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

Laurin Melzig; Christian B. Rauhut; Paul Knochel

doi:10.1055/s-0028-1087984

PSP

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;

Abstract

All articles of this category

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

Full Text

References

1a Kleemann A. Engel J. Kutscher B. Reichert D. Pharmaceutical Substances Georg Thieme Verlag; Stuttgart: 2001.

1b Valeur B. Molecular Fluorescence Wiley-VCH; Weinheim: 2002.

1c Hartung CG. Snieckus V. In Modern Arene Chemistry Astruc D. Wiley-VCH; Weinheim: 2002. p.330

1d Schlosser M. Organometallics in Synthesis: A Manual Schlosser M. Wiley; Chichester: 2002. p.1

1e Knochel P. Handbook of Functionalized Organometallics Knochel P. Wiley-VCH; Weinheim: 2005.

2a Eaton PE. Lee CH. Xiong Y. J. Am. Chem. Soc. 1989, 111: 8016

2b Clososki GC. Rohbogner CJ. Knochel P. Angew. Chem. Int. Ed. 2007, 46: 7681

3a Rieke RD. Science 1989, 246: 1260

3b Rieke RD. Hanson MV. Tetrahedron 1997, 53: 1925

3c Lee J. Velarde-Ortiz R. Guijarro A. Wurst JR. Rieke RD. J. Org. Chem. 2000, 65: 5428

3d Krasovskiy A. Malakhov V. Gavryushin A. Knochel P. Angew. Chem. Int. Ed. 2006, 45: 6040

3e Piller FM. Appukkuttan P. Gavryushin A. Helm M. Knochel P. Angew. Chem. Int. Ed. 2008, 47: 6802

4a Knochel P. Dohle W. Gommermann N. Kneisel FF. Kopp F. Korn T. Sapountzis I. Vu V.-V. Angew. Chem. Int. Ed. 2003, 42: 4302

4b Krasovskiy A. Knochel P. Angew. Chem. Int. Ed. 2004, 43: 3333

4c Ren H. Krasovskiy A. Knochel P. Org. Lett. 2004, 6: 4215

4d Ren H. Krasovskiy A. Knochel P. Chem. Commun. 2005, 543

4e Kopp F. Knochel P. Org. Lett. 2007, 9: 1639

4f Kopp F. Wunderlich S. Knochel P. Chem. Commun. 2007, 2075

5a Oae S. Kawai T. Furukawa N. Tetrahedron Lett. 1984, 25: 69

5b Kawai T. Furukawa N. Tetrahedron Lett. 1984, 25: 2549

5c Furukawa N. Shibutani T. Fujihara H. Tetrahedron Lett. 1989, 30: 7091

5d Shibutani T. Fujihara H. Furukawa N. Tetrahedron Lett. 1991, 32: 2943

5e Uenishi J. Yamamoto A. Takeda T. Wakabayashi S. Oae S. Heteroat. Chem. 1992, 3: 73

6a Hoffmann RW. Hölzer B. Knopff O. Harms K. Angew. Chem. Int. Ed. 2000, 39: 3072

6b Satoh T. Akita K. Chem. Pharm. Bull. 2003, 51: 181

6c Sugiyama S. Shimizu H. Satoh T. Tetrahedron Lett. 2006, 47: 8771

6d Ferber B. Kagan HB. Adv. Synth. Catal. 2007, 349: 493

6e Brebion F. Goddard J.-P. Fensterbank L. Malacria M. Org. Lett. 2008, 10: 1917

7a Guillaneux D. Kagan HB. J. Org. Chem. 1995, 60: 2502

7b Kloetzing RJ. Knochel P. Tetrahedron: Asymmetry 2006, 17: 116

7c Thaler T. Geittner F. Knochel P. Synlett 2007, 2655

8 Quesnelle C. Iihama T. Aubert T. Terrier H. Snieckus V. Tetrahedron Lett. 1992, 33: 2625

9a Krasovskiy A. Krasovskaya V. Knochel P. Angew. Chem. Int. Ed. 2006, 45: 2958

9b Lin W. Baron O. Knochel P. Org. Lett. 2006, 8: 5673

9c Rohbogner CJ. Clososki GC. Knochel P. Angew. Chem. Int. Ed. 2007, 46: 7681

10 Rauhut CB. Melzig L. Knochel P. Org. Lett. 2008, 10: 3891

11a Negishi E. Valente LF. Kobayashi M. J. Am. Chem. Soc. 1980, 102: 3298

11b Negishi E. Acc. Chem. Res. 1982, 15: 340

11c Negishi E. Quian M. Zeng F. Anastasia L. Babinski D. Org. Lett. 2003, 5: 1597

11d Zeng X. Quian M. Hu Q. Negishi E. Angew. Chem. Int. Ed. 2004, 43: 2259

12a Villieras J. Rambaud M. Synthesis 1982, 924

12b Villieras J. Rambaud M. Org. Synth. 1988, 66: 220

13 Peyronneau M. Roques N. Mazieres S. Le Roux C. Synlett 2003, 631

14a Brewster RQ. Schroeder W. Org. Synth. 1943, 19: 79

14b Jendralla H. Chen L. Synthesis 1990, 827