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Synthesis 2009(6): 1041-1048  
DOI: 10.1055/s-0028-1087984
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© Georg Thieme Verlag Stuttgart ˙ New York

Meta- and Para-Difunctionalization of Arenes via an Ortho-Magnesiation and a Subsequent Sulfoxide-Magnesium Exchange

Laurin Melzig, Christian B. Rauhut, Paul Knochel*
Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, Haus F, 81377 München, Germany
Fax: +49(89)218077680; e-Mail: paul.knochel@cup.uni-muenchen.de;
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Publication History

Received 29 September 2008
Publication Date:
02 March 2009 (online)

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Abstract

Highly functionalized 1,2,4-trisubstituted arenes can be prepared on large scale by a two-step sequence, triggered by an aryl sulfoxide­ group. In the first step, the sulfoxide moiety acts as a metalation directing group, allowing a smooth magnesiation with tmpMgCl˙LiCl. After a quenching reaction with an electrophile, the resulting sulfoxide is converted with i-PrMgCl˙LiCl into a second magnesium reagent (sulfoxide-magnesium exchange), which can be trapped with various electrophiles. The highly chemoselective tmpMgCl˙LiCl and i-PrMgCl˙LiCl are compatible with a broad range of functional groups (FG = F, Cl, CF3, CN, CO2 t-Bu, alkynyl).

Key words

metalation - ortho-magnesiation - sulfoxide-magnesium exchange - polyfunctional Grignard reagents

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