Formal Nucleophilic Silyl Substitution of Aryl Halides with Silyllithium Reagents via Halogenophilic Attack of Silyl Nucleophiles

Published as part of the Cluster Silicon in Synthesis and Catalysis

Abstract

A new reaction has been developed for the formal nucleo­philic silyl substitution of aryl halides with silyllithium or silylpotassium reagents. Dimethylphenylsilyllithium reacted with various aryl halides to form the corresponding arylsilanes in moderate to good yields with concomitant formation of the disilanes under the optimized reaction conditions. Mechanistic studies indicated that this silyl substitution reaction progresses through polar halogenophilic attack of silyl nucleo­philes.

Key words

halogenophilic attack - silyl nucleophiles - silyl substitution - organohalides - organosilanes

• References and Notes

• 1 New address: Department of Chemistry, Graduate School of Science, Kyushu University, Motooka 477, Nishi-ku, Fukuoka 819-0395, Japan.
• 2a Showell GA. Mills JS. Drug Discovery Today 2003; 8: 551
• 2b You Y. An C.-G. Kim J.-J. Park SY. J. Org. Chem. 2007; 72: 6241
• 2c Liu X.-M. He C. Huang J. Xu J. Chem. Mater. 2005; 17: 434
• 2d Denmark SE. Ober MH. Aldrichimica Acta 2003; 36: 75

For reviews see:
• 3a Brook MA. In Silicon in Organic, Organometallic, and Polymer Chemistry . Wiley-Interscience; New York: 2000. 1st ed. 115
• 3b Hiyama T. In Organometallics in Synthesis Third Manual . Schlosser M. Wiley; Hoboken: 2013: 373
• 4a Murakami K. Hirano K. Yorimitsu H. Oshima K. Angew. Chem. Int. Ed. 2008; 47: 5833
• 4b Murakami K. Yorimitsu H. Oshima K. J. Org. Chem. 2009; 74: 1415
• 4c Morita E. Murakami K. Iwasaki M. Hirano K. Yorimitsu H. Koichiro O. Bull. Chem. Soc. Jpn. 2009; 82: 1012 ; and references cited therein

For silylation of aryl halides with disilanes, see:
• 5a Matsumoto H. Nagashima S. Yoshihiro K. Nagai Y. J. Organomet. Chem. 1975; 85: C1
• 5b Azarian D. Dua SS. Eaborn C. Walton DR. M. J. Organomet. Chem. 1976; 117: C55
• 5c Matsumoto H. Yoshihiro K. Nagashima S. Watanabe H. Nagai Y. J. Organomet. Chem. 1977; 128: 409
• 5d Matsumoto H. Shono K. Nagai Y. J. Organomet. Chem. 1981; 208: 145
• 5e Eaborn C. Griffiths RW. Pidcock A. J. Organomet. Chem. 1982; 225: 331
• 5f Matsumoto H. Kasahara M. Matsubara I. Takahashi M. Arai T. Hasegawa M. Nakano T. Nagai Y. J. Organomet. Chem. 1983; 250: 99
• 5g Hatanaka Y. Hiyama T. Tetrahedron Lett. 1987; 28: 4715
• 5h Babin P. Bennetau B. Theurig M. Dunoguès J. J. Organomet. Chem. 1993; 446: 135
• 5i Shirakawa E. Kurahashi T. Yoshida H. Hiyama T. Chem. Commun. 2000; 1895
• 5j Gooßen LJ. Ferwanah A.-RS. Synlett 2000; 1801
• 5k Denmark SE. Kallemeyn JM. Org. Lett. 2003; 5: 3483
• 5l Iwasawa T. Komano T. Tajima A. Tokunaga M. Obora Y. Fujihara T. Tsuji Y. Organometallics 2006; 25: 4665
• 5m McNeill E. Barder TE. Buchwald SL. Org. Lett. 2007; 9: 3785
• 5n Minami Y. Shimizu K. Tsuruoka C. Komiyama T. Hiyama T. Chem. Lett. 2014; 43: 201
• 5o Yamamoto Y. Matsubara H. Murakami K. Yorimitsu H. Osuka A. Chem. Asian J. 2015; 10: 219
• 5p For silylation of aryl halides with silylborane, see: Guo H. Chen X. Zhao C. He W. Chem. Commun. 2015; 17410
• 6a Däschlein C. Bauer SO. Strohmann C. Eur. J. Inorg. Chem. 2011; 1454
• 6b Strohmann C. Bindl M. Fraaß VC. Hörnig J. Angew. Chem. Int. Ed. 2004; 43: 1011

For related reactions involved in the halogenophilic attack process, see:
• 7a Mori M. Kaneta N. Isono N. Shibasaki M. Tetrahedron Lett. 1991; 32: 6139
• 7b Nagashima Y. Takita R. Yoshida K. Hirano K. Uchiyama M. J. Am. Chem. Soc. 2013; 135: 18730
• 7c Cheung MS. Marder TB. Lin Z. Organometallics 2011; 30: 3018
• 8a Yamamoto E. Izumi K. Horita Y. Ito H. J. Am. Chem. Soc. 2012; 134: 19997
• 8b Yamamoto E. Ukigai S. Ito H. Chem. Sci. 2015; 6: 2943
• 8c Uematsu R. Yamamoto E. Maeda S. Ito H. Taketsugu T. J. Am. Chem. Soc. 2015; 137: 4090
• 9a Kawachi A. Minamimoto T. Tamao K. Chem. Lett. 2001; 30: 1216
• 9b Hata T. Kitagawa H. Masai H. Kurahashi T. Shimizu M. Hiyama T. Angew. Chem. Int. Ed. 2001; 40: 790
• 9c O’Brien JM. Hoveyda AH. J. Am. Chem. Soc. 2011; 133: 7712
• 9d Ito H. Horita Y. Yamamoto E. Chem. Commun. 2012; 8006
• 9e Oshima K. Ohmura T. Suginome M. Chem. Commun. 2012; 8571
• 9f Kleeberg C. Borner C. Eur. J. Inorg. Chem. 2013; 2799
• 9g Shintani R. Fujie R. Takeda M. Nozaki K. Angew. Chem. Int. Ed. 2014; 53: 6546
• 9h Nagao K. Ohmiya H. Sawamura M. Org. Lett. 2015; 17: 1304
• 9i Wu H. Garcia JM. Haeffner F. Radomkit S. Zhugralin AR. Hoveyda AH. J. Am. Chem. Soc. 2015; 137: 10585

For reviews, see:
• 9j Oestreich M. Hartmann E. Mewald M. Chem. Rev. 2013; 402
• 9k Cuenca AB. Shishido R. Ito H. Fernández E. Chem. Soc. Rev. 2017; 46: 415
• 10 Abeywickrema AN. Beckwith AL. J. J. Chem. Soc., Chem. Commun. 1986; 464
• 11 Typical Procedure for Silyl Substitution Reaction with Silyllithium Reagent A vial with a screw cap and a silicon-coated rubber septum was connected to a vacuum/nitrogen manifold through a needle, and it was evacuated and refilled with nitrogen three times. Dimethylphenylsilyllithium (0.4 M in THF, 2.5 mL, 2.0 equiv) was added to the vial under nitrogen atmosphere. 1-Bromo-3,5-dimethylbenzene (93.5 mg, 0.51 mmol) was added to the vial, then stirred at 30 °C. After 1 h, the reaction mixture was analyzed by GC to check completeness of the reaction. When the reaction was complete, H₂O was added and the mixture was extracted three times with Et₂O. The organic layer was washed with water and the combined organic layer was then dried over MgSO₄ followed by filtration and evaporation. The crude product was purified by silica-gel column chromatography with hexane eluent, then further purified by gel permeation chromatography to give 3da in 63% isolated yield (76.5 mg, 0.318 mmol). ¹H NMR (392 MHz, CDCl₃): δ = 0.53 (s, 6 H), 2.30 (s, 6 H), 7.01 (s, 1 H), 7.13 (s, 2 H), 7.30–7.38 (m, 3 H), 7.49–7.55 (m, 2 H). ¹³C NMR (99 MHz, CDCl₃): δ = –2.3 (CH₃), 21.4 (C), 127.7 (CH), 129.0 (CH), 130.9 (CH), 131.9 (CH), 134.2 (CH), 137.1 (C), 137.9 (C), 138.5 (C). HRMS (EI): m/z [M]⁺ calcd for C₁₆H₂₀Si: 240.13343; found: 240.13281.