Iron‐Catalyzed Cross‐Coupling of 1‐Alkynylcyclopropyl Tosylates and Related Substrates

Abstract

GeneralAll reactions were carried out under Ar in flame-dried glassware. The solvents were purified by distillation over the indicated drying agents and were transferred under Ar: THF, Et2O (Mg/anthracene), CH2Cl2 (CaH2), NEt3 and pyridine were dried by an absorption solvent purification system based on molecular sieves. TMEDA was purified by distillation over CaH2 and transferred under Ar. Flash chromatography: Merck Geduran ® Si 60 (40-63 μm) or Merck Silica gel 60 (0.015-0.040 mm). NMR: Spectra were recorded on Bruker AV VIII 300, AV 400, or AV 500 spectrometers in the indicated solvents; chemical shifts (δ) are given in ppm relative to TMS, coupling constants (J) in Hz. The solvent signals were used as references (CDCl3: δC = 77.16 ppm; residual CHCl3 in CDCl3: δH = 7.26 ppm; CD2Cl2: δC = 53.84 ppm; residual CHDCl2 in CD2Cl2: δH = 5.32 ppm); proton and carbon assignments were established using NOESY, HSQC, and HMBC experiments. IR: Perkin-Elmer Spectrum One spectrometer, wavenumbers (ṽ) in cm −1 . MS: EI: Finnigan MAT 8400 (70 eV), ESI: Thermo Scientific LTQ-FT or Thermo Scientific Exactive; GC-EI: Thermo Scientific Trace GC Ultra with a Thermo Scientific ISQ spectrometer; accurate mass determinations: Finnigan MAT 95, Thermo Scientific LTQ FT, or Thermo Scientific Exactive.Unless stated otherwise, all commercially available compounds (ABCR, Acros, Aldrich) were used as received. Fe(acac)3 was purchased from Aldrich (≥99.9% metals basis). C2D5MgBr was prepared according to a literature procedure. 1 SubstratesRepresentative Procedure for the Preparation of 1-Alkynylcyclopropanols. 1-(5-((tert-Butyldimethylsilyl)oxy)pent-1-yn-1-yl)cyclopropan-1-ol (S1). MeMgCl (2.92 M in THF, 4.2 mL, 12.26 mmol) was added dropwise to a solution of 1-ethoxycyclopropanol (1.24 g, 12.14 mmol) 2 in THF (25 mL) at 0°C. The resulting suspension was stirred at 0 °C for 30 min. In a separate flask, a solution of tertbutyldimethyl(pent-4-yn-1-yloxy)silane (2.48 g, 12.50 mmol) 3 in THF (25 mL) was treated at -78 °C with nBuLi (1.6 M in hexane, 8.0 mL, 12.80 mmol). The mixture was stirred at -78 °C for 1 h and then transferred via canula into the suspension of the magnesium salt of 1-ethoxycyclopropanol. Stirring was continued at room temperature overnight. The reaction was quenched with sat. aq. NH4Cl (20 mL) and the aqueous phase extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with sat. aq. NaHCO3 (20 mL) and brine (20 mL), dried over Na2SO4, and concentrated in vacuo. The crude material was purified by flash chromatography (silica, hexane/EtOAc, 10:1) to give the title compound as a colorless liquid (2.12 g, 69%). 1 H NMR (400 MHz, CDCl3): δ = 3.67 (t, J = 6.0 Hz, 2 H), 2.29 (t, J = 7.1 Hz, 2 H), 1. 8, 129.6, 121.6, 115.1, 89.4, 77.6, 56.3, 45.6, 17.5; IR (film): ṽ = 3366 (br), 1716, 1597, 1493, 1456, 1375, 1302, 1212, 1173, 1054, 1080, 1005, 1028, 989, 970, 751, 690 Compound S5. A solution of LiAlH4 (1 M in THF, 3.3 mL, 3.25 mmol) was added dropwise to a solution of compound S4 (1.04 g, 5.21 mmol) in T...

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Regioselective Iron‐Catalysed Cross‐Coupling Reaction of Aryl Propargylic Bromides and Aryl Grignard Reagents

“…In 2016, the same group extended the reaction to 1‐alkynylcyclopropyl tosylates using aryl‐ and alkylmagnesium reagents, obtaining excellent propargyl:allene ratios, except in the case of phenyl‐ and benzyl‐magnesium reagents, in which a decrease of the regioselectivity was observed (Scheme b). Lastly, in 2018, our group described a new method using aryl and alkyl propargylic bromides together with alkyl Grignard reagents (Scheme c) .…”