biostudies-literatureChan HSSNIGMS NIH HHS1481-1487https://www.ebi.ac.uk/biostudies/studies/S-EPMC10243502biostudies-literatureUnknown376(6600)Catalyst-controlled site-selective activation of β- and γ-methylene carbon-hydrogen (C-H) bonds of free carboxylic acids is a long-standing challenge. Here we show that, with a pair of palladium catalysts assembled with quinoline-pyridone ligands of different chelate ring sizes, it is possible to perform highly site-selective monolactonization reactions with a wide range of dicarboxylic acids, generating structurally diverse and synthetically useful γ- and δ-lactones via site-selective β- or γ-methylene C-H activation. The remaining carboxyl group serves as a versatile linchpin for further synthetic applications, as demonstrated by the total synthesis of two natural products, myrotheciumone A and pedicellosine, from abundant dicarboxylic acids.Science (New York, N.Y.)Catalyst-controlled site-selective methylene C-H lactonization of dicarboxylic acids.PMC10243502R01 GM084019Chan HSSYu JQYang JMfalseCatalyst-controlled site-selective methylene C-H lactonization of dicarboxylic acids.Catalyst-controlled site-selective activation of β- and γ-methylene carbon-hydrogen (C-H) bonds of free carboxylic acids is a long-standing challenge. Here we show that, with a pair of palladium catalysts assembled with quinoline-pyridone ligands of different chelate ring sizes, it is possible to perform highly site-selective monolactonization reactions with a wide range of dicarboxylic acids, generating structurally diverse and synthetically useful γ- and δ-lactones via site-selective β- or γ-methylene C-H activation. The remaining carboxyl group serves as a versatile linchpin for further synthetic applications, as demonstrated by the total synthesis of two natural products, myrotheciumone A and pedicellosine, from abundant dicarboxylic acids.2022-01-01T00:00:00Z2022 Jun2025-04-04T03:00:07.646Z2025-02-19T04:29:12.417ZS-EPMC102435023561737310.1126/science.abq3048