The Pd - tppts - HOTs (tppts = P(C6H4-m-SO3Na)3, HOTs = p-toluenesulfonic acid) catalyzed hydrocarboxylation of N-allylacetamide in an aqueous medium afforded 4-acetamidobutyric acid and 3-acetamido-2-methylpropanoic acid under mild conditions, with a high regioselectivity towards the linear isomer. During the hydrocarboxylation an acid catalyzed hydrolysis of the amide moieties of both the substrate and the products took place, as well as the formation of acetamide and propanal, presumably via a Pd-catalyzed allylic substitution reaction of N-allylacetamide. The hydrolysis reaction was suppressed by lowering the amount of Brønsted acid cocatalyst (HOTs) or by employing a weaker Brønsted acid such as propanoic acid. The allylic substitution reaction was minimized by increasing the CO pressure but unfortunately this caused a decrease in the regioselectivity. A sudden inhibition took place after ca. 70% conversion, presumably caused by one of the side products. By increasing the tppts concentration to 13.1 mmol L-1 (20 equiv per Pd) the inhibition was circumvented and a quantitative conversion of N-allylacetamide was achieved.Key words: aqueous media, olefins, palladium, hydrocarboxylation, N-allylacetamide.
Chiral Brønsted acid-catalyzed intramolecular SN2′ reaction for enantioselective construction of a quaternary stereogenic center
