Synlett 2002(11): 1799-1802
DOI: 10.1055/s-2002-34865
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Reactivity of Aryl- and Heteroaryl-Magnesium Reagents Bearing Keto Groups

Florian Felix Kneisel, Paul Knochel*
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377 München, Germany
Fax: +49(89)21807680; e-Mail: Paul.Knochel@cup.uni-muenchen.de;
Weitere Informationen

Publikationsverlauf

Received 8 August 2002
Publikationsdatum:
21. Oktober 2002 (online)

Abstract

The reaction of iodophenyl ketones with neo-pentylmagnesium bromide in THF or THF:NMP or THF:DMAC mixtures allows the first preparation of aryl- and heteroarylmagnesium species bearing a ketone. Under appropriate conditions, these new reagents react with a range of electrophiles, leading to polyfunctional products.

    References

  • 1a Boudier A. Bromm LO. Lotz M. Knochel P. Angew. Chem. Int. Ed.  2000,  39:  4415 
  • 1b Knochel P. Millot N. Rodriguez AL. Tucker CE. Organic Reactions   Vol. 58:  Overman LE. Wiley & Sons Ltd.; New York: 2001.  p.417 
  • 2 Jensen AE. Dohle W. Sapountzis I. Lindsay DM. Vu VA. Knochel P. Synthesis  2002,  565 
  • 3a Alexakis A. Malan C. Lea L. Benhaim C. Fournioux X. Synlett  2001,  927 
  • 3b Yuan T.-M. Yeh S.-M. Hsieh Y.-T. Luh T.-Y. J. Org. Chem.  1994,  59:  8192 
  • 3c Tuckmantel W. Oshima K. Nozaki H. Chem. Ber.  1986,  119:  1581 
  • 3d Tamura M. Kochi JK. Bull. Chem. Soc. Jpn.  1971,  44:  3063 
  • 4 Villieras J. Rambaud M. Synthesis  1982,  11:  924 
  • 5 Takahashi Y. Ito T. Sakai S. Ishii Y. Chem. Comm.  1970,  1065 
  • 6 Allen DW. Hutley BG. Mellor MTJ. J. Chem. Soc., Perkin Trans. 2  1972,  63 
  • 7a Negishi E. Acc. Chem. Res.  1982,  15:  340 
  • 7b Negishi E. Valente LF. Kobayashi M. J. Am. Chem. Soc.  1980,  102:  3298 
  • 7c Kobayashi M. Negishi E. J. Org. Chem.  1980,  45:  5223 
  • 7d Tamaru Y. Ochiai H. Nakamura T. Yoshida Z. Tetrahedron Lett.  1986,  27:  955 
  • 7e Klement I. Rottländer M. Tucker CE. Majid TN. Knochel P. Venegas P. Cahiez G. Tetrahedron  1996,  52:  7201 
  • 8 Knochel P. Yeh MCP. Berk SC. Talbert J. J. Org. Chem.  1988,  53:  2390 
  • Typical procedures:
  • 9a

    Preparation of 2-[2-(2,2-dimethylpropionyl)-benzyl]-acrylic acid ethyl ester (3d) using Method A (entry 4 of Table [1] ):
    A dry and argon flushed 50 mL Schlenk tube, equipped with a septum and a magnetic stirrer was charged with 1-(2-iodophenyl)-2,2-dimethylpropan-1-one(1b) (288 mg, 1.0 mmol) in dry THF (0.5 mL). The solution was cooled to -50 °C and NpMgBr (3.6 mL, 0.6 M in THF, 2.25 mmol) was slowly added. The pale yellow mixture was stirred for 3 d at -40 °C until GC-analysis of a reaction aliquot indicated complete iodine-magnesium exchange. Then CuCN·2LiCl [8] (2.3 mL, 1.0 M in THF, 2.3 mmol) was slowly added. After 15 min, ethyl (2-bromomethyl)acrylate [4] (500 mg, 0.35 mL, 2.5 mmol) was added and the reaction mixture was allowed to warm up to room temperature overnight. After quenching with sat. aq NH4Cl (5 mL), the aqueous phase was extracted with dichloromethane (3 × 30 mL) and the combined organic phases were dried with sat. aq. NaCl and concentrated in vacuo. The residue was purified by flash chromatography (95:5 pentane/ether) yielding 2-[2-(2,2-dimethylpropionyl)-benzyl]acrylic acid ethyl ester (3d) as a clear oil (215 mg, 81%).

  • 9b

    Preparation of 2,2-dimethyl-1-(2-phenylthio-phenyl)-propan-1-one (3f) using Method B (entry 6 of Table [1] ):
    A dry and argon flushed 10 mL Schlenk flask, equipped with a septum and a magnetic stirrer, was charged with 1-(2-iodophenyl)-2,2-dimethylpropan-1-one (1b) (145 mg, 0.5 mmol) in dry THF (0.5 mL). The solution was cooled to
    -45 °C and NpMgBr (1.0 mL, 0.6 M in THF, 0.6 mmol), then NMP (0.5 mL) were slowly added. The yellow mixture was rapidly stirred and warmed up to -25 °C within 15 min, with formation of a sticky, brownish precipitate. At this temperature, GC-analysis of a reaction aliquot indicated complete iodine-magnesium exchange. Diphenyl disulphide (220 mg, 1.0 mmol) was added. The reaction mixture was stirred for 8 h and slowly warmed up to room temperature. GC-analysis indicated complete conversion. After quenching with sat. aq NH4Cl (3 mL), the aqueous phase was extracted with dichloromethane (3 × 20 mL) and the combined organic phases were dried with sat. aq. NaCl and concentrated in vacuo. The residue was purified by flash chromatography (95:5 pentane/ether), yielding 2,2-dimethyl-1-(2-phenylthiophenyl)-propan-1-one (3f) as a clear oil (99 mg, 74%).

  • 9c

    Preparation of 1-(5-trimethylstannylthiophen-2-yl)-butan-1-one (13) using Method B (entry 8 of Table [1] ):
    A dry and argon flushed 50 mL Schlenk tube, equipped with a septum and a magnetic stirrer, was charged with 2-butyryl-5-iodothiophene (9) (280 mg, 1.0 mmol) in dry THF (5 mL) and DMAC (1.0 mL). The reaction mixture was cooled to
    -90 °C and NpMgBr (2.0 mL, 0.6 M in THF, 1.2 mmol) was slowly added. The mixture was rapidly stirred for 1 h at -78 °C with formation of a white precipitate. Chlorotrimethylstannane (2.0 mL, 1.0 M in THF, 2.0 mmol) was slowly added and the reaction mixture was allowed to warm up to room temperature over 12 h. The reaction mixture was quenched by the addition of sat. aq. NH4Cl (5 mL). The aqueous phase was extracted with dichloromethane (3 × 30 mL) and the combined organic phases were dried with sat. aq NaCl and concentrated in vacuo. The residue was purified by flash chromatography (95:5 pentane/ethyl acetate), yielding 1-(5-trimethylstannyl-thiophen-2-yl)-butan-1-one (13) as a clear liquid (190 mg, 60%).