Wacker oxidations palladium® bromide

While such a process had initially been observed as an undesired side-reaction in transformations where copper salts were employed as re-oxidants [13], Chemler demonstrated that various aminohalogenation reactions proceed in THF or acetonitrile in the presence of potassium carbonate as base [14]. These reactions employ palladium trifluoroacetate or palladium dibromide as catalyst source and require a moderate excess of the copper oxidant (3-4 equiv) giving moderate to excellent yields. However, they usually suffer from rather low selectivity, either in the initial aminopalladation or via subsequent rearrangement pathways to provide mixtures of pyrrolidines and piperazines (Scheme 4.2, Eq. (4.3)). A stoichiometric control reaction in the presence of palladium bromide led only to the Wacker cydization together with an alkene isomerization product, suggesting that the presence of copper(II) salts is crucial for the overall process. The exact role of the copper(II) salts has not yet been darified and palladium intermediates of different oxidation states may be involved in the final stage of carbon-halogen bond formation. 

In another example, in the presence of a high concentration of bromide aniones, the typical Wacker oxidation can again be suppressed in favor of a palladium(ll)-catalyzed 1,2-dibromination reaction. The development of such a reaction had been widely neglected, probably due to the fact that 1,2-dibromides are usually obtained via direct bromination of alkenes. However, the use of palladium(II) catalysts 157 and 158 with a chiral 2,2 -Bis(diphenylphosphino)-l,l -binaphthyl (BINAP) ligand offers an attractive approach to prepare compounds 159 in enantiomerically enriched form from 154 (Scheme 16.43) [109]. 

The metal-catalysed autoxidation of alkenes to produce ketones (Wacker reaction) is promoted by the presence of quaternary ammonium salts [14]. For example, using copper(II) chloride and palladium(II) chloride in benzene in the presence of cetyltrimethylammonium bromide, 1-decene is converted into 2-decanone (73%), 1,7-octadiene into 2,7-octadione (77%) and vinylcyclohexane into cyclo-hexylethanone (22%). Benzyltriethylammonium chloride and tetra-n-butylammo-nium hydrogen sulphate are ineffective catalysts. It has been suggested that the process is not micellar, although the catalysts have the characteristics of those which produce micelles. The Wacker reaction is also catalysed by rhodium and ruthenium salts in the presence of a quaternary ammonium salt. Generally, however, the yields are lower than those obtained using the palladium catalyst and, frequently, several oxidation products are obtained from each reaction [15]. 

Tri- and tetra-substituted dihydropyranones and furanones have also been synthesized by a Wacker/Mizoroki-Heck domino process (Scheme 8.72). Gouvemeur and cowoikers [151] very recently prepared these kinds of compounds using different palladium sources, copper acetate as redox mediator, oxygen as oxidant and lithium bromide as additive. The coupling of two electron-poor substrates, ethyl acrylate and -hydroxy alkynones 294, led to the desired compounds 295a-e in moderate yields. 

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