Fragmentation Reactions

Introduction:

Fragmentation Reactions, which are similar to β-elimination reactions can be useful for the formation of alkenes, particularly from carbocyclic compounds.

Fragmentation reactions occur most easily from conformationally locked 1,3-difunctionalized compounds, in which the breaking C X and C-C bonds are aligned antiperiplanar.

1) Eschenmoser Fragmentation

Fragmentation of the hydrazones of α,β - epoxy ketones is known as the Eschenmoser fragmentation.

Deprotonation of the hydrazone promotes ring-opening of the epoxide to give an alkoxy species.

This alkoxy species then fragments, displacing nitrogen gas and the sulfinate, to give an alkynone.

a) Example 1:

The reaction was made use of in a synthesis of exo-brevicomin, starting with the epoxy ketone.

The starting material for an Eschenmoser fragmentation is the epoxide of an a,b-unsaturated ketone.

b) Example 2 & 3:

The fragmentation happens when this epoxy-ketone is treated with tosylhydrazine, and one of the remarkable things about the product is that it is an alkyne.

The fragmentation happens across the epoxide, and the product contains both a ketone (in a different place to the ketone in the starting material) and an alkyne.

c) Example 4:

The Eschenmoser fragmentation does not have to be a ring expansion, and it is a useful synthetic method for making keto-alkynes.

The following reaction, which we will use to discuss the fragmentation's mechanism, was used to make an intermediate in the synthesis of an insect pheromone, exo-brevicomin.

The reaction starts with formation of the tosylhydrazone from the epoxy-ketone.

The tosylhydrazone is unstable with respect to opening of the epoxide in an elimination reaction, and it is this elimination that sets up the familiar 1, 2, 3, 4 system ready for fragmentation.

The 'push' comes from the newly created hydroxyl group, and the '€˜pull' from the irresistible concerted loss of a good leaving group (Ts-€“) and an even better one (N2).

Notice how all the bonds that break are parallel to one another, held anti-periplanar by two double bonds.

Mechanism :