Pauson-Khand reaction

What is Pauson-Khand reaction?

The Pauson-Khand reaction is a one-step synthesis of an α,β-unsaturated cyclopentenone through a [2+2+1] cycloaddition of an alkyne, alkene, and carbon monoxide CO, which is mediated or promoted by dicobalt octacarbonyl Co2(CO)8. This reaction was first reported by Khand and Pauson in 1973 and is also known as the Pauson-Khand cyclization or Pauson-Khand cycloaddition.

Other names used for this reaction include the Pauson-Khand annulation, multicomponent cycloaddition, carbonylative cocyclization, bicyclization, Khand annulation, cycloaddition, and cyclization. However, the Pauson-Khand reaction is the most commonly used name.

Intermolecular Pauson-Khand reaction - general reaction scheme - Pauson-Khand cyclization - Pauson-Khand cycloaddition
Intermolecular Pauson-Khand reaction
 Intramolecular Pauson-Khand reaction - general reaction scheme - Pauson-Khand cyclization - Pauson-Khand cycloaddition
Intramolecular Pauson-Khand reaction

The Pauson-Khand reaction involves the formation of an alkynedicobalt hexacarbonyl complex from an alkyne and Co2(CO)8, followed by alkene coordination at one of the two enantiotopic Co atoms with CO insertion, and final reductive elimination of the metal to an α,β-unsaturated cyclopentenone. The reaction can be promoted at ambient temperature by adding tertiary amine N-oxides, or by heating the reaction mixture in toluene at 110 ºC. Stereochemical control is achieved by designing intramolecular reactions or using cyclic alkenes such as norbornene, which is more reactive than cyclohexene and cyclopentene.

Although the Pauson-Khand reaction is a powerful method for forming complex structures with stereochemical control, it has some drawbacks, including the use of a stoichiometric amount of Co2(CO)8, high pressure of CO, troublesome purification protocols, and low yields depending on the alkynes and alkenes. Thus, the original protocol has been modified by using different catalysts or reaction conditions.