Palladium-Catalyzed Nucleophilic Addition and Substitution

The Wacker Reaction and Related Oxidations. An important industrial process based on Pd-alkene complexes is the Wacker reaction, a catalytic method for conversion of ethene to acetaldehyde. The first step is addition of water to the Pd(n)-activated alkene. The addition intermediate undergoes the characteristic elimination of Pd(0) and H+ to generate the enol of acetaldehyde. 

The reaction is run with only a catalytic amount of Pd. The co-reagents CuCl2 and 02 serve to reoxidize the Pd(0) to Pd(II). The net reaction consumes only alkene and oxygen. 

The relative reactivity profile of the simple alkenes toward Wacker oxidation is quite shallow and in the order ethene propene 1-butene Zi-2-butene Z-2-butene.102 This order indicates that steric factors outweigh electronic effects and is consistent with substantial nucleophilic character in the rate-determining step. (Compare with oxymercuration see Part A, Section 5.8.) The addition step is believed to occur by an internal ligand transfer through a four-center mechanism, leading to syn addition. 

The stereochemistry, however, is sensitive to the concentration of chloride ion, shifting to anti when chloride is present.103 

The Wacker reaction can also be applied to laboratory-scale syntheses.104 When the Wacker conditions are applied to terminal alkenes, methyl ketones are formed.105 

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