Wharton reaction

The Wharton olefin synthesis or the Wharton reaction is a chemical reaction that involves the reduction of α,β-epoxy

Mechanism and scope

The mechanism of the Wharton reaction begins with reaction of the ketone (1) with hydrazine to form a hydrazone (2). Rearrangement of the hydrazone gives intermediate 3, which can decompose giving off nitrogen gas forming the desired product 4. The final decomposition can proceed by an ionic or a radical pathway, depending on reaction temperature, solvent used, and structure of intermediate 3.^[5]

The Wharton olefin synthesis allows the transformation of an α,β unsaturated ketone into an

• The classical Wharton olefin synthesis conditions are not free from the presence of water, so reactants undergoing the Wharton olefin synthesis should not be sensitive to water.
• For
  stereoisomers
  .

Applications

The methodology has been implemented in synthesis of complex molecules:

• The total synthesis of the
  anticancer natural product OSW-1 provides a practical application of the Wharton olefin synthesis. An α,β-epoxyketone reacts with hydrazine hydrate to yield an allylic alcohol.^[7]
• In the synthesis of warburganal, a bioactive natural product, the α,β-epoxyketone is formed from a cyclic α,β-unsaturated ketone and in a separate step reacts under the classical Wharton olefin synthesis conditions to yield an allylic diol.^[8]

References