Pauson-Khand Reaction
The Pauson-Khand reaction is the transition metal catalyzed formal [2+2+1] cycloaddition of alkynes, alkenes, and carbon-monoxide to form substituted cyclopentenones.
General features:
1. The reaction can be inter- and intramolecular. 2. Internal alkynes tend to give lower yields than terminal alkynes. 3. Strained cyclic alkenes react faster, followed by terminal alkenes, disubstituted alkenes, and trisubstituted alkenes. Alkenes with strongly electron-withdrawing groups are less reactive. 4. The reaction is highly regioselective: the larger alkyne substituent ends up next to the carbonyl group in the product. 5. Intramolecular reactions proceed with excellent regio- and stereoselectivity. 6. General reaction conditions: elevated temperatures and pressures in benzene, toluene, tetrahydrofuran, or 1,2-dichloroethane as a solvent.
Pauson-Khand Reaction
Reaction Mechanism
1. Formation of an alkyne-dicobalt intermediate. 2. Loss of CO and alkene coordination to the 16 electron complex. 3. Alkene insertion followed by CO insertion. 4. Final reductive elimination delivers the cyclopentenone and regenerates the catalyst.
Experimental Procedure
To a flame dried round bottom flask at 23 °C equipped with a magnetic stir bar was added the alkyne (0.94 mmol, 1.0 eq). Fully degassed mesitylene (20 mL, 3 cycles of the freeze-pump-thaw method) was then added under an argon atmosphere. Co2(CO)8 (1.1 eq, weighed out in a glove box and placed in a plastic micro-centrifuge tube) was added to the reaction flask in a single portion. After stirring for 2 h, the reaction system was degassed with CO and heated to 160 °C using a pre-heated oil bath. The solution was stirred at this temperature for an additional 24 h. Upon completion, the reaction mixture was directly loaded onto a column (silica gel) and eluted with hexanes to remove mesitylene. Subsequent flash column chromatography gave the cyclic enone (50% yield).
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