We shall be using ring structures throughout the rest of the book, and you will learn how their conformation affects their chemistry extensively. In many reactions of six-membered rings, the outcome may depend on whether a functional group is axial or equatorial. We shall conclude this chapter with two examples in which a functional group will be held in its axial or equatorial position by ‘locking’ the ring using a t-butyl group or a fused ring system such as trans-decalin. In the last chapter we looked at two mechanisms for nucleophilic substitution: SN1 and SN2. We saw that the SN2 reaction involved an inversion at the carbon centre. Recall that the incoming nucleophile had to attack the σ* orbital of the C–X bond. This meant that it had to approach the leaving group directly from behind, leading to inversion of configuration.

What do you think would happen if a cyclohexane derivative underwent an SN2 reaction? If the conformation of the molecule is fixed by a locking group, the inversion mechanism of the SN2 reaction means that, if the leaving group is axial, then the incoming nucleophile will end up equatorial and vice versa.

Substitution reactions are not very common for substituted cyclohexanes. The electrophilic carbon in a cyclohexane ring is a secondary centre—in the last chapter we saw that secondary centres do not react well via either SN1 or SN2 mechanisms . To encourage an SN2 mechanism, we need a good attacking nucleophile and a good leaving group. 

The substitution of an axial substituent proceeds faster than the substitution of an equatorial substituent. There are several contributing factors making up this rate difference, but the most important is the direction of approach of the nucleophile. The nucleophile must attack the σ* of the leaving group, that is, directly behind the C–X bond. In the case of an equatorially substituted compound, this line of attack is hindered by the (green) axial hydrogens—it passes directly through the region of space they occupy. For an axial leaving group, the direction of attack is parallel with the (orange) axial hydrogens anti-periplanar to the leaving group, and approach is much less hindered.

We must assume that this holds even for simple unsubstituted cyclohexanes, and that substitution reactions of cyclohexyl bromide, for example, occur mainly on the minor, axial conformer. This slows down the reaction because before it can react, the prevalent equatorial conformer must fi rst flip to the axial. If this flip to an axial leaving group is not possible, it may be that the reaction just won’t happen at all. This is exactly what happens in a trans-decalin. There are two diastereoisomers of this simple substituted trans-decalin: one with an equatorial and one with an axial leaving group (X could be Br, OTs, etc.).

Attack by a nucleophile on the compound with the axial leaving group is straightforward. The nucleophile can approach along the axis of the C–X bond and normal SN2 reaction occurs with inversion—the product is the equatorial compound. The equatorial leaving group, on the other hand, would require the nucleophile to approach through the middle of the mole culeand that cannot be achieved. A totally different reaction occurs.

مواضيع ذات صلة

E1 reactions can be stereoselective

The role of the leaving group

Substrate structure may allow E1

E1 and E2 mechanisms

Size

Elimination happens when the nucleophile attacks hydrogen instead of carbon

Axially and equatorially substituted rings react differently

Steroid

Decalins

What happens with more than one substituent on the ring

Substituted cyclohexanes

The ring inversion (flipping) of cyclohexane