Eschenmoser fragmentation

The Eschenmoser fragmentation (also called the Eschenmoser-Tanabe fragmentation) is the chemical reaction of α,β-epoxyketones (1) with aryl sulfonylhydrazines (2) to give alkynes (3) and carbonyl compounds (4).^[1]^[2]^[3]^[4] This reaction is named after Albert Eschenmoser, a Swiss chemist.

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Several examples exist in the literature.^[5]^[6]

Reaction mechanism

The mechanism of the Eschenmoser fragmentation begins with reaction of the α,β-epoxyketone (1) with aryl sulfonylhydrazine (2) to give the intermediate hydrazone (3). Proton transfer leads to intermediate 4, which undergoes the key fragmentation to the alkyne (6) and the carbonyl compound (7).

The proton transfers from hydrazone (3) to intermediate (4) can be catalyzed by pyridine, sodium bicarbonate, sodium carbonate, or silica gel.

References

^ A. Eschenmoser, D. Felix and G. Ohloff (1967). "Eine neuartige Fragmentierung cyclischer ?, β-ungesättigter Carbonylsysteme; Synthese von Exalton und rac-Muscon aus Cyclododecanon Vorläufige Mitteilung". Helvetica Chimica Acta 50 (2): 708-713. doi:10.1002/hlca.19670500232.
^ J. Schreiber, D. Felix, A. Eschenmoser, M. Winter, F. Gautschi, K. H. Schulte-Elte, E. Sundt, G. Ohloff, J. Kalovoda, H. Kaufmann, P. Wieland and G. Anner (1967). "Die Synthese von Acetylen-carbonyl-Verbindungen durch Fragmentierung von α-β-Epoxy-ketonen mit p-Toluolsulfonylhydrazin. Vorläufige Mitteilung". Helvetica Chimica Acta 50 (7): 2101-2108. doi:10.1002/hlca.19670500747.
^ Masato Tanabe, David F. Crowe and Robert L. Dehn (1967). "A novel fragmentation reaction of α,β-epoxyketones the synthesis of acetylenic ketones". Tetrahedron Letters 8 (40): 3943-3946. doi:10.1016/S0040-4039(01)89757-4.
^ D. Felix, J. Schreiber, G. Ohloff and A. Eschenmoser (1971). "α-β-Epoxyketon → Alkinon-Fragmentierung I: Synthese von exalton und rac - muscon aus cyclododecanon über synthetische methoden, 3. Mitteilung". Helvetica Chimica Acta 54 (8): 2896-2912. doi:10.1002/hlca.19710540855.
^ Dorothee Felix, Claude Wintner, and A. Eschenmoser (1988). "Fragmentation of α-β-Epoxyketones to Acetylenic Aldehydes and Ketones: Preparation of 2,3-Epoxycyclohexanone and its fragmentation to 5-Hexynal". Org. Synth.; Coll. Vol. 6: 679.
^ W. Dai and J. A. Katzenellenbogen (1993). "New approaches to the synthesis of alkyl-substituted enol lactone systems, inhibitors of the serine protease elastase". J. Org. Chem. 58 (7): 1900-1908. doi:10.1021/jo00059a049.