemization of sensitive reactions partners. 

The big difference between the extent of asymmetric induction on the addition to a prostereogenic carbonyl group of simple carbanions a to a chiral sulfoxide on the one hand and enolates of sulfinyl esters on the other, can be attributed to the capacity of the ester function to chelate magnesium in the transition states and intermediates. The results already described for the addition of chiral thioacetal monosulfoxide to aldehydes (see Section 1.3.6.5.) underscore the importance of other functions, e.g., sulfide, for the extent of asymmetric induction. 

McDowell and Stirling194 studied electronic effects upon the reactivity of aryl vinyl sulfones towards amines. Rate constants for t-butylamine addition in ethanol at 25 °C were well correlated by the Hammett equation, with p = 1.59. Comparison of this with p values for H-D exchange mentioned above191 suggested considerable carbanionic character in the transition state, perhaps in a concerted mechanism. Rates of addition of amines to alkenyl, allenyl and alkynyl p-tolyl sulfones have also been measured195. 

Polymerization of t-butyl methacrylate initiated by lithium compounds in toluene yields 100% isotactic polymers 64,65), and significantly, of a nearly uniform molecular-weight, while the isotactic polymethyl methacrylate formed under these conditions has a bimodal distribution. Significantly, the propagation of the lithium pairs of the t-Bu ester carbanion, is faster in toluene than in THF. In hydrocarbon solvents the monomers seem to interact strongly with the Li+ cations in the transition state of the addition, while the conventional direct monomer interaction with carbanions, that requires partial dissociation of ion-pair in the transition state of propagation, governs the addition in ethereal solvents. 

Only transition states with considerable carbanion character are considered in this table. 

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