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. 2021 Jun 9;143(22):8272-8277.
doi: 10.1021/jacs.1c04335. Epub 2021 May 26.

Total Synthesis of Penicibilaenes via C-C Activation-Enabled Skeleton Deconstruction and Desaturation Relay-Mediated C-H Functionalization

Yibin Xue  1 , Guangbin Dong  1
Affiliations

Total Synthesis of Penicibilaenes via C-C Activation-Enabled Skeleton Deconstruction and Desaturation Relay-Mediated C-H Functionalization

Yibin Xue et al. J Am Chem Soc. .

Abstract

Herein, we describe the first total synthesis of sesquiterpene penicibilaenes A and B through a "C-C/C-H" approach. In the "C-C" stage, the Rh-catalyzed "cut-and-sew" transformation between trisubstituted alkene and cyclobutanone has been employed to construct the unique tricyclo[6.3.1.01,5]dodecane skeleton and the all-carbon quaternary center. Critical linker and Lewis acid effects have been identified for the C-C activation process. In the "C-H" stage, a desaturation relay-based strategy involving consecutive ketone α,β-dehydrogenation and β-functionalization has been adopted to introduce the 1,3,5-triad stereocenters to the core. The synthesis of penicibilaenes A and B has been completed in 13 and 14 steps, respectively, in the longest linear sequence.

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Figures

Figure 1.
Figure 1.
Linker effect in the “cut-and-sew” reaction.
Scheme 1.
Scheme 1.
Approaches for Terpene Synthesis
Scheme 2.
Scheme 2.
Our Strategy to Synthesize Penicibilaenes
Scheme 3.
Scheme 3.
Synthesis of the “Cut-and-Sew” Precursor
Scheme 4.
Scheme 4.
Completing the Synthesis of Penicibilaenes A and B.
See this image and copyright information in PMC

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