On the Effect of the Nature of Ion Pairs as Nucleophiles in a Metal-Catalyzed Substitution Reaction

• Published in: Journal of the American Chemical Society 1998-01, Vol.120 (1), p.70-79
• Main Authors: Trost, Barry M, Bunt, Richard C
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja9726522

Two mechanistic features of the palladium-catalyzed allylic alkylation reaction of dienyl acetatesvinyl (π-allyl)palladium intermediate equilibration and palladium-catalyzed ionization of the bisallylic malonate productsaccount for the observed product ratios and nucleophile counterion effects. Three hexadienyl acetate substrates, isomeric with respect to the location of the leaving group to the dienyl system, were studied. The sodium, cesium, tetramethylammonium, and tetrahexylammonium salts of dimethyl malonate and dimethyl benzylmalonate were employed as nucleophiles, and both triphenylphosphine and tributylphosphine ligands were tested. The observed alkylation product ratios varied in a consistent way with the identity of the nucleophile counterion. The palladium-catalyzed ionization of bisallyl malonate products (i.e., the nucleophile serves as a leaving group for palladium ionization) was found to alter the observed product distribution only under certain circumstances such as extended reaction times or temperatures. Nucleophile crossover experiments demonstrated that the monoallylic products did not reionize or isomerize. These results are most consistent with a reaction mechanism where the vinyl (π-allyl)palladium(II) intermediate proximal to the leaving group is formed initially and nucleophilic addition occurs either competitive with or after complete thermodynamic equilibration of the two isomeric vinyl (π-allyl)palladium(II) intermediates. The observed product distribution primarily reflects the kinetic balance of these two processesnucleophilic addition and intermediate equilibration. Thus, the cesium and tetrahexylammonium counterions slow down the rate of nucleophilic addition relative to intermediate equilibration and allow the vinyl (π-allyl)palladium isomerization process to completely equilibrate the intermediates prior to nucleophilic addition. This effect may relate to the ability of these counterions to affect higher levels of asymmetric induction than other counterions in enantioselective alkylation reactions.