Elcb process

In many eliminations to form C=0 and C=N bonds the initial step is loss of a positive group (normally a proton) from the oxygen or nitrogen. These may also be regarded as ElcB processes. 

This occurs because 3-pyridyne (3,4-didehydropyridine) is formed by an alternative mechanism is the ElcB process [elimination (first order) from the conjugate base], SowM 3-Pyridyne then adds ammonia the addition is not regiospecific and two second step, amino derivatives are formed. 

Nucleophilic Additions to Alkenes. Nucleophilic additions to alkenes (Scheme 3.9) are mechanistically very closely related to an ElcB process. In fact, the addition process simply involves a reversal of the steps in response to an equilibrium constant that favors the addition product over the alkene. A notable example is the Michael addition of an enolate to an alkene bearing a strong electron-withdrawing group (EWG). 

The mode of the elimination can be recognised by the composition of the products if the olefin formed has such substituents on the double bond that cis and trans stereoisomers may be distinguished. The question is of interest with respect to the concerted E2 mechanism, because in the pure El and ElcB processes, the intermediate carbonium ion or carbanion, respectively, usually have enough time to rotate around the Ca—Cp bond, equilibrate and give the same cis/trans ratio from different conformers. 

King and Gill have been studying the reaction of alkyl 2,2,2-difluoroethanesulfonate esters (desylates) (308) in aqueous base (pH >9) in the presence of a primary or secondary amine.282 Reaction witii hydroxide is found to be a reversible ElcB process and reaction witii water is die normal sulfonic ester hydrolysis. 

Base-catalysed hydrogen/deuterium exchange is still probably the only definitive probe for the ElcB process in which H/D exchange occurs in the starting material at a rate faster... 

We are done, but let s take an overview of the reasonable routes (Fig. 10.7). The reaction path is shown vertically in the center, and the alternate routes are shown to the side. The path abbreviation for the forward reaction only is shown. To summarize the route Proton transfer generates the nucleophile, which reacts by AdN2, and then the ElcB process gives us the product. 

The (3-elimination reaction of carbonyl compounds having a leaving group at the p-position is promoted by superbases via an ElcB process. Allin et al. described a synthesis of deplacheine (107) [32], in which the p-methanesulfonyloxycarbonyl compound 105 obtained from the aldol reaction of 104 and acetaldehyde was selectively converted into the desired -isomer 106 by the use of DBN in THE This enone 106 was successfully led to the natural product 107 (Scheme 7.22). 

The DBU promoted epoxide opening reaction through an ElcB process has been applied to natural product synthesis. Trudeau and Morken reported a synthesis of fraxinellone (113) [34] (Scheme 7.24). Treatment of epoxide 111 with DBU in benzene gave allylic alcohol 112, which was led to the natural product by oxidation of the resulting alcohol with TEAR... 

Scheme 734. A representation of an Elcb process. In the first step, an acidic proton is removed from the 3-carbon by the exogenous base to generate the conjugate base of the substrate (a carbanion).The product-determining step contains only the carbanion.

Finally, for the Elcb process, if formation of the carbanion is rate determining and the carbanion, once formed, more rapidly goes on to product than it returns to starting material, the Elcb reduces to the E2 process and an E2 isotope effect would be expected. However, if the rate of return to reactant from carbanion is comparable with the rate of product formation or if the rate of return to reactant is faster than the rate of product formation, then the kinetic expression becomes much more difficult to evaluate and it is not clear that an Elcb mechanism can be identified. 

The Ef,l reaction involves the same intermediate carbonium ion as an Sjyl replacement of Y and its rate is governed by similar considerations. Likewise, the ElcB process involves an initial step analogous to a prototropic reaction (Y replacing hydrogen). Both reactions are of EOg type and the effect of structure on their rates can be predicted in the same way as the rates of S,yl reactions (p. 237) or of deprotonations by base (p. 243). Thus the Effl reaction will be favored by -I, E, and —E substituents a to X and the lcB reaction by -H/, E, or -f substituents a to Y. Indeed, elimination reactions involving a proton a to a powerful -f group such as acyl always take place by the ElcB mechanism, as in the conversion of )S-chloroethyl ketones to vinyl ketones. 

You may be wondering why we have looked at the mechanisms in this order. First, the El and ElcB processes have a clear and well-defined answer on the subject of regiochemistry, whereas that for E2 requires rather more subtlety. Also, in thinking about what happens in the E2 process, these well-defined answers from the other mechanisms will help our understanding. The transition state for an E2 reaction may be, but is not necessarily, symmetric. If we draw the transition states for each process (Figure 10.18), we see that E2, in bond breaking at least, has some features of both of the other mechanisms. 

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