Catalyst-controlled site-selective methylene C–H lactonization of dicarboxylic acids.

Catalyst-controlled site-selective activation of b- and g-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 g- and d-lactones via site-selective b- or g-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. [ABSTRACT FROM AUTHOR]