Total Synthesis of the Marine Diterpenoids Caucanolide E and F by Alkyne <i>gem</i>‐Hydrogenation: Rigorous Reassignment of Two Almost Indistinguishable Diastereomers

Abstract As the spectra of the diastereomeric marine seco ‐cembranoids caucanolide E and F are almost identical, the isolation team had not been able to firmly assign their stereostructure. The puzzle has now been solved by a synthetic approach predicated on biogenetic considerations, which suggested that both natural products are 10 S configured but differ in the configuration of their C8 stereocenter. Under this proviso, they can be distinguished by comparison with synthetic samples that are deliberately 8 S ,10 S and 8 S ,10 R configured: only one natural product can match sign and magnitude of the [α] D of one of these reference compounds; this particular caucanolide must be the 8 S ,10 S isomer. Both reference compounds needed for this benchmarking exercise were accessible from a single precursor via ruthenium catalyzed gem ‐hydrogenation of an enyne to furnish an alkoxyfuran in the first place, followed by hydrolysis; this key transformation leverages the electrophilic character of the pianostool ruthenium carbene intermediates passed through. The recorded data showed that the assignment proposed in the literature is incorrect and needs to be reversed; this conclusion was independently confirmed by a combined NMR/DFT approach using a CP3 probability analysis.