Weiss-Cook condensation

What is Weiss-Cook condensation?

The Weiss-Cook condensation is a reaction reported by Weiss and Edwards in 1968. It involves an α-dicarbonyl molecule and two equivalents of 3-oxoglutarate in a slightly acidic aqueous medium to form a cis-bicyclo[3.3.0]octane-3,7-dione derivative. The reaction is also referred to as the Weiss-Cook condensation or the Cook-Weiss process.

Weiss-Cook condensation - general reaction scheme - Weiss-Cook condensation - Cook-Weiss process
Weiss-Cook condensation

The reaction is similar to a Diels-Alder reaction in terms of generating molecular complexity in a single reaction. However, four carbon-carbon connections and two rings are built in a single Weiss-Cook condensation, whereas only two carbon-carbon connections and one ring are generated in a Diels-Alder reaction.

The efficiency of this reaction is indicated by the yield of cis-bicyclo[3.3.0]octane-3,7-dione derivative to the new carbon-carbon bond formations. Only cis-bicyco[3.3.0]octane-3,7-dione derivatives are obtained in the Weiss-Cook condensation, indicating that a series of thermodynamic equilibria favor the cis isomer over its trans isomer.

The Weiss-Cook condensation can also take place under basic conditions, and it has been used to synthesize various polyquinanes and polyquinenes. The polyquinane natural products synthesized by the Weiss-Cook condensation include bifurcarenone, gymnomitrol, isocomene, loganin, modhephene, pentalenene, and quadrone.

References

Weiss, U., and Edwards, J. M. (1968). A one-step synthesis of ketonic compounds of the pentalane, [3,3,3]- and [4,3,3]-propellane series. Tetrahedron Letters, 9(47), 4885-4887. https://doi.org/10.1016/S0040-4039(00)72784-5

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