Supporting Information Copper- Mediated Oxidative luorination of Aryl Stannanes with luoride Raymond. Gamache, Christopher Waldmann and Jennifer M. Murphy *, Department of Chemistry and Biochemistry, Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging, David Geffen School of Medicine University of California Los Angeles Los Angeles, California 90095, United States Email: jmmurphy@mednet.ucla.edu S1
Table of Contents I. General Procedures and Materials and Methods S3 II. Experimental Data S4 A. Synthesis of Aryl Stannanes S4 B. Synthesis of aryl fluoride reference compounds S6 C. Optimization Data S7 D. Synthesis and Characterization of the luorinated Products S12 III. References IV. 1 H, 13 C, and 19 NMR Spectra S20 S21 S2
General Procedures NMR spectra were obtained on a Bruker AV300 (300 MHz for 1 H; 282 MHz for 19 ), a Bruker AV500 (500 MHz for 1 H; 125 MHz for 13 C), and a Bruker AV600 (600 MHz for 1 H; 150 MHz for 13 C). 1 H and 13 C chemical shifts are reported in parts per million (ppm) using the solvent resonance as an internal reference. 19 NMR spectra are calibrated to the internal standard 1- fluoro- 3- nitrobenzene, which appears at - 112.0 ppm. The coupling constants, J, are reported in Hertz (Hz), and the multiplicities are reported as follows: singlet (s), broad single (br s) doublet (d), triplet (t), quartet (q), and multiplet (m). High- resolution electrospray mass spectrometry data was collected with a Waters LCT Premier XE time- of- flight instrument controlled by MassLynx 4.1 software. High- resolution mass spectra were obtained on Thermo Scientific Exactive Mass Spectrometer with DART ID- CUBE. Samples were dissolved in methanol and infused using direct loop injection from a Waters Acquity UPLC into the Multi- Mode Ionization source. Materials and Methods All fluorination reactions were conducted in an inert argon atmosphere glovebox or using standard Schlenk techniques unless otherwise stated. All chemicals and reagents were purchased from commercial sources and used without further purification unless noted otherwise. All deuterated solvents were purchased from Cambridge Isotope Laboratories. (4- chlorophenyl)tributylstannane, [4- (benzyloxy)phenyl]tributylstannane, 4- (tributylstannyl)pyridine, tetrabutyl ammonium triphenyldifluorosilicate (TBAT) and 1- fluoro- 3- nitrobenzene were purchased from Sigma Aldrich. 4- Pyridyltributylstannane was purchased from Alfa Chemistry. Cu(OTf)2 was purchased from Strem. Anhydrous solvents were obtained by filtration through activated alumina columns unless indicated otherwise. Solvents used for extractions and chromatography were not anhydrous. All other aryl stannanes were synthesized following known literature procedures and characterization data match that which was previously reported. Reactions and S3
chromatography fractions were analyzed by thin- layer chromatography (TLC) using Merck precoated silica gel 60 254 glass plates (250 μm) and visualized by ultraviolet irradiation, potassium permanganate stain, and phosphomolybdic acid. lash column chromatography was performed using E. Merck silica gel 60 (230 400 mesh) with compressed air. Prepatory plate isolation was performed using Merck precoated silica gel 60 254 glass plates (1,000 μm). Experimental Data Synthesis of aryl stannanes SnBu 3 Et 2 N [4- (diethylaminomethyl)phenyl]tributylstannane. To a solution of 4- (diethylaminomethyl)- bromobenzene (0.6 g, 2.48 mmol, 1.0 equiv) in TH (12 ml) at - 78 C was added dropwise n- butyl lithium (2.5 M, 1.2 ml, 2.98 mmol, 1.2 equiv). The solution was kept at - 78 C and allowed to stir for 10 min. To the reaction mixture was added dropwise a solution of Bu3SnCl (0.843 ml, 2.98 mmol, 1.2 equiv) in TH (3.6 ml) and the reaction was allowed to warm to 23 C and stirred for 1 h. The solution was diluted with 48 ml of a 1:1 solution of Et2O:hexanes and washed with water (2 x 70 ml) followed by brine (40 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo. The desired product was purified by column chromatography 10% w/w K2CO3 in silica and eluted with 1:9:90 NEt3:EtOAc:Hexane (Rf = 0.3 ) to afford 923 mg of the desired compound as a yellow oil (82% Yield). NMR Spectroscopy: 1 H NMR (600 MHz, CDCl3): δ 7.39 (d, J = 7.75 Hz, 2H), 7.29 (d, J = 7.26 Hz, 2H), 3.56 (s, 2H), 2.54 (br s, 4H), 1.56-1.51 (m, 6H), 1.33 (dd, J = 7.32 Hz, 7.32 Hz, 3H), 1.31 (dd, J = 7.32 Hz, 7.32 Hz, 3H), 1.06 1.02 (m, 12H), 0.88 (t, J = 7.32 Hz, 9H). 13 C NMR (150 MHz, CDCl3): δ 139.66, 136.37, 136.17, 128.57, 57.38, 46.60, 29.02, 27.32, 13.61, 11.64, 9.44. HRMS- ESI (m/z) [M+H] + calcd for C23H44NSn, 454.2495; found 454.2468. S4
SnBu 3 EtS [4- (ethyl- methylenesulfide)phenyl]tributylstannane. To a solution of ethanethiol (0.041 ml, 0.56 mmol, 1.1 equiv) in TH (2 ml) at 0 C was added 60% NaH (0.024 g, 0.606 mmol, 1.15 equiv). The solution was stirred for 40 min at 0 C. To the reaction mixture was added [4- (methylsulfonyl)1- methylene]phenyltributylstannane (0.24 g, 1.0 equiv, 0.51 mmol) in TH (1.0 ml) The solution was allowed to stir overnight at 23 C. The reaction was quenched with water and extracted with ethyl acetate (2 x 6 ml). The organic layer was washed with 5 ml of 5% NaHCO3, dried over Na2SO4 and concentrated in vacuo. The reaction was purified by column chromatography 10% w/w K2CO3 in silica and eluted with 1:50 EtOAc:Hexane to afford 170.5 mg of the desired compound as a clear oil (69% Yield) Rf=.3 in hexane. NMR Spectroscopy: 1 H NMR (500 MHz, CDCl3): δ 7.40 (d, J = 7.85 Hz, 2H), 7.27 (d, J = 7.30 Hz, 2H), 3.70 (s, 2H), 2.45 (q, J = 7.49 Hz, 2H), 1.58-1.47 (m, 6H), 1.37-1.28 (m, 6H), 1.24 (t, J = 7.35 Hz, 3H), 1.11-0.97 (m, 6H), 0.88 (t, J = 7.30 Hz, 9H). 13 C NMR (150 MHz, CDCl3): δ 140.18, 138.09, 136.46, 128.24, 35.83, 28.97, 27.25, 25.21, 14.27, 13.54, 9.44. HRMS- ESI (m/z) [M+H] + calcd for C21H39SSn, 443.1794; found 443.1765. SnBu 3 PrHN [4- (propylaminomethyl)phenyl]tributylstannane. To a solution of propylamine (0.21 ml, 2.4 mmol, 1.1 equiv), K2CO3 (0.594 g, 4.3 mmol, 2.0 equiv) in DM (9 ml) was added [4- (chloromethyl)phenyl]tributylstannane (900 mg, 2.18 mmol, 1 equiv) after 30 min of stirring. The reaction was monitored by TLC and allowed to stir until complete consumption of starting material. The mixture was diluted with Et2O (10 ml) and water (10 ml). The organic layer was separated and washed with water (3 x 3 ml) followed by brine (3 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo. The desired product was purified by column S5
chromatography 10% w/w K2CO3 in silica and eluted with 1:19:80 NEt3:EtOAc:Hexane (Rf = 0.25) to afford 350 mg of the desired compound as a yellow oil (37% yield). NMR Spectroscopy: 1 H NMR (600 MHz, CDCl3): δ 7.45 (d, J = 7.02 Hz, 2H), 7.31 (d, J = 8.40 Hz, 2H), 3.79 (s, 2H), 2.63 (dd, J = 7.08 Hz, 7.10 Hz, 2H), 2.26 (s 1H), 1.58-1.53 (m, 8H), 1.36 (dd, J = 7.5 Hz, 7.5 Hz, 3H), 1.34 (dd, J = 7.3, 7.3 Hz, 3H), 1.10-1.05 (m, 6H), 0.94 (t, J = 7.32 Hz, 3H), 0.90 (t, J = 7.32 Hz, 9H). 13 C NMR (150 MHz, CDCl3): δ 140.23, 139.86, 136.57, 127.84, 53.97, 51.35, 29.10, 27.39, 23.08, 13.69, 11.79, 9.55. HRMS- ESI (m/z) [M+H] + calcd for C22H42NSn, 440.2339; found 440.2305. Synthesis of aryl fluoride reference compounds Et 2 N reference standard N,N- diethyl- (4- fluorobenzyl)amine. Diethylamine (3.5 mmol, 0.36 ml, 2.2 equiv) was added to a solution containing DCM (2 ml) and 4- fluorobenzylbromide (1.6 mmol, 0.2 ml, 1 equiv) at 0 C. The solution was allowed to warm to 23 C and stirred overnight. The organic layer was diluted with ethyl acetate and washed with KOH (2x10 ml) and brine (10 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo resulting in 203 mg of the desired product as a red- orange oil (70% yield). 1 H NMR (500 MHz, CDCl3): δ 7.29 (dd, J = 8.29, 5.62 Hz, 2H), 6.98 (t, J = 8.73 Hz, 2H), 3.53 (s, 2H), 2.51 (q, J=7.14 Hz, 4H), 1.03 (t, J=7.12 Hz, 6H). 13 C NMR (125 MHz, CDCl3): δ 161.83 (d, J = 242.78 Hz), 135.38, 130.33 (d, J = 7.80 Hz), 114.90 (d, J = 21.0 Hz), 56.69, 46.57, 11.63. 19 NMR(282 MHz, CDCl3): δ - 116.47. S6
EtS reference standard Ethyl 4- fluorobenzyl sulfide. Under argon, TH (6 ml) was added to ethanethiol (1.32 mmol, 0.095 ml, 1.1 equiv) and the mixture was cooled to 0 C. NaH (1.44 mmol, 58 mg, 1.2 equiv) was added, slowly, at 0 C. The solution was stirred for an additional 20 min at 0 C before 4- fluorobenzylbromide (1.2 mmol, 227 mg, 1 equiv) was added. The mixture was allowed to warm to 23 C and stirred overnight. The reaction was quenched with water and extracted with ethyl acetate (2 x 10 ml). The organic layer was washed with 10 ml of 5% NaHCO3, dried over Na2SO4 and concentrated in vacuo. The crude oil was purified by silica column chromatography and eluted with hexane to afford 166 mg of the desired compound as a colorless oil (81% Yield) 1 H NMR (500 MHz, CDCl3): δ 7.31-7.24 (m, 2H), 6.99 (dd, J = 8.65 Hz, 8.67 Hz, 2H), 3.69 (s, 2H), 2.43 (q, J = 7.38 Hz, 2H), 1.23 (t, J = 7.40 Hz, 3H). 13 C NMR (125 MHz, CDCl3): δ 161.84 (d, J = 243.63 Hz), 134.31 (d, J = 3.16 Hz), 130.29 (d, J = 7.98 Hz), 115.29 (d, J = 21.28 Hz), 35.14, 25.22, 14.35. 19 NMR (282 MHz, CDCl3): δ - 115.91. Optimization Data: Copper Source Screen To a vial containing K (0.05mmol, 2.8 mg, 2.0 equiv) and MeCN (300 µl) was added a copper salt (0.05mmol, 18.1 mg, 2.0 equiv). The vial was sealed with a Teflon cap and removed from the glovebox and stirred for 10 min at 60 C. After 10 min, 4- (biphenyl)tributylstannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at 60 C for 3 h in a sealed vial and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) and MeCN or DCM. The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR resonance of 4- fluorobiphenyl (- 118.1 ppm) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). S7
[Cu] (2 equiv) K (2 equiv) MeCN, 60 ºC, 10 min Ph SnBu 3 MeCN, 60 ºC, 1h Ph Entry 1 2 [Cu] Cu(OTf) 2 (MeCN) 4 CuOTf Yield 58 0 3 (py) 4 Cu(OTf) 2 0 4 Cu 2 0 luoride Source Screen To a vial containing the fluoride source (0.05mmol, 2.0 equiv) and additive in MeCN (300 µl) was added Cu(OTf)2 (0.05 mmol, 18.1 mg, 2.0 equiv). The vial was sealed with a Teflon cap, removed from the glovebox and stirred for 10 min at 60 C. After 10 min, 4- (biphenyl)tributylstannane (0.025 mmol, 1 equiv) was added and the reaction was stirred at 60 C for 3 h in a sealed vial and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) and MeCN or DCM (0.5 ml). The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR resonance of 4- fluorobiphenyl (- 118.1 ppm) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). Cu(OTf) 2 (2 equiv) -, additive MeCN, 60 ºC, 10 min Ph SnBu 3 MeCN, 60 ºC, 3h Entry - (2 eq) Additive Yield (%) 1 2 3 K Cs TBAT --- --- --- 58 71 83 4 5 6 7 8 TBA TBAT (tin) --- --- 21 69 Na K 18 C 6 (2 eq) 18 C 6 (2 eq) 44 71 Cs 18 C 6 (2 eq) 70 Ph S8
Effect of pre- stirring To a vial containing a fluoride source (0.05mmol, 2.0 equiv) in MeCN (300 µl) was added Cu(OTf)2 (0.05mmol, 18.1 mg, 2.0 equiv). The vial was sealed with a Teflon cap, removed from the glovebox and stirred at 60 C for the indicated time. 4- (biphenyl)tributylstannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at 60 C for 3 h in a sealed vial and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) and MeCN or DCM. The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR resonance of 4- fluorobiphenyl (- 118.1 ppm) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). Cu(OTf) 2 (2 equiv) Entry - Pre-Stir (min) Yield (%) 1 K 0 46 2 3 4 5 6 7 - (2 equiv) MeCN, 60 ºC, min Ph SnBu 3 MeCN, 60 ºC, 3h Cs TBAT K K 0 0 10 20 14 83 58 58 Cs TBAT 10 10 71 83 Ph Nitrile Solvent Screen To a vial containing Cs (0.05 mmol, 27 mg, 2.0 equiv) in 300 µl of various nitrile solvents was added Cu(OTf)2 (0.05 mmol, 18.1 mg, 2.0 equiv). The reaction mixture was stirred in a sealed vial at 60 C for 10 min. After 10 min 4- (biphenyl)tributylstannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at 60 C for 3 h and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) and MeCN. The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR resonance of 4- fluorobiphenyl (- 118.1 ppm) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). S9
SnBu 3 Cu(OTf) 2 (2 equiv) Cs (2 equiv) 60 ºC, 10 min solvent Ph 1 60 ºC, 3 h Ph 2 entry solvent yield (%) 1 2 3 4 MeCN EtCN i PrCN t BuCN 71 50 34 6 Additives Screen To a vial containing Cs (0.05mmol, 27 mg, 2.0 equiv) in MeCN (300 µl) was added Cu(OTf)2 (0.05mmol, 18.1 mg, 2.0 equiv) and an additive. The reaction mixture was stirred in a sealed vial at 60 C for 10 min. After 10 min 4- (biphenyl)tributylstannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at 60 C for 3 h and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) and MeCN or DCM. The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR resonance of 4- fluorobiphenyl (- 118.1 ppm) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). Cu(OTf) 2 (2 equiv) Cs (2 equiv), additive MeCN, 60 ºC, 10 min Ph SnBu 3 MeCN, 60 ºC, 3h Ph Entry Additive Yield (%) 1 2 a O 2 (1 atm) DMP (1 equiv) 67 0 TEMPO (2 equiv) 0 3 a 4 5 6 7 8 nbu 4 NOMs (1 equiv) nbu 4 NOMs (1 equiv) nbu 4 NP 6 (1 equiv) H 4 NP 6 (1 equiv) LiCl (2 equiv) a) TBAT (2 equiv) was used instead of Cs 28 17 70 67 0 S10
Concentration Screen To a vial containing Cs (0.05mmol, 7.6 mg, 2.0 equiv) in the indicated volume of MeCN was added Cu(OTf)2 (0.05mmol, 18.1 mg, 2.0 equiiv). The vial was then sealed with a Teflon cap, removed from the glovebox and stirred for 10 min at 60 C. After 10 min, 4- (biphenyl)tributylstannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at 60 C for 3 h in a sealed vial and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) and MeCN or DCM. The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR resonance of 4- fluorobiphenyl (- 118.1 ppm) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). Cu(OTf) 2 (2 equiv) Cs (2 equiv) MeCN, 60 ºC, 10 min Ph SnBu 3 MeCN, 60 ºC, 3h Ph Entry Volume (µl) Yield (%) 1 2 3 200 300 400 73 71 75 4 500 54 5 6 600 700 26 27 Temperature Screen To a vial containing Cs (0.05mmol, 7.6 mg, 2.0 equiv) in MeCN (300 µl) was added Cu(OTf)2 (0.05mmol, 18.1 mg, 2.0 equiv). The vial was then sealed with a Teflon cap, removed from the glovebox and stirred at room temp. After 10 min, 4- (biphenyl)tributylstannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at the indicated temperature for 2 h in a sealed vial and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) and MeCN or DCM. The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR S11
resonance of 4- fluorobiphenyl (- 118.1 ppm) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). Cu(OTf) 2 (2 equiv) Cs (2 equiv) MeCN, RT, 10 min Ph SnBu 3 MeCN, temp, 2h Ph Entry Temp (ºC) Yield (%) 1 2 3 4 RT 60 70 80 55 71 74 66 (General Procedure A): Optimized Reaction Condition In a glovebox, to a vial containing tetrabutylammonium triphenyldifluorosilicate (TBAT) (0.05mmol, 27 mg, 2.0 equiv) in MeCN (300 µl) was added Cu(OTf)2 (0.05mmol, 18.1 mg, 2.0 equiv). The vial was sealed with a Teflon cap, removed from the glovebox and stirred for 10 min at 60 C. After 10 min the stannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at 60 C for 3 h in a sealed vial and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) as the internal standard and DCM (0.5 ml). The resulting solution was analyzed by 19 NMR spectroscopy. Yields were determined by comparing the integration of the 19 NMR resonance of the product peak with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). (General Procedure B): Optimized conditions isolation In a glovebox, to an 8 ml vial containing tetrabutylammonium triphenyldifluorosilicate (TBAT) (2 equiv) in MeCN was added Cu(OTf)2 (2 equiv) to form a 0.083M solution. The solution was stirred for 10 min at 23 C and the stannane was added. The vial was sealed with a Teflon cap, removed from the glovebox and stirred for 3 h at 60 C. The resulting solution was diluted with 8 ml of Et2O and washed with 2x8 ml of water. The organic layer was washed with 2x10ml of a 0.22 M solution of lithium sulfide. The organic layer was dried over Na2SO4 and S12
concentrated in vacuo at 30 C. The residue was purified by preparative TLC to afford the desired product. Substrates Ph 2 ollowing general procedure B, 4- fluorobiphenyl was synthesized from (4- biphenyl)tributylstannane 1 in 79% yield, 31 mg was isolated as a white solid using preparative TLC with 1% triethylamine in pentane as the eluent. The 1 H, 13 C and 19 NMR spectroscopic data of the purified material correctly match data previously reported. 1 BnO 3 ollowing general procedure B, 1- (benzyloxy)- 4- fluorobenzene was synthesized from [4- (benzyloxy)phenyl]tributylstannane in 66% yield, 28 mg was isolated as a white solid using preparative TLC with 3% EtOAc/Hexanes as the eluent. The 1 H, 13 C and 19 NMR spectroscopic data of the purified material correctly match data previously reported. 2 Cl 4 ollowing general procedure A, 1- chloro- 4- fluorobenzene was synthesized from (4- chlorophenyl)tributylstannane in 74% yield as determined by 19 NMR spectroscopic analysis. 19 NMR (282 MHz, CH3CN): δ - 117.85. The 19 NMR spectroscopic data match NMR data for 1- chloro- 4- fluorobenzene previously reported in the literature. 3 S13
t Bu 5 ollowing general procedure A, fluoro- 4- tert- butylbenzene was synthesized from (4- tert- butylphenyl)tributylstannane in 68% yield as determined by 19 NMR spectroscopic analysis. 19 NMR (282 MHz, CH3CN): δ - 120.64. The 19 NMR spectroscopic data match NMR data for fluoro- 4- tert- butylbenzene previously reported in the literature. 4 O ollowing general procedure B, 1- acetyl- 4- fluorobenzene was synthesized from (4- acetylphenyl)tributylstannane 5 in 59% yield (70% brsm), 20 mg was isolated as a colorless oil using preparative TLC with 3% EtOAc/Hexanes as the eluent. The 1 H, 13 C and 19 NMR spectroscopic data of the purified material correctly match data previously reported. 4 6 EtO 2 C 7 ollowing general procedure B, ethyl 4- fluorobenzoate was synthesized from ethyl 4- (tributylstannyl)benzoate 1 in 64% yield, 25 mg was isolated as a colorless oil using preparative TLC with 3% EtOAc/Hexane as the eluent. The 1 H, 13 C and 19 NMR spectroscopic data of the purified material correctly match data previously reported. 1 S14
HO 8 ollowing general procedure B, 4- fluorobenzyl- alcohol was synthesized from 4- (tributylstannyl)benzyl alcohol 1 in 60% yield, 19 mg was isolated as a colorless oil using silica gel column chromatography with 10:1 Hexane:EtOAc as the eluent. The 1 H, 13 C and 19 NMR spectroscopic data of the purified material correctly match data previously reported. 1 9 ollowing general procedure A, 1- fluoro- 2- methylbenzene was synthesized from (2- methylphenyl)tributylstannane in 50% yield as determined by 19 NMR spectroscopic analysis. 19 NMR (282 MHz, CH3CN): δ - 120.07. The 19 NMR spectroscopic data match NMR data for 1- fluoro- 2- methylbenzene previously reported in the literature. 3 O 2 N 10 ollowing general procedure A, 1- nitro- 4- fluorobenzene was synthesized from (4- nitrophenyl)tributylstannane 5 in 58% yield as determined by 19 NMR spectroscopic analysis. 19 NMR (282 MHz, CH3CN): δ - 104.87. The 19 NMR spectroscopic data match NMR data for 1- nitro- 4- fluorobenzene previously reported in the literature. 4 S15
O H 11 ollowing general procedure A, 4- fluorobenzaldehyde was synthesized from (4- formylphenyl)tributylstannane 6 in 55% yield as determined by 19 NMR spectroscopic analysis. 19 NMR (282 MHz, CH3CN): δ - 105.59. The 19 NMR spectroscopic data match NMR data for 4- fluorobenzaldehyde previously reported in the literature. 6 NC 12 ollowing general procedure A, 1- cyano- 4- fluorobenzene was synthesized from (4- cyanophenyl)tributylstannane 1 in 55% yield as determined by 19 NMR spectroscopic analysis. 19 NMR (282 MHz, CH3CN): δ - 104.87. The 19 NMR spectroscopic data match NMR data for 1- cyano- 4- fluorobenzene previously reported in the literature. 1 O S O 13 ollowing general procedure B, 1- fluoro- 4- methylsulfonylbenzene was synthesized from [4- (methylsulfonyl)phenyl]tributylstannane, 1 except stirring was increased to 5 h. 27 mg of the desired product was isolated as a light yellow solid in 63% yield using preparative TLC with 50% EtOAc/Hexane as the eluent. The 1 H, 13 C and 19 NMR spectroscopic data of the purified material correctly match data previously reported. 1 S16
N 14 In a glovebox, Cu(OTf)2 (4 equiv) was added to a 8 ml vial containing TBAT (2 equiv) and dissolved in MeCN to form a 0.083M solution. The solution was stirred for 10 min at 23 C after which the 6- (quinolinyl)tributylstannane 6 (0.10 g, 1 equiv) was added. The vial was sealed with a teflon cap, removed from the glovebox and stirred for an additional 3 h at 60 C. The resulting solution was diluted with 2 ml of MeCN, after which 1 g of poly- 4- vinyl pyridine was added and the mixture was stirred overnight. The solution was diluted with 10 ml of Et2O, washed with 2x10 ml of water and extracted. The organic layer was washed aggressively with 2x10ml of a 0.22 M solution of lithium sulfide. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by preparative TLC to give 17 mg of 6- fluoroquinoline as a colorless oil in 50% yield. The 1 H, 13 C and 19 NMR spectroscopic data of the purified material correctly match data previously reported. 6 PrHN 15 In a glovebox, Cu(OTf)2 (247 mg, 0.684 mmol, 4 equiv) was added to a 8 ml vial containing TBAT (184 mg, 0.342 mmol, 2 equiv) and dissolved in MeCN to form a 0.083M solution. The solution was stirred for 10 min at 23 C after which [4- (propylaminomethyl)phenyl]tributylstannane (75 mg, 0.171 mmol, 1 equiv) was added. The vial was sealed with a teflon cap, removed from the glovebox and stirred for an additional 3 h at 60 C. The mixture was diluted with 8 ml of Et2O and washed with 3x5 ml of 1.0N HCl. The aqueous phase was brought to a ph of 10 and extracted with 3x10 ml of DCM. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by preparative TLC using 1:19:80 NEt3:EtOAc:Hexane to give 14 mg of the desired product as a colorless oil in 49% S17
yield. NMR Spectroscopy: 1 H NMR (600 MHz, CDCl3): δ 7.28 (dd, J = 8.70 Hz, 5.52 Hz, 2H), 7.00 (dd, J = 8.76 Hz, 8.77 Hz, 2H), 3.75 (s, 2H), 2.58 (dd, J = 7.20 Hz, 6.10 Hz, 2H), 1.56 1.49 (m, 3H), 0.92 (dd, J = 7.44 Hz, 7.38 Hz, 3H). 13 C NMR (125 MHz, CDCl3): δ 161.9 (d, J = 242.99 Hz), 136.19, 129.64 (d, J = 7.87 Hz), 115.12 (d, J = 21.08 Hz), 53.23, 51.28, 23.13, 11.77. 19 NMR (282 MHz, CDCl3): δ - 117.63. HRMS- ESI (m/z) [M+H] + calcd for C10H15N, 168.1188; found 168.1173. Et 2 N 16 In a glovebox, Cu(OTf)2 (253 mg, 0.7 mmol, 4 equiv) was added to a 8 ml vial containing TBAT (189 mg, 0.35mmol, 2 equiv) and dissolved in MeCN to form a 0.083M solution. The solution was stirred for 10 min at 23 C after which [4- (diethylaminomethyl)phenyl]tributylstannane (80 mg, 0.177 mmol, 1 equiv) was added. The vial was sealed with a teflon cap, removed from the glovebox and stirred for an additional 3 h at 60 C. The mixture was diluted with 8 ml of Et2O and washed with 3x5 ml of 1N HCl. The aqueous phase was brought to a ph of 10 and extracted with 3x10 ml of DCM. The organic layer was dried over Na2SO4, concentrated in vacuo. The identity of the product was confirmed by 19 NMR spectroscopic analysis to the fully characterized reference, N,N- diethyl- (4- fluorobenzyl)amine, on S6. N 17 ollowing general procedure A, with the exception of heating the reaction to 80 C, 4- fluoropyridine was synthesized in 28% yield from 4- tributylstannanylpyridine. The mixture was then diluted with 0.5 ml of MeCN and 0.3 g of poly- 4- vinyl pyridine was added and the mixture was stirred overnight. The yield was determined by 19 NMR spectroscopic analysis. NMR Spectroscopy: 19 NMR (282 MHz, CD3CN): δ - S18
104.85. The 19 NMR spectroscopic data match NMR data for 4- fluoropyridine previously reported in the literature. 4 EtS In a glovebox, Cu(OTf)2 (0.075 mmol, 27 mg, 3.0 equiv) was added to a vial containing TBAT (0.075 mmol, 40.5 mg, 3.0 equiv) and MeCN (300 µl). The vial was sealed with a teflon cap, removed from the glovebox and stirred for 10 min at 60 C. After 10 min [4- (ethyl- methylenesulfide)phenyl]tributylstannane (0.025 mmol, 1.0 equiv) was added and the reaction was stirred at 60 C for 3 h and subsequently cooled to 23 C. To the reaction mixture was added 1- fluoro- 3- nitrobenzene (3.0 µl, 0.0282 mmol) as the internal standard and MeCN or DCM (0.5 ml). The resulting solution was analyzed by 19 NMR spectroscopy. A yield of 37% was determined by comparing the integration of the 19 NMR resonance of Ethyl 4- fluorobenzyl sulfide (- 118.02 ppm, previously synthesized and characterized on S7) with that of 1- fluoro- 3- nitrobenzene (- 112.0 ppm). Product identification was further confirmed via 19 NMR spectroscopy by spiking the crude product mixture with the reference compound and by matching the analytical HPLC retention time of both the crude product mixture and the reference compound. 19 NMR (282 MHz, CH3CN): δ - 118.02. 18 O 19 ollowing general procedure B, 3- deoxy- 3- fluoroestrone was synthesized from 3- deoxy- 3- (tributylstannyl)estrone 1 in 76% yield, 25 mg was isolated as a white solid using preparative TLC with 10% EtOAc/Hexane as the eluent. The 1 H, 13 C and 19 S19
NMR spectroscopic data of the purified material correctly match data previously reported. 1 References: 1. Tang, P.; uruya, T.; Ritter, T., Silver- Catalyzed Late- Stage luorination. J. Am. Chem. Soc. 2010, 132, 12150-12154. 2. Kim, A.; Powers, J. D.; Toczko, J.., Novel Synthesis of Desymmetrized Resorcinol Derivatives: Aryl luoride Displacement on Deactivated Substrates. J. Org. Chem. 2006, 71, 2170-2172. 3. Ye, Y.; Sanford, M. S., Mild Copper- Mediated luorination of Aryl Stannanes and Aryl Trifluoroborates. J. Am. Chem. Soc. 2013, 135, 4648-4651. 4. Ye, Y.; Schimler, S. D.; Hanley, P. S.; Sanford, M. S., Cu(OTf)2- Mediated luorination of Aryltrifluoroborates with Potassium luoride. J. Am. Chem. Soc. 2013, 135, 16292-16295. 5. Kosugi, M.; Shimizu, K.; Ohtani, A.; Migita, T., Palladium Catalyzed Reaction of Hexabutylditin with Aryl Bromides: Preparation of Negatively Substituted Aryltributyltin. Chem. Lett. 1981, 10, 829-830. 6. uruya, T.; Strom, A. E.; Ritter, T., Silver- Mediated luorination of unctionalized Aryl Stannanes. J. Am. Chem. Soc. 2009, 131, 1662-1663. S20
1 H NMR SnBu 3 N rg-156 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 1.9582 2.1839 7.4343 7.4221 7.4026 7.3897 7.3704 7.3582 7.2979 7.2858 2.0835 4.1006 5.6930 6.0599 11.8948 9.0000 3.5585 2.5426 2.5353 1.5605 1.5501 1.5481 1.5428 1.5390 1.5347 1.5298 1.5257 1.5223 1.5180 1.5087 1.3440 1.3317 1.3194 1.3072 1.2950 1.0667 1.0648 1.0557 1.0506 1.0414 1.0395 1.0369 1.0339 1.0233 0.8938-2 0 2 4 6 8 8 6 4 2 S21
13 C NMR SnBu 3 N tertiary-amine-stannane 2 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 139.6565 139.4006 136.3706 136.2065 136.1722 136.0176 128.5738 128.4548 57.3788 46.5958 29.0248 27.3153 13.6093 11.6371 11.5599 9.4445 0 5 10 15 20 200 150 100 50 S22
1 H NMR H N SnBu 3 secondary-amine-stannane 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 7.4696 7.4500 7.4383 7.4276 7.4060 7.3124 7.3002 3.7887 2.6473 2.6349 2.6231 2.2622 1.5818 1.5694 1.5575 1.5517 1.5450 1.5332 1.3692 1.3567 1.3445 1.3324 1.1225 1.1088 1.0953 1.0809 1.0672 1.0536 1.0375 1.0238 1.0101 0.9575 0.9453 0.9328 0.9186 0.9173 0.9065 0.9050 0 2 4 6 8 10 12 2.1689 1.9907 1.7868 1.8049 0.8775 8.1000 6.5556 6.6686 2.9468 9.6153 8 6 4 2 S23
13 C NMR H N SnBu 3 2ndaminestannane-pure2 1 1 /Users/myrbx200/Desktop/NMR/AV500 140.2305 139.8613 136.5721 127.8413 53.9699 51.3516 29.0985 27.3930 23.0811 13.6893 11.7909 9.5507 0 2 4 6 8 150 100 50 S24
1 H NMR SnBu 3 S rg-2-80 1 1 /Users/myrbx200/Desktop/NMR/DRX500 default proton parameters 2.0000 1.6675 2.0015 1.9935 6.1129 6.6483 3.0463 6.0384 9.7023 7.4469 7.4324 7.4098 7.3941 7.3715 7.3568 7.2736 2.4735 2.4587 2.4440 2.4292 1.5636 1.5489 1.5425 1.5373 1.5329 1.5269 1.5221 1.5178 1.5128 1.5015 1.3474 1.3326 1.3178 1.3033 1.2888 1.2522 1.2375 1.2227 1.0559 1.0449 1.0393 1.0361 1.0232 1.0058 0.9748 0.9617 0.8978 0 2 4 6 8 10 8 6 4 2 S25
13 C NMR SnBu 3 S rg-2-s-sn 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 140.1768 138.0864 136.4627 128.2400 35.8301 28.9679 27.2545 25.2104 14.2688 13.5443 9.4458-1 0 10 20 30 200 150 100 50 S26
1 H NMR Reference Et 2 N fluoroamine 2 1 /Users/myrbx200/Desktop/NMR/AV500 2.0000 1.9944 2.0525 4.1874 6.1920 7.3031 7.2919 7.2866 7.2753 6.9980 6.9806 6.9631 3.5289 2.5308 2.5165 2.5022 2.4880 1.0486 1.0343 1.0201 0 2 4 6 8 10 12 8 6 4 2 S27
13 C NMR Reference Et 2 N fluoroamine 1 1 /Users/myrbx200/Desktop/NMR/AV500 0 2 4 6 162.8080 160.8658 135.3847 130.3648 130.3024 114.9823 114.8143 56.6920 46.5710 11.6266 150 100 50 S28
19 NMR Reference Et 2 N fluoroamine 1 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters -116.4682 0 10 20 30 40-100 - 110-120 - 130-140 S29
1 H NMR Reference EtS fluorosulfide 2 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters 1.6165 1.7156 1.9167 1.9123 3.0046 7.3203 7.2999 7.2936 7.2817 7.2716 7.2597 7.2536 7.0205 6.9916 6.9627 3.6930 2.4636 2.4390 2.4144 2.3899 1.2521 1.2275 1.2029 0 5 10 15 20 8 6 4 2 S30
13 C NMR Reference fluorosulfide 1 1 /Users/myrbx200/Desktop/NMR/AV500 EtS 162.7847 160.8357 134.3199 134.2946 130.3163 130.2525 128.8175 128.4640 115.3755 115.2052 35.1417 25.2156 14.3508 0 5 10 15 150 100 50 S31
19 NMR Reference EtS fluorosulfide 1 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters -115.9056 0 5 10 15 20 25-80 - 100-120 - 140 S32
1 H NMR Ph rg2-31 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 2 3.9594 2.4253 1.2295 2.0000 7.6309 7.6290 7.6171 7.5698 7.5690 7.5626 7.5582 7.4699 7.4578 7.4468 7.4455 7.3808 7.3788 7.3689 7.3584 7.1628 7.1485 7.1343 0 10 20 30 8 6 4 2 S33
5 10 15 Ph default proton parameters /Users/myrbx200/Desktop/NMR/AV600 200 150 20 1 0 2 141.1494 140.1646 137.2382 128.7085 128.6422 128.6039 128.5507 127.1477 127.0593 126.9139 115.5675 115.4257 rg2-31 163.1905 161.5583 2 13C NMR 100 50 S34
19 NMR Ph rg-2-biphenyl 4 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters 2-118.7963-0 1 2 3 4-90 - 100-110 - 120-130 S35
1 H NMR BnO rg2-32 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 3 4.8025 4.0388 2.0000 7.4313 7.4109 7.4030 7.3537 7.3480 6.9896 6.9877 6.9765 6.9742 6.9292 6.9269 6.9227 5.0394 0 5 10 15 20 25 8 6 4 2 S36
2 4 6 8 10 default proton parameters 200 1 0 BnO /Users/myrbx200/Desktop/NMR/AV600 150 70.6076 2 136.7857 128.4821 127.8993 127.3253 115.8711 115.8179 115.7727 115.6196 rg2-32 158.0785 156.4988 154.8045 13C NMR 3 100 50 S37
19 NMR BnO 4 1 3 /Users/myrbx200/Desktop/NMR/AV300-0.0 0.5 1.0 1.5 2.0-126.8667-126.8707 default proton parameters rg-2-ether - 100-110 - 120-130 - 140 S38
19 NMR Cl /Users/myrbx200/Desktop/NMR/AV300 4-0.0 0.5 1.0 1.5-117.8491 1-112.0020 3 rg-212-100 - 105-110 - 115-120 - 125-130 S39
19 NMR rg-230 5 1 /Users/myrbx200/Desktop/NMR/AV300 5-0 1 2 3-112.0001-120.6447-110 - 115-120 - 125 S40
1 H NMR O rg-2-49b 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 6 1.9291 1.8898 3.0000 7.9975 7.9884 7.9826 7.9736 7.1463 7.1317 7.1174 3.4938 3.4821 3.4704 3.4587 2.5919 1.2178 1.2061 1.1944 0 2 4 6 8 10 8 6 4 2 S41
13C NMR O 2 1 6 /Users/myrbx200/Desktop/NMR/AV600 rg-2-49b default proton parameters 12 0 2 4 6 8 10 26.3966 115.6022 115.4570 133.4940 133.4741 130.8479 130.7863 166.4973 164.8093 196.3486 6 200 150 100 50 S42
19 NMR O rg-2-133 1 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters 6-107.8838-0 1 2 3 4-90 - 100-110 - 120-130 S43
1 H NMR O OEt 7 rg-2-183-5 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 1.9898 2.0000 2.0563 3.0627 8.0731 8.0695 8.0639 8.0611 8.0583 8.0528 8.0492 7.2632 7.1193 7.1159 7.1077 7.1049 7.1020 7.0938 7.0905 4.3877 4.3758 4.3639 4.3520 1.4033 1.3914 1.3795 0 10 20 30 8 6 4 2 S44
200 150 0 2 4 6 8 default proton parameters OEt 100 14.1595 /Users/myrbx200/Desktop/NMR/AV600 60.9204 1 115.3479 115.2030 2 131.9446 131.8829 129.3937 128.1503 126.6610 rg2-38 166.4122 165.5042 164.7357 13C NMR O 7 50 S45
19 NMR O EtO rg-2-ester 4 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters 7-107.4596 0 10 20 30 40-90 - 100-110 - 120-130 S46
1 H NMR HO rg2-11d 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters 8 2.0482 1.8282 2.0000 7.3514 7.3423 7.3370 7.3279 7.0616 7.0471 7.0326 4.6693 1.6057 0 5 10 15 20 8 6 4 2 S47
13 C NMR HO rg2-11b 2 1 /Users/myrbx200/Desktop/NMR/AV500 8-0.0 0.5 1.0 1.5 163.3102 161.3571 136.5882 136.5630 128.8077 128.7430 115.4949 115.3245 64.7006 200 150 100 50 S48
19 NMR HO 4 1 /Users/myrbx200/Desktop/NMR/AV300 rg-2-benzyl-oh 8 0 20 40-118.4937 60 default proton parameters - 100-110 - 120-130 - 140 S49
19 NMR rg-2-101 1 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters 9-111.9996-120.0737-0 1 2 3-100 - 110-120 - 130 S50
19 NMR /Users/myrbx200/Desktop/NMR/AV300 10 2.0 1.5 1.0 0.5-0.0 1-112.0014 2-104.8679 rg-209 O2N - 100-110 - 120-130 S51
19 NMR O rg-231 3 1 /Users/myrbx200/Desktop/NMR/AV300 H 11-105.5911-112.0005-0.0 0.5 1.0 1.5 2.0 2.5-100 - 105-110 - 115-120 - 125 S52
19 NMR rg-209 3 1 /Users/myrbx200/Desktop/NMR/AV300 N 12-104.8694-112.0017-0.0 0.5 1.0 1.5 2.0-100 - 110-120 - 130 S53
1 H NMR O S rg-2-51 1 1 /Users/myrbx200/Desktop/NMR/AV600 default proton parameters O 13 1.9242 1.9996 3.0000 0 5 10 7.9830 7.9796 7.9746 7.9714 7.9682 7.9633 7.9598 7.2677 7.2649 7.2534 7.2392 3.0597 8 6 4 2 S54
13C NMR O S 2 1 O 13 /Users/myrbx200/Desktop/NMR/AV600 rg-2-51 0 5 10 15 44.5546 116.6393 116.4894 136.5642 130.2061 130.1431 166.5234 164.8248 20 default proton parameters 200 150 100 50 S55
19 NMR rg-2-sulfone 4 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters O S O 13-107.9338-0.0 0.5 1.0 1.5-100 - 110-120 - 130-140 S56
1 H NMR rg-250b 1 1 /Users/myrbx200/Desktop/NMR/AV300 14 N 1.0000 2.0603 3.2226 8.9307 8.1916 8.1745 8.1611 8.1518 8.1460 7.5699 7.5604 7.5417 7.5396 7.5325 7.5302 7.5016 7.4972 7.4881 7.4733 7.4679 7.4592 7.4474 1.2875 1.2239 0.9523 0.9281 0.9039 0 10 20 30 40 8 6 4 2 S57
200 150 100-0.0 0.5 1.0 1.5 2.0 2.5 3.0 default proton parameters 14 83.1254 3.1596 121.6945 119.8417 119.6716 110.6668 110.5230 /Users/myrbx200/Desktop/NMR/AV600 3.5386 3.4915 3.2447 135.5072 131.7105 1 3.4401 3 149.3420 145.0867 rg-250b 161.1565 159.5099 13C NMR N 50 S58
19 NMR rg-250b 2 1 /Users/myrbx200/Desktop/NMR/AV300 14 N 0 10 20 30-113.0472-110 - 115-120 - 125 S59
1 H NMR N H 15 rg-2-145p1 2 1 /Users/myrbx200/Desktop/NMR/AV500 2.2094 2.1777 2.0000 2.0364 2.9706 3.2853 7.2868 7.2714 7.2600 7.2552 7.0072 6.9902 6.9735 3.7435 2.5762 1.5234 1.5100 0.9257 0.9121 0.8982 0 5 10 15 20 25 8 6 4 2 S60
13 C NMR N H 15 rg-2-145p1 1 1 /Users/myrbx200/Desktop/NMR/AV500-0 1 2 3 4 162.8668 160.9224 136.3754 129.6607 129.5978 115.2156 115.0471 53.1837 51.2409 23.1604 11.7360 200 150 100 50 S61
19 NMR rg-2-94-2 3 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters N H 15-117.6383 15 0 5 10 15 20 25-90 - 100-110 - 120-130 S62
19 NMR N rg-2-86 12 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters 16-111.9997-119.0400-2 0 2 4 6 8 10 12-105 - 110-115 - 120-125 S63
19 NMR N rg-2-67-2 4 1 /Users/myrbx200/Desktop/NMR/AV300 default proton parameters 17-104.5886-111.7353-0 1 2 3 4-105 - 110-115 - 120-125 S64
19 NMR S rg-282 1 1 /Users/myrbx200/Desktop/NMR/AV300 18-0 1 2-112.0009-118.0236-100 - 110-120 - 130 S65
6 4 2 3.3505 2.1504 4.2481-0.0 0.5 1.0 1.5 default proton parameters 2.0 1.1277 1.0235 1.1213 1.1464 2.1682 1.1934 2.0546 1 2.9088 2.9008 2.8939 2.5362 2.5216 2.5042 2.4899 2.4105 2.4037 2.3986 2.3881 2.3836 2.2814 2.2637 2.2518 2.2446 2.1834 2.1684 2.1532 2.1365 2.1215 2.0849 2.0756 2.0648 2.0617 2.0556 2.0401 2.0322 2.0275 2.0126 2.0082 1.9789 1.9742 1.9635 1.9590 1.9536 1.6535 1.6477 1.6328 1.6177 1.6126 1.6063 1.6022 1.5876 1.5833 1.5249 1.5225 1.5197 1.5155 1.5127 1.5058 1.4934 1.4861 1.4708 1.4647 1.4512 1.4341 0.9182 1 2.0000 rg-2-182 1.1283 7.2467 7.2367 7.2325 7.2229 6.8881 6.8784 6.8690 6.8559 6.8513 6.8418 6.8372 1H NMR O 19 /Users/myrbx200/Desktop/NMR/AV600 S66
0.0 0.1 0.2 0.3 0.4 /Users/myrbx200/Desktop/NMR/AV500 200 150 100 50 0.5 1 50.3999 47.9509 44.0053 38.1231 35.8597 31.5441 29.4850 29.4733 26.3294 25.9068 21.5943 13.8375 1 138.7091 138.6533 135.3558 135.3322 134.9912 130.1453 127.9419 126.8362 126.7728 115.2249 115.0642 112.5980 112.4330 rg-2-40b 161.9953 160.0548 220.7816 13C NMR O 19 S67
19 NMR O 4 1 /Users/myrbx200/Desktop/NMR/AV300 40 rg-2-estrone 19 0 10 20 30 M -119.5204 default proton parameters - 110-120 - 130 S68