Pauson–Khand reaction

In it, an alkyne, an alkene, and carbon monoxide combine into a α,β-cyclopentenone in the presence of a metal-carbonyl catalyst[1] [2] Ihsan Ullah Khand (1935–1980) discovered the reaction around 1970, while working as a postdoctoral associate with Peter Ludwig Pauson (1925–2013) at the University of Strathclyde in Glasgow.

[6] The traditional reaction requires a stoichiometric amounts of dicobalt octacarbonyl, stabilized by a carbon monoxide atmosphere.

[8][9][10][11] While the mechanism has not yet been fully elucidated, Magnus' 1985 explanation[12] is widely accepted for both mono- and dinuclear catalysts, and was corroborated by computational studies published by Nakamura and Yamanaka in 2001.

Typical Pauson-Khand conditions are elevated temperatures and pressures in aromatic hydrocarbon (benzene, toluene) or ethereal (tetrahydrofuran, 1,2-dichloroethane) solvents.

Adsorbing the metallic complex onto silica or alumina can enhance the rate of decarbonylative ligand exchange as exhibited in the image below.

[clarification needed] Additionally using a solid support restricts conformational movement (rotamer effect).

Lewis basic additives, such as n-BuSMe, are also believed to accelerate the decarbonylative ligand exchange process.

[20] Sulfur compounds are typically hard to handle and smelly, but n-dodecyl methyl sulfide[21] and tetramethylthiourea[22] do not suffer from those problems and can improve reaction performance.

It is believed that these additives remove carbon monoxide ligands via nucleophilic attack of the N-oxide onto the CO carbonyl, oxidizing the CO into CO2, and generating an unsaturated organometallic complex.

Density functional investigations show the variation arises from different transition state metal geometries.

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.

1:
Alkyne coordination , insertion and ligand dissociation to form an 18-electron complex ;
2:
Ligand dissociation to form a 16-electron complex;
3:
Alkene coordination to form an 18-electron complex;
4:
Alkene insertion and ligand association ( synperiplanar , still 18 electrons);
5:
CO migratory insertion;
6, 7:
Reductive elimination of metal (loss of [Co 2 (CO) 6 ]);
8:
CO association, to regenerate the active organometallic complex. [ 14 ]
The PK reaction has poor regioselectivity with monosubstituted alkenes. Phenylacetylene and 1-octene produce at least 4 isomeric products. ("tol" = toluene )
An electron-withdrawing group (ethyl benzoatyl) prefers the C 3 position. ("Tol" = toluene )
An intramolecular Pauson-Khand reaction
An intramolecular Pauson-Khand reaction produces a bicycle with 97% syn to the bridgehead and 3% anti.
Pauson-Khand in DME (dimethoxyethane? dimethyl ether?) at 120°C
Original reaction: 24 hours at 60°C with 30% yield. Dry reaction: silica, oxygen, 45°C for 0.5 hours for 75% yield.
Adding silica improved this reaction rate by a factor of ≈50.
Reaction in cyclohexanamine fails to proceed, but with neo-butyl methyl sulfide it runs to 79% yield.
NMO = N ‑methylmorpholine N ‑oxide , DCM = dichloromethane
(NMO = N ‑methylmorpholine N ‑oxide , DCM = dichloromethane ) A step in the total synthesis of epoxydictymene: temperature and ultrasound failed to improve the d.r. for the desired diastereomer (the red hydrogen). But the N -oxide additive, while lower yielding, gave a d.r. of 11:1. [ 28 ]
The key step in Takayama et al 's asymmetric total synthesis of the Lycopodium alkaloid huperzine-Q : Co 2 (CO) 8 catalyzes an enyne cyclization. [ 33 ] The siloxane ring ensures [ 34 ] that only a single product enantiomer forms. [ 33 ]
PK reaction with Wilkinson's catalyst
PK reaction with Wilkinson's catalyst
PK reaction with molybdenum hexacarbonyl
Molybdenum catalyzes a Pauson-Khand reaction at an allene's internal double bond. Rhodium would catalyze a reaction at this substrate's terminal double-bond instead.
Pauson Khand reaction Seigal 2005
Pauson Khand reaction Seigal 2005