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. 2014 Sep 26;53(40):10733-6.
doi: 10.1002/anie.201404802. Epub 2014 Aug 19.

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

Tao Xu  1 , Guangbin Dong
Affiliations

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

Tao Xu et al. Angew Chem Int Ed Engl. .

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.

Keywords: CC activation; Rh catalysis; cycloinumakiol; structure elucidation; total synthesis.

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Figures

Figure 1
Figure 1
Representative Natural Products from Podocarpaceae.
Figure 2
Figure 2
Carboacylation with other substrates containing tri-substituted olefins. [a] 5 mol % [Rh(CO)2Cl]2, 40 mol % P(C6F5)3, in THF at 130 °C for 36 h.
Figure 3
Figure 3
Structure Elucidation of the Natural Cycloinumakiol.
Scheme 1
Scheme 1
Synthetic Strategy Design.
Scheme 2
Scheme 2
Chemo and Site-selective Arene Functionalization.
Scheme 3
Scheme 3
Synthetic Sequence.
None
See this image and copyright information in PMC

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