Pauson–Khand reaction
The Pauson–Khand reaction is a chemical reaction described as a cycloaddition between an alkyne, an alkene and carbon monoxide to form a α,β-cyclopentenone. The reaction was discovered by Ihsan Ullah Khand, who was working as a postdoctoral associate with Peter Ludwig Pauson at the University of Strathclyde in Glasgow. This reaction was originally mediated by stoichiometric amounts of dicobalt octacarbonyl, but newer versions are both more efficient and catalytic.
With unsymmetrical alkenes or alkynes, regioselectivity can be problematic, but less so with intramolecular reactions.
The reaction works with both terminal and internal alkynes although internal alkynes tend to give lower yields. The order of reactivity for the alkene is strained cyclic alkene > terminal alkene > disubstituted alkene > trisubstituted alkene. Unsuitable alkenes are tetrasubstituted alkenes and alkenes with strongly electron withdrawing groups.
Takayama and co-workers used an intramolecular Pauson–Khand reaction to cyclise an enyne containing a tert-butyldiphenylsilyl protected primary alcohol. This was a key step in the asymmetric total synthesis of the Lycopodium alkaloid huperzine-Q. The inclusion of a cyclic siloxane moiety in the reagent ensures that the product is formed with the desired conformation - only a single enantiomer of the product was obtained in the Pauson–Khand reaction sequence.
Variations
, based on the transition metal rhodium, also effectively catalyses PK reactions but requires silver triflate as a co-catalyst.
Molybdenum hexacarbonyl is a carbon monoxide donor in PK-type reactions between allenes and alkynes with dimethyl sulfoxide in toluene.
Cyclobutadiene also lends itself to a cycloaddition although this reactant is generated in situ from decomplexation of stable cyclobutadiene iron tricarbonyl with ceric ammonium nitrate.
An example of a newer version is the use of the chlorodicarbonylrhodium dimer, 2, in the synthesis of -phorbol by Phil Baran. In addition to using a rhodium catalyst, this synthesis features an intramolecular cyclization that results in the normal 5-membered α,β-cyclopentenone as well as 7-membered ring.
