Elimination reactions ElcB mechanism

The remaining examples of the ElcB reaction which lead to olefin products are supported by less sound evidence. To explain the abnormal stereochemistry of a beta-elimination, the ElcB mechanism has often been invoked rather than the E2 mechanism, the classic example being the base induced dehydrochlorination of /3-benzene hexachloride in which all the adjacent chlorine atoms are situated trans to each other . Stereochemical evidence alone is insufficient proof of the carbanion mechanism this aspect is discussed more fully elsewhere (see Section 2.3). 

There is another useiiil way of depicting the ideas embodied in the variable transition state theory of elimination reactions. This is to construct a three-dimensional potential energy diagram. Suppose that we consider the case of an ethyl halide. The two stepwise reaction paths both require the formation of high-energy intermediates. The El mechanism requires formation of a carbocation whereas the Elcb mechanism proceeds via a caibanion intermediate. 

It has been noticed that the reverse reaction of Eq. (5) is a particular type of the Hofmann elimination reaction (26) via either an E2 or an ElcB mechanism. An E2 mechanism seems to be more obvious for this reaction than an ElcB mechanism, however. 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

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. 

The fact that the rate law of hydrogen bromide elimination is first order with respect to the base may be interpreted by an E2 mechanism. The antiperiplanar position of the hydrogen and the bromine atoms in Ih also makes this mechanism very likely. Earlier the same mechanism was proposed for the elimination reaction of some tertiary a-halo ketones (ref. 19). Other mechanism, such as ElcB or El, seems to be very improbable considering the lack of any deuteration at C-2 or the lack of any rearrangement and the fact that the generation of a-keto cations requires acidic conditions (ref. 20). 

The second product must incorporate two equivalents of the enol ether. We form C3-C5, C5-C4, and C5-S1 bonds, and we transfer a H from SI to C4. A hetero-ene reaction forms the C3-C5 bond and transfers the H. As for the other two bonds, since SI and C5 are at the ends of a four-atom unit, we might expect a Diels-Alder reaction. We can get to the requisite diene by eliminating the elements of BuOH by an Elcb mechanism. The hetero-Diels-Alder reaction gives the product with ertdo stereoselectivity and the expected regioselectivity. 

The difficulty of distinguishing mechanisms at the ElcB-E2 borderline has also been discussed for reactions of secondary halides (1-X and 2-X) which feature a f-hydrogen made acidic by incorporation of an a-indenyl substituent (Scheme 1). 1,2-Elimination reactions of (/f,5 )-l-(l-X-ethyl)indene (1-X, X = Cl, Br, I, OBs) and the corresponding R,R isomers (2-X) promoted by water containing 25 vol.% acetonitrile... 

Effect of solvent on El vs. E2 vs. ElcB. With any reaction a more polar environment enhances the rate of mechanisms that involve ionic intermediates. For neutral leaving groups, it is expected that El and ElcB mechanisms will be aided by increasing polarity of solvent and by increasing ionic strength. With certain substrates, polar aprotic solvents promote elimination with weak bases (the E2C reaction). 

Fluorines present in the /i-position (/f-fluorination) can also influence the outcome of elimination reactions of fluorocarbons as earbanion intermediates are involved in the ElcB elimination mechanism.83 The regio- and stereoselectivity of the elimination step is governed by CH acidities,84 which, as has been discussed, arc influenced by /f-fluorination. 

The mechanistic borderline between E2 and ElcB mechanisms has been studied under various conditions.1,2 The mechanism of the elimination reaction of 2-(2-fluoroethyl)-1-methylpyridinium has been explored explored by Car-Parrinello molecular dynamics in aqueous solution.3 The results indicated that the reaction mechanism effectively evolves through the potential energy region of the carbanion the carbon-fluoride bond breaks only after the carbon-hydrogen bond. 

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