Directed regioselective ortho,ortho′-magnesiations of aromatics and heterocycles using sBu2Mg in toluene |
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Authors: | Andreas Hess Jan P Prohaska Sabrina B Doerrich Florian Trauner Ferdinand H Lutter Sbastien Lemaire Simon Wagschal Konstantin Karaghiosoff Paul Knochel |
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Institution: | Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377 München Germany.; Janssen Pharmaceutica, Chemical Process Research & Development, Turnhoutseweg 30, B-2340 Beerse Belgium ; Janssen Pharmaceutica, Chemical Process Research & Development, Hochstrasse 201, 8200 Schaffhausen Switzerland |
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Abstract: | Aryl azoles are ubiquitous as bioactive compounds and their regioselective functionalization is of utmost synthetic importance. Here, we report the development of a toluene-soluble dialkylmagnesium base sBu2Mg. This new reagent allows mild and regioselective ortho-magnesiations of various N-arylated pyrazoles and 1,2,3-triazoles as well as arenes bearing oxazoline, phosphorodiamidate or amide directing groups. The resulting diarylmagnesium reagents were further functionalized either by Pd-catalyzed arylation or by trapping reactions with a broad range of electrophiles (aldehydes, ketones, allylic halides, acyl chlorides, Weinreb amides, aryl halides, hydroxylamine benzoates, terminal alkynes). Furthermore, several double ortho,ortho′-magnesiations were realized in the case of aryl oxazolines, N-aryl pyrazoles as well as 2-aryl-2H-1,2,3-triazoles by simply repeating the magnesiation/electrophile trapping sequence allowing the preparation of valuable 1,2,3-functionalized arenes.A toluene solution of sBu2Mg allowed a regioselective ortho-magnesiation of aromatic and heterocyclic systems. A second ortho,ortho′-functionalization was achieved in the case of aryl oxazolines, N-aryl pyrazoles as well as N-aryl triazoles. |
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