Enantioselective total synthesis of clavirolide C. Applications of Cu-catalyzed asymmetric conjugate additions and Ru-catalyzed ring-closing metathesis.
The first enantioselective total synthesis of clavirolide C, a member of the dolabellane family of diterpenes isolated from Pacific soft coral Clavularia viridis, is disclosed. The total synthesis features the application of chiral amino acid based ligands in Cu-catalyzed asymmetric conjugate addition (ACA) reactions and a relatively rare application of catalytic ring-closing metathesis to access an 11-membered ring structure. The total synthesis effort has spawned the development of a new protocol for NHC.Cu-catalyzed ACA of alkylaluminum reagents to beta-substituted cycloalkenones. The enantioselective clavirolide C synthesis requires 17 steps (longest linear sequence), affords the target molecule in 3.5% overall yield, and confirms the stereochemical assignment for the natural product.
Brown
M Kevin
MK
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Hoveyda
Amir H
AH
D000818:Animals; D037421:Anthozoa / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis*; D013237:Stereoisomerism
D004224:Diterpenes; C533148:clavirolide C; D003300:Copper
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