Soluble individual metal atoms and ultrasmall clusters catalyze key synthetic steps of a natural product synthesis.

Metal individual atoms and few-atom clusters show extraordinary catalytic properties for a variety of organic reactions, however, their implementation in total synthesis of complex organic molecules is still to be determined. Here we show a 11-step linear synthesis of the natural product (±)-Licarin B, where individual Pd atoms (Pd) catalyze the direct aerobic oxidation of an alcohol to the carboxylic acid (steps 1 and 6), Cu clusters catalyze carbon-oxygen cross couplings (steps 3 and 8), Pd clusters catalyze a Sonogashira coupling (step 4) and Pt clusters catalyze a Markovnikov hydrosylilation of alkynes (step 5), as key reactions during the synthetic route. In addition, the new synthesis of Licarin B showcases an unexpected selective alkene hydrogenation with metal-free NaBH and an acid-catalyzed intermolecular carbonyl-olefin metathesis as the last step, to forge a trans-alkene group. These results, together, open new avenues in the use of metal individual atoms and clusters in organic synthesis, and confirm their exceptional catalytic activity in late stages during complex synthetic programmes.