Stereochemistry of the E2 Reaction

Reactions such as the E2 elimination, in which several bonds are made and broken simultaneously, usually have strict requirements for the stereochemical relationship of these bonds as the reaction proceeds. These stereoelectronic requirements occur because the 

In the syn-periplanar conformation, the C—H and C—L sigma bonds are coplanar and on the same side of the C—C bond. As the bonds to the hydrogen and the leaving group start to break, the hybridization at each carbon begins to change to sp2, and the two sp3 orbitals, which have some pi-type overlap initially, change to the p orbitals of the pi bond. 

Mechanism of E2 elimination from syn-periplanar and anti-periplanar conformations. 

Closer examination reveals that the syn-periplanar conformation has all the bonds eclipsed, whereas the anti-periplanar conformation has these bonds staggered, as shown in the following Newman projections  

Because El reactions often occur with a competing SnI reaction, El reactions of alkyl halides are much less useful than E2 reactions. 

Problem 8.16 Draw both the S. j1 and E1 products of each reaction. 

Although the E2 reaction does not produce products with tetrahedral stereogenic centers, its transition state consists of four atoms that react at the same time, and they react only if they possess a particular stereochemical arrangement. 

The transition state of an E2 reaction consists of four atoms from the alkyl halide—one hydrogen atom, two carbon atoms, and the leaving group (X)—all aligned in a plane. There are two ways for the C-H and C X bonds to be coplanar. 

The dihedral angle for the C-H and C-X bonds equals 0° for the syn periplanar arrangement and 180° for the anti periplanar arrangement. 

All evidence suggests that E2 elimination occurs most often in the anti periplanar geometry. 

Draw the anti periplanar geometry for the E2 reaction of (CH3)2CHCH2Br with base. Then draw the product that results after elimination of HBr. 

Of these possible conformations, the anti-coplanar arrangement is most commonly seen in E2 reactions. The transition state for the anti-coplanar arrangement is a staggered conformation, with the base far away from the leaving group. In most cases, this transition state is lower in energy than that for the syn-coplanar elimination. 

Enzyme-catalyzed eliminations generally proceed by E2 mechanisms and produce only one stereoisomer. Two catalytic groups are involved One abstracts the hydrogen, and the other assists in the departure of the leaving group. The groups are positioned appropriately to allow an anti oplanar elimination. 

Concerted transition states of the E2 reaction. The orbitals of the hydrogen atom and the halide must he aligned so they can begin to form a pi bond in the transition state. 

Oiapter 6 Alkyl Halides Nucleophilic Substitution and Elimination 

Models are helpful whenever complex stereochemistry is involved. 

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First-Order Elimination The E1 Reaction 258 Key Mechanism 6-8 The E1 Reaction 258 Mechanism 6-9 Rearrangement in an E1 Reaction 261 Summary Carbocation Reactions 262 6-18 Positional Orientation of Elimination Zaitsev s Rule 263 6-19 Second-Order Elimination The E2 Reaction 265 Key Mechanism 6-10 The E2 Reaction 266 6-20 Stereochemistry of the E2 Reaction 267... 

Mechanism 7-1 Dehydrohalogenation by the E2 Mechanism 304 Mechanism 7-2 Stereochemistry of the E2 Reaction 306 Mechanism 7-3 E2 Debromination of a Vicinal Dibromide 310... 

Experimental data indicate that the anti pathway for E2 reactions is favored over the syn pathway. In one of the earliest studies of the stereochemistry of the E2 reaction, Cristol found the rate constant for the dehydrochlorination of the )3 isomer of benzene hexachloride (1,2,3,4,5,6-hexachlorocyclohexane, 6), in which each chlorine is cis to the hydrogen atoms on either side of it, to be only 10" times those of the other benzene hexachloride isomers. Since each of the other isomers has at least one hydrogen atom trans to a chlorine atom on an adjacent carbon atom, the low reactivity of 6 suggested that the E2 reaction occurs preferentially when there is a trans relationship for the hydrogen atom and chlorine atom on cyclohexane. ... 

Now the problem is to find an experiment that will let us see this level of detail. As usual, we will use a stereochemical analysis, and this recquires a certain complexity of substitution in the substrate molecule. For example, there is no use in examining the stereochemistry of the E2 reaction of a molecule as simple as 2-chloro-2,3-dimethylbutane because there is only one tetrasubstituted alkene possible (Fig. 7.82). 

Stereochemical experiments are used here for the first time to probe the details of reaction mechanisms. The observation of inversion of configuration in the 8 2 reaction shows that the incoming nucleophile must approach the leaving group from the rear, the side opposite the leaving group. Similarly, if the stereochemistry of the E2 reaction is monitored, it can be shown that there is a strong preference for the anti (180°) E2 reaction in acyclic molecules. 

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