Ligand-guided remote desaturation converts simple aliphatic acids into gamma-lactones
Researchers report a ligand-enabled palladium-catalyzed method that activates distal γ-C(sp3)–H bonds in unbiased aliphatic carboxylic acids (from fatty and cyclic feedstocks) using designed O-allyl amido ester ligands, directly furnishing distal desaturated γ-lactones and double-desaturated γ-spirolactones. Mechanistic data support Pd(II)-mediated γ-C(sp3)–H activation, followed by dehydrogenation and intramolecular cyclization; the approach enables rapid assembly of biologically relevant scaffolds (e.g., muricatacin) from simple acids, offering a streamlined route to complex natural products and pharmaceuticals.




