Synlett 2016; 27(03): 471-476
DOI: 10.1055/s-0035-1560812
letter
© Georg Thieme Verlag Stuttgart · New York

Iron-Catalyzed Cross-Coupling of Benzylic Manganese Chlorides with Aryl and Heteroaryl Halides

Andreas D. Benischke
a   Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, 81377 Munich, Germany   Email: Paul.Knochel@cup.uni-muenchen.de
,
Antoine J. A. Breuillac
b   Institut de Recherche de Chimie Paris, CNRS, Chimie ParisTech, 11 Rue Pierre et Marie Curie, 75005 Paris, France
,
Alban Moyeux
b   Institut de Recherche de Chimie Paris, CNRS, Chimie ParisTech, 11 Rue Pierre et Marie Curie, 75005 Paris, France
c   Université Paris 13, Sorbonne Paris Cité, 74 Rue Marcel Cachin, 93017 Bobigny, France
,
Gérard Cahiez
b   Institut de Recherche de Chimie Paris, CNRS, Chimie ParisTech, 11 Rue Pierre et Marie Curie, 75005 Paris, France
,
Paul Knochel*
a   Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, 81377 Munich, Germany   Email: Paul.Knochel@cup.uni-muenchen.de
› Author Affiliations
Further Information

Publication History

Received: 30 July 2015

Accepted after revision: 02 October 2015

Publication Date:
22 October 2015 (online)


Abstract

The use of FeCl2 (10 mol%) allows a convenient iron-catalyzed cross-coupling reaction of benzylic manganese(II) chlorides with various aryl and heteroaryl chlorides, bromides and iodides leading to polyfunctionalized diaryl- and arylheteroarylmethane derivatives.

Supporting Information

 
  • References and Notes

  • 6 For the preparation of benzylic indium reagents, see: Chen Y.-H, Sun M, Knochel P. Angew. Chem. 2009; 121: 2270
  • 7 For the preparation of benzylic aluminum reagents, see: Blümke TD, Groll K, Karaghiosoff K, Knochel P. Org. Lett. 2011; 13: 6440
  • 9 Peng Z, Knochel P. Org. Lett. 2011; 13: 3198
  • 10 Quinio P, Benischke AD, Moyeux A, Cahiez G, Knochel P. Synlett 2015; 26: 514
  • 14 Reducing the catalyst loading to 5.0 mol% led in some cases to decreased reaction yields.
  • 15 Hansch C, Leo R, Taft RW. Chem. Rev. 1991; 91: 165
  • 16 General Procedure for the Preparation of Benzylic Manganese(II) Chlorides (1a–f): A dry and argon-flushed Schlenk tube, equipped with a magnetic stirring bar and a rubber septum, was charged with magnesium (0.18 g, 7.20 mmol, 2.40 equiv), followed by freshly distilled THF (3.0 mL) or MTBE (1.9 mL) and a solution of MnCl2·2LiCl (3.8 mL, 3.80 mmol, 1.25 equiv, 1.0 M in THF). The mixture was cooled to 0 °C, the benzyl chloride (3.0 mmol, 1.0 equiv) was added at once and maintained at 0 °C until complete conversion of the starting material was observed. The completion of the metalation was monitored by GC analysis of hydrolyzed and iodolyzed aliquots. When the oxidative insertion was complete, the solution of benzylic manganese(II) chloride was separated from the resulting salts via a syringe equipped with a filter and transferred to another pre-dried and argon-flushed Schlenk tube, before being titrated with iodine. General Procedure for the Iron-Catalyzed Cross-Coupling of Benzylic Manganese(II) Chlorides 1a–f with Electrophiles: A dry and argon-flushed Schlenk flask, equipped with a magnetic stirring bar and a rubber septum, was charged with FeCl2 (10 mol%, 99.5% pure), the corresponding electrophile (1.0 equiv) and freshly distilled THF. Thereupon, the benzylic manganese(II) chloride solution (1.05–1.10 equiv) was added dropwise at 0 °C. After the addition was complete, the reaction mixture was stirred for a given time at the prior adjusted temperature and then allowed to warm to r.t. The reaction completion was monitored by GC analysis of the quenched aliquots. A saturated aqueous solution of NH4Cl was added and the aqueous layer was extracted three times with Et2O or EtOAc (3 × 50 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the crude products by flash column chromatography afforded the desired products. Ethyl 5-(3-Fluorobenzyl)furan-2-carboxylate (5): To a solution of FeCl2 (12.7 mg, 0.10 mmol, 0.10 equiv) and ethyl 5-bromofuran-2-carboxylate (3b; 220 mg, 1.0 mmol, 1.0 equiv) in THF (1.0 mL) the benzylic manganese(II) chloride solution (1b, 4.0 mL, 0.26 M, 1.05mmol, 1.05 equiv) was added dropwise at 0 °C. Then, the reaction mixture was stirred for 2 h at 0 °C and allowed to warm to r.t. A saturated aqueous solution of NH4Cl was added and the aqueous layer was extracted three times with Et2O (3 × 50 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Finally the crude product was purified by flash column chromatography (SiO2, i-hexane–Et2O, 99:1, Rf 0.11) leading to the desired product 5 (174 mg, 0.70 mmol, 70%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.20–7.24 (m, 1 H), 7.05 (d, J = 3.4 Hz, 1 H), 6.98 (dd, J = 8.0, 1.3 Hz, 1 H), 6.90 (m, 2 H), 6.06 (dt, J = 3.4, 0.8 Hz, 1 H), 4.31 (q, J = 7.1 Hz, 2 H), 3.99 (s, 2 H), 1.32 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 163.0 (d, 1 J C–F = 245 Hz), 158.9, 158.6, 144.1, 139.3 (d, 3 J C–F = 7.0 Hz), 130.2 (d, 3 J C–F = 8.0 Hz), 124.6 (d, 4 J C–F = 3.0 Hz), 119.0, 115.9 (d, 2 J C–F = 22 Hz), 113.9 (d, 2 J C–F = 20 Hz), 109.2, 60.9, 34.5, 14.5. 19F NMR (376 MHz, CDCl3): δ = –113.0. IR (ATR): 3128, 2983, 2361, 1713, 1616, 1591, 1519, 1488, 1448, 1383, 1368, 1297, 1251, 1205, 1173, 1126, 1075, 1016, 970, 944, 912, 866, 789, 760, 731, 681 cm–1. MS (EI, 70 eV): m/z (%) = 249 (10), 248 (67), 220 (10), 219 (23), 203 (42), 176 (17), 175 (100), 147 (16), 146 (40), 127 (10). HRMS (EI, 70 eV): m/z calcd for C14H13FO3: 248.0849; found: 248.0845. Ethyl 2-[3-(Trifluoromethyl)benzyl]nicotinate (6): To a solution of FeCl2 (12.7 mg, 0.10 mmol) and ethyl 2-chloronicotinate (3c; 186 mg, 1.0 mmol, 1.0 equiv) in THF (1.0 mL) the benzylic manganese(II) chloride solution (1c, 3.3 mL, 0.34 M, 1.1 mmol, 1.1 equiv) was added dropwise at 0 °C. The reaction mixture was stirred for 2 h at 0 °C and allowed to warm to r.t. A saturated aqueous solution of NH4Cl was added and the aqueous layer was extracted three times with Et2O (3 × 50 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the crude product by flash column chromatography (SiO2, i-hexane–Et2O, 8:2, Rf 0.17) afforded the desired product 6 (200 mg, 0.65 mmol, 65%) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ = 8.62 (dd, J = 4.8, 1.8 Hz, 1 H), 8.13 (dd, J = 7.9, 1.8 Hz, 1 H), 7.49 (s, 1 H), 7.40–7.17 (m, 4 H), 4.56 (s, 2 H), 4.26 (q, J = 7.1 Hz, 2 H), 1.26 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 166.4, 160.4, 152.2, 140.7, 138.9, 132.6 (q, 4 J C–F = 2.4 Hz), 130.6 (q, 2 J C–F = 32 Hz), 128.7, 126.2, 125.9 (q, 3 J C–F = 3.8 Hz), 124.4 (q, 1 J C–F = 271 Hz), 123.1 (q, 3 J C–F = 3.9 Hz), 121.7, 61.7, 42.2, 14.2. 19F NMR (376 MHz, CDCl3): δ = –62.5. IR (ATR): 3049, 2985, 2363, 1720, 1583, 1570, 1448, 1438, 1368, 1328, 1300, 1259, 1190, 1161, 1118, 1094, 1073, 1057, 1017, 917, 862, 822, 793, 782, 747, 734, 701, 676, 660 cm–1. MS (EI, 70 eV): m/z (%) = 310 (18), 309 (83), 308 (92), 290 (12), 281 (54), 264 (52), 263 (59), 262 (13), 237 (16), 236 (100), 235 (59), 234 (65), 216 (18), 167 (31), 139 (11). HRMS (EI, 70 eV): m/z calcd for C16H14F3NO: 309.0977; found: 309.0966.