Expeditious synthesis of the fused hexacycle of puberuline C via a radical-based cyclization/translocation/cyclization process

Chemical Science
Koichi HagiwaraMasayuki Inoue

Abstract

The fused 6/7/5/6/6/6-hexacyclic ring system of puberuline C was assembled in 18 steps from 2-(ethoxycarbonyl)cyclohexanone. After the azabicyclo[3.3.1]nonane derivative was sequentially coupled with propargyl magnesium bromide, 2-iodo cyclopentenone and allyl bromide, the pentacycle was constructed in a single step via a radical-based cyclization/translocation/cyclization process. The C11-bridgehead radical generated via C-Br homolysis participated in a 7-endo cyclization, and the 1,5-hydrogen translocation of the resultant radical was followed by transannular 6-exo cyclization to simultaneously realize the construction of the two rings and the introduction of the five contiguous stereocenters. The last 6-exo cyclization was induced by the Mukaiyama aldol reaction, and the C16-ketone was stereoselectively reduced by the action of SmI2/t-BuOH, leading for the first time to the synthesis of the entire hexacycle of puberuline C.

References

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Citations

Jun 15, 2017·The Journal of Antibiotics·Kosuke MinagawaMasayuki Inoue
Nov 5, 2019·Angewandte Chemie·Daiki KamakuraMasayuki Inoue
Mar 24, 2018·Chemistry, an Asian Journal·Zhengchao LvLiang Xu
Apr 28, 2021·The Journal of Organic Chemistry·Hiroyuki MutohMasayuki Inoue
Nov 5, 2016·The Journal of Organic Chemistry·Toshiki TabuchiMasayuki Inoue
Jul 24, 2018·Journal of the American Chemical Society·Isabel KerschgensRichmond Sarpong

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Methods Mentioned

BETA
X-ray
NMR

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