Cornforth rearrangement

The reaction is used in the synthesis of amino acids, where the corresponding oxazoles occur as intermediates.

It was shown that the reaction gave good yields, over 90%, when using nitrogen-containing heterocycles at the R3 position.

[1][3] The mechanism of the Cornforth rearrangement begins by a thermal pericyclic ring opening which furnishes a nitrile intermediate 1, which then undergoes rearrangement to the oxazole, which is isomeric to the starting compound.

The ylide intermediate has several resonance contributors and the stability of said structures affects the outcome of the reaction, since the intermediate will revert to the starting material if the third resonance structure is most stable.

Whether the reaction takes place is dependent on the energy difference between the starting material and the product.