Total Synthesis of Crotophorbolone. Issue 48 (23rd October 2015)

• Record Type: Journal Article
• Authors: Asaba, Taro; Katoh, Yuki; Urabe, Daisuke; Inoue, Masayuki
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 48(2015)
• Page Start: 14457
• Page End: 14461
• Publication Date: 2015-10-23
• Subjects: cross‐coupling -- natural products -- radical reactions -- terpenoids -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201509160
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The complex ABC‐tricyclic structure of crotophorbolone, a derivative of the tigliane diterpenoids, was assembled by coupling of simple fragments. The six‐membered C‐ring fragment, having five contiguous stereocenters, was stereoselectively constructed from ( R )‐carvone. After attachment of the five‐membered A‐ring through the π‐allyl Stille coupling reaction, the α‐alkoxy bridgehead radical reaction effected the endo ‐cyclization of the seven‐membered B‐ring by forming the sterically congested bond at C9 and C10 stereospecifically and stereoselectively, respectively. Finally, the functional groups on the 5/7/6‐membered ring system were manipulated by rhodium‐catalyzed C2 olefin isomerization, C13 decarboxylative oxidation, and C4 hydroxylation, thus completing the first total synthesis of crotophorbolone. Abstract : The complex ABC‐tricyclic structure of crotophorbolone was assembled from ( R )‐carvone. After coupling of the six‐membered C‐ring and the five‐membered A‐ring through the π‐allyl Stille coupling reaction, the α‐alkoxy bridgehead radical reaction effected the endo ‐cyclization of the seven‐membered B‐ring by forming the sterically congested bond between the A‐ and C‐rings. Functional‐group manipulations resulted in the first total synthesis.