And ElcB elimination

I Primary alkyl halides S 2 substitution occurs if a good nucleophile is used, 2 elimination occurs if a strong base is used, and ElcB elimination occurs if the leaving group is two carbons away from a carbonyl group. 

We need a formaldehyde equivalent that is less electrophilic than formaldehyde itself and will therefore add only once to enol(ate)s. The solution is the Mannich reaction.7 Formaldehyde is combined with a secondary amine to give an iminium salt that adds 47 to the enol of the aldehyde or ketone in slightly acidic conditions to give the amino ketone (or Mannich base ) 48. If the product of the aldol reaction 50 is wanted, alkylation on nitrogen provides a good leaving group and ElcB elimination does the trick. 

It just turns out that the termoiecular rate constant k3 is actually the product of an equilibrium constant K and a genuine bimolecular rate constant k2 such that k3 = Ki x k2. You saw a similar thing in the rate expressions for amide hydrolysis (Chapter 13) and ElcB elimination (Chapter 19, p. 497)... 

P-Elimination can be subdivided into Het -Het elimination and Het -elimination. Three different modes of action, E1-, E2- and Elcb elimination are known. An elimination proceeds as syn-elimination if both substituents leave the molecule from the same side of the newly formed C=C double bond and as anti-elimination if the two substituents leave the molecule from different faces. In Het -H elimination, control of the regioselectivity is problematic if two atoms are present. This can lead to a mixture of the less-substituted alkene, the so-called Hofmann product, and the more highly substituted alkene, the so-called Saytzew product. These problems do not occur in Het -Het elimination. In many cases Het -Het eliminations are either syn- or anti-selective by their mode of action. High stereoselectivity is observed in these cases, if both the a- and the P-carbon are stereogenic centers. 

The Knoevenagel reaction, the condensation of 1,3-dicarbonyl compounds with aldehydes to give unsaturated compounds, is catalyzed by 2° amines. A perfectly reasonable mechanism involving deprotonation of the 1,3-dicarbonyl compound by base, aldol reaction with the ketone, and Elcb elimination of H2O can be drawn. However, the Knoevenagel reaction does not proceed nearly so well using 3° amines, suggesting that the amine does not simply act as a base. 

The discussion of elimination reactions considers the classical E2, El, and Elcb eliminations that involve removal of a hydrogen and a leaving group. We focus on the kinetic and stereochemical characteristics of elimination reactions as key indicators of the reaction mechanism and examine how substituents influence the mechanism and product composition of the reactions, paying particular attention to the nature of transition structures in order to discern how substituent effects influence reactivity. We also briefly consider reactions involving trisubstituted silyl or stannyl groups. Thermal and concerted eliminations are discussed elsewhere. 

Apparently the hypothesis of a nucleophile-catalyzed reaction fits well with all the experimental data. However, there is still an additional question being the transformation of zwitterion 7 into the Baylis-Hillman product 3. Intermediate 7 may evolve to compound 3 either by an E2 or by an ElcB elimination process (Scheme 32.6). Based on experimental evidence, we only know that the fission of the vinylic a-proton should occur at some stage after the rate-determining step, because no deuterium KIE is detected. Only with this data in hand, it is impossible to decide between the E2 and ElcB elimination processes (Scheme 32.6). 

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