Iron-Catalyzed C(sp²)–C(sp³) Cross-Coupling Reactions of Di(hetero)arylmanganese Reagents and Primary and Secondary Alkyl Halides

Abstract

An iron-catalyzed cross-coupling between di(hetero)arylmanganese reagents and primary and secondary alkyl halides is reported. No rearrangement of secondary alkyl halides to unbranched products was observed in these C–C bond-forming reactions.

Key words

iron - catalysis - cross-coupling - manganese - alkyl halides

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• 12 Typical Procedure for the Iron-Catalyzed Cross-Coupling of Di(hetero)arylmanganese Reagents with Alkyl Halides A dry and argon-flushed 20 mL Schlenk tube, equipped with a stirring bar and a septum, was charged with anhydrous FeCl₂ (25 mg, 0.20 mmol, 20 mol%). The alkyl halide (1 mmol, 1.0 equiv) in THF (1 mL) was added, and the mixture was cooled to –20 °C. The di(hetero)arylmanganese reagent (0.7 mmol, 0.7 equiv) was added dropwise, and the mixture was allowed to warm to r.t. overnight. A sat. aq solution of NH₄Cl (5 mL) and EtOAc (5 mL) were added, the phases were separated, and the aqueous phase was extracted with EtOAc (3 × 20 mL). The combined organic phases were washed with brine, dried over Na₂SO₄, and the solvents were evaporated. The residue was subjected to column chromatography purification (SiO₂; i-hexane/EtOAc) yielding the corresponding title compound. 1-(3-Isopropylcyclohexyl)-4-methoxybenzene (3b) Following the typical procedure, 1d (252 mg, 1.0 mmol, 1.0 equiv, in 1 mL THF) reacts with di(p-anisyl)manganese (2a, 0.7 mmol, 0.7 equiv) at –20 °C. The solution was allowed to warm to r.t., was stirred for 16 h, and was worked up as usual. The crude product was purified by column chromatography on silica using i-hexane/EtOAc (100:2) as an eluent to afford 3b as a colorless oil (51%, 119 mg, 0.51 mmol, dr = 83:17). ¹H NMR (400 MHz, CDCl₃): δ = 7.19–7.12 (m, 2 H), 6.90–6.83 (m, 2 H), 3.80 (s, 3 H), 2.48 (tt, J = 11.7, 3.4 Hz, 1 H), 1.95–1.81 (m, 3 H), 1.76 (dtt, J = 11.6, 3.4, 1.8 Hz, 1 H), 1.54–1.33 (m, 3 H), 1.33–1.21 (m, 2 H), 1.12 (dt, J = 12.8, 11.8 Hz, 1 H), 0.90 (dd, J = 6.8, 3.7 Hz, 6 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 157.8, 140.5, 127.8, 113.8, 55.4, 44.6, 44.0, 38.4, 34.7, 33.2, 29.5, 27.0, 20.0, 19.9 ppm. FTIR (ATR): 2954, 2922, 2852, 1512, 1462, 1444, 1244, 1176, 1038, 824, 806 cm^–1. MS (EI, 70 eV): m/z (%) = 232 (55), 189 (78), 147 (100), 134 (68), 121 (77). HRMS (EI, 70 eV): m/z calcd for [C₁₆H₂₄O]: 232.1827; found: 232.1821. tert-Butyl{3-[2-fluoro-(1,1′-biphenyl)-4-yl]butoxy}dimethylsilane (3p) Following the typical procedure, tert-butyl(3-iodobutoxy)dimethylsilane (1j, 314 mg, 1.0 mmol, 1.0 equiv, in 1 mL THF) reacts with 2f (0.7 mmol, 0.7 equiv) at –20 °C. The solution was allowed to warm to r.t., was stirred for 16 h, and was worked up as usual. The crude product was purified by column chromatography on silica using i-hexane/EtOAc (100:4) as an eluent to afford 3p as colorless oil (80%, 288 mg, 0.80 mmol). ¹H NMR (600 MHz, CDCl₃): δ = 7.57–7.54 (m, 2 H), 7.46–7.42 (m, 2 H), 7.38–7.34 (m, 2 H), 7.05 (dd, J = 7.8, 1.7 Hz, 1 H), 7.00 (dd, J = 12.0, 1.7 Hz, 1 H), 3.59 (dt, J = 10.2, 6.2 Hz, 1 H), 3.52 (dt, J = 10.2, 6.7 Hz, 1 H), 2.95 (h, J = 7.1 Hz, 1 H), 1.82 (dt, J = 7.1, 6.3 Hz, 2 H), 1.29 (d, J = 7.0 Hz, 3 H), 0.90 (s, 9 H), 0.03 (d, J = 1.5 Hz, 6 H) ppm. ¹³C NMR (150 MHz, CDCl₃): δ =159.9 (d, J = 247.4 Hz), 149.3 (d, J = 6.7 Hz), 136.1, 130.6, 129.1, 128.5, 127.5, 126.5 (d, J = 13.4 Hz), 123.3, 114.7 (d, J = 22.6 Hz), 61.1, 41.1, 35.9, 26.1, 22.2, 18.4, –5.2 ppm. FTIR (ATR): 2956, 2928, 2856, 1484, 1472, 1462, 1418, 1254, 1098, 1076, 1010, 980, 900, 870, 832, 810, 774, 766, 724, 696 cm^–1. MS (EI, 70 eV): m/z (%) = 302 (22), 301 (100), 207 (22), 179 (77), 165 (35). HRMS (EI, 70 eV): m/z calcd for [C₂₁H₂₈FOSi⁺]: 343.1888; found: 343.1872 [M⁺ – CH₃].