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DOI: 10.1055/s-0028-1087984
Meta- and Para-Difunctionalization of Arenes via an Ortho-Magnesiation and a Subsequent Sulfoxide-Magnesium Exchange
Publication History
Publication Date:
02 March 2009 (online)

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
- 1a
Kleemann A.Engel J.Kutscher B.Reichert D. Pharmaceutical Substances Georg Thieme Verlag; Stuttgart: 2001.MissingFormLabel - 1b
Valeur B. Molecular Fluorescence Wiley-VCH; Weinheim: 2002.MissingFormLabel - 1c
Hartung CG.Snieckus V. In Modern Arene ChemistryAstruc D. Wiley-VCH; Weinheim: 2002. p.330MissingFormLabel - 1d
Schlosser M. Organometallics in Synthesis: A ManualSchlosser M. Wiley; Chichester: 2002. p.1MissingFormLabel - 1e
Knochel P. Handbook of Functionalized OrganometallicsKnochel P. Wiley-VCH; Weinheim: 2005.MissingFormLabel - 2a
Eaton PE.Lee CH.Xiong Y. J. Am. Chem. Soc. 1989, 111: 8016MissingFormLabel - 2b
Clososki GC.Rohbogner CJ.Knochel P. Angew. Chem. Int. Ed. 2007, 46: 7681MissingFormLabel - 3a
Rieke RD. Science 1989, 246: 1260MissingFormLabel - 3b
Rieke RD.Hanson MV. Tetrahedron 1997, 53: 1925MissingFormLabel - 3c
Lee J.Velarde-Ortiz R.Guijarro A.Wurst JR.Rieke RD. J. Org. Chem. 2000, 65: 5428MissingFormLabel - 3d
Krasovskiy A.Malakhov V.Gavryushin A.Knochel P. Angew. Chem. Int. Ed. 2006, 45: 6040MissingFormLabel - 3e
Piller FM.Appukkuttan P.Gavryushin A.Helm M.Knochel P. Angew. Chem. Int. Ed. 2008, 47: 6802MissingFormLabel - 4a
Knochel P.Dohle W.Gommermann N.Kneisel FF.Kopp F.Korn T.Sapountzis I.Vu V.-V. Angew. Chem. Int. Ed. 2003, 42: 4302MissingFormLabel - 4b
Krasovskiy A.Knochel P. Angew. Chem. Int. Ed. 2004, 43: 3333MissingFormLabel - 4c
Ren H.Krasovskiy A.Knochel P. Org. Lett. 2004, 6: 4215MissingFormLabel - 4d
Ren H.Krasovskiy A.Knochel P. Chem. Commun. 2005, 543MissingFormLabel - 4e
Kopp F.Knochel P. Org. Lett. 2007, 9: 1639MissingFormLabel - 4f
Kopp F.Wunderlich S.Knochel P. Chem. Commun. 2007, 2075MissingFormLabel - 5a
Oae S.Kawai T.Furukawa N. Tetrahedron Lett. 1984, 25: 69MissingFormLabel - 5b
Kawai T.Furukawa N. Tetrahedron Lett. 1984, 25: 2549MissingFormLabel - 5c
Furukawa N.Shibutani T.Fujihara H. Tetrahedron Lett. 1989, 30: 7091MissingFormLabel - 5d
Shibutani T.Fujihara H.Furukawa N. Tetrahedron Lett. 1991, 32: 2943MissingFormLabel - 5e
Uenishi J.Yamamoto A.Takeda T.Wakabayashi S.Oae S. Heteroat. Chem. 1992, 3: 73MissingFormLabel - 6a
Hoffmann RW.Hölzer B.Knopff O.Harms K. Angew. Chem. Int. Ed. 2000, 39: 3072MissingFormLabel - 6b
Satoh T.Akita K. Chem. Pharm. Bull. 2003, 51: 181MissingFormLabel - 6c
Sugiyama S.Shimizu H.Satoh T. Tetrahedron Lett. 2006, 47: 8771MissingFormLabel - 6d
Ferber B.Kagan HB. Adv. Synth. Catal. 2007, 349: 493MissingFormLabel - 6e
Brebion F.Goddard J.-P.Fensterbank L.Malacria M. Org. Lett. 2008, 10: 1917MissingFormLabel - 7a
Guillaneux D.Kagan HB. J. Org. Chem. 1995, 60: 2502MissingFormLabel - 7b
Kloetzing RJ.Knochel P. Tetrahedron: Asymmetry 2006, 17: 116MissingFormLabel - 7c
Thaler T.Geittner F.Knochel P. Synlett 2007, 2655MissingFormLabel - 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: 2958MissingFormLabel - 9b
Lin W.Baron O.Knochel P. Org. Lett. 2006, 8: 5673MissingFormLabel - 9c
Rohbogner CJ.Clososki GC.Knochel P. Angew. Chem. Int. Ed. 2007, 46: 7681MissingFormLabel - 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: 3298MissingFormLabel - 11b
Negishi E. Acc. Chem. Res. 1982, 15: 340MissingFormLabel - 11c
Negishi E.Quian M.Zeng F.Anastasia L.Babinski D. Org. Lett. 2003, 5: 1597MissingFormLabel - 11d
Zeng X.Quian M.Hu Q.Negishi E. Angew. Chem. Int. Ed. 2004, 43: 2259MissingFormLabel - 12a
Villieras J.Rambaud M. Synthesis 1982, 924MissingFormLabel - 12b
Villieras J.Rambaud M. Org. Synth. 1988, 66: 220MissingFormLabel - 13
Peyronneau M.Roques N.Mazieres S.Le Roux C. Synlett 2003, 631 - 14a
Brewster RQ.Schroeder W. Org. Synth. 1943, 19: 79MissingFormLabel - 14b
Jendralla H.Chen L. Synthesis 1990, 827MissingFormLabel