Transition-Metal-Free Synthesis of Polysubstituted Cyclopropane Derivatives from N-Tosylhydrazones and their Cytotoxic Activities

We describe a general method for metal‐free cyclopropanation of different electron‐deficient olefins with N‐tosylhydrazones as a source of diazo compounds. This method works with N‐tosylhydrazones derived from acetophenones or benzophenones. This reaction is carried out in the presence of LiOtBu as...

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Bibliographic Details
Published in:Asian journal of organic chemistry 2015-10, Vol.4 (10), p.1144-1154
Main Authors: Lawson, Marie, Bignon, Jérôme, Brion, Jean-Daniel, Hamze, Abdallah, Alami, Mouad
Format: Article
Language:English
Subjects:
alkenes
cyclopropanation
cyclopropanes
isocombretastatine A4
N-tosylhydrazones
Organic chemistry
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Summary:We describe a general method for metal‐free cyclopropanation of different electron‐deficient olefins with N‐tosylhydrazones as a source of diazo compounds. This method works with N‐tosylhydrazones derived from acetophenones or benzophenones. This reaction is carried out in the presence of LiOtBu as a base to generate diazo species in situ. This method is compatible with various electron‐donating or electron‐withdrawing substituents and allows us to obtain a large library of functionalized tetrasubstituted cyclopropanes. Furthermore, we have used this method to synthesize isocombretastatine A4 analogues, which have submicromolar cytotoxicity against HCT‐116 cell lines. I'm all 4 it: The synthesis of various tetrasubstituted cyclopropane derivatives was accomplished with good yields by using N‐tosylhydrazones and electron‐deficient olefin partners. This protocol was further extended in a one‐pot manner allowing the use of two different activated olefins. Cyclopropane derivative 4 y was found to have good antiproliferative activity against human colon tumor (HCT116) cells, with a GI50 value in the submicromolar range.
ISSN:2193-5807
2193-5815
DOI:10.1002/ajoc.201500289