Supporting Information Sustainable Radical Reduction through Catalytic Hydrogen Atom Transfer Andreas Gansäuer,* Chun-An Fan, Frederik Piestert Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard Domagk Strasse 1, 53121 Bonn, Germany E-mail: andreas.gansaeuer@uni-bonn.de Experimental Section: General procedures: All reactions were performed in oven-dried (100 C) glassware under Ar. THF was freshly distilled from K under Ar. The products were purified by flash chromatography 1 on Merck silica gel 60 (eluents given in brackets, PE refers to Petrol Ether 40-60, MTBE to tert-butylmethylether, EE to Ethyl acetate and CH to Cyclohexane). Collidine hydrochloride was dried directly prior to use by heating under vacuum until beginning sublimation in the reaction flask. Yields refer to analytically pure samples. Isomer ratios were determined by suitable 1 H NMR integrals of cleanly separated signals. NMR: Bruker DPX 300, DPX 400; 1 H NMR, [D 5 ]-benzene (7.16 ppm) and CHCl 3 (7.26 ppm) in the indicated solvent as internal standard in the same solvent; 13 C NMR: CDCl 3 (77.16 ppm) and C 6 D 6 (128.06 ppm) as internal standard in the same solvent; integrals in accord with assignments, coupling constants are measured in Hz and always constitutes J H,H coupling constants. IR spectra: Perkin-Elmer 1600 series FT-IR, PARAGON 500, Nicolet Magna 500 as neat films on KBr plates and Thermo Nicolet 380 as ATRmeasurements. The MS data were obtained with the ESI-technique, using a microtof-q spectrometer from Bruker Daltonics, Bremen, Germany. High resolution measurements were calibrated against Sodiumformate. Optical rotations were measured using a 1 ml cell with a 1 dm path length on Perkin Elmer 341 polarimeter, and concentrations (c) were reported in g (100 ml)-1. Chiral GC analysis was performed on a Trace GC 2000 (ThermoQuest CE Instruments).
The following epoxides were prepared according to the literature: 2-Methyl-2-phenethyloxirane (3) 2, 9-(2-Methyloxiran-2-yl)nonyl 4- methylbenzenesulfonate (7) 3, 9-(2-Methyloxiran-2-yl)nonyl pivalate (9) 3, 2-(9- Chlorononyl)-2-methyloxirane (11) 3, 2-Methyl-2-phenyloxirane (15) 4, 2,3-Bis(tertbutoxymethyl)oxirane (17) 5, 2,3-Bis(propoxymethyl)oxirane (20) 5, 2,3- Bis(ethoxymethyl)oxirane (22) 5. General Reaction Procedure for the Radical Generation and Reduction by Hydrogen-Atom-Transfer: A mixture of titanocene catalyst, dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl and Mn dust (131 mg, 2.00 mmol) was placed under an atmosphere of hydrogen gas. Then, a solution of epoxide (1.00 mmol) in dry THF (5 ml) was added. The mixture was stirred under a hydrogen atmosphere (1 or 4 bar) for the indicated time, diluted with CH 2 Cl 2 (20 ml) and washed with phosphate buffer (10 ml). The combined organic layers were washed with brine (5 ml) and dried (MgSO 4 ). The volatiles were removed under reduced pressure and the crude product was purified by SiO 2 chromatography. Synthesis of 6: According to the general procedure, 3 (162 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, 0.10 mmol) and Mn dust (165 mg, 3.00 mmol) in dry THF (5 ml) for 20 hours under H 2 (1 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (111.2 mg, 68 %). According to the general procedure, 3 (162 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, 0.10
mmol) and Mn dust (165 mg, 3.00 mmol) in dry THF (5 ml) for 20 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (138.2 mg, 84 %). According to the general procedure, 3 (162 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, 0.10 mmol) and zink dust (194 mg, 3.00 mmol) in dry THF (5 ml) for 20 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (133.4 mg, 81 %). According to the general procedure, 3 (162 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, 0.10 mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (23 mg, 0.025 mmol) and Mn dust (155 mg, 3.00 mmol) in dry THF (5 ml) for 20 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (132.4 mg, 81 %). mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (23 mg, 0.025 mmol) and Mn dust (155 mg, 3.00 mmol) in dry THF (5 ml) for 48 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (118.7 mg, 72 %). mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (23 mg, 0.025 mmol) and Mn dust (155 mg, 3.00 mmol) in dry THF (2.5 ml) for 20 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (111.8 mg, 68 %). mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (9.3 mg, 0.01 mmol) and Mn dust (155 mg, 3.00 mmol) in dry THF (5 ml) for 8 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (120.2 mg, 73 %). mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (9.3 mg, 0.01 mmol) and Mn dust (155 mg, 3.00 mmol) in dry THF (2.55 ml) for 8 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (90.3 mg, 55 %). mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (9.3 mg, 0.01 mmol) and Mn dust (155 mg, 3.00 mmol) in dry THF (2.55 ml) for 8 hours at 50 C under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (75.6 mg, 46 %).
mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (9.3 mg, 0.01 mmol) and Mn dust (155 mg, 3.00 mmol) in dry THF (2.55 ml) for 20 hours at 0 C under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (55.9 mg, 34 %). According to the general procedure, 3 (162 mg, 1.00 mmol), acetophenone (120 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, 0.10 mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (46 mg, 0.05 mmol) and Mn dust (165 mg, 3.00 mmol) in dry THF (5 ml) for 20 hours under H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 6 (132.5 mg, 81 %) and acetophenone (104.6 mg, 87 %). The spectral data are in accordance with the literature. 6 Synthesis of 8: According to the general procedure, 7 (354.5 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, H 2 (4 bar). SiO 2 chromatography (PE:Et 2 O 85:15) yielded 8 (293.7 mg, 82 %). The spectral data are in accordance with the literature. 3 Synthesis of 10: According to the general procedure, 9 (286 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, 0.10 mmol) and Mn dust (165 mg, 3.00 mmol) in dry THF (5 ml) for 16 hours under H 2 (4 bar). SiO 2 chromatography (PE:MTBE 4:1) yielded 10 (202.1 mg, 71 %). The spectral data are in accordance with the literature. 3 Synthesis of 12:
According to the general procedure, 11 (218.7 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, H 2 (4 bar). SiO 2 chromatography (PE:MTBE 4:1) yielded 12 (147.3 mg, 67 %). The spectral data are in accordance with the literature. 3 Synthesis of 14: O OTBS O OTBS HO OTBS 9 9 9 S1 13 14 Synthesis of S1 To a solution of tert-butyl-chlordimethylsilane (1M, 10.0 ml, 10.00 mmol) and dry pyridine (2.0 g, 25.00 mmol) in dry THF (10 ml) was slowly added a solution of 11- hydroxyundecan-2-one (1.5 g, 8.20 mmol) 7 in dry THF (5 ml). The reaction mixture was allowed to warm to room temperature and stirring was continued for 16 hours. After adding Water (50 ml) and tert-butylmethylether (50 ml), the organic phase was separated and washed with water (50 ml) and brine (20 ml). After drying (MgSO 4 ), the solvents were removed under reduced pressure and the crude product was purified by SiO 2 chromatography yielding S1 (2.21 g, 7.40 mmol, 90 %) as a colorless oil. 1 H (300.13 MHz, Benzene-d 6, RT): =3.58 (t, 2H, 3 J H-H =6.3 Hz), 1.94 (t, 2H, 3 J H- H=7.4 Hz), 1.66 (s, 3H, 1.61-1.43 (m, 4H), 1.42-1.07 (m, 10H),1.00 (s, 9H), 0.08 (s, 6H). 13 C (75.48 MHz, Benzene-d 6, RT): = 206.2, 65.4, 43.4, 33.3, 29.9, 29.8, 29.9, 29.5, 26.2, 24.1, 29.3, 26.2, 18.7, -5.1. IR (ATR): 2927 (s), 2854 (s), 1718 (s), 1463 (m), 1408 (w), 1387 (w), 1360 (m), 1253 (m), 1161 (w), 1095 (s), 1006 (w), 939 (w), 833 (s), 773 (s), 716 (w), 661 (w). R F 0.33 (PE:MTBE: 9:1), MS (ESI): 323.2 (M+Na + ). HR-MS ( M+Na + ): calculated: 323.2382, found: 323.2374.
Synthesis of 13: To a solution of trimethylsulfoxonium iodide (2.42 g, 11.00 mmol) in dry THF (50 ml) was added NaH (60 %, suspension in mineral oil, 400 mg, 10.00 mmol). After stirring for 2 hours a solution of S1 (2.21 g, 7.40 mmol) in dry THF (10 ml) was added. Stirring was continued for 16 hours. After adding H 2 O (100 ml) and tert- Butylmethylether (200 ml), the organic phase was separated and washed with H 2 O (100 ml) and brine (50 ml). After drying (MgSO 4 ), the solvents were removed under reduced pressure and the crude product was purified by SiO 2 chromatography to yield 13 (1.57 g, 5.00 mmol, 68 %) as a colorless oil. 1 H (300.13 MHz, Benzene-d 6, RT): = 3.58 (t, 2H 3 J H-H =6.4 Hz), 2.32 (d, 1H, 2 J H- H=4.7 Hz), 2.24 (d, 1H, 2 J H-H =4.9 Hz), 1.59-1.51 (m, 2H, 1.47-1.16 (m, 14H, 1.12 (s, 3H, 1.00 (s, 9H), 0.07 (s, 6H). 13 C (75.48 MHz, Benzene-d 6, RT): = 63.4, 56.2, 53.2, 37.1, 33.1, 30.1, 30.0, 30.0, 29.9, 26.3, 25.6, 26.2, 21.1, 18.6, -5.1. IR (ATR): 2927 (s), 2855 (s), 1463 (m), 1388 (m), 1361 (m), 1253 (m), 1095 (s), 1006 (m), 938 (w), 902 (w), 833 (s), 773 (s), 711 (w), 661 (w). R F 0.59 (PE:MTBE: 9:1), MS (ESI): 337.3 (M+Na + ). HR-MS (M+Na + ): calculated: 337.2539, found: 337.2536. Synthesis of 14: According to the general procedure, 13 (314.6 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, H2 (4 bar). SiO 2 chromatography (PE:MTBE 85:15) yielded 14 (250.3 mg, 79 %). 1 H (400.13 MHz, Benzene-d 6, RT): = 3.58 (t, 2H, 3 J H-H =6.4 Hz), 3.27 (dd, 1H, 2 J H- H=10.2 Hz), 3 J H-H =5.7 Hz), 3.18 (dd, 1H, 2 J H-H =10.3 Hz), 3 J H-H =6.4 Hz), 1.61-1.13 (m, 16H), 1.01 (s, 9H), 0.86 (d, 3H, 3 J H-H =6.7 Hz), 0.09 (s, 6H). 13 C (100.62 MHz, Benzene-d 6, RT): = 68.2, 63.4, 36.2, 33.6, 33.4, 30.8, 30.4, 30.1, 29.9, 27.5, 26.4, 26.2, 18.6, 16.9, -5.1. IR (ATR): 3343 (s), 2925 (m), 2854 (m), 1463 (m), 1387 (w), 1361 (w), 1253 (m), 1098 (m), 1039 (w), 1006 (w), 938 (w), 833 (s), 773 (s), 721 (w).
R F 0.21 (PE:MTBE: 85:15), MS (ESI): 339.3 (M+Na + ). HR-MS (M+Na + ): calculated: 339.2695, found: 339.2690. Synthesis of 16: According to the general procedure, 15 (134.1 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, H 2 (4 bar). SiO 2 chromatography (CH:EE 4:1) yielded 16 (89.7 mg, 66 %). The spectral data are in accordance with the literature. 8 Synthesis of 18: According to the general procedure, 17 (216.3 mg, 1.00 mmol), Cp 2 TiCl 2 (24.9 mg, H2 (4 bar). SiO 2 chromatography (PE:Et 2 O 85:15) yielded 18 (124.0 mg, 57 %). According to the general procedure, 17 (216.3 mg, 1.00 mmol), 19 (52.5 mg, 0.1 mmol), dry collidine hydrochloride (394 mg, 2.50 mmol), Rh(PPh 3 ) 3 Cl (92 mg, 0.10 mmol) and Mn dust (165 mg, 3.00 mmol) in dry THF (5 ml) for 16 hours under H 2 (4 bar). SiO 2 chromatography (PE:Et 2 O 85:15) yielded 18 (131.9 mg, 60 %, er: 93:7). The spectral data are in accordance with the literature. 5 The enantiomeric ratio was determined by GC on a heptakis(2,6-di-o-methyl-o-pentyl)--cyclodextrin/ov1701 (1/4) column according to the same reference. 5 Synthesis of 21:
According to the general procedure, 20 (188.3 mg, 1.00 mmol), 19 (52.5 mg, 0.10 mmol) and Mn dust (165 mg, 3.00 mmol) in dry THF (5 ml) for 16 hours under H 2 (4 bar). SiO 2 chromatography (PE:Et 2 O 85:15) yielded 21 (122.0 mg, 64 %, er: 97:3). The spectral data are in accordance with the literature. 5 The enantiomeric ratio was determined by GC on an Ivadex 7/ OV-1701;G/294 column according to the same reference. 5 Synthesis of 23: According to the general procedure, 22 (160.2 mg, 1.00 mmol), 19 (52.5 mg, 0.10 mmol) and Mn dust (165 mg, 3.00 mmol) in dry THF (5 ml) for 16 hours under H 2 (4 bar). SiO 2 chromatography (PE:Et 2 O 85:15) yielded 23 (122.1 mg, 75 %, er: 96:4). The spectral data are in accordance with the literature. 5 The enantiomeric ratio was determined by GC on a heptakis(2,6-di-o-methyl-o-pentyl)--cyclodextrin/ov1701 (1/4) column according to the same reference. 5 References: (1) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923-2925. (2) Charlton, J. L.; Williams, G. J.; Lypka, G. N. Can. J. Chem. 1980, 58, 1271-1274. (3) Gansäuer, A.; Bluhm, H.; Pierobon, M. J. Am. Chem. Soc. 1998, 120, 12849-12859. (4) Ciaccio, J. A.; Drahus, A. L.; Meis, R. M.; Tingle, C. T.; Smrtka, M.; Genestre, R. Synthetic Commun. 2003, 33, 2135-2143. (5) (a) Gansäuer, A.; Bluhm, H.; Lauterbach, T. Adv. Synth. Catal. 2001, 343, 785-787. (b) Gansäuer, A.; Bluhm, H.; Rinker, B.; Narayan, S.; Schick, M.; Lauterbach, T.; Pierobon, M.; Chem. Eur. J. 2003, 9, 531-542.
(6) Namy, J. L.; Boireau, G.; Abenhaim, D. Bull. Soc. Chim. Fr. 1971, 3191-3195. (7) Cornell, C. N.; Sigman, M. S.; Org. Lett. 2006, 8, 4117-4120. (8) Winstein, S.; Schreiber, K. C. J. Am. Chem. Soc. 1952, 74, 2171-2178.