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Rapid Access to Orthogonally Functionalized Naphthalenes: Application to the Total Synthesis of the Anticancer Agent Chartarin
Author(s) -
Unzner Teresa A.,
Grossmann Adriana S.,
Magauer Thomas
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201605071
Subject(s) - cyclopropane , chemistry , substituent , retrosynthetic analysis , regioselectivity , total synthesis , combinatorial chemistry , chloride , fragmentation (computing) , natural product , molecule , stereochemistry , organic chemistry , catalysis , ring (chemistry) , computer science , operating system
Abstract We report the synthesis of orthogonally functionalized naphthalenes from simple, commercially available indanones in four steps. The developed method proceeds through a two‐step process that features a thermally induced fragmentation of a cyclopropane indanone with simultaneous 1,2‐chloride shift. Migration of the chloride substituent occurs in a regioselective manner to preferentially afford the para ‐chloronaphthol substitution pattern. The obtained naphthols are versatile building blocks that can be selectively modified and used for the efficient construction of biologically active molecules. This has enabled the total synthesis of the potent anticancer natural product chartarin through a highly convergent retrosynthetic bond disconnection.