Gram-Scale Synthesis of Flavoring Ketones in One Pot via Alkylation-Decarboxylation on Benzylic Carbon Using a...

The gram-scale synthesis of important flavoring ketones via alkylation of acetoacetic ester on substituted benzylic carbon followed by decarboxylation using a heterogeneous, commercial, solid acid catalyst is reported. The flavoring ketones were synthesized by the alkylation of acetoacetic ester, which proceeds through an S_N1-type reaction to generate an alkylated (β-ketoester) intermediate at the benzylic carbon, which is decarboxylated under the acidic condition. Among the solid acid catalysts used, Amberlyst-15 was found to be the best catalyst under the solvent-free condition. This protocol was successfully employed for the synthesis of various flavoring ketones such as raspberry ketone and ginger ketone with almost complete conversion and 82% isolated yield. The para-donating groups on the benzylic alcohol showed a high rate of reaction. The catalyst was easily recovered and reused 6 times without losing its activity and selectivity. Moreover, this reaction was demonstrated at a 10 g scale, which implicated the potential applicability of the protocol in the industry.