We can also compare the E1cB mechanism with the other elimination reactions you have met by thinking of the relative timing of proton removal and leaving group departure. E1 is at one end of the scale: the leaving group goes first and proton removal follows in a second step. In E2 reactions, the two events happen at the same time: the proton is removed as the leaving group leaves. In E1cB the proton removal moves in front of leaving group departure.

We talked about regio- and stereoselectivity in connection with E1 and E2 reactions. With E1cB, the regioselectivity is straightforward: the location of the double bond is defined by the position of (a) the acidic proton and (b) the leaving group.

E1cB reactions may be stereoselective—the one above, for example, gives mainly the E alk ene product (2:1 with Z). The intermediate anion is planar, so the stereochemistry of the start ing materials is irrelevant, the less sterically hindered (usually E) product is preferred. This double E1cB elimination, for example, gives only the E,E product.

To finish this chapter we need to tell you about two E1cB eliminations that you may meet in unexpected places. We have saved them till now because they are unusual in that the leaving group is actually part of the anion-stabilizing group itself. First of all, try spotting the E1cB elimination in this step from the first total synthesis of penicillin V.

The reaction is deceptively simple—formation of an amide in the presence of base—and you would expect the mechanism to follow . But the acyl chloride is, in fact, set up for an E1cB elimination—and you should expect this whenever you see an acyl chloride with acidic protons next to the carbonyl group used in the presence of a base such as triethylamine.

The product of the elimination is a substituted ketene—a highly reactive species whose parent structure is the molecule CH₂=C=O that you will meet in the next chapter. It is the ketene that reacts with the amine to form the amide.

The second ‘concealed’ E1cB elimination is disguised in the mechanism of formation of methanesulfonates (mesylates). we avoided (uncharacteristically, you may say) explaining the mechanism by which they are formed from sulfonyl chlorides. This was deliberate because, while TsCl reacts with alcohols by the mechanism you might predict, the reaction with MsCl involves an elimination step. Here is the mechanism by which alkyl tosylates are formed from alcohols. The alcohol acts as a nucleophile towards the electrophilic sulfonyl chloride, and pyridine removes a proton to give the product.

Methanesulfonyl chloride by contrast has a feature it shares with the acyl chlorides just above: a relatively acidic proton that can be removed by base. This deprotonation, followed by loss of chloride, is the first step in the formation of a mesylate ester. It is an E1cB elimination and the product is called a sulfene.

The sulfene is electrophilic in a slightly odd way: the alcohol acts as a nucleophile for sulfur and generates an anion of carbon which undergoes a proton transfer to give the mesylate. It is not uncommon for anions to form adjacent to sulfur, as you will see again. 

مواضيع ذات صلة

Distinguishing acid derivatives by carbon NMR is difficult

Anion-stabilizing groups allow another mechanism—E1cB

The regioselectivity of E2 eliminations

E2 elimination from vinyl halides: how to make alkynes

E2 eliminations from cyclohexanes

E2 eliminations can be stereospecific

E2 eliminations have anti-periplanar transition states

E1 reactions can be stereoselective

The role of the leaving group

Substrate structure may allow E1

E1 and E2 mechanisms

Size