ElcB reactions

ElcB Reaction OH bond breaks first, giving a carbanion... 

In the ElcB reaction, C-H bond-breaking occurs first. A base abstracts a proton to give an anion, followed by loss of the leaving group from the adjacent carbon in a second step. The reaction is favored when the leaving group is two carbons removed from a carbonyl, which stabilizes the intermediate anion by resonance. Biological elimination reactions typically occur by this ElcB mechanism. 

Subsequent dehydration of /3-hydroxybutyryl ACP by an ElcB reaction in step 7 yields trans-ciotonyl ACP, and the carbon-carbon double bond of crotonyl ACP is reduced by NADPH in step 8 to yield butyryl ACP. The doublebond reduction occurs by conjugate addition of a hydride ion from NADPH to the /S carbon of fraus-crotonyl ACP. In vertebrates, the reduction occurs by an overall syn addition, but other organisms carry out similar chemistry with different stereochemistry. 

Problem 29.8 Look at the entire glycolysis pathway and make a list of the kinds of organic reactions that take place—nucleophilic acyl substitutions, aldol reactions, ElcB reactions, and so forth. 

ElcB reaction (Section 11.10) A unimolecular elimination reaction in which a proton is first removed to give a car-banion intermediate, which then expels the leaving group in a separate step. 

Diels-Alder reaction, 493 El reaction, 391-392 ElcB reaction, 393 E2 reaction, 386 Edman degradation, 1032 electrophilic addition reaction, 147-148. 188-189 electrophilic aromatic substitution, 548-549 enamine formation, 713 enol formation, 843-844 ester hydrolysis, 809-811 ester reduction, 812 FAD reactions. 1134-1135 fat catabolism, 1133-1136 fat hydrolysis, 1130-1132 Fischer esterification reaction, 796 Friedel-Crafts acylation reaction, 557-558... 

The results of a thorough study of the kinetics, products and stereochemical course for the nucleophilic substitution and elimination reactions of ring-substituted 9-(l-Y-ethyl)fluorenes ([31]-Y, Y = Br, I, brosylate) have been reported (Scheme 19).121,122. The reactions of the halides [31]-Br and [31]-I were proposed to proceed exclusively by a solvent-promoted ElcB reaction or an E2 reaction with a large component of hydron transfer in the transition state .122... 

Finally, crown ethers have also been shown to produce marked changes in the stereochemistry of ElcB-reactions of methoxyacenaphthenes [189] promoted by KOt-Bu/t-BuOH (Hunter and Shearing, 1971). Addition of dicyclohexyl-18-crown-6 increases the ratio of the rates of exchange and elimination from 1.3 to 3.2, while for both exchange and elimination the cis/trans ratio decreases. 

There was no evidence of a second-order term in amine, nor did amine self-association account for the non-linear behaviour. Hammett p values (for variation of RNHSO2) determined for formation of the complex [S.amine] (p = 1.64) and for expulsion of the anion ( ONp) (pacyi = -1-78) are consistent with an E cB process and uncomplicated by any steric effects of bound amine in the complex. The value of Pacyi is identical with that reported previously for ElcB reaction of the same esters in 50% acetonitrile-water and much greater than for their 2-type reactions in chloroform. Consequently, an ElcB mechanism involving extensive S-O bond cleavage with the formation of a A(-sulfonylamine, ArN=S02, is supported. 

As indicated in Scheme 3.7, the first step of an ElcB mechanism can be reversible and therefore deprotonation at the 3-carbon does not always lead to product formation. By applying a steady-state approximation to the carbanion concentration, the following rate law is obtained for an ElcB reaction ... 

Heo and Bunting have examined the rate-determining steps in conjugate additions and Elcb reactions in aqueous solutions12. They examined the reactions between a range... 

It is not always easy to distinguish an elimination reaction that is following the Elcb mechanism from one that follows the E2 pathway because the Elcb reaction usually exhibits second-order kinetics also. However, because the Elcb reaction is not concerted, there are no strict requirements concerning the stereochemistry of the reaction. In contrast to the preferred anti elimination that occurs in the E2 mechanism, Elcb reactions often produce a mixture of stereoisomers, as illustrated in the following equation ... 

The first looks El (stabilized cation) the second E2—but in fact both are ElcB reactions. The most reliable way to spot a likely ElcB elimination is to see whether the product is a conjugated carbonyl group. If it is, the mechanism is probably ElcB. 

The rate-determining elimination step in an ElcB reaction is unimolecular, so you might imagine it would have a first-order rate equation. But, in fact, the rate is also dependent on the concentration of base. This is because the unimolecular elimination involves a species—the anion—whose concentration is itself determined by the concentration of base by the equilibrium we have just been discussing. Using the following general ElcB reaction, the concentration of the anion can be expressed as shown. 

ElcB reactions may be stereoselective—this one, for example, gives mainly the E-alkene product (2 1 with Z). The intermediate anion is planar, so the sterochemistry of the starting materials is irrelevant, the less sterically hindered (usually E) product is preferred. This double ElcB elimination, for example, gives only the E,E-product. 

Now the leaving group can be expelled by the enol the double bond moves back into its original position in this step, which is exactly the same as the final step of an ElcB reaction (Chapter 19). The new1 double bond expulsion oj the leaving group from the enol intermediate... 

These are elimination reactions, and you met them in Chapter 19. You cannot normally eliminate water from an alcohol in basic solution and it is the carbonyl group that allows it to happen here. A second enolization reaction starts things off, and these are ElcB reactions, the enolization step the elimination step... 

The most reliable method for making the enone is to alkylate the Mannich base with Mel and then treat the ammonium salt with base. Enolate ion formation leads to an ElcB reaction rather like the dehydration of aldols, but with a better leaving group. 

The find stage is dehydration of the aldol and an ElcB reaction that involves the carbonyi group sa in a standard aldol reaction (Chapter 27). Another enolate must form In the same position as the last, the Robinson anneletlon mechanism—stage 3t the ElcB dehydration... 

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