Chem 30A, F01 Prof.

Garrell Stereochemistry of E2 Reactions The preferred transition state geometry for the E2 reaction has the five atoms involved (nucleophilic atom, H, C, C, leaving group) lying in the same plane, with the H-C-C-L dihedral angle 180. This is called an anti periplanar transition state. It provides the proper overlap of orbitals for the developing bond.
[Aside: For certain rigid molecules that cannot assume the anti conformation, the E2 reaction can proceed through a syn periplanar transition state (H-C-C-L dihedral angle 0).]

B H C C L

This geometric requirement affects the outcomes of E2 reactions. As shown through the example described on the next two pages, E2 reactions can be stereoselective. In a stereoselective reaction, one stereoisomer is formed or destroyed in preference to all others. Case studies: Neomenthyl chloride and menthyl chloride Neomenthyl chloride and menthyl chloride are diastereomers. In neomenthyl chloride, the chlorine and isopropyl groups are cis, and two elimination products are possible. In menthyl chloride, the chlorine and isopropyl groups are trans. This species can only undergo elimination when in its less stable chair conformation, so the reaction is slow. (Attaining the less stable conformation requires energy!) Furthermore, only one elimination product can be formed. Elimination is thus stereoselective, with neomenthyl chloride reacting faster than menthyl chloride. Elimination is also regioselective, with (a) neomenthyl chloride showing a ~3:1 preference to form the more stable alkene (Zaitsevs rule);and (b) menthyl chloride forming exclusively the less stable alkene.

Chem 30A, F01 Prof. Garrell Example 1: Neomenthyl chloride is shown below left in the preferred conformation, with the isopropyl group equatorial and the chlorine substituent in an axial position. In this conformation, there are two hydrogen atoms in axial positions, anti and coplanar with the chlorine. Thus, two E2 products are possible when neomenthyl chloride reacts with a strong base such as ethoxide ion. Path (a) gives the more highly substituted alkene, which is preferred (Zaitsevs rule). A mix of products is formed (~3:1 ratio).

a) Et b) Et
H 3C O H

O H

a)

H 3C

1 4 3 2 1-menthene (78%) (more stable alkene)

CH(CH3) 2

2 5
H Cl

E2
H

b)
H 3C CH(CH3) 2

neomenthyl chloride 2-menthene (22%) (less stable alkene)

The 3D structures below show neomethyl chloride, at left in the preferred chair conformation (as was illustrated in the reaction above), and at right in the less stable chair conformation. Notice that in the picture at right, the isopropyl group is axial and the chlorine equatorial. In this conformation, the hydrogen-chlorine orienation is equatorial-equatorial, so an E2 reaction is not possible.

Neomenthyl cloride: more stable conformation H H

less stable conformation

Cl

Cl

Chem 30A, F01 Prof. Garrell Example 2: Menthyl chloride also has two possible chair conformations. The more stable one, shown at left, has the methyl, isopropyl and chlorine all in equatorial positions. An E2 reaction is not possible for this conformation, as there is no hydrogen anti to chlorine (the chloride leaving group). For chlorine to be in an axial position, the methyl and isopropyl groups must be in axial positions as well. This conformation is much higher in energy. An elimination reaction is possible now, because there is a hydrogen atom anti and coplanar with chlorine. Deprotonation and chloride elimination results in formation of 2-menthene in 100% yield. Note that formation of this product is contrary to Zaitsevs rule.
H H H 3C CH3 Cl Cl CH(CH3) 2 H H Et O H H

2 5
H H

CH(CH3) 2

menthyl chloride (more stable conformation)

menthyl chloride (less stable conformation)

X
H 3C CH(CH3) 2

No E2 product
2-menthene (100%) (less stable alkene, but the only possible elimination product)

MENTHYL CHLORIDE more stable conformer less stable conformer Both Cl and isopropyl substituents are equatorial Both Cl and isopropyl substituents are axial.