Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany
Complete Switch of Migratory Aptitude in Aluminum-Catalyzed 1,2-Rearrangement of Differently α,α-disubstituted α-siloxy Aldehydes Kohsuke hmatsu, Takayuki Tanaka, Takashi oi, and Keiji Maruoka* Department of Chemistry, Graduate School of Science, Kyoto University Sakyo, Kyoto 606-8502, Japan General. Infrared (IR) Spectra were recorded on a Shimadzu FT-IR. 1 H and 13 C NMR spectra were measured on JEL JNM-FX400 (400 MHz) and JEL AL-400 (400 MHz) spectrometers. Chemical shifts of 1 H NMR spectra were reported in ppm relative to tetramethylsilane (δ 0). Chemical shifts of 13 C NMR spectra were reported in ppm relative to the residual solvent (chloroform, δ 77.07). Analytical high performance liquid chromatography (HPLC) was performed on a Shimadzu LC-10AT instrument equipped with a column of Daicel Chiralcel D-H and J-H. ptical rotations were measured on a JASC DIP-1000 digital polarimeter. The high-resolution mass spectra (HRMS) were measured on an BRUKER DALTNICS microtf focus-kr spectrometer. Analytical thin layer chromatography (TLC) was performed on Merck precoated TLC plates (silica gel 60 GF 254, 0.25 mm) throughout this work. Flash column chromatography was performed on silica gel 60 (Merck 1.09386.9025, 230-400 mesh). EYELA PSL-1400 and EYELA PSL-1800 constant temperature baths were used for low temperature 1,2-rearrangement reactions. All air- and moisture-sensitive reactions were performed under an atmosphere of argon in flame-dried, round bottom flasks fitted with rubber septa. The manipulations for Al-catalyzed 1,2-rearrangements were carried out with standard Schlenk techniques under nitrogen. In experiments requiring dry solvent, toluene and dichloromethane were purified by both A2 alumina and Q5 reactant using a GlassContour solvent dispensing system. Tetrahydrofuran (THF) was purchased from Kanto Chemical Co., Ltd. as dehydrated. Trimethylaluminum and dimethylaluminum chloride were kindly supplied from Tosoh-Finechem Co., Ltd., Japan. ther simple chemicals were purchased and used as such. S1
Representative Procedure for Preparation of α,α-disubstituted α-siloxy Aldehydes I 2 (10 mol %) CH Et 3 SiCN (1 equiv) CH 2 Cl 2 CN 0ºC,1h LDA (1.2 equiv) THF 78ºC,30min CH 2 Br (1.2 equiv) Et 3 Si CN 78ºC,1h DIBAL(2equiv) CH 2 Cl 2 78 ºC, 30 min Et 3 Si 2a CH 2-enyl-2-(triethylsiloxy)acetonitrile: To a solution of benzaldehyde (1.0 ml, 10 mmol) and triethylsilylcyanide (1.4 g, 10 mmol) in dichloromethane (30 ml) was added iodine (253.8 mg, 1.0 mmol) at 0 ºC under argon. After stirring for 1 h, the reaction mixture was quenched with saturated Na 2 S 3 and extractive workup was conduced with EtAc. The combined extracts were washed with brine and dried over anhydrous Na 2 S 4. After filtration and concentration, the resulting liquid was used for next step without any purification. 1 NMR of the title compound (400 MHz, CDCl 3 ) δ 7.47-7.49 (2H, m, -H), 7.38-7.44 (3H, m, -H), 5.51 (1H, s, CHCN), 0.98 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.67-0.74 (6H, m CH 3 CH 2 Si). 2,3-Diphenyl-2-(triethylsiloxy)propanenitrile: To a solution of diisopropylamine (1.7 ml, 12 mmol) in THF (10 ml) was added a 1.5 M hexane solution of n-buli (8.0 ml, 12 mmol) at 78 ºC under argon, and the mixture was stirred for 15 min. A solution of crude 2-phenyl-2-(triethylsiloxy)acetonitrile in THF (10 ml) was transferred into this mixture at the same temperature and the resulting mixture was kept for 30 min. After addition of benzyl bromide (1.4 ml, 12 mmol), the whole reaction mixture was stirred for additional 1 h at 78 ºC. Then, the solution was poured into water and extracted with EtAc. The organic extracts were washed with brine and dried over anhydrous Na 2 S 4. After evaporation of solvents and drying under vacuum, the resulting crude oil was used for next step without any purification. 1 NMR of the title compound (400 MHz, CDCl 3 ) δ 7.44-7.47 (2H, m, -H), 7.33-7.37 (3H, m, -H), 7.23-7.25 (3H, m, -H), 7.09-7.11 (2H, m, -H), 3.24 (1H, d, J = 13.6 Hz, CH 2 ), 3.12 (1H, d, J = 13.6 Hz, CH 2 ), 0.81 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.45-0.62 (6H, m, CH 3 CH 2 Si). 2,3-Diphenyl-2-(triethylsiloxy)propanal (2a): To a solution of crude 2,3-diphenyl-2-(triethylsiloxy)propanenitrile in dichloromethane (20 ml) under argon was introduced a 1 M toluene solution of DIBAH (20 ml, 20 mmol) at 78 C, and the reaction mixture was stirred for 1 h at the same temperature. Then, the mixture was S2
quenched with 1 N HCl and extracted with ether. The organic extracts were washed with brine and dried over anhydrous Na 2 S 4, and concentrated. The residual oil was purified by column chromatography on silica gel (CH 2 Cl 2 /hexane = 1/4 as eluant) to give the title compound (2.8 g, 8.2 mmol, 82% yield for three steps) as colorless oil. 1 H NMR (400 MHz, CDCl 3 ) δ 9.77 (1H, s, CH), 7.26-7.33 (5H, m, -H), 7.12-7.14 (3H, m, -H), 6.95-6.98 (2H, m, -H), 3.32 (1H, d, J = 14.2 Hz, CH 2 ), 3.25 (1H, d, J = 14.2 Hz, CH 2 ), 0.89 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.58 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 199.8, 139.4, 135.4, 130.7, 128.2, 127.6, 127.5, 126.3, 126.0, 85.1, 44.9, 7.0, 6.8; IR (neat) 2954, 2937, 2910, 2875, 2808, 1734, 1496, 1454, 1242, 1143, 1076, 1008, 956, 761, 729, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 21 H 28 Na 2 Si ([M+Na] + ): 363.1751, Found: 363.1762. Characterization Data for Substrates Data for 2c and 2e; see Ref. [1]. Et 3 Si CH p-me-c 6 H 4 2-(4-Methoxylphenyl)-3-phenyl-2-(triethylsiloxy)propanal (2b) 1 H NMR (400 MHz, CDCl 3 ) δ 9.71 (1H, s, CH), 7.23 (2H, d, J = 8.8 Hz, Ar-H), 7.13-7.14 (3H, m, Ar-H), 6.96-6.99 (2H, m, Ar-H), 6.85 (2H, d, J = 8.8 Hz, Ar-H), 3.79 (3H, s, MeC 6 H 4 ), 3.29 (1H, d, J = 14.2 Hz, CH 2 ), 3.22 (1H, d, J = 14.2 Hz, CH 2 ), 0.89 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.57 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 199.8, 159.1, 135.6, 131.2, 130.7, 127.5, 127.3, 126.2, 113.6, 84.7, 55.0, 44.7, 7.0, 6.8; IR (neat) 2954, 2910, 2875, 1734, 1608, 1508, 1456, 1417, 1300, 1251, 1176, 1141, 1101, 1035, 1006, 962, 829, 729, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 22 H 30 Na 3 Si ([M+Na] + ): 393.1856, Found: 393.1867. Et 3 Si CH 2-(Furan-2-yl)-3-phenyl-2-(triethylsiloxy)propanal (2d) 1 H NMR (400 MHz, CDCl 3 ) δ 9.67 (1H, s, CH), 7.44-7.45 (1H, m, Ar-H), 7.20-7.22 (3H, m, -H), 7.07-7.10 (2H, m, -H), 6.36-6.37 (1H, m, Ar-H), 6.28-6.29 (1H, m, Ar-H), 3.37 (1H, d, J = 14.0 Hz, CH 2 ), 3.32 (1H, d, J = 14.0 Hz, CH 2 ), 0.85 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.45 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 200.0, 152.2, 142.2, 134.6, 130.5, 127.7, 126.6, 110.6, 108.8, 80.4, 43.3, 6.8, 5.8; IR (neat) 2954, 2875, 1741, 1496, 1456, 1238, 1155, 1010, 738, 700 cm -1 ; HRMS (ESI-TF) Calcd. for C 19 H 26 Na 3 Si ([M+Na] + ): 353.1543, Found: 353.1554. S3
Et 3 Si CH 2-enyl-2-(triethylsiloxy)pent-4-ynal (2f) 1 H NMR (400 MHz, CDCl 3 ) δ 9.53 (1H, s, CH), 7.32-7.44 (5H, m, -H), 3.06 (1H, dd, J = 17.6, 2.8 Hz, CH 2 C CH), 2.82 (1H, dd, J = 17.6, 2.8 Hz, CH 2 C CH), 1.90 (1H, t, J = 2.8 Hz, C CH), 1.00 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.67-0.75 (6H, m, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 198.3, 138.0, 128.4, 128.1, 126.0, 82.9, 79.0, 71.7, 28.2, 6.9, 6.4; IR (neat) 3309, 2954, 2912, 2875, 2806, 1737, 1448, 1259, 1242, 1141, 1008, 769, 742, 729, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 17 H 24 Na 2 Si ([M+Na] + ): 311.1437, Found: 311.1449. Et 3 Si CH 3-Cyclopropyl-2-phenyl-2-(triethylsiloxy)propanal (2g) 1 H NMR (400 MHz, CDCl 3 ) δ 9.68 (1H, s, CH), 7.26-7.41 (5H, m, -H), 1.98 (1H, dd, J = 14.4, 7.2 Hz, CH 2 c-pro), 1.91 (1H, dd, J = 14.4, 6.0 Hz, CH 2 c-pro), 0.98 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.67-0.73 (1H, m, c-pro), 0.67 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si), 0.33-0.40 (1H, m, c-pro), 0.18-0.25 (1H, m, c-pro), 0.03-0.02 (1H, m, c-pro), 0.22-0.17 (1H, m, c-pro); 13 C NMR (100 MHz, CDCl 3 ) δ 200.5, 139.7, 128.2, 127.5, 126.1, 85.1, 43.2, 7.0, 6.7, 5.4, 5.1, 4.6; IR (neat) 2954, 2910, 2875, 2804, 1735, 1458, 1238, 1211, 1136, 1089, 1074, 1016, 977, 827, 783, 727, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 18 H 28 Na 2 Si ([M+Na] + ): 327.1750, Found: 327.1765. Et 3 Si CH 2-Cyclohexyl-2-phenyl-2-(triethylsiloxy)acetaldehyde (2h) 1 H NMR (400 MHz, CDCl 3 ) δ 9.80 (1H, s, CH), 7.24-7.40 (5H, m, -H), 2.00-2.05 (1H, m, CH(-CH 2 -) 5 ), 1.56-1.76 (4H, m, c-hex), 1.12-1.25 (6H, m, c-hex), 0.80 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.69 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 201.2, 139.6, 128.1, 127.2, 126.0, 87.7, 46.4, 27.6, 26.4, 26.3, 26.3, 25.7, 7.4, 7.1; IR (neat) 2933, 2873, 2854, 1735, 1489, 1446, 1246, 1205, 1195, 1165, 1141, 1128, 1006, 974, 939, 833, 727, 700 cm -1 ; HRMS (ESI-TF) Calcd. for C 20 H 32 Na 2 Si ([M+Na] + ): 355.2063, Found: 355.2068. General Procedure for 1,2-Rearrangement of α,α-disubstituted α-siloxy Aldehydes With Dimethylaluminum Chloride Et 3 Si CH Me 2 AlCl (10 mol %) toluene 0ºC,24h 2a 3a To a solution of 2a (170.3 mg, 0.5 mmol) in toluene (5.0 ml) was added a 1 M toluene solution of dimethylaluminum chloride (50 µl, 0.05 mmol) at 0 C under S4
nitrogen. After stirring for 24 h, sodium fluoride (8.4 mg, 0.2 mmol) and water (2.7 µl, 0.15 mmol) were added and the whole mixture was stirred for 30 min at room temperature. To remove precipitates, filtration through celite with EtAc was carried out. Concentration of the filtrate and purification by column chromatography on silica gel (CH 2 Cl 2 /hexane = 1/4 as eluant) afforded a mixture of 3a and 4a (154.9 mg, 0.455 mmol, 91% yield, 3/4 = >20:1) as colorless oil. With Al Catalyst 6b NHTf Me 2 AlCl NHTf (1.1 equiv) CH 2 Cl 2 r.t., 30 min Tf N AlCl N Tf 6b Et 3 Si 2a CH 6b (10 mol %) CH 2 Cl 2 20 ºC, 12 h 4a To a solution of 2,2 -bis(trifluoromethanesulfonylamino)-1,1 -biphenyl (24.6 mg, 0.055 mmol) in dichloromethane (5.0 ml) was added a 1 M toluene solution of dimethylaluminum chloride (50 µl, 0.05 mmol) was added at room temperature under positive nitrogen pressure and the resulting mixture was kept for 30 min with stirring. Then, this solution was cooled to 20 ºC, and 2a (170.3 mg, 0.5 mmol) was introduced into it. After stirring for 12 h at the same temperature, sodium fluoride (8.4 mg, 0.2 mmol) and water (2.7 µl, 0.15 mmol) were added and the whole mixture was stirred for 30 min at room temperature. To remove precipitates, filtration through celite with EtAc was carried out. Concentration of the filtrate and purification by column chromatography on silica gel (Et 2 /hexane = 1/10 as eluant) afforded a mixture of 3a and 4a (169.9 mg, 0.5 mmol, 99% yield, 3/4 = 1>20) as colorless oil. S5
With Al Catalyst 6c NHTf Me 2 AlCl AgNTf 2 (1 equiv) CH 2 Cl 2 r.t., 12 h NHTf (1.1 equiv) r.t., 1 h N N Tf AlNTf 2 Tf 6c Et 3 Si CH 6c (10 mol %) p-f-c 6 H 4 C 6 H 4 (p-f) CH 2 Cl 2 40 ºC, 24 h 2c 4c An oven-dried Schlenk tube equipped with direct light excluded was charged with AgNTf 2 (19.4 mg, 0.05 mmol) and dichloromethane (3.0 ml). A 1 M toluene solution of dimethylaluminum chloride (50 µl, 0.05 mmol) was added under nitrogen and the resulting mixture was stirred at room temperature for 12 h. To this mixture was added a solution of 2,2 -bis(trifluoromethanesulfonylamino)-1,1 -biphenyl (24.6 mg, 0.055 mmol) in dichloromethane (1.0 ml) and stirred for another 1 h. After being cooled to 40 C, a solution of 2c (179.3 mg, 0.5 mmol) in dichloromethane (1.0 ml) was transferred into this mixture and the stirring was maintained at 40 C for 24 h. Then, the reaction mixture was quenched with 1N HCl and extracted with EtAc. The organic extracts were washed with brine and dried over anhydrous Na 2 S 4. After evaporation, the residual oil was purified by column chromatography on silica gel (CH 2 Cl 2 /hexane = 1/4 as eluant) to afford a mixture of 3c and 4c (175.9 mg, 0.49 mmol, 98% yield, 3/4 = 1:>20) as colorless oil. Characterization Data for Products Data for 3a, 3c and 3e; see Ref. [1]. 1,3-Diphenyl-1-(triethylsiloxy)propan-2-one (4a) 1 H NMR (400 MHz, CDCl 3 ) δ 7.44 (2H, d, J = 7.0 Hz, -H), 7.18-7.36 (6H, m, -H), 7.01 (2H, d, J = 7.0 Hz, -H), 5.18 (1H, s, SiCH), 3.90 (1H, d, J = 16.6 Hz, CH 2 ), 3.72 (1H, d, J = 16.6 Hz, CH 2 ), 0.91 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.59 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 207.3, 138.4, 134.1, 129.6, 128.4, 128.2, 128.0, 126.6, 125.9, 80.7, 42.6, 6.6, 4.6; IR (neat) 2954, 2937, 2910, 2875, 1726, 1494, 1452, 1413, 1240, 1188, 1130, 1095, 1068, 1004, 864, 727, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 21 H 28 Na 2 Si S6
([M+Na] + ): 363.1750, Found: 363.1755. p-me-c 6 H 4 1-(4-Methoxyphenyl)-3-phenyl-2-(triethylsiloxy)propan-1-one (3b) 1 H NMR (400 MHz, CDCl 3 ) δ 8.08-8.11 (2H, m, Ar-H), 7.19-7.29 (5H, m, Ar-H), 6.91-6.94 (2H, m, Ar-H), 4.87 (1H, dd, J = 8.8, 4.4 Hz, SiCH), 3.88 (3H, s, MeC 6 H 4 ), 3.08 (1H, dd, J = 13.6, 4.4 Hz, CH 2 ), 2.99 (1H, dd, J = 13.6, 8.8 Hz, CH 2 ), 0.75 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.33-0.41 (6H, m, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 199.2, 163.3, 137.7, 131.5, 129.6, 128.1, 127.7, 126.4, 113.5, 78.8, 55.3, 42.4, 6.4, 4.4; IR (neat) 2954, 2937, 2910, 2875, 1683, 1670, 1598, 1573, 1508, 1456, 1417, 1311, 1257, 1170, 1111, 1016, 1006, 979, 835, 779, 742, 729, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 22 H 30 Na 3 Si ([M+Na] + ): 393.1856, Found: 393.1859. C 6 H 4 (p-me) 1-(4-Methoxyphenyl)-3-phenyl-1-(triethylsiloxy)propan-2-on e (4b) 1 H NMR (400 MHz, CDCl 3 ) δ 7.34 (2H, d, J = 9.0 Hz, Ar-H), 7.19-7.25 (3H, m, Ar-H), 7.02 (2H, d, J = 6.8 Hz, Ar-H), 6.87 (2H, d, J = 9.0 Hz, Ar-H), 5.13 (1H, s, SiCH), 3.88 (1H, d, J = 16.4 Hz, CH 2 ), 3.80 (3H, s, MeC 6 H 4 ), 3.72 (1H, d, J = 16.4 Hz, CH 2 ), 0.91 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.58 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 207.3, 159.4, 134.1, 130.5, 129.5, 128.2, 127.2, 126.5, 113.8, 80.2, 55.1, 42.6, 6.6, 4.6; IR (neat) 2954, 2937, 2910, 2875, 1724, 1608, 1508, 1496, 1456, 1417, 1301, 1247, 1170, 1132, 1111, 1085, 1031, 1004, 864, 821, 723, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 22 H 30 Na 3 Si ([M+Na] + ): 393.1856, Found: 393.1866. C 6 H 4 (p-f) 1-(4-Fluorophenyl)-3-phenyl-2-(triethylsiloxy)propan-1-one (4c) 1 H NMR (400 MHz, CDCl 3 ) δ 7.38-7.41 (2H, m, Ar-H), 7.19-7.26 (3H, m, Ar-H), 7.00-7.05 (4H, m, Ar-H), 5.15 (1H, s, SiCH), 3.88 (1H, d, J = 16.2 Hz, CH 2 ), 3.74 (1H, d, J = 16.2 Hz, CH 2 ), 0.91 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.59 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 207.3, 162.6 (d, J C-F = 247 Hz), 134.3 (d, J C-F = 2.5 Hz), 133.9, 129.5, 128.3, 127.6 (d, J C-F = 8.2 Hz), 126.6, 115.4 (d, J C-F = 22.2 Hz), 80.0, 42.7, 6.6, 4.6; IR (neat) 2956, 2877, 1726, 1506, 1222, 1085, 1014, 862, 819, 731, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 21 H 27 FNa 2 Si ([M+Na] + ): 381.1656, Found: 381.1653. 1-(Furan-2-yl)-3-phenyl-2-(triethylsiloxy)propan-1-one (3d) 1 H NMR (400 MHz, CDCl 3 ) δ 7.62-7.63 (1H, m, Ar-H), 7.39-7.41 (1H, m, Ar-H), 7.20-7.28 (5H, m, -H), 6.52-6.54 (1H, m, Ar-H), 4.76 (1H, dd, J = 8.8, 4.0 Hz, SiCH), 3.08 (1H, dd, J = 13.6, 4.0 Hz, CH 2 ), 2.94 (1H, dd, J = S7
13.6, 8.8 Hz, CH 2 ), 0.77 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.35-0.46 (6H, m, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 189.7, 150.4, 146.7, 137.3, 129.7, 128.1, 126.5, 119.8, 112.0, 78.0, 42.3, 6.4, 4.3; IR (neat) 2954, 2912, 2875, 1685, 1670, 1558, 1463, 1392, 1149, 1116, 1012, 854, 744, 696 cm -1 ; HRMS (ESI-TF) Calcd. for C 19 H 26 Na 3 Si ([M+Na] + ): 353.1543, Found: 353.1536. 1-(Furan-2-yl)-3-phenyl-1-(triethylsiloxy)propan-2-one (4d) 1 H NMR (400 MHz, CDCl 3 ) δ 7.39-7.41 (1H, m, Ar-H), 7.14-7.31 (5H, m, Ar-H), 6.32-6.36 (2H, m, Ar-H), 5.18 (1H, s, SiCH), 3.98 (1H, d, J = 16.2 Hz, CH 2 ), 3.92 (1H, d, J = 16.2 Hz, CH 2 ), 0.90 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.56 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 205.1, 151.4, 133.9, 129.6, 128.3, 126.7, 110.5, 108.8, 74.4, 44.1, 6.5, 4.4; IR (neat) 2954, 2875, 1732, 1496, 1456, 1232, 1151, 1085, 1012, 810, 736, 700 cm -1 ; HRMS (ESI-TF) Calcd. for C 19 H 26 Na 3 Si ([M+Na] + ): 353.1543, Found: 353.1547. (E)-1,5-Diphenyl-1-(triethylsiloxy)pent-4-en-2-one (4e) 1 H NMR (400 MHz, CDCl 3 ) δ 7.44-7.46 (2H, m, -H), 7.17-7.37 (8H, m, -H), 6.34 (1H, d, J = 16.0 Hz, CH=CH), 6.19 (1H, dt, J = 16.0, 6.8 Hz, CH=CH), 5.15 (1H, s, SiCH), 3.55 (1H, dd, J = 18.0, 6.8 Hz, CH=CHCH 2 ), 3.37 (1H, dd, J = 18.0, 6.8 Hz, CH=CHCH 2 ), 0.93 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.62 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 208.2, 138.5, 137.0, 133.3, 128.5, 128.4, 128.1, 127.2, 126.1, 125.9, 122.1, 80.7, 39.9, 6.6, 4.6; IR (neat) 2954, 2875, 1718, 1492, 1450, 1240, 1138, 1095, 1068, 1014, 964, 848, 734, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 23 H 30 Na 2 Si ([M+Na] + ): 389.1907, Found: 389.1922. 1-enyl-2-(triethylsiloxy)pent-4-yn-1-one (3f) 1 H NMR (400 MHz, CDCl 3 ) δ 8.05-8.08 (2H, m, -H), 7.44-7.59 (3H, m, -H), 4.96 (1H, dd, J = 7.2, 6.0 Hz, SiCH), 2.75 (1H, ddd, J = 17.2, 6.0, 2.8 Hz, CH 2 C CH), 2.67 (1H, ddd, J = 17.2, 7.2, 2.8 Hz, CH 2 C CH), 2.02 (1H, t, 2.8 Hz, C CH), 0.91 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.61 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 199.1, 134.7, 133.2, 129.2, 128.4, 79.8, 75.3, 71.0, 25.9, 6.6, 4.7; IR (neat) 3309, 2954, 2912, 2875, 1697, 1683, 1597, 1448, 1417, 1240, 1114, 1002, 979, 918, 839, 769, 742, 729, 694 cm -1 ; HRMS (ESI-TF) Calcd. for C 17 H 24 Na 2 Si ([M+Na] + ): 311.1437, Found: 311.1434. 1-enyl-1-(triethylsiloxy)penta-3,4-dien-2-one (4f) 1 H NMR (400 MHz, CDCl 3 ) δ 7.44 (2H, d, J = 7.2 Hz, -H), 7.27-7.35 (3H, m, -H), 6.20 (1H, t, J = 6.4 Hz, CH=C=CH 2 ), 5.34 (1H, s, SiCH), 5.22 (1H, dd, J = 15.2, 6.4 Hz, CH=C=CH 2 ), 5.16 (1H, dd, J = 15.2, S8
6.4 Hz, CH=C=CH 2 ), 0.92 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.61 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 216.5, 198.0, 138.6, 128.4, 128.0, 126.2, 90.9, 79.2, 79.1, 6.6, 4.6; IR (neat) 2956, 2877, 1959, 1923, 1695, 1558, 1506, 1494, 1417, 1338, 1234, 1192, 1141, 1099, 1016, 842, 742, 729, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 17 H 24 Na 2 Si ([M+Na] + ): 311.1437, Found: 311.1434. 3-Cyclopropyl-1-phenyl-2-(triethylsiloxy)propan-1-one (3g) 1 H NMR (400 MHz, CDCl 3 ) δ 8.06 (2H, d, J = 7.2 Hz, -H), 7.54 (1H, t, J = 7.6 Hz, -H), 7.40-7.46 (2H, m, -H), 4.89 (1H, dd, J = 8.0, 5.2 Hz, SiCH), 1.87 (1H, ddd, J = 18.0, 8.0, 6.4 Hz, c-proch 2 ), 1.53 (1H, ddd, J = 18.0, 8.4, 5.2 Hz, c-proch 2 ), 0.91 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.85-0.88 (1H, m, c-pro), 0.54-0.64 (6H, m, CH 3 CH 2 Si), 0.38-0.52 (2H, m, c-pro), 0.01-0.11 (2H, m, c-pro); 13 C NMR (100 MHz, CDCl 3 ) δ 201.3, 135.1, 132.8, 129.0, 128.2, 77.8, 41.2, 7.7, 6.6, 5.0, 4.6, 4.2; IR (neat) 2954, 2910, 2875, 1699, 1681, 1456, 1238, 1155, 1101, 1016, 1002, 972, 904, 846, 763, 729, 696 cm -1 ; HRMS (ESI-TF) Calcd. for C 18 H 28 Na 2 Si ([M+Na] + ): 327.1750, Found: 327.1751. 3-Cyclopropyl-1-phenyl-1-(triethylsiloxy)propan-2-one (4g) 1 H NMR (400 MHz, CDCl 3 ) δ 7.41 (2H, d, J = 6.8 Hz, -H), 7.25-7.35 (3H, m, -H), 5.09 (1H, s, SiCH), 2.51 (1H, dd, J = 18.0, 6.8 Hz, c-proch 2 ), 2.31 (1H, dd, J = 18.0, 6.8 Hz, c-proch 2 ), 0.91 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.86-0.90 (1H, m, c-pro), 0.60 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si), 0.37-0.47 (2H, m, c-pro), 0.05-0.01 (1H, m, c-pro), 0.18-0.14 (1H, m, c-pro); 13 C NMR (100 MHz, CDCl 3 ) δ 210.2, 138.6, 128.3, 127.8, 125.7, 80.6, 41.0, 6.6, 5.6, 4.6, 4.3, 4.1; IR (neat) 2954, 2910, 2875, 1718, 1456, 1415, 1240, 1151, 1095, 1068, 1016, 1006, 975, 856, 827, 742, 729, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 18 H 28 Na 2 Si ([M+Na] + ): 327.1750, Found: 327.1756. 2-Cyclohexyl-1-phenyl-2-(triethylsiloxy)ethanone (3h) 1 H NMR (400 MHz, CDCl 3 ) δ 8.09 (2H, d, J = 7.2 Hz, -H), 7.54 (1H, t, J = 7.2 Hz, -H), 7.43 (2H, t, J = 7.2 Hz, -H), 4.23 (1H, d, J = 6.8 Hz, SiCH), 1.04-1.89 (11H, m, c-hex), 0.88 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.55 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 201.3, 135.4, 132.8, 129.2, 128.2, 82.5, 42.6, 29.3, 28.4, 26.1, 25.9, 25.9, 6.6, 4.6; IR (neat) 2929, 2875, 2852, 1699, 1681, 1448, 1263, 1240, 1151, 1136, 1099, 1002, 835, 771, 727 cm -1 ; HRMS (ESI-TF) Calcd. for C 20 H 32 Na 2 Si ([M+Na] + ): 355.2063, Found: 355.2060. S9
1-Cyclohexyl-2-phenyl-2-(triethylsiloxy)ethanone (4h) 1 H NMR (400 MHz, CDCl 3 ) δ 7.41 (2H, d, J = 7.6 Hz, -H), 7.25-7.34 (3H, m, -H), 5.11 (1H, s, SiCH), 2.83-2.89 (1H, m, CH(-CH 2 -) 5 ), 1.56-1.73 (4H, m, c-hex), 1.15-1.37 (6H, m, c-hex), 0.92 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.59 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si); 13 C NMR (100 MHz, CDCl 3 ) δ 212.9, 138.8, 128.3, 127.8, 126.1, 80.4, 44.7, 29.5, 28.7, 25.7, 25.6, 25.5, 6.6, 4.7; IR (neat) 2931, 2875, 1707, 1450, 1417, 1240, 1190, 1157, 1120, 1095, 1068, 1002, 975, 854, 835, 729, 698 cm -1 ; HRMS (ESI-TF) Calcd. for C 20 H 32 Na 2 Si ([M+Na] + ): 355.2063, Found: 355.2066. Preparation of ptically Active Substrate via Kinetic Resolution. To a solution of (S,S)-2-hydroxy-2 -[3,5-bis(trifluoromethyl)]phenyl-3-{2-[3,5-bis(trifluoromethyl)]ben zenesulfonylamino}phenyl-1,1 -binaphthyl (233.5 mg, 0.275 mmol) in toluene (25 ml) was added a 1 M toluene solution of trimethylaluminum (250 µl, 0.25 mmol) at room temperature under nitrogen and stirred for 30 min. After being cooled to 20 C, 2a (1.7 g, 5.0 mmol) was added to this solution and the stirring was maintained at 20 C for 18 h. Then, sodium fluoride (42.0 mg, 1.0 mmol) and water (13.5 µl, 0.75 mmol) were added and the whole mixture was stirred for 30 min at room temperature. To remove precipitates, filtration through celite with EtAc was carried out. Concentration of the filtrate and purification by column chromatography on silica gel (CH 2 Cl/hexane = 1/4 as eluant) afforded (R)-2a (646.3 mg, 1.9 mmol, 38% recover, 97% ee). Data for Chiral Siloxy Ketones (R)-3a [α] 25 D +39.1º (c 1.47, CHCl 3, 94% ee); HPLC condition: DAICEL Chiralcel D-H, hexane/i-prh = 99:1, flow rate = 0.3 ml/min, λ = 210 nm, retention time: 15.4 min (S), 16.9 min (R). (R)-4a [α] 28 D 40.9º (c 1.03, CHCl 3, 75% ee); HPLC condition: DAICEL Chiralcel J-H, hexane/i-prh = 99:1, flow rate = 0.3 ml/min, λ = 220 nm, retention time: 18.8 min (S), 20.6 min (R). Absolute configuration was established by comparison of the optical rotation with a known literature value 2 after derivatization. 4a (75% ee) 1N HCl THF r.t. Cu(Tf) 2 Ac 2 CH 2 Cl 2 r.t. R Ac [α] 27 D +156.8º (c = 1.01, benzene) A solution of 4a (68.1 mg, 0.2 mmol, 75% ee) in THF (2.0 ml) was treated with 1N S10
HCl (1.0 ml) with vigorous stirring. After being kept for 2h, the reaction mixture was extracted with EtAc, and the organic extracts were washed with brine and dried (Na 2 S 4 ). Filtration, Evaporation and further drying under vacuum were conducted. Then, to a solution of this crude compound and acetic anhydride (38 µl, 0.4 mmol) in dichloromethane (1.0 ml) was added copper(ii) trifluoromethanesulfonate (1.8 mg, 5.0 µmol) at room temperature under argon. After being stirred for 1 h, the mixture was quenched by the addition of sat. NaHC 3. Extractive workup was performed with EtAc and the combined organics were washed with water, brine and dried over anhydrous Na 2 S 4. After concentration, resulting crude product was purified by column chromatography on silica gel (EtAc/hexane = 1/4 as eluant) to afford pure 2-oxo-1,3-diphenylpropyl acetate (48.8 mg, 0.18 mmol, 90% yield for two steps). Synthesis of 13 C Labeled Substrate 7. Benzaldehyde (510 µl, 5.0 mmol) was slowly added to a stirred solution of sodium hydrogensulfite (58% assay, mixture of NaHS 3 and Na 2 S 2 5, 1.8 g, 10 mmol) in distilled water (3.0 ml) at room temperature to afford a white precipitate. The mixture was allowed to stir for 2 h once addition was complete, at which point the mixture was cooled to 0 ºC and a solution of potassium cyanide- 13 C (>99.5 atom % 13 C, 650 mg, 10 mmol) in water (2.0 ml) was added. After being warmed up to room temperature, this mixture was stirred for additional 2 h, and the precipitate gradually disappeared. The reaction mixture was extracted with ether and the ethereal extracts were washed with brine and then dried (Na 2 S 4 ). After filtration and evaporation, further drying of residue in vacuo was conducted. To a solution of this crude compound and N,N-diisopropylethylamine (1.0 ml, 6.0 mmol) in dichloromethane (15 ml) was added triethylsilyl chloride (1.0 ml, 6.0 mmol) at 0 ºC under argon. The reaction mixture was warmed up to room temperature and maintained for 2 h with stirring. Then, this mixture was poured into water and extracted with EtAc. The combined organics were washed with brine and dried over anhydrous Na 2 S 4. Filtration, removal of solvents and further drying under vacuum afforded almost pure 2-phenyl-2-(triethylsiloxy)acetonitrile in which 13 C was incorporated in cyano position. Further, the same manipulations for the preparation of 2a gave the 13 C labeled substrate 7. 1 H NMR (400 MHz, CDCl 3 ) δ 9.76 (1H, d, J C-H = 178.4 Hz, 13 CH), 7.26-7.32 (5H, m, -H), 7.12-7.13 (3H, m, -H), 6.95-6.97 (2H, m, -H), 3.31 (1H, dd, J = 14.4, J C-H = 3.6 Hz, CH 2 ), 3.25 (1H, dd, J = 14.4, J C-H = 2.4 Hz, CH 2 ), 0.89 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.58 (6H, q, J = 8.0 Hz, CH 3 CH 2 Si). S11
1 H NMR of 13 C incorporated siloxy ketone 8 (400 MHz, CDCl 3 ) δ 8.04-8.07 (2H, m, -H), 7.43-7.58 (3H, m, -H), 7.19-7.29 (5H, m, -H), 4.94 (1H, ddd, J = 8.8, 4.4, J C-H = 146.0 Hz, Si 13 CH), 3.05 (1H, ddd, J = 13.6, 4.4, J C-H = 2.4 Hz, CH 2 ), 2.99 (1H, ddd, J = 13.6, 8.8, J C-H = 6.2 Hz, CH 2 ), 0.75 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.36-0.42 (6H, m, CH 3 CH 2 Si). 1 H NMR of 10 (400 MHz, CDCl 3 ) δ 7.42-7.45 (2H, m, -H), 7.29-7.34 (3H, m, -H), 7.18-7.23 (3H, m, -H), 7.00-7.02 (2H, m, -H), 5.18 (1H, d, J C-H = 147.6 Hz, Si 13 CH), 3.89 (1H, d, J = 16.4 Hz, CH 2 ), 3.72 (1H, d, J = 16.4 Hz, CH 2 ), 0.91 (9H, t, J = 8.0 Hz, CH 3 CH 2 Si), 0.59 (6H, m, CH 3 CH 2 Si). References and Notes Current address: Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya, 464-8603 Japan. [1] oi, T.; hmatsu, K.; Maruoka, K. J. Am. Chem. Soc. 2007, 129, 2410. [2] Enders, D.; Bhushan, V. Tetrahedron Lett. 1988, 29, 2437. S12
Et 3 Si p-me-c 6 H 4 2b CH S13
Et 3 Si CH 2d S14
Et 3 Si CH 2f S15
Et 3 Si CH 2g S16
Et 3 Si CH 2h S17
4a S18
p-me-c 6 H 4 3b S19
C 6 H 4 (p-me) 4b S20
C 6 H 4 (p-f) 4c S21
3d S22
4d S23
4e S24
3f S25
4f S26
3g S27
4g S28
3h (3h:4h =3/1) S29
4h S30