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Synlett 2010(2): 304-308  
DOI: 10.1055/s-0029-1219165
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© Georg Thieme Verlag Stuttgart ˙ New York

Directed ortho- and meta-Magnesiation or Zincation of Polyfunctional Aryl Nonaflates

Gabriel Monzon, Paul Knochel*
Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandstr. 5-13, 81377 München, Germany
Fax: +49(89)218077680; e-Mail: Paul.Knochel@cup.uni-muenchen.de;
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Publication History

Received 20 October 2009
Publication Date:
22 December 2009 (online)

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Abstract

The selective metalation of aryl nonaflates was performed with TMPMgCl˙LiCl and TMPZnCl˙LiCl. Whereas the magnesiation allows formal metalation in the meta-position, zincation is well suited for an ortho-metalation. No benzyne formation was observed.

Key words

aryl nonaflates - functionalized organometallics - cross-coupling - zinc - magnesium

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Typical Procedure 1; Preparation of Ethyl 2-benzoyl-4-(nonafluorobutane-1-sulfonyloxy)benzoate (6a): In a flame-dried Schlenk flask that was previously flushed with argon, ethyl 4-(nonafluorobutane-1-sulfonyloxy)benzoate (1a; 553 mg, 1.0 mmol) dissolved in THF (1 mL) was reacted with a solution of TMPMgCl˙LiCl (2; 1.31 M in THF, 0.85 mL, 1.1 mmol) at -20 ˚C and the reaction mixture was then stirred at this temperature for 3 h. CuCN˙2LiCl (1 M in THF, 1.1 mL, 1.1 mmol) was added and stirred at
-20 ˚C for 30 min. Benzoyl chloride (183 mg, 1.3 mmol) was added dropwise at -20 ˚C and the mixture was allowed to warm slowly to 25 ˚C over 3 h. The resulting mixture was then quenched with a sat. aq NH4Cl (30 mL), extracted with Et2O (3 × 50 mL) and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. Purification by flash chromatography (pentane-Et2O, 9:1) furnished compound 6a (360 mg, 65%) as a yellowish oil. ¹H NMR (300 MHz, CDCl3): δ = 8.17 (d, J = 8.6 Hz, 1 H), 7.76-7.73 (m, 2 H), 7.60 (t, J = 7.5 Hz, 1 H), 7.51-7.43 (m, 3 H), 7.31 (s, 1 H), 4.10 (q, J = 7.1 Hz, 2 H), 1.06 (t, J = 7.1 Hz, 3 H). ¹³C (75 MHz, CDCl3): δ = 194.2, 164.4, 151.8, 144.1, 136.3, 133.7, 132.7, 129.5, 129.4, 128.8, 122.3, 120.8, 62.1, 13.6. ¹9F (282 MHz, CDCl3): δ = -80.6, -108.4, -120.7, -125.7. HRMS (ESI+): m/z calcd for C20H17F9NO6S [M + NH4]+: 570.0633; found: 570.0629. IR (ATR): 3073, 2985, 2941, 2366, 1723, 1678, 1598, 1580, 1450, 1430, 1368, 1353, 1282, 1273, 1237, 1226, 1200, 1170, 1143, 1121, 1088, 1032, 1010, 975, 883, 872, 846, 785, 768, 748, 735, 696, 686, 650, 639, 612 cm-¹.

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Typical Procedure 2; Preparation of Ethyl 2-benzoyl-4-(3-ethoxycarbonylpropyl)benzoate (8): In a flame-dried Schlenk flask that had been flushed with argon, ethyl 4-nonafluorobutane-1-sulfonyloxy)benzoate (6a; 276 mg, 0.5 mmol), Pd(dba)2 (15 mg, 5 mol%) and dppf (14 mg, 5 mol%) dissolved in THF (2 mL) were transferred via cannula to a solution of 4-ethoxy-4-oxybutylzinc bromide (0.67 M in THF, 1.1 mL, 0.75 mmol). The resulting mixture was stirred at 60 ˚C for 8 h and then quenched with a sat. aq NH4Cl (30 mL), extracted with Et2O (3 × 50 mL) and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. Purification by flash chromatography (pentane-Et2O, 55:45) furnished compound 8 (145 mg, 79%) as a yellowish oil. ¹H NMR (300 MHz, CDCl3): δ = 7.99 (d, J = 8.0 Hz, 1 H), 7.76-7.73 (m, 2 H), 7.56-7.51 (m, 1 H), 7.44-7.36 (m, 3 H), 7.19 (s, 1 H), 4.08 (dq, J = 7.3, 7.1 Hz, 4 H), 2.74 (t, J = 7.7 Hz, 2 H), 2.33 (t, J = 7.5 Hz, 2 H), 2.02-1.92 (m, 2 H), 1.23 (t, J = 7.1 Hz, 3 H), 1.02 (t, J = 7.1 Hz, 3 H). ¹³C (75 MHz, CDCl3): δ = 197.1, 173.1, 165.8, 146.7, 142.0, 137.3, 133.0, 130.4, 129.5, 129.3, 128.5, 127.6, 127.1, 61.3, 60.4, 35.0, 33.5, 26.0, 14.2, 13.6. HRMS (ESI+): m/z calcd for C22H25O5 [M + H]+: 369.1702; found: 369.1697. IR (ATR): 3631, 3449, 3332, 3061, 3028, 2981, 2938, 2907, 2872, 1716, 1673, 1603, 1598, 1580, 1512, 1476, 1449, 1415, 1390, 1368, 1314, 1277, 1206, 1176, 1138, 1085, 1048, 1024, 1002, 973, 934, 905, 852, 834, 782, 703, 688, 640, 616 cm-¹.