Saturday, 29 October 2011

Wacker Oxidation (Palladium-catalysed oxidation of alkenes)

The oxidation of ethene to ethanal by oxygen and a solution of a palladium(II) salt in aqueous hydrochloric acid is an important industrial process (the Wacker reaction). The palladium(II) is simultaneously reduced to the metal, but the reaction is made catalytic by addition of copper(II) chloride in the presence of air or oxygen, whereby the palladium is continuously re-oxidized to palladium(II)

Wacker Oxidation Mechanism
TheWacker reaction has found most use for the oxidation of terminal alkenes to give methyl ketones. It is believed to take place by an initial trans hydroxypalladation of the alkene to form an unstable complex that undergoes rapid beta-elimination to the enol 112. Hydropalladation then reductive elimination completes the overall process that involves transfer of hydride ion from one carbon to the other, via the palladium atom. The hydride migration is required to explain the observation that when the reaction is conducted in deuterium oxide, no deuterium is incorporated in the aldehyde produced.

Experimental Technique
Conversion of a terminal alkene to a methyl ketone is a useful transformation in organic synthesis. The reaction is typically carried out in aqueous DMF as solvent, using palladium(II) chloride as a catalyst (commonly 10 mol%) with copper(II) or copper(I) chloride and 1 atmosphere of oxygen. Copper(I) chloride is normally preferable as this avoids the formation of chlorinated ketones. Many different functional groups are tolerated and the reaction is selective for the oxidation of terminal alkenes in the presence of di- or trisubstituted alkenes. For example, only the terminal alkene is converted to a ketone on oxidation of the dienes 113 and 114
The Wacker reaction provides a method for the preparation of 1,4-dicarbonyl compounds, by formation of an enolate, allylation with an allyl halide, followed by palladium-catalysed oxidation of the terminal alkene. The product 1,4-dicarbonyl compounds can be treated with base to promote intramolecular aldol reaction
(Robinson annulation to give cyclopentenones.

Experimental Procedure
Palladium(II) acetate (0.2 mmol), benzoquinone (9 mmol), and the inorganic acid (HCl, HClO4, HBF4, H2SO4, or HNO3, 0.1 M) were dissolved in acetonitrile/water (7:1 v/v, 50 mL). The solution was deoxygenated by purging with argon for at least 30 min and stirred vigorously until the Pd(OAc)2 had dissolved. The olefin (10 mmol) was then added to the flask (by syringe), and the reaction mixture was stirred for 10 min. The products were separated from the catalyst by extraction into hexane or diethyl ether, washed with 30% aqueous sodium hydroxide, water and concentrated to a residue.
Reference:  J. Org. Chem. 55, 2924-2927 (1990)

Natural Product Synthesis
Thus, in a synthesis of pentalenene, Wacker oxidation of the 2-allyl ketone 115 gave the 1,4- diketone 116, which was converted to the cyclopentenone 117.

Regioselectivity of Wacker Reaction
Oxidation of 1,2-disubstituted alkenes occurs more slowly than that of terminal alkenes and a mixture of the two regioisomeric products is normally formed. With certain substrates, however, very high levels of regioselectivity have been obtained. For example, oxidation of the allylic ether 118 gave only the beta-alkoxy ketone 119.

The regioselectivity in oxidation reactions of unsymmetrical 1,2- disubstituted alkenes can be explained by electronic and neighbouring group effects, the latter involving co-ordination of a heteroatom or even an allylic hydrogen atom to the palladium atom in the intermediate.

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