The Pauson–Khand reaction, a powerful synthetic tool for the synthesis of complex molecules

Abstract

There are still some synthetic chemists who hesitate to use metal-mediated or -catalysed reactions. The Pauson-Khand reaction (PKR) is a powerful transformation that has now been sufficiently well developed to be routinely considered when planning a synthesis, especially of polycyclic complex molecules. This tutorial review aims to encourage the use of this process explaining the best ways of performing a PKR both in the stoichiometric and the catalytic version, showing the scope of the process and its limitations. Additionally, asymmetry can be introduced in the reaction using several strategies, which will be discussed. The most recent examples of the synthetic applications of the PKR in natural product synthesis will give the reader an idea of the great usefulness of this reaction.

Graphitic carbon nitride materials: variation of structure and morphology and their use as metal-free catalysts

“…The availability of produced CO was checked in a bifunctional catalytic scheme, where the CO generated from the oxidation of benzene with CO 2 was used up in a Pausen-Khand reaction 76,77 with an alkene (1-hexene) and an alkyne (dimethyl acetylene dicarboxylate, DMAD).…”

Metal‐Free Activation of CO2 by Mesoporous Graphitic Carbon Nitride

“…To confirm that CO really is produced in the reaction and is available for further reaction, we quenched it in a Pauson-Khand (PK) reaction. This reaction, the cyclotrimerization of CO, an alkene, and an alkyne to form a cyclopentenone, is a very useful synthetic tool and in our case serves as evidence for the formation of CO. [21,22] We added 1-hexene and dimethylacetylene-1,2-dicarboxylate (DMAD) to the standard reaction mixture (Scheme 4). The production of dimethyl-4-butylcyclopent-2-en-1-one-2,3-dicarboxylate (the expected Pauson-Khand product) in rather high yield (70 % at 100 % conversion with respect to DMAD) indeed proved the presence of CO. Interestingly, no phenol was detected and all the formed biphenyl was consumed in a Diels-Alder reaction with DMAD to form dimethylphenanthrenedicarboxylate (30 % yield).…”

Cascade Reactions Involving Pauson—Khand and Related Processes

“…Only a few of other reactions like the Diels-Alder, or the cyclotrimerization of alkynes can compete with the PKR, which consists formally of a [2 + 2 + 1] cycloaddition in which a triple bond, a double bond and carbon monoxide form a cyclopentenone [2][3][4][5][6][7][8][9][10][11][12]. This constitutes one of the best ways to construct cyclopentenones, which upon further transformations can be converted into structures present in numerous natural products (Scheme 1).…”