CH Bond Arylation in the Synthesis of Aryltetralin Lignans: A Short Total Synthesis of Podophyllotoxin

A short total synthesis of podophyllotoxin, the prototypical aryltetralin lignan natural product, is reported. Key to the success of this synthetic pathway is a Pd‐catalyzed C(sp3)–H arylation reaction enabled by a conformational biasing element to promote C–C reductive elimination over an alternati...

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Published inAngewandte Chemie Vol. 126; no. 12; pp. 3179 - 3183
Main Authors Ting, Chi P., Maimone, Thomas J.
Format Journal Article
LanguageEnglish
German
Published Weinheim WILEY-VCH Verlag 17.03.2014
WILEY‐VCH Verlag
Subjects
Bonding
C-H-Aktivierung
Carbon-carbon composites
Lignan
Lignans
Natural products
Naturstoffe
Palladium
Pathways
Strategy
Synthesis
Totalsynthesen
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Summary:A short total synthesis of podophyllotoxin, the prototypical aryltetralin lignan natural product, is reported. Key to the success of this synthetic pathway is a Pd‐catalyzed C(sp3)–H arylation reaction enabled by a conformational biasing element to promote C–C reductive elimination over an alternative CN bond‐forming pathway. This strategy allows for access to the natural product in five steps from commercially available bromopiperonal, and sheds light on subtle conformational effects governing reductive elimination pathways from high‐valent palladium centers. Neue Taktik auf dem Prüfstand: In einer kurzen Synthese von Podophyllotoxin mit einer palladiumkatalysierten Arylierung als Schlüsselschritt bestimmen kleinste konformative Effekte den Verlauf der reduktiven Eliminierung vom hochvalenten Palladiumzentrum. Diese Route zu Aryltetralinlignan‐Derivaten könnte für die Wirkstoff‐Forschung interessant sein.
Bibliography:ArticleID:ANGE201311112
We thank UC-Berkeley for generous start-up funding and the NSF for a predoctoral fellowship to C.P.T. (DGE-1106400). We thank Dr. Antonio DiPasquale and Dr. Chris Canlas for X-ray crystallographic and NMR spectroscopic assistance, respectively.
ark:/67375/WNG-JZH2G9XT-W
NSF - No. DGE-1106400
istex:C0353FD0D0F7D81F9C4121DAB2BB3D0388192365
We thank UC‐Berkeley for generous start‐up funding and the NSF for a predoctoral fellowship to C.P.T. (DGE‐1106400). We thank Dr. Antonio DiPasquale and Dr. Chris Canlas for X‐ray crystallographic and NMR spectroscopic assistance, respectively.
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SourceType-Scholarly Journals-1
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ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201311112