Total syntheses of (+)- and (-)-didemnenones A and B. Antiselectivity in the intramolecular carbomercuration reaction

Article abstract of DOI:10.1021/ja00165a038

Total synthese of the title compounds were achieved in 11 steps and ca. 7% overall yield from the chiral synthon 10. In conjuction with previous chiroptical stuudies, this work allowed the assignment of absolute configurations to didemnenones A-D (1-4, respectively), a series of cytotoxic cyclopentanoid marine natural products isolated from the tunicates Trididemnum cf. cyanophorum and Didemnum voeltzkowi. Thus, 1 and 2 were shown to have the 2R,6R configuration; 3 was shown to have the 2S,6S, and 4, most plausibly, the 2S,6R configurations. Featured in the syntheses are an efficient 1,3 chirality transfer to establish the C2 configuration, one-pot mercuric chloride induced intramolecular cyclization/iodination reactions of an ε-alkynyl silyl enol ether to form a cis-6-oxabicyclo[3.3.0]oct-3-en-2-one system bearing an exocyclic C8-vinyl iodide and an installation of the C11 oxidation level and diene moiety by sequential SeO₂/t-BuOOH oxidation and Pd-mediated vinyl cross-coupling with n-Bu₃SnCHCH₂. In examining the intramolecular carbomercurations of cyclopentenone silyl enol ethers bearing β-(2-propynyloxy) side chains, an apparently exclusive and unexpected antiselectivity was revealed.