The Pauson-Khand reaction is a cycloaddition, promoted or catalysed by cobalt, between an alkene and an alkyne with insertion of a carbon monoxyde molecule to give a cyclopentenone. This reaction, discovered by Pauson and Khand in 1973 is nowadays one of the main synthetic methods to build cyclopentanic compounds. As seen in the figure, if the olefin is disubstituted, two new stereogenic centres can be created in this reaction. During the last years, our group has developed efficient methods of asymmetric synthesis based on the use of chiral auxiliaries. We have also been able to design chiral ligands for enantioselective Pauson-Khand reactions.

Among the ligands designed for this reaction, we must highlight two families; the ones derived from natural products like PuPHOS and the PNSO type derived from commercial chiral sulfinamides. These are bidentate P, S ligands. The most important characteristic of these ligands is the really narrow separation of only one carbon atom, between the sulfur and phosphorous atoms. In front a bimetallic complex, this favors a bridged structure where the sulfur and the phosphorus are coordinated to different metal atoms.

These ligands have been successfully applied in the Pauson-Khand reaction. For example, when a PNSO ligand is coordinated to the dicobalthexacarbonyl complex of the trimethylsilyacetilene, the two possible diastereomers were obtained in a 12:1 ratio. The major one can be isolated in good yield by crystallisation. The reaction with norbornadiene of this complex leads to the corresponding cyclopentenone with a high optic purity (96-97 % ee). As it has already been shown, these products are useful building blocks in the enantioselective synthesis of cyclopentanic compounds. Both enantiomers of PNSO ligands are available in a multigram scale, thus giving access to both enantiomers of the final cyclopetenone products.

We are currently studying the utilisation of these ligands and others in an asymmetric and enantioselective version of the intramolecular reaction of PK. With this aim, through monitoring techniques of the reaction in situ (FT-IR), we are evaluating the ideal properties these ligands must have for this transformation. The challenge for the future is being able to make the reaction with catalytic quantities of both the linker and the metal.