The Pauson-Khand Cycloaddition Reaction for Synthesis of Cyclopentenones

Schore, Neil E.


The Pauson–Khand reaction is a cocycloaddition of alkynes, alkenes, and carbon monoxide to generate cyclopentenones in a formal [2 + 2 + 1] cycloaddition process. The reaction was discovered and first reported in detail by Ihsan U. Khand and Peter L. Pauson in 1973 in the course of a study aimed principally at the preparation and characterization of various alkene and alkyne complexes derived from Co2(CO)8. The generality of the reaction, typically carried out by heating a mixture of the alkene and the readily formed Co2(CO)6 complex of the alkyne in hydrocarbon or ethereal solvent, was established primarily by an extensive series of studies carried out by the Pauson group throughout the 1970s.

The earliest studies established that synthetically reasonable yields, usually in the 40–60% range, and significant regio- and stereoselectivity could be expected even for relatively simple examples. Development of this reaction has reached the point where predictable success and control of selectivity are possible. The variety of successful reactions and systems accessible by means of this cycloaddition is now quite substantial.

This chapter addresses the scope and generality of this reaction as well as the current state of the art with regard to control of regio- and stereochemistry. Both inter- and intramolecular versions of the cycloaddition are presented, and current models that have been put forth concerning the reaction mechanism are noted. Synthetic applications of the Pauson–Khand reaction have taken many forms, and representative examples of all major types of systems accessed are presented. The process exemplifies a nearly ideal merging of organometallic with synthetic chemistry, in which advances in each area have promoted development in the other in an almost symbiotic manner. Excellent shorter reviews on the Pauson–Khand reaction have been published. This chapter will provides the reader with both an overview of the reaction as well as a sufficiently detailed understanding of its complexities to permit meaningful evaluation as a possible solution to current or future research needs.