General Considerations. Tetrakis(THF)lithium dimesityl-1,8-naphthalenediylborate was synthesized by following the published procedure (Hoefelmeyer, J. D.; Gabbaï, F. P. Organometallics 2002, 21, 982-985). Dimesitylboron fluoride, methyl triflate, potassium fluoride and potassium cyanide were purchased from Aldrich, dimethyl disulfide from Alfa Aesar. Solvents were dried by passing through an alumina column (hexanes, dichloromethane) or refluxing under N2 over Na/K (Et2O).
UV-vis spectra were recorded on an Ocean Optics USB4000 spectrometer with an Ocean Optics ISS light source. Elemental analyses were performed by Atlantic Microlab (Norcross, GA). pH Measurements were carried out with a Radiometer PHM290 pH meter equipped with a VWR SympHony electrode. NMR spectra were recorded on Varian Unity Inova 400 FT NMR (399.59 MHz for 1H, 128.19 MHz for 11B, 100.45 MHz for 13C) spectrometers at ambient temperature. Chemical shifts are given in ppm, and are referenced against external BF3·Et2O (11B and 19F).
Crystallography. The crystallographic measurements were performed using a Bruker APEX-II CCD area detector diffractometer (Mo-K radiation, = 0.71069 Å) for [30]OTf, 30-F, and 30-CN. In each case, a specimen of suitable size and quality was selected and mounted onto a nylon loop. The structures were solved by direct methods, which successfully located most of the non-hydrogen atoms. Subsequent refinement on F2 using the SHELXTL/PC package (version 5.1) allowed location of the remaining non-hydrogen atoms.
Synthesis of borane 30. Dimethyl disulfide (0.247g, 2.62mmol) was added to a suspension of tetrakis(THF)lithium dimesityl-1,8-naphthalenediylborate in diethyl ether(40 mL) at -20 ºC. After stirring overnight at room temperature, the reaction was quenched with water and extracted with diethyl ether (3 x 50 mL). The organic phases were combined and dried over MgSO4 and filtered. The solvent was removed under reduced pressure yielding light yellow solid. The solid was washed with hexanes to afford compound 30 (0.73 g, yield 73%). 1H NMR (400 MHz, CDCl3) δ 1.81 (s, 3H), 1.98 (s, 12H), 2.23 (s, 6H), 6.74 (br s, 4H, Mes-CH), 7.39-7.47 (m, 3H, nap-CH), 7.66
(dd, 1H, 3JH-H = 9.4 Hz, 4JH-H = 1.4 Hz, nap-CH), 7.74 (t, 1H, 3JH-H = 6.2Hz), 7.83 (dd, 1H, 3JH-H = 10.8 Hz, 4JH-H = 1.2 Hz, nap-CH). 13C NMR (100 MHz, CDCl3) δ 20.98, 23.22, 24.59, 125.46, 126.95, 128.72, 129.12, 129.25, 131.45, 133.41, 136.66, 139.42, 141.11. 11B NMR (128 MHz, CDCl3) δ + 77 (bs).
Synthesis of [30]OTf. Methyl triflate (0.23 mL, 2.05 mmol) was added to a solution of compound 30 (0.72 g, 1.71 mmol) in dichloromethane (25 mL) at room temperature. The mixture was refluxed overnight and cooled to room temperature. The solvent was removed in vacuo to yield a yellow solid as crude. The solid was washed by hexanes to afford the pale product (0.8g, yield 88%). Single crystals of [30]OTf were obtained by evaporation of mixture solution of dichloromethane and diethyl ether. 1H NMR (400 MHz, CDCl3) δ 0.73 (s, 3H), 1.84 (s, 3H), 2.16 (s, 3H), 2.19 (s, 3H), 2.34 (s, 6H), 2.46 (s, 3H), 3.21 (s, 3H), 6.54 (s, 1H, Mes-CH), 6.84 (s, 1H, Mes-CH), 6.94 (s, 2H, Mes-CH), 7.58 (t, 1H, 3JH-H = 10.0 Hz, nap-CH), 7.69 (d, 1H, 3JH-H = 9.2 Hz, nap-CH), 7.92 (t, 1H, 3JH-H = 9.2 Hz, nap-CH), 8.09 (d, 1H, 3JH-H = 10.8 Hz, nap-CH), 8.27 (d, 1H,
3JH-H = 10.0 Hz, nap-CH), 8.73 (d, 1H, 3JH-H = 9.6 Hz, nap-CH). 13C NMR (100 MHz, CDCl3) δ 21.33, 21.52, 22.54, 23.02, 23.93, 24.45, 27.02, 33.67, 123.35, 128.14, 128.42, 128.63, 129.38, 130.98, 132.41, 133.46, 136.49, 137.60, 140.10, 141.15, 141.90, 144.32.
11B NMR (128 MHz, CDCl3) δ + 67 (bs). Anal. Calcd for C31H36BF3O4S2
([30]OTf·H2O): C, 61.5; H, 6.00. Found: C, 61.03; H, 5.74.
Synthesis of 30-F. 30-OTf (1.00 g, 1.7 mmol) was added to 20 ml methanol solution of KF (0.70 g) which resulted in the formation of a colorless precipitate. This precipitate was isolated by filtration, washed with methanol, and dried under vacuum to afford 30-F (0.45 g, yield 58%). Single crystals of 30-F were obtained by evaporation of a solution of acetonitrile. The purity of this compound was established by NMR spectroscopy (Figure 24). 1H NMR (400 MHz, CD3CN) δ 1.54 (bs, 3H, Mes-CH3), 1,83 (bs, 6H, Mes-CH3), 2.02 (bs, 3H, Mes-CH3), 2.16 (bs, 6H, S-CH3), 2.41 (bs, 3H, Mes-CH3), 3.09 (bs, 3H, Mes-CH3), 6.49 (bs, 3H, Mes-CH), 6.66 (s, 1H, Mes-CH), 7.24 (t, J
= 7.6 Hz, 1H, nap-CH), 7.56-7.66 (m, 3H, nap-CH), 8.09 (d, J = 7.6 Hz, 1H, nap-CH), 8.16 (d, J = 8.0 Hz, 1H, Nap-CH); 13C NMR (100 MHz, CD3CN) δ 20.21(s, 2C, Mes -CH3), 23.79(s, 2C, S-CH3), 24.42(s, 1C, Mes-CH3), 26.84(s, 1C, Mes-CH3), 30.18(s, 1C, Mes-CH3), 31.35(s, 1C, Mes-CH3), 123.95, 125.40, 126.54, 128.05, 128.24, 128.75, 129.18, 132.47, 135.11, 136.08, 136.23, 137.62, 137.70, 140.36, 142.26 (Ar-H); 11B NMR (128 MHz, CD3CN) δ 9.0 (bs). 19F NMR (375.9 MHz, CD3CN) δ -161 (bs).
Figure 24.1H NMR can 13C NMR spectra of 30-F
Synthesis of 30-CN. [30]OTf (0.025g, 0.043mmol) was added to saturated KCN methanol solution. After stirring 30 min, the pale solid was formed. The solid was filtered, washed with methanol, and dried by vacuum to afford the product (0.015 mg, yield 75%). Single crystals of 30-CN were obtained by evaporation of dichloromethane solution. 1H NMR (400 MHz, CDCl3) δ 1.69 (s, 3H), 1.79 (s, 3H), 1.88 (s, 3H), 2.21 (s, 3H), 2.25 (s, 3H), 2.31 (s, 3H), 2.36 (s, 3H), 3.27 (s, 3H), 6.50 (s, 1H, Mes-CH), 6.70 (s,
1H, Mes-CH), 6.78 (s, 1H, Mes-CH), 6.83 (s, 1H, Mes-CH), 7.35 (t, 1H, 3JH-H = 7.6 Hz, nap-CH), 7.55 (d, 1H, 3JH-H = 7.6 Hz, nap-CH), 7.69 (d, 1H, 3JH-H = 8.0 Hz, nap-CH), 7.81 (d, 1H, 3JH-H = 7.6 Hz, nap-CH), 7.92 (d, 1H, 3JH-H = 6.4 Hz, nap-CH), 8.17 (d, 1H,
3JH-H = 7.6 Hz, nap-CH). 13C NMR (100 MHz, CDCl3) δ 20.74, 20.78, 24.93, 25.27, 25.33, 27.55, 30.28, 31.44, 33.04, 123.46, 125.12, 126.71, 127.60, 127.66, 128.83, 129.22, 129.60, 129.92, 133.22, 133.42, 135.90, 136.66, 137.60, 141.04, 141.60, 142.80, 143.39. 11B NMR (128 MHz, CDCl3) δ -13.0 (s). Anal. Calcd for C31.5H35BNClS (30-CN·0.5CH2Cl2, the single crystal contains one CH2Cl2 molecule in the unit cell and partial solvent was probably lost in the sample for analysis): C, 74.78; H, 6.97. Found: C, 73.57; H, 6.83.
Fluoride titration in THF: H2O, 9/1, v/v. A solution of [30]OTf (3ml, 4.36 × 10-5 M in THF/H2O, 9:1, vol.) was placed in the cuvette and titrated with incremental amounts of fluoride anions by addition of a solution of TBAF in THF (9.5 × 10-3 M).
The absorbance was monitored at = 337 nm (ε = 16350 for [30]OTf, ε = 4900 for 30-F). The experimental data obtained was fitted to a 1:1 binding isotherm which indicated that the fluoride binding constant of [30]OTf is about 2.05(±0.5) × 105 M-1 (Table 4).
Table 4. Absorbance of a solution of [30]+ after successive additions of fluoride anions in THF/H2O, 9:1, vol.
CFluoride Absexp Abscalc
0 0.713 0.713
1.5807E-05 0.560 0.556
3.15615E-05 0.435 0.425
4.72637E-05 0.341 0.336
6.29139E-05 0.294 0.290
7.85124E-05 0.269 0.266
9.40594E-05 0.252 0.252
0.000109555 0.243 0.244
0.000125 0.237 0.238
0.000140394 0.233 0.233
0.000155738 0.229 0.230
Cyanide titration in THF. A solution of [30]OTf (3ml, 4.67 × 10-5 M in THF) was placed in the cuvette and titrated with incremental amounts of cyanide anions by addition of a solution of KCN in MeOH (7.5 × 10-3 M). The absorbance was monitored at = 337 nm (ε = 16350 for [30]OTf, ε = 5800 for 30-F). The experimental data obtained was fitted to a 1:1 binding isotherm which indicated that the fluoride binding constant of [30]OTf exceeds 107 M-1 (Table 5).
Table 5. Absorbance of a solution of [30]+ after successive additions of cyanide anions in THF.
Ccyanide Absexp Abscalc
0 0.74 0.763
1.24792E-05 0.645 0.630208
2.49169E-05 0.531 0.49801
3.73134E-05 0.37 0.367008
4.96689E-05 0.275 0.273348
6.19835E-05 0.258 0.269493
7.42574E-05 0.258 0.268584
8.64909E-05 0.272 0.26796
Computational details: DFT calculations (full geometry optimization) were carried out with the Gaussian 03 program using the gradient-corrected Becke exchange functional (B3LYP) and the Lee-Yang-Parr correlation functional (Figure 25, Figure 26, Figure 27, Table 6, Table 7, Table 8). Geometry optimization was carried out with the following mixed basis set: 31+g(d’) for the boron, nitrogen and fluorine atom, 6-31+g(d) for the sulfur atom, 6-31g basis set was used for other remained carbon and hydrogen atoms. Frequency calculations, which were carried out on the optimized structure of the compound, confirmed the absence of any imaginary frequencies. The Natural Bond Orbital (NBO) analysis was carried out using the stand along PC version of GENNBO 5.0 program.
Figure 25. DFT optimized structure of [30]+
Figure 26. DFT optimized structure of 30-F
Table 6. Atom coordinates for the optimized structure of [30]+ C53 -1.594169 -1.606229 -0.796935 H54 -0.560302 -1.964540 -0.759268 H55 -1.629068 -0.749371 -1.486608 H56 -2.203713 -2.397213 -1.243784 S57 1.004309 0.975475 -1.737057
Table 7. Atom coordinates for the optimized structure of 30-F H57 -1.289674 -1.873883 -0.738072 H58 -1.622070 -3.421084 0.061621
Figure 27. DFT optimized structure of 30-CN.
Table 8. Atom coordinates for the optimized structure of 30-CN H55 -1.854692 -2.564199 -0.245154 H56 -1.917884 -3.874843 0.938864 C67 -0.374299 -0.371059 -0.084044 N68 -0.423592 -0.558614 -1.236253
CHAPTER III
THE APPLICATION OF A SULFONIUM BORANE IN FLUORIDE TRANSFER PROCESS*
3.1 Introduction
The incorporation of fluorine in organic molecules and materials is gaining momentum because of the beneficial properties imparted by this small and highly electronegative halogen. Such properties may include: increased stability in the case of organic materials as well as increased metabolic stability, lipophilicity; and bioavailability in the case of drugs.63-67 Fluorination chemistry is also becoming important in the domain of [18F]-positron emission tomography (PET), a technique that necessitates the radiolabeling of organic molecules with [18F]-fluorine atoms.68-71
For the reasons enumerated in the preceding paragraph, the field of fluorination chemistry is experiencing a surge of interest. While electrophilic fluorination strategies remain preponderant,72-80 there is a growing need for the development of nucleophilic pathways. These research needs have fueled a series of recent efforts that have already afforded an array of nucleophilic fluorinating agents reviewed in the following sections.81-95
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*Reprinted in part with permission from, “Nucleophilic Fluorination Reactions Starting from Aqueous Fluoride Ion Solutions”; Zhao, H.; Gabbaï, F. P.Org. Lett. 2011, 1444.
Copyright 2011 American Chemical Society.