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Synthesis of Aryl- and Alkyl-Containing 3-Methylene-5-hydroxy Esters via a Barbier Allylation Reaction |
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| Authors: | Albert T H Bartholomäus Dávid Roman Walid K Al-Jammal Prof Dr Ivan Vilotijević Prof Dr Christine Beemelmanns |
| Institution: | 1. Chemical Biology of Microbe-Host Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Beutenberstrasse 11a, 07745 Jena, Germany
These authors contributed equally to this work.;2. Chemical Biology of Microbe-Host Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Beutenberstrasse 11a, 07745 Jena, Germany Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Campus E8, 66123 Saarbrücken, Germany These authors contributed equally to this work.;3. Institute for Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena, Humboldtstrasse 10, 07743 Jena, Germany;4. Chemical Biology of Microbe-Host Interactions, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Beutenberstrasse 11a, 07745 Jena, Germany |
| Abstract: | The formation of C−C bonds via the allylation of carbonyl compounds has been widely applied in total syntheses. Amongst the many possible strategies, the Barbier-type allylation in aqueous media has received only moderate attention over the last decades despite its mild reaction conditions. In this study, we investigated the indium (In0) and zinc (Zn0) mediated Barbier allylation reaction to efficiently synthesize base-labile 3-methylene-5-hydroxy containing building blocks for natural product total synthesis. As model study we selected the allylation of lipidic undecanal with ethyl 3-(bromomethyl)but-3-enoate in the presence of either Zn0 or In0 and investigated the effects of additives on yields and selectivities. We then applied the optimized reaction conditions to sterically demanding allyl bromides and functionalized aromatic aldehydes yielding eleven new homoallylic alcohols, one of which was further transformed via oxidation and reduction sequences. |
| Keywords: | synthetic methods allyl bromide Barbier reaction C−C bond formation natural products |