“On-seawater” accelerated aquacatalysis by edible fatty acids: harnessing the remarkable salting-out effect

Medium-chain fatty acids (MCFAs) are widely recognized for their metabolic and therapeutic benefits, yet their potential as catalysts for chemical reactions remains elusive. Herein, we report the development of a sustainable aquacatalytic system utilizing MCFAs, particularly caprylic acid, for Brønsted acid-catalyzed carbonyl allylation under “on-water” conditions. This approach leveraged the salting-out effect induced by NaCl to suppress micelle formation and enhance interfacial catalysis. By employing unrefined seawater and edible sea salt as cost-effective additives, the system enables the efficient allylation of aldehydes without a catalyst and the caprylic acid-catalyzed allylation of ketones. This reaction is scalable to gram-scale synthesis using a chromatography-free purification process, offering a practical and sustainable route for producing active pharmaceutical ingredients. Furthermore, the mild reaction conditions and compatibility with aqueous media facilitated successful on-DNA allylation, underscoring the potential of DNA-encoded library applications in drug discovery. This study highlights the unprecedented utility of MCFAs as renewable catalysts and establishes a versatile and environmentally friendly platform for aquatic organic transformations.