Total Synthesis of (−)-Chromodorolide B By a Computationally-Guided Radical Addition/Cyclization/Fragmentation Cascade

The first total synthesis of a chromodorolide marine diterpenoid is described. The core of the diterpenoid is constructed by a bimolecular radical addition/cyclization/fragmentation cascade that unites two complex fragments and forms two C–C bonds and four contiguous stereogenic centers of (−)-chrom...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2018-02, Vol.140 (8), p.3091-3102
Main Authors: Tao, Daniel J, Slutskyy, Yuriy, Muuronen, Mikko, Le, Alexander, Kohler, Philipp, Overman, Larry E
Format: Article
Language:English
Subjects:
Cyclization
Diterpenes - chemical synthesis
Diterpenes - chemistry
Free Radicals - chemistry
Molecular Conformation
Quantum Theory
Stereoisomerism
Thermodynamics
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Summary:The first total synthesis of a chromodorolide marine diterpenoid is described. The core of the diterpenoid is constructed by a bimolecular radical addition/cyclization/fragmentation cascade that unites two complex fragments and forms two C–C bonds and four contiguous stereogenic centers of (−)-chromodorolide B in a single step. This coupling step is initiated by visible-light photocatalytic fragmentation of a redox-active ester, which can be accomplished in the presence of an iridium or a less-precious electron-rich dicyanobenzene photocatalyst, and employs equimolar amounts of the two addends. Computational studies guided the development of this central step of the synthesis and provide insight into the origin of the observed stereoselectivity.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.7b13799