Making ambrox asymmetrically

Chemists have made (–)-ambrox—a compound that’s popular in perfumes—starting from (3 E ,7 E )-homofarnesol. A team led by the Max Planck Institute for Kohlenforschung’s Benjamin List developed the route, which achieves asymmetric cyclization of a polyene using a scant amount of a chiral imidodiphosphorimidate catalyst in a fluorinated alcohol solvent ( Nature 2024, DOI: 10.1038/s41586-024-07757-7 ). This type of asymmetric polyene cyclization has long eluded synthetic chemists, who have been looking for alternatives to gathering (–)-ambrox from ambergris, a waxy substance vomited by sperm whales. List calls the reaction “a provocation by nature to us chemists” because nature easily makes the desired isomer, but synthetic chemists struggle to achieve the same selectivity. Previous attempts have used stoichiometric amounts of chiral acids and were not as successful as the new route. David Sarlah , a synthetic chemist at Rice University who was not involved in the work, calls the synthesis