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Coupling of sterically hindered trisubstituted olefins and benzocyclobutenones by C-C activation: total synthesis and structural revision of cycloinumakiol.

ABSTRACT: The first total syntheses of the proposed structure of cycloinumakiol (1) and its C5 epimer (18) are achieved in a concise and efficient fashion. Starting from the known 3-hydroxybenzocyclobutenone, 1 and 18 are obtained in nine and five steps with overall yields of 15% and 33%, respectively. The key for the success of this approach is the use of a catalytic C-C activation strategy for constructing the tetracyclic core of 1 through carboacylation of a sterically hindered trisubstituted olefin with benzocyclobutenone. In addition, the structure of the natural cycloinumakiol was reassigned to 19-hydroxytotarol (7) through X-ray diffraction analysis. This work demonstrates the potential of C-C activation for streamlining complex natural product synthesis.

SUBMITTER: Xu T

PROVIDER: S-EPMC4214140 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Coupling of sterically hindered trisubstituted olefins and benzocyclobutenones by C-C activation: total synthesis and structural revision of cycloinumakiol.

Xu Tao T Dong Guangbin G

Angewandte Chemie (International ed. in English) 20140819 40

The first total syntheses of the proposed structure of cycloinumakiol (1) and its C5 epimer (18) are achieved in a concise and efficient fashion. Starting from the known 3-hydroxybenzocyclobutenone, 1 and 18 are obtained in nine and five steps with overall yields of 15% and 33%, respectively. The key for the success of this approach is the use of a catalytic C-C activation strategy for constructing the tetracyclic core of 1 through carboacylation of a sterically hindered trisubstituted olefin wi ...[more]

PMID: 25138969

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