S-1 Selective Alkyl Ether Cleavage by Cationic Bis(Phosphine)
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Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is © The Royal Society of Chemistry 2018 Selective alkyl ether cleavage by cationic bis(phosphine)iridium complexes. Caleb A.H. Jones† and Nathan D. Schley*,† †Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235 United States [email protected] Supporting Information I. General Information S–1 II. Functional Group Compatibility S–2 III. Synthesis and Characterization S–2 IV. NMR Spectra S–22 V. References S–75 I. General Information General Considerations. Syntheses and manipulations were conducted in air unless otherwise specified. Tetrahydrofuran, toluene, dichloromethane, pentane, and diethyl ether were degassed with argon and dried over activated alumina using a solvent purification system. All reagents and building blocks including 3-benzyloxy-propanol were procured from commercial vendors. Complex 21, BArF3,2 and [CPh3]BArF43-4 were prepared using reported procedures. Spectroscopy. 1H, 13C and 31P NMR spectra were recorded on Bruker NMR spectrometers at ambient temperature unless otherwise noted. 1H and 13C chemical shifts are referenced to residual solvent signals; 31P chemical shifts are referenced to an external H3PO4 standard. Mass Spectrometry. High resolution mass spectrometry was conducted by the Center for Innovative Technology at Vanderbilt University. Acetonitrile solutions of purified products were diluted into a carrier solvent of 20:80 H2O:MeCN containing 0.1% formic acid analyzed in either positive or negative ion mode by APCI or ESI. S-1 II. Functional Group Compatibility III. Synthesis and Characterization 6a Benzyl heptyl ether: This compound was prepared using a reported method5 6b Benzyl cyclohexyl ether: This compound was prepared using a reported method5 6c Benzyl tert-butyl ether: This compound was prepared using a reported method6 6d Methyl octyl ether: This compound was prepared using a reported method7 6e Tert-butyl hepty ether: A 50 mL round bottom flask was charged with a stir bar and fitted with a reflux condenser and Mg(ClO4)2 (0.310 g, 1.09 mmol, 0.1 equiv.) and heptanol (1.6 mL, 10.9 mmol, 1.0 equiv.) were combined in 16 mL dichloromethane. This solution was treated with di-tert-butyl dicarbonate (5.47 g, 25.1 mmol, 2.3 equiv.) and was refluxed while the reaction progress was monitored by TLC. Upon completion, the sample was diluted with 40 mL of water and extracted with three 30 mL portions of dichloromethane. The combined organic layers were then dried with Na2SO4, filtered S-2 and concentrated on a rotary evaporator. The crude oil was then purified by silica gel chromatography (5 % EtOAc/hexanes) to give the product as a colorless oil. Yield: 0.6725 g (36%). Spectroscopic data for this product has been previously reported.8 1H NMR (300 MHz, C6D6) δ: 3.37 (t, J = 6.5 Hz, 2H), 1.70 (p, J = 6.1Hz, 2H), 1.46-1.50 (m, 2H), 1.36 (bs, 6H), 1.24 (s, 9H), 0.96-0.98 (m, 3H) 6f 2-(octyloxy)-2,3-dihydro-1H-indene: A flame-dried Schlenk flask was charged with NaH (90%, 0.546 g, 22.8 mmol, 2.2 equiv.) and THF (43.5 mL) in the glove box and fitted with a rubber stopper. The vessel was then brought outside of the box and attached to an oil bubbler. 1-indanol (2.78 g, 20.17 mmol, 2.0 equiv.) was added slowly using a syringe. The resulting mixture was allowed to stir at room temperature for 30 minutes after which 1-bromooctane (1.8 mL, 10.4 mmol, 1.0 equiv.) was added dropwise. The reaction mixture was then refluxed for 6 hours at which point the reaction was quenched with saturated NH4Cl and the layers separated. The aqueous layer was extracted with three 50 mL portions of ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated. The resulting oil was then purified by silica gel chromatography (10% EtOAc/hexanes) to give the product as a colorless oil. Yield: 1.15 g (45%). 1H NMR (400 MHz, CDCl3) δ 7.12-7.22 (m, 4H), 4.33 (p, J = 6.5 Hz, 1H), 3.48 (t, J = 6.8 Hz, 2H), 2.94-3.20 (ddd, J = 16.5, 8.2, 6.8 Hz, 4H), 1.59 (p, J = 7.0 Hz, 2H), 1.28-1.36 (m, 10H), 0.89 (t, J = 7.3 Hz, 3H) 13C{1H} NMR (100 MHz, CDCl3) δ 141.15, 126.59, 124.83, 80.43, 69.49, 39.51, 31.98, 30.11, 29.61, 29.42, 26.40, 22.81, 14.25 HRMS (APCI/Q-TOF) m/z [M+H]+ calcd for C17H26OH+: 247.2062, found: 247.2054 6g ((3-methoxypropoxy)methyl)benzene: A flame-dried Schlenk flask was charged with NaH (90%, 0.330 g, 13.8 mmol, 1.2 equiv.) and THF (11.5 mL) in the glove box and fitted with a rubber stopper. The vessel was then brought outside of the box and attached to an oil bubbler. 3-benzyloxy-propanol (1.9 mL, 11.46 mmol, 1.0 equiv.) was added slowly using a syringe. The resulting mixture was allowed to stir at room temperature for 30 minutes after which iodomethane (2.1 mL, 34.4 mmol, 3.0 equiv.) was added dropwise. The reaction progress was monitored by TLC. Upon completion, the reaction was quenched with saturated NH4Cl and the layers separated. The aqueous layer was extracted with three 50 mL portions of ethyl acetate. The combined organic layers were S-3 dried over Na2SO4, filtered and concentrated on a rotary evaporator to give the product as a yellow oil. Yield: 1.65 g (80%). The compound has been previously reported.9 1H NMR (500 MHz, CDCl3) δ 7.26-7.37 (m, 5H), 4.52 (s, 2H), 3.57 (t, J = 5.4 Hz, 2H), 3.50 (t, J = 5.9 Hz, 2H), 3.34 (s, 3H), 1.90 (p, J = 6.3 Hz, 2H) 6h (3-(benzyloxy)propyl)(phenyl)sufane: Triethylamine (6.4 mL, 45.9 mmol, 4.0 equiv.) was added to a solution of 3-benzyloxy-1-propanol (1.9 mL, 11.5 mmol, 1.0 equiv.) in 88 mL THF. Methanesulfonyl chloride (2.6 mL, 22.9 mmol, 2.0 equiv.) was then added and the solution was allowed to stir overnight at room temperature. The reaction was then quenched with 25 mL saturated NH4Cl. The layers were separated and the aqueous layer was extracted twice with ether. The combined organic layers were then dried over Na2SO4, filtered and concentrated to give an orange oil. This oil was taken up in 1.8 mL DMF and was treated with thiophenol (1.8 mL, 17.2 mmol, 1.5 equiv.) and K2CO3 (2.38 g, 17.2 mmol, 1.5 equiv.). The resulting suspension was stirred at room temperature for 2 hours, after which the reaction was quenched with a 5% aqueous KOH solution and then extracted with three 20 mL portions of dichloromethane. The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The resulting residue was purified by silica gel chromatography (2%-10% EtOAc/hexanes) to give the product as an oil. Yield: 0.3375 g (11%). Spectroscopic data for this product has been previously reported.10 1H NMR (400 MHz, CDCl3) δ 7.20-7.38 (m, 10H), 4.52 (s, 2H), 3.62 (t, J = 6.0 Hz, 2H), 3.08 (t, J = 7.1 Hz, 2H), 1.98 (p, J = 6.6 Hz, 2H) 6i ((3-azidopropoxy)methyl)benzene: Triethylamine (3.4 mL, 24.1 mmol, 4.0 equiv.) was added to a solution of 3-benzyloxy-1-propanol (0.95 mL, 6.0 mmol, 1.0 equiv.) in 46 mL THF. Methanesulfonyl chloride (0.95 mL, 12.0 mmol, 2.0 equiv.) was then added and the solution was allowed to stir overnight at room temperature. The reaction was then quenched with 25 mL saturated NH4Cl. The layers were separated and the aqueous layer was extracted twice with ether. The combined organic layers were then dried over Na2SO4, filtered and concentrated to give an orange oil. This oil was taken up in 40 mL DMF and was treated with NaN3 (2.0 g, 30.1 mmol, 5.0 equiv.) and then heated to 60 °C for five hours. The crude reaction mixture was then treated with brine and extracted with diethyl ether. The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. This crude residue was purified by silica gel chromatography (10% EtOAc/hexanes) to give the product as a colorless oil. Yield: 0.424 g (37%). Spectroscopic data for this product has been previously reported.11 S-4 1H NMR (500 MHz, C6D6) δ 7.18-7.32 (m, 5H), 4.30 (s, 2H), 3.23 (t, J = 6.1 Hz, 2H), 2.99 (t, J = 6.5 Hz, 2H), 1.54 (p, J = 6.2 Hz, 2H) 6j 4-(benzyloxy)butanenitrile: This compound was prepared using a reported method.12 6k (Z)-((hex-4-en-1-yloxy)methyl)benzene: This compound was prepared using a reported method.13 6l ((but-3-yn-1-yloxy)methyl)benzene: This compound was prepared using a reported method.14 6m (4-(benzyloxy)but-1-yn-1-yl)benzene: This compound was prepared using a reported method.15 6n N-(3-benzyloxy)propyl)-4-methylbenzenesulfonamide: This compound was prepared using a reported method.16 6o 2-(2-(benzyloxy)ethyl)-1,3-dioxolane: This compound was prepared using a reported method.17 7a 3-(benzyloxy)propanal: DMSO (8.5 mL, 120.3 mmol, 10 equiv.), triethylamine (6.7 mL, 48.1 mmol, 4 equiv.), and SO3·pyridine (5.7g, 36.1 mmol, 3.0 equiv.) were added sequentially to a solution of 3-benzyloxy-1-propanol (1.9 mL, 12.0 mmol, 1.0 equiv.) in S-5 60 mL dichloromethane at 0 °C and the resulting mixture was stirred for 1.5 hours.