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Asymmetric Total Synthesis of (−)‐Dehydrocostus Lactone by Domino Metathesis
Author(s) -
Kaden Felix,
Nowotni Susanne,
Höfner Franziska,
Lorenz Melanie,
Barthel André,
Jäger Anne,
Hennersdorf Felix,
Weigand Jan J.,
Metz Peter
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100681
Subject(s) - chemistry , metathesis , stereocenter , enantioselective synthesis , enantiopure drug , domino , total synthesis , lactone , aldol reaction , stereoselectivity , stereochemistry , hydroboration , combinatorial chemistry , organic chemistry , catalysis , polymerization , polymer
An efficient total synthesis of the sesquiterpenoid (−)‐dehydrocostus lactone is reported. Our earlier approach by a domino enediyne metathesis was extended by a domino dienyne metathesis strategy to give access to suitably functionalized hydroazulene cores. Highly stereoselective asymmetric anti aldol reactions provided the enantiopure substrates for this key step of our synthesis. Multiple hydroboration/oxidation of the resulting hydroazulenes set up three out of four stereogenic centers in a single step. First, oxidation to give a diketo‐γ‐lactone enabled an enantioselective formal synthesis of the target guaianolide. Subsequently, the final steps of this approach were improved by using a double carbonyl olefination at the stage of a masked γ‐butyrolactone, which completed the synthesis in a much more efficient way.