Supporting Information
Copper(I) Only Catalyzed Reactions of (E)-2,3Difluoro-3-stannylacrylic Ester with Acid Chlorides and Mechanistic Studies of the “Copper Effect” in Stille Coupling Reactions
Yi Wang and Donald J. Burton* Department of Chemistry, University of Iowa, Iowa City, Iowa 52242
[email protected] Supporting Information Available: Experimental procedure for the synthesis of 3-8 and their characterization by 1H, 19F, 13C NMR and HRMS; Copies of 1H, 19F and 13C NMR of compounds 2-8; Copy of the 19F NMR of the reaction mixture of 1 with CuI; Copies of the 19F NMR of 9, 10 and mixture of the two tin esters. This material is available free of charge via the Internet at http://pubs.acs.org.
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Table of Contents General Procedures…………………………………………………………………………….….3 Synthesis of Ethyl (2Z)-2,3-difluoro-4-(4-nitrophenyl)-4-oxobut-2-enoate (3)…………….…….3 Synthesis of Ethyl (2Z)-2,3-difluoro-4-(4-methoxyphenyl)-4-oxobut-2-enoate (4)………...….…4 Synthesis of Ethyl (2Z)-2,3-difluoro-5,5-dimethyl-4-oxohex-2-enoate (5)…………………….....4 Synthesis of Ethyl (2Z)-2,3-difluoro-4-oxotridec-2-enoate (6)……………………………...……4 Synthesis of Ethyl (2Z)-2,3-difluoro-4-(4-iodophenyl)-4-oxobut-2-enoate (7)……….………….5 Preparation of Ethyl (2E)-2,3-difluoro-3-iodoacrylate (8)………………………………………..5 Preparation of zinc reagent and copper reagents......................................................................…...6 1
H, 19F, 13C NMR spectra of 2 ………………………………………………..…………….…..7-9
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H, 19F, 13C NMR spectra of 3………………………………………………………….…….10-12
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H, 19F, 13C NMR spectra of 4………………………………………………………………..13-15
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H, 19F, 13C NMR spectra of 5…………………………………………………….………….16-18
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H, 19F, 13C NMR spectra of 6………………………………………………………..………19-21
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H, 19F, 13C NMR spectra of 7………………………………………………………………..22-24
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H, 19F, 13C NMR spectra of 8………………………………………………………………..25-27
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F NMR spectrum of reaction mixture of equilibrium………………………………………….28
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F
NMR
spectrum
of
9……………………………………………………………………….….29 19
F
NMR
spectrum
of
10……………………………………………………………….………...30 19
F NMR spectrum of mixture of the two tin esters……………………………………………...31
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General procedures. 1H, 19F and 13C NMR spectra of the final products were recorded on a 300 MHz or 400 MHz spectrometer. Chemical shifts have been reported in ppm relative to internal Me4Si and CFCl3 respectively. Unless noted otherwise, CDCl3 was used as the NMR lock solvent. Low resolution mass spectra were obtained at 70 eV in the electron impact mode, using a DB-1-column (0.25 mm ID × 15 m). High resolution mass spectra (HRMS) were obtained by the University of Iowa High Resolution Mass Spectrometry Facility. Column chromatography was carried out using silica gel (Silica Gel 60, particle size 0.063-0.200 mm, 70-230 mesh ASTM). Thin layer chromatography was carried out using 40×80 mm Polygram Sil G/UV254 plates. All melting points were obtained in 1.2 mm capillary tube and were uncorrected. All solvents were stored in brown bottles capped with rubber septa and sealed with copper wire and parafilm. N,N-Dimethylformamide (DMF) was dried at stirring overnight over CaH2, then distilled at reduced pressure. Pd(PPh3)4 was prepared by Coulson’s procedure (Coulson, D. R. Inorg. Synth. 1972, 13, 121). CuI was purified by reported procedure (Kauffman, G. D.; Fang, L. Y. Inorg. Synth. 1983, 22, 101). All other reagents were used as received. N2 was used without further purification. Ethyl (2Z)-2,3-difluoro-4-(4-nitrophenyl)-4-oxobut-2-enoate (3) To a mixture of CuI (0.02 g, 0.11 mmol), 4-nitrobenzoyl chloride (0.19 g, 1.0 mmol) in 3 mL of dry DMF was added 1 (0.42 g, 1 mmol) under N2. The mixture was stirred at room temperature for 12 h.
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F NMR showed the reaction was complete. The mixture was purified by column
chromatography (hexane/ethyl acetate = 10:1) and 0.20 g yellow oil was obtained.
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F NMR
(CDCl3) δ -123.5 (s, 1 F), -143.5 (s, 1 F) ppm; 1H NMR (CDCl3) δ 8.39 (dm, J = 9.0 Hz, 2 H),
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8.15 (dm, J = 9.0 Hz, 2 H), 4.20 (q, J = 7.1 Hz, 2 H), 1.17 (t, J = 7.1 Hz, 3 H) ppm; 13C NMR (CDCl3) δ 182.8 (dd, J = 22.6, 1.3 Hz), 159.1 (dd, J = 28.2, 7.3 Hz), 151.2, 147.8 (dd, J = 280.1, 12.3 Hz), 139.8 (dd, J = 273.1, 15.3 Hz), 138.8 (d, J = 2.4 Hz), 130.3 (d, J = 0.8 Hz), 124.3, 63.1, 13.7 ppm; HRMS calcd 285.0449 for C12H9F2NO5, found 285.0441. Ethyl (2Z)-2,3-difluoro-4-(4-methoxyphenyl)-4-oxobut-2-enoate (4) To a mixture of CuI (0.02 g, 0.11 mmol), 4-methoxybenzoyl chloride (0.20 g, 1.2 mmol) in 3 mL of dry DMF was added 1 (0.42 g, 1 mmol) under N2. The mixture was stirred at room temperature for 5 h.
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F NMR showed the reaction was complete. The mixture was purified by
column chromatography (hexane/ethyl acetate = 10:1) and 0.18 g colorless oil was obtained. 19F NMR (CDCl3) δ -120.4 (s, 1 F), -148.0 (s, 1 F) ppm; 1H NMR (CDCl3) δ 7.93 (d, J = 8.9 Hz, 2 H), 7.00 (d, J = 8.9 Hz, 2 H), 4.14 (q, J = 7.1 Hz, 2 H), 3.90 (s, 3 H), 1.08 (t, J = 7.1 Hz, 3 H) ppm; 13C NMR (CDCl3) δ 182.6 (dd, J = 21.7, 0.9 Hz), 165.2, 159.3 (dd, J = 29.2, 7.6 Hz), 149.6 (dd, J = 282.1, 11.2 Hz), 138.8 (dd, J = 265.1, 15.4 Hz), 132.0, 127.4 (d, J = 2.4 Hz), 114.5, 62.5, 55.7, 13.5 ppm; HRMS calcd 270.0704 for C13H12F2O4, found 270.0704. Ethyl (2Z)-2,3-difluoro-5,5-dimethyl-4-oxohex-2-enoate (5) To a mixture of CuI (0.02 g, 0.11 mmol), trimethylacetyl chloride (0.15 mL, 1.2 mmol) in 3 mL of dry DMF was added 1 (0.42 g, 1 mmol) under N2. The mixture was stirred at room temperature for 12 h. 19F NMR showed the reaction was complete along with reductive product. The mixture was purified by column chromatography (hexane/ethyl acetate = 10:1) and 0.13 g colorless oil was obtained. 19F NMR (CDCl3) δ -124.0 (d, J = 1.2 Hz, 1 F), -146.9 (d, J = 1.2 Hz, 1 F) ppm; 1H NMR (CDCl3) δ 4.30 (q, J = 7.1 Hz, 2 H), 1.32 (t, J = 7.2 Hz, 3 H), 1.28 (s, 9 H) ppm;
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C NMR (CDCl3) δ 199.4 (d, J = 19.7 Hz), 159.5 (dd, J = 28.4, 7.3 Hz), 150.2 (dd, J =
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285.8, 11.8 Hz), 138.7 (dd, J = 268.4, 15.5 Hz), 62.6, 44.0 (t, J = 2.3 Hz), 26.1 (d, J = 1.8 Hz), 13.9 ppm. Ethyl (2Z)-2,3-difluoro-4-oxotridec-2-enoate (6) To a mixture of CuI (0.02 g, 0.11 mmol), decanoyl chloride (0.21 mL, 1 mmol) in 3 mL dry of DMF was added 1 (0.42 g, 1 mmol) under N2. The mixture was stirred at room temperature for 12 h. 19F NMR showed the reaction was complete along with reductive product. The mixture was purified by column chromatography (hexane/ethyl acetate = 20:1) and 0.24 g colorless oil was obtained. 19F NMR (CDCl3) δ -136.5 (t, J = 1.8 Hz, 1 F), -139.6 (s, 1 F) ppm; 1H NMR (CDCl3) δ 4.34 (q, J = 7.1 Hz, 2 H), 2.71 (td, J = 7.3, 2.2 Hz, 2 H), 1.68-1.63 (m, 2 H), 1.38-1.27 (m, 15 H), 0.88 (t, J = 6.7 Hz, 3 H) ppm; 13C NMR (CDCl3) δ 193.6 (dd, J = 26.0, 2.5 Hz), 159.3 (dd, J = 28.9, 6.3 Hz), 147.8 (dd, J = 277.6, 12.3 Hz), 140.7 (dd, J = 274.2, 16.0 Hz), 62.9, 31.9, 29.4, 29.35, 29.28, 29.0, 28.9, 23.0, 22.7, 14.1, 13.8 ppm; HRMS calcd 163.0207 for C15H24F2O3C9H19, found 163.0203. Ethyl (2Z)-2,3-difluoro-4-(4-iodophenyl)-4-oxobut-2-enoate (7) To a mixture of CuI (0.02 g, 0.11 mmol), 4-iodobenzoyl chloride (0.27 g, 1 mmol) in 3 mL dry of DMF was added 1 (0.42 g, 1 mmol) under N2. The mixture was stirred at room temperature for 5 h. 19F NMR showed the reaction was complete along with reductive product. The mixture was purified by column chromatography (hexane/ethyl acetate = 15:1) and 0.22 g colorless oil was obtained. 19F NMR (CDCl3) δ -122.1 (s, 1 F), -145.8 (s, 1 F) ppm; 1H NMR (CDCl3) δ 7.91 (d, J = 8.6 Hz, 2 H), 7.65 (d, J = 8.6 Hz, 2 H), 4.16 (q, J = 7.1 Hz, 2 H), 1.12 (t, J = 7.1 Hz, 3 H) ppm; 13C NMR (CDCl3) δ 183.6 (dd, J = 22.2, 1.5 Hz), 159.1 (dd, J = 28.7, 7.4 Hz), 148.6 (dd, J = 281.3, 11.8 Hz), 139.3 (dd, J = 268.9, 15.3 Hz), 138.6, 133.7 (d, J = 2.6 Hz), 130.5 (d, J = 0.7
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Hz), 128.3 (d, J = 3.5 Hz), 62.7, 13.6 ppm; HRMS calcd 365.9565 for C12H9F2IO3, found 365.9558. Ethyl (2E)-2,3-difluoro-3-iodoacrylate (8): Iodine (0.24 g, 0.94 mmol) was added to a solution of 1 (0.34 g, 0.8 mmol) in 5 mL of ether. After 8 h at room temperature, Co(OAc)2.4H2O (0.50 g, 2 mmol) was added. The mixture was stirred for 10 min. Ether (25 mL) was added and the organic phase was washed with aqueous sodium sulfite, brine, dried over anhydrous Na2SO4, concentrated by rotary evaporation. The crude product was purified by column chromatography (hexane/ethyl acetate = 10:1) and 0.18 g colorless oil was obtained. 19F NMR (CDCl3) δ -77.7 (d, J = 11.3 Hz, 1 F), -130.1 (d, J = 11.3 Hz, 1 F) ppm; 1H NMR (CDCl3) δ 4.34 (q, J = 7.1 Hz, 2 H), 1.37 (t, J = 7.1 Hz, 3 H) ppm; 13C NMR (CDCl3) δ 159.4 (dd, J = 27.3, 7.1 Hz), 140.3 (dd, J = 267.2, 14.4 Hz), 106.0 (dd, J = 333.1, 25.2 Hz), 62.5, 14.0 ppm; HRMS calcd 261.9302 for C5H5F2IO2, found 261.9316. Preparation of zinc reagent and copper reagents: In a flask, 8 (0.26 g, 1 mmol) was added into a slurry of acid washed zinc dust (0.07 g, 1.1 mmol) in 3 mL of dry DMF at room temperature. After 6 h, 19F NMR showed two sets of peaks: -114 (s), -145 (s) and -116 (s), -144 (s), which were identified as bis and monomer respectively. The 19
F NMR yield was 93%. Then copper iodide (0.23 g, 1.2 mmol) was added to the mixture. After
1 h, 19F NMR showed -100 (s) and -146 (s). The 19F NMR yield was 74%.
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