Supporting Information

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1 Supporting Information Copper-catalyzed Borylation of Primary and Secondary Alkyl Halides with Bis(neopentyl glycolate) Diboron at Room Temperature Xin Lou,* 1,2 Zhen-Qi Zhang, 2 Jing-Hui Liu, 2 and Xiao-Yu Lu 2 1 School of Material Science and Chemical Engineering, Chuzhou University, Chuzhou , P. R. China 2 Anhui Province Key Laboratory of Biomass Clean Energy, Department of Chemistry, University of Science and Technology of China, Hefei , P. R. China (Received September 22, 2015; CL ; louxin@ustc.edu.cn) Copyright The Chemical Society of Japan

2 I. General Information 1-2 II. Copper-Catalyzed Borylation of Primary and Secondary Alkyl Halides 2-6 III. NMR Spectra and GC-MS Analysis 7-29 I. General Information a. Materials All reactions were carried out in oven-dried Schlenk tubes under an argon or nitrogen atmosphere (purity %). Copper(I) iodide was purchased from Sinopharm Chemical Reagent Co., Ltd as an off-white powder and refluxed in THF for further purification. The following chemicals were purchased and used as received: LiOtBu (99.9%, Alfa-Aesar), NaOtBu, KOtBu, LiOMe(99%, Acros), 2-bromopentane, 3-bromo pentane, 3-bromo-2-methylbutanenitrile, cyclohexyl bromide, cyclopentyl bromide, bromocycloheptane, 3-bromocyclohex-1-ene, ethyl 3-bromobutanoate, 3-bromobutyl benzoate, 4-(6-bromohexyloxy) benzonitrile, 4-bromo-tetrahydropyran, benzyl 4-bromo piperidine-1-carboxylate, 4-bromo-1-tosylpiperidine, 1-(3-iodobutyl)-4- methoxybenzene, 5-(3-iodobutyl)benzo[d][1,3]dioxole, PPh3, bis(neopentyl glycolato) diboron, DMAc (TCI), Anhydrous DMF (Acros) and anhydrous THF (Acros) were stored over 4 molecular sieves under an argon atmosphere in a septum-capped bottle. All other reagents and solvents mentioned in this text were purchased from commercial sources and used without purification. b. Analytical Methods 1 H, 11 B, 13 C NMR spectra were recorded either on Bruker Avance 400 or Varian Mercury 400 spectrometer at ambient temperature in CDCl3 unless otherwise noted; 11 B NMR signals are quoted relative to BF3 Et2O. Data for 1H-NMR are reported as follows: chemical shift (δ ppm), multiplicity, integration, and coupling constant (Hz). Data for 13C-NMR are reported in terms of chemical shift (δ ppm), multiplicity, and coupling constant (Hz). Gas chromatographic (GC) analysis was acquired on a Shimadzu GC-2014 Series GC System equipped with a flame-ionization detector. GC-MS analysis was performed either on Thermo Scientific AS 3000 Series GC-MS System or Agilent 6890N gas chromatograph coupled to an Agilent 5973 inert mass selective detector. HRMS 1

3 analysis was performed on Finnigan LCQ advantage Max Series MS System. Elementary Analysis was carried out on Elementar Vario EL III elemental analyzer. II. Copper-Catalyzed Borylation of Primary and Secondary Alkyl Halides Experimental Procedure A for Examples Described in Table 1. In air, Cu-catalyst (0.025 mmol), ligand (0. 025mmol), base (0.5 mmol) and bis(neopentyl glycolato) diboron (0.375 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). Solvent (0.5 ml) and 2-bromopentane (0.25 mmol) were added in turn under an argon atmosphere. The reaction mixture was stirred at the mentioned temperature for the indicated amount of time, then diluted with EtOAc, filtered through silica gel with copious washings (petroleum ether or EtOAc), and biphenyl (38.5mg, 0.25mmol) was added as internal standard. The product yield was determined by GC. Experimental Procedure B for Examples Described in Table 2. In air, CuBr (0.025 mmol), PPh3 ( mmol), base (0.5 mmol) and diboron reagent (0.375 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). Solvent (0.5 ml), and 2-bromopentane (0.25 mmol) were added in turn under an argon atmosphere. The reaction mixture was stirred at the mentioned temperature for the indicated amount of time, then diluted with EtOAc, filtered through silica gel with copious washings (petroleum ether or EtOAc), and biphenyl (38.5mg, 0.25mmol) was added as internal standard. The product yield was determined by GC. Experimental Procedure C for Examples Described in Table 3. 2

4 In air, CuBr (7.1 mg, 0.05 mmol), PPh3 (17.03 mg, mmol), LiOtBu(80 mg, 1 mmol), and bis(neopentyl glycolato) diboron (168mg, 0.75 mmol ) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). DMAc (1 ml), alkyl halide (0.5 mmol) were added in turn by syringe under an argon atmosphere (if the alkyl halide is a solid, it was added along with the CuBr). The resulting reaction mixture was stirred vigorously at 25 ºC for 18 h. The reaction mixture was then diluted with EtOAc, filtered through silica gel with copious washings (petroleum ether to EtOAc), concentrated, and purified by column chromatography. 5,5-dimethyl-2-(pentan-2-yl)-1,3,2-dioxaborinane Following procedure C to give 3a (58mg, 63%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 3.59 (s, 4H), (m, 5H), 0.95 (s,6h), 0.88 (t,7.2hz,3h), 094(d,12.8Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 72.12, 31.75, 23.96, 22.18, 21.98, 15.81, 14.46; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C10H21BO2 (M-H + ) ; found ,5-dimethyl-2-(pentan-3-yl)-1,3,2-dioxaborinane Following procedure C to give 3b (53mg, 58%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 3.60 (s, 1H), (m, 4H), (m, 1H), 0.96 (s, 6H), 0.89 (t, J = 7.4 Hz, 6H); 13 C NMR (101 MHz, CDCl3) δ 72.03, 31.60, 24.01, 22.00, 13.89; 11 B NMR (128 MHz, CDCl3) δ HRMS[EI] calcd for C10H21BO2(M + ) ; found (5,5-dimethyl-1,3,2-dioxaborinan-2-yl)butanenitrile Following procedure C to give 3c (38mg, 42%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 3.60 (s, 4H), 2.42 (dd, J = 16.8, 5.9 Hz, 1H), 2.26 (dd, J = 16.8, 8.3 Hz, 1H), (m, 1H), 1.11 (d, J = 7.5 Hz, 3H), 0.95 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ , 72.24, 31.78, 21.83, 20.47, 15.33; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C9H19BO2 (M-H + ): ; found

5 ethyl 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)butanoate Following procedure C to give 3d (60.4mg, 60%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 4.11 (q, J = 7.1 Hz, 1H), 3.59 (s, 4H), 2.35 (qd, J = 16.2, 7.2 Hz, 2H), (m, 1H), 1.24 (t, J = 7.1 Hz, 3H), 0.97 (d, J = 8Hz, 3H), 0.96 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ , 71.99, 60.05, 37.84, 31.68, 21.84, 15.36, 14.31; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C11H22BO4(M-H + ): ; found (5,5-dimethyl-1,3,2-dioxaborinan-2-yl)butyl benzoate Following procedure C to give 3e (113mg, 78%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ (m, 2H), (m, 1H), (m, 2H), 4.38 (td, J = 6.8, 3.3 Hz, 2H), 3.55 (s, 4H), 1.96 (m, 1H), 1.71 (m, 1H), (m, 1H), 1.06 (d, J = 6.8, 3H), 0.94 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ , , , , , 71.92, 65.02, 32.27, 31.79, 21.96, 15.77; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C16H24BO4 (M-H + ): ; found cyclopentyl-5,5-dimethyl-1,3,2-dioxaborinane Following procedure C to give 3f (45mg, 50%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 3.59 (s, 4H), (m, 2H), (m, 6H), (m, 1H), 0.95 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ 77.16, 72.18, 31.67, 28.77, 26.97, 21.94; 11 B NMR (128 MHz, CDCl3) δ HRMS[EI] calcd for C10H19BO2(M + ) ; found cyclohexyl-5,5-dimethyl-1,3,2-dioxaborinane Following procedure C to give 3g (77mg, 79%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 3.58 (s, 4H), (m, 4H), (m,4h), 0.94 (s,6h), (m,1H); 13 C NMR (101 MHz, CDCl3) δ, 71.90, 31.76, 28.33, 27.54, 26.89, 21.83; 11 B NMR (128 MHz, CDCl3) δ HRMS[EI] calcd for C11H21BO2(M + ): ; found

6 2-cycloheptyl-5,5-dimethyl-1,3,2-dioxaborinane Following procedure C to give 3h (69mg, 66%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 3.59 (s, 4H), (m, 13H), 0.94 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ 71.94, 31.72, 29.87, 29.06, 28.49, 21.85; 11 B NMR (128 MHz, CDCl3) δ HRMS[EI] calcd for C12H23BO2(M + ) ; found (cyclohex-2-enyl)-5,5-dimethyl-1,3,2-dioxaborinane Following procedure C to give 3i (62mg, 64%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 5.74 (broad d, J = 10.1 Hz, 1H), (m, 1H), 3.60 (s, 4H), 1.98(d, J = 1.8 Hz, 2H), (m, 4H), 0.95(s, 6H) (m, 1H); 13 C NMR (101 MHz, CDCl3) δ , , 72.17, 31.81, 25.19, 24.27, 22.71, 21.81; 11 B NMR (128 MHz, CDCl3) δ HRMS [EI]calcd for C11H19BO2(M + ): ; found (6-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)hexyloxy) benzonitrile Following procedure C to give 3j (126mg, 80%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.9 Hz, 1H), 6.93 (d, J = 8.9 Hz, 1H), 3.99 (t, J = 6.6 Hz, 2H), 3.59 (s, 4H), (m, 2H), (m,6h), 0.96 (s, 6H), 0.73 (t, J = 7.5 Hz, 2H); 13 C NMR (101 MHz, CDCl3) δ , , , , , 72.06, 68.53, 32.16, 31.70, 28.94, 25.79, 24.05, 21.92; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C18H27BNO3(M-H + ) ; found (tetrahydro-2H-pyran-4-yl)-5,5-dimethyl-1,3,2-dioxaborinane Following procedure C to give 3i (50mg, 51%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ (m, 2H), 3.58 (s, 4H), (m, 2H), (m, 4H), (m, 1H), 0.94 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ, 72.09, 69.21, 31.73, 27.93, 21.78; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C10H20BO3(M-H + ) ; found

7 benzyl 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)piperidine-1-carboxylate Following procedure C to give 3l (101mg, 61%) as a colorless liquid. H NMR (400 MHz, CDCl3) δ (m, 5H), 5.11 (s, 2H), (m, 2H), 2.90 (t, J = 17.8 Hz, 2H), (m, 2H) (m, 2H) (m, 1H), 0.94 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ , , , , 72.00, 66.77, 45.31, 31.64, 27.07, 21.75; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C18H27BO4(M-H + ) ; found (5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1-tosylpiperidine Following procedure C to give 3m (112, 64%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 3.54 (s, 4H), 3.49 (dd, J = 7.7, 3.5 Hz, 2H), 2.44 (s, 3H), 2.34 (dd, J = 11.0, 2.8 Hz, 2H), (m, 2H), (m, 2H), 0.87 (s, 6H), (m, 1H); 13 C NMR (101 MHz, CDCl3) δ , , , , 72.16, 47.39, 31.81, 26.46, 21.64, 21.49; 11 B NMR (128 MHz, CDCl3) δ HRMS [ESI] calcd for C17H27BNO4S(M-H + ) ; found (4-(4-methoxyphenyl)butan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane. Following procedure C to give 3n (62mg, 45%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 7.11 (m, 2H), (m, 2H), 3.77 (s, 3H), 3.56 (s, 4H), (m, 2H), (m, 1H), (m, 1H), 0.956(d,13.2 Hz, 3H), 0.94(s,6H), (m, 1H); 13 C NMR (101 MHz, CDCl3) δ , , , , 71.77, 55.19, 35.47, 34.26, 31.71, 22.07, 15.82; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C16H26BO3(M-H + ) found (4-(benzo[d][1,3]dioxol-6-yl)butan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane Following procedure C to give 3o (77mg, 53%) as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ (m, 3H), 5.90 (s, 2H), 3.57 (s, 4H), (m, 2H), 1.73 (ddt, J = 13.1, 9.8, 6.6 Hz, 1H), (m, 1H), (m, 1H), 0.953(d, J=10Hz, 3H), 0.94(s,6H); 13 C NMR (101 MHz, CDCl3) δ , , , , , , , 71.95, 35.56, 35.09, 31.61, 21.84, 15.68; 11 B NMR (128 MHz, CDCl3) δ HRMS[ESI] calcd for C16H24BO4M-H + ) ; found

8 III. 1 H, 13 C and 11 B NMR SPECTRA FOR 3a-3o 1. 5,5-dimethyl-2-(pentan-2-yl)-1,3,2-dioxaborinane 7

9 2. 5,5-dimethyl-2-(pentan-3-yl)-1,3,2-dioxaborinane 8

10 9

11 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)butanenitrile 10

12 ethyl 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)butanoate 11

13 12

14 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)butyl benzoate 13

15 4-(6-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)hexyloxy)benzonitrile 14

16 15

17 2-cyclopentyl-5,5-dimethyl-1,3,2-dioxaborinane 16

18 2-cyclohexyl-5,5-dimethyl-1,3,2-dioxaborinane 17

19 18

20 2-cycloheptyl-5,5-dimethyl-1,3,2-dioxaborinane 19

21 2-(cyclohex-2-enyl)-5,5-dimethyl-1,3,2-dioxaborinane 20

22 21

23 2-(tetrahydro-2H-pyran-4-yl)-5,5-dimethyl-1,3,2-dioxaborinane 22

24 benzyl 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)piperidine-1-carboxylate 23

25 24

26 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1-tosylpiperidine 25

27 2-(4-(4-methoxyphenyl)butan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane 26

28 27

29 2-(4-(benzo[d][1,3]dioxol-6-yl)butan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane 28

30 29