Enantioselective Organocatalytic Michael Addition of Malonates to α, β-unsaturated Ketones Pengfei Li, Shigang Wen, Feng Yu, Qiaoxia Liu, Wenjun Li, Yongcan Wang, Xinmiao Liang, * Jinxing Ye * Dalian Institute of Chemical Physics, Chinese Academy of Science, 457 Zhongshan Road, Dalian 11623, P. R. China. Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, 13 Meilong Road, Shanghai 2237, P. R. China. liangxm@dicp.ac.cn; yejx@ecust.edu.cn Supporting Information Contents A: General Information and Starting Materials S2 B: General Procedure for Asymmetric Michael Addition S2 C: Characterization Data of Addition Products S3 D: Copies of CSP-GC or CSP-HPLC Analysis of Addition Products S1 E: Copies of 1 H and 13 C NMR spectra of Adducts S33 F: References S56 S1
A: General Information and Starting Materials General. The 1 H-NMR and 13 C-NMR were recorded on a Bruke DRX 4 (4 MHz) instrument. (s = singlet, d = doublet, dd = double doublet, t = triplet, q = quartet, m = multiplet). Chromatography was carried out with silica gel (2-3 mesh) using mixtures of petroleum ether and ethyl acetate as eluent. High resolution mass spectrometry was carried out using an ACQUITY Ultra Performance Liquid Chromatography system (Waters, Milford MA) coupled TM with a Q-TOF premier (Waters MS Technologies, Manchester, U.K) by electrospray ionization (ESI). Optical rotations were measured on an Autopol III automatic polarimeter (Rudolph Research analytical); concentrations (c) are reported in g per 1 ml. Enantiomeric excess was detered by chiral HPLC using Agilent 12 Series or chiral GC using Agilent GC689 and GC 789. Chiralpak IA (.46cm x 25 cm), Chiralpak OD-H (.46cm x 25 cm), Chiralpak AS-H (.46cm x 25 cm) or Chirasil Dex CB (# CP 752). Materials. All solvent and inorganic reagents were of p.a. quality and used without purification. Both aromatic enones and heteroaromatic enone were prepared following the literature procedures. [1] Unless otherwise noted, materials were obtained from commercial sources and used without purification. B: General Procedure for Asymmetric Michael Addition To a solution of THF (2. ml) was added α, β-unsaturated ketone 8 or 11 (1. mmol), malonate 9 (3. mmol), catalyst (.5-.1 mmol). The reaction mixture was stirred at given temperature for the time indicated in Table 2 or Table 3 and then the solvent was removed under vacuum. The residue was purified by column chromatography on silica gel to yield the desired addition product. S2
C: Characterization Data of Addition Products [2] diethyl 2-(3-oxocyclohexyl)malonate (1aa) Prepared according to general procedure. The product was obtained in 95% O yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.25-1.29 (m, 6H), 1.46-1.56 (m, 1H), 1.63-1.74 (m, 1H), 1.94-1.98 (m, 1H), 2.4-2.1 (m, 1H), COOEt 2.21-2.3 (m, 2H), 2.38-2.57 (m, 3H), 3.29 (d, J = 8. Hz, 1H), 4.17-4.24 (m, 4H);. 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.9, 24.4, 28.6, 37.9, 4.8, 44.9, COOEt 56.7, 61.3, 167.6, 167.7, 29.3. [α] 25.5 D = + 3.88 (c = 1.7 in CHCl 3, 96% ee), literature value reported by Steven 2a for the R enantiomer [α] 2 D = + 3.3 (c = 1 in CHCl 3, 93% ee). HRMS: exact mass calculated for [M+Na] + (C 13 H 2 O 5 Na) requires m/z 279.128, found m/z 279.1198. The enantiomeric excess was detered by GC. [Chirasil-Dex CB column, 1 C/ from 7 C to 16 C then hold for 3 ]: 31.487 (major), 31.773 (or). dimethyl 2-(3-oxocyclohexyl)malonate (1ab) Prepared according to general procedure. The product was obtained in 83% O yield, white solid. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.46-1.55 (m, 1H), 1.64-1.73 (m, 1H), 1.93-1.96 (m, 1H), 2.6-2.9 (m, 1H), 2.23-2.29 (m, 2H), COOMe 2.39-2.45 (m, 2H), 2.53-2.56 (m, 1H), 3.35 (d, J = 8. Hz, 1H), 3.75 (s, 6H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 24.5, 28.7, 38.1, 4.9, 45., 52.5, 56.5, COOMe 168.1, 168.2, 29.4. [α] 25. D = + 3.6 (c = 1.4 in CHCl 3, 96% ee), literature value 2a-2c reported for the R enantiomer [α] 2 D = + 2.4 (c = 1 in CHCl 3, 83% ee). HRMS: exact mass calculated for [M+Na] + (C 11 H 16 O 5 Na) requires m/z 251.895, found m/z 251.895. The enantiomeric excess was detered by GC. [Chirasil-Dex CB column, 1 C/ from 7 C to 16 C then hold for 25 ]: 23.938 (major), 24.2 (or). diisopropyl 2-(3-oxocyclohexyl)malonate (1ac) O Prepared according to general procedure. The product was obtained in 95% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.24-1.27 (m, 12H), 1.47-1.57 (m, 1H), 1.63-1.71 (m, 1H), 1.96-2.1 (m, 2H), 2.21-2.31 COOi-Pr (m, 2H), 2.38-2.54 (m, 3H), 3.22 (d, J = 7.6 Hz, 1H), 5.3-5.1 (m, 2H). COOi-Pr 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 21.6, 21.6, 24.5, 28.7, 37.9, 41., 45.1, 57.2, 69.1, 167.3, 167.4, 29.7. [α] 26.1 D = + 4.62 (c = 1.3 in CHCl 3, 96% ee). HRMS: exact mass calculated for [M+Na] + (C 15 H 24 O 5 Na) requires m/z 37.1521, found m/z 37.1515. The enantiomeric excess was detered by GC. [Chirasil-Dex CB column, 1 C/ from 7 C to 15 C then hold for 5 ]: 49.111 (major), 49.669 (or). diethyl 2-(3-oxocycloheptyl)malonate (1ba) O COOEt COOEt Prepared according to general procedure. The product was obtained in 83% yield, yellow oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.27 (t, J = 7.2 Hz, 6H), 1.39-1.6 (m, 3H), 1.86-1.97 (m, 3H), 2.46-2.6 (m, 5H), 3.3 (d, J = 6.8 Hz, 1H), 4.18-4.24 (m, 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 14., 24.4, 28.7, 34.1, 35.6, 43.5, 47.1, 57.4, 61.4, 168., 168.1, 212.5. [α] 26.7 D = + 41.72 (c = 1.2 in CHCl 3, 93% ee), literature value reported by Steven 2a for S3
the R enantiomer [α] 2 D = + 23.4 (c =.1 in CHCl 3, 89% ee). HRMS: exact mass calculated for [M+Na] + (C 14 H 22 O 5 Na) requires m/z 293.1365, found m/z 293.1291. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 9:1,.8 ml/]: 23.553 (major), 28.749 (or). diethyl 2-(3-oxocyclopentyl)malonate (1ca) Prepared according to general procedure. The product was obtained in 64% O yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.24-1.29 (m, 6H), 1.62-1.71 (m, 1H), 1.98-2.5 (m, 1H), 2.17-2.27 (m, 2H), 2.28-2.36 (m, 1H), COOEt 2.47-2.53 (m, 1H), 2.81-2.88 (m, 1H), 3.32 (d, J = 9.2 Hz, 1H), 4.17-4.24 (m, COOEt 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 14., 27.4, 36.3, 38.1, 42.8, 56.4, 61.5, 168., 168.1, 217.1. [α] 27.5 D = + 5.84 (c = 1.7 in CHCl 3, 63% ee), literature value reported by Steven 2a for the R enantiomer [α] 2 D = + 22.2 (c =.9 in CHCl 3, 3% ee). HRMS: exact mass calculated for [M+Na] + (C 12 H 18 O 5 Na) requires m/z 265.152, found m/z 265.152. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 4:1,.8 ml/]: 52.918 (or), 56.799 (major). diethyl 2-(2,2-dimethyl-5-oxocyclohexyl)malonate (1da) O Prepared according to general procedure. The product was obtained in 77% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.6 (s, 6H), 1.25-1.3 (m, 6H), 1.65-1.7 (m, 2H), 2.28-2.46 (m, 3H), 2.5-2.56 (m, 1H), COOEt 2.61-2.67 (m, 1H), 3.57 (d, J = 4.8 Hz, 1H ), 4.16-4.12 (m, 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.9, 2.1, 28.7, 33.1, 37.7, 4., 4.4, 45.1, 52.2, COOEt 61.4, 61.7, 168.6, 168.7, 21.. [α] 27.7 D = + 11.82 (c = 1.3 in CHCl 3, 91% ee). HRMS: exact mass calculated for [M+Na] + (C 15 H 24 O 5 Na) requires m/z 37.1521, found m/z 37.1514. The enantiomeric excess was detered by HPLC. [IA column, 22 nm, hexane: IPA = 2:1,.8 ml/]: 15.16 (major), 18.719 (or). diethyl 2-(3-oxo-1-phenylbutyl)malonate (12aa) EtOOC Prepared according to general procedure. The product was obtained in 92% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.1 (t, J = 7.2 Hz, 3H), 1.25 (t, J = 7.2 Hz, 3H), 2.2 (s, 3H), 2.91-2.95 (m, 2H), 3.69 (d, J = 1. Hz, 1H), 3.92-4. (m, 3H), 4.19 (q, J = 7.2 Hz, 2H), 7.18-7.29 (m, 5H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 14., 14.3, 3.5, 4.7, 47.7, 57.7, 61.6, 61.9, 127.5, 128.4, 128.7, 14.7, 167.9, 168.5, 26.3. [α] 28.2 D = + 17.84 (c = 1.2 in CHCl 3, 96% ee), literature value reported by Steven 2a for the S enantiomer [α] 2 D = + 15.8 (c = 1.1 in CHCl 3, 87% ee). HRMS: exact mass calculated for [M+Na] + (C 17 H 22 O 5 Na) requires m/z 329.1365, found m/z 329.1353. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/]: 1.915 (major), 13.463 (or). dimethyl 2-(3-oxo-1-phenylbutyl)malonate (12ab) MeOOC COOEt O COOMe O Prepared according to general procedure. The product was obtained in 92% yield, yellow oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 2.5 (s, 3H), 2.9-3.2 (m, 2H), 3.52 (s, 3H), 3.74-3.76 (m, 4H), 3.97-4.3 (m, 1H), 7.2-7.31 (m, 5H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 3.2, 4.4, 47.1, 52.3, 52.6, 57.1, 127.2, 128., 128.5, 14.4, 168., 168.5, 25.9. [α] 29.2 D = + 13. (c = 1.1 in CHCl 3, 94% ee), literature value reported by Steven 2a for the S enantiomer [α] 2 D = + 11.4 (c = 1 in CHCl 3, 89% ee). HRMS: exact mass calculated for [M+Na] + (C 15 H 18 O 5 Na) S4
requires m/z 31.152, found m/z 31.996. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 4:1,.8 ml/]: 15.135 (major), 19.54 (or). diisopropyl 2-(3-oxo-1-phenylbutyl)malonate (12ac) Prepared according to general procedure. The product was obtained in 9% i-prooc COOi-Pr O yield, yellowy oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm).98 (d, J = 6.4 Hz, 3H), 1.5 (d, J = 6. Hz, 3H), 1.25 (dd, J =2., 6.4 Hz, 6H), 2.3 (s, 3H), 2.86-2.99 (m, 2H), 3.65 (d, J = 1.4 Hz, 1H), 3.93-3.99 (m, 1H), 4.76-4.82 (m, 1H), 5.3-5.1 (m, 1H), 7.18-7.29 (m, 5H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 21.2, 21.3, 21.5, 21.6, 3.3, 4.4, 47.7, 57.7, 68.8, 69.2, 127.1, 128.2, 128.4, 14.5, 167.1, 167.8, 26.1. [α] 29.1 D = + 18.94 (c = 1.2 in CHCl 3, 96% ee). HRMS: exact mass calculated for [M+Na] + (C 19 H 26 O 5 Na) requires m/z 357.1678, found m/z 357.1678. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/]: 7.678 (major), 1.268 (or). diethyl 2-(1-(4-chlorophenyl)-3-oxobutyl)malonate (12ba) Cl Prepared according to general procedure. The product was obtained in 95% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.5 (t, J = 7.2 Hz, 3H), 1.25 (t, J = 7. Hz, 3H), 2.3 (s, 3H), 2.85-2.99 (m, 2H), 3.66 (d, J = 9.6 Hz, 1H), 3.92-4. (m, 3H), 4.16-4.22 (m, 2H), 7.18-7.27 (m, 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.8, 14., 3.3, 39.7, 47.1, 57.1, 61.4, 61.7, 128.6, 129.6, 132.9, 139.1, 167.4, 168., 25.6. [α] 29.3 D = + 16.42 (c = 1.1 in CHCl 3, 93% ee), literature value reported by Steven 2a for the S enantiomer [α] 2 D = + 13.9 (c = 1.2 in CHCl 3, 83% ee). HRMS: exact mass calculated for [M+Na] + (C 17 H 21 ClO 5 Na) requires m/z 363.975, found m/z 363.979. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/]: 12.4 (major), 13.463 (or). diethyl 2-(1-(2-bromophenyl)-3-oxobutyl)malonate (12ca) EtOOC EtOOC Br COOEt O COOEt O Prepared according to general procedure. The product was obtained in 94% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.11 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7. Hz, 3H), 2.9 (s, 3H), 3.6 (d, J = 7.2 Hz, 2H), 3.95 (d, J = 8.8 Hz, 1H), 4.5 (q, J = 7.2 Hz, 2H), 4.11-4.2 (m, 2H), 4.46 (dd, J = 7., 15. Hz, 1H), 7.5 (m, 1H), 7.22-7.28 (m, 2H), 7.55 (d, J = 8. Hz, 1H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.8, 13.9, 3., 39.1, 45.6, 55.2, 61.4, 61.5, 124.7, 127.5, 128.7, 129., 133.4, 139.6, 167.6, 168., 25.8. [α] 28.8 D = + 8.78 (c =.99 in CHCl 3, 94% ee), literature value reported by Steven 2a for the S enantiomer [α] 2 D = + 1.6 (c =.5 in CHCl 3, 6% ee). HRMS: exact mass calculated for [M+Na] + (C 17 H 21 BrO 5 Na) requires m/z 47.47, found m/z 47.431. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 9:1,.8 ml/.]: 11.542 (major), 12.763 (or). diethyl 2-(1-(4-bromophenyl)-3-oxobutyl)malonate (12da) Prepared according to general procedure. The product was obtained in 94% yield, colorless oil. S5
Br 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.6 (t, J = 7.2 Hz, 3H), 1.26 (t, J = 7. Hz, 3H), 2.4 (s, 3H), 2.85-2.99 (m, 2H), 3.66 (d, J = 1. Hz, 1H), 3.92-4. (m, 3H), 4.18-4.2 (m, 2H), 7.13-7.41 (m, 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.8, 14., 3.3, 39.7, 47.1, 57., 61.4, 61.7, 121., 13., 131.5, 139.6, 167.4, 167.9, 25.6. [α] 28.8 D = + 14.76 (c = 1.5 in CHCl 3, 94% ee), literature value reported by Steven 2a for the S enantiomer [α] 2 D = + 12.3 (c = 1.1 in CHCl 3, 85% ee). HRMS: exact mass calculated for [M+Na] + (C 17 H 21 BrO 5 Na) requires m/z 47.47, found m/z 47.462. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 4:1,.8 ml/.]: 22.179 (major), 23.15 (or). diethyl 2-(1-(2-nitrophenyl)-3-oxobutyl)malonate (12ea) Prepared according to general procedure. The product was obtained in 97% EtOOC COOEt O yield, orange oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.1 (t, J = 7.2 Hz, 3H), 1.24 (t, J = 7.2 Hz, 3H), 2.11 (s, 3H), 3.6-3.18 (m, 2H), 3.99-4.7 (m, 3H), 4.14-4.23 (m, 2H), 4.45-4.51 (m, 1H), 7.35-7.39 (m, 1H), 7.47-7.55 (m, NO 2H), 7.8-7.82 (d, J = 8.4 Hz, 1H). 13 2 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.7, 13.9, 29.9, 34.6, 46.1, 55.7, 61.6, 61.7, 124.6, 127.9, 129.2, 132.6, 135.4, 15.3, 167.4, 168., 25.6. [α] 29.4 D = - 14.32 (c = 1.4 in CHCl 3, 94% ee). HRMS: exact mass calculated for [M+Na] + (C 17 H 21 NO 7 Na) requires m/z 374.1216, found m/z 374.1219. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane:ipa =9:1,.8 ml/.]: 21.668 (major), 23.295 (or). diethyl 2-(1-(4-nitrophenyl)-3-oxobutyl)malonate (12fa) O 2 N EtOOC EtOOC COOEt O COOEt O Prepared according to general procedure. The product was obtained in 9% yield, yellow oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.6 (t, J = 7.2 Hz, 3H), 1.26 (t, J = 7. Hz, 3H), 2.6 (s, 3H), 2.93-3.8 (m, 2H), 3.73 (d, J = 9.6 Hz, 1H), 3.96-4.1 (m, 2H), 4.6-4.12 (m, 1H), 4.17-4.23 (m, 2H), 7.45 (d, J = 8.8 Hz, 2H), 8.13 (d, J = 8.4 Hz, 2H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.8, 14., 3.2, 39.8, 46.7, 56.5, 61.6, 61.9, 129.3, 129.6, 147., 148.5, 167.2, 167.6, 25.1. [α] 28.7 D = + 18.46 (c = 1.2 in CHCl 3, 93% ee). HRMS: exact mass calculated for [M+Na] + (C 17 H 21 NO 7 Na) requires m/z 374.1216, found m/z 374.1214. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/.]: 32.472 (major), 36.585 (or). diethyl 2-(3-oxo-1-o-tolylbutyl)malonate (12ga) EtOOC COOEt O Prepared according to general procedure. The product was obtained in 92% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm).99 (t, J = 7. Hz, 3H), 1.27 (t, J = 7. Hz, 3H), 2. (s, 3H), 2.48 (s, 3H), 2.93-2.95 (m, 2H), 3.7 (d, J = 9.6 Hz, 1H), 3.91-3.96 (m, 2H), 4.17-4.29 (m, 3H), 7.6-7.15 (m, 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.6, 14., 19.7, 3.4, 35.2, 47.7, 57.1, 61.2, 61.6, 126., 126.1, 126.8, 13.7, 136.9, 139.1, 167.7, 168.3, 26.. [α] 28.9 D = + 4.96 (c = 1.2 in CHCl 3, 93% ee). HRMS: exact mass calculated for [M+Na] + (C 18 H 24 O 5 Na) requires m/z 343.1521, found m/z 343.1521. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 9:1,.8 ml/.]: 8.79 (major), 9.357 (or). S6
diethyl 2-(3-oxo-1-m-tolylbutyl)malonate (12ha) EtOOC Prepared according to general procedure. The product was obtained in 86% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.3 (t, J = 7. Hz, 3H), 1.26 (t, J = 7.2 Hz, 3H), 2.3 (s, 3H), 2.31 (s, 3H), 2.91-2.94 (m, 2H), 3.68 (d, J = 1. Hz, 1H), 3.91-3.99 (m, 3H), 4.17-4.22 (m, 2H), 7.-7.4 (m, 3H), 7.15 (t, J = 7.2 Hz, 1H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.7, 14., 21.4, 3.2, 4.4, 47.4, 57.4, 61.2, 61.5, 125., 127.9, 128.3, 128.9, 137.9, 14.3, 167.6, 168.2, 26.1. [α] 29. D = + 16.3 (c = 1.2 in CHCl 3, 94% ee). HRMS: exact mass calculated for [M+Na] + (C 18 H 24 O 5 Na) requires m/z 343.1521, found m/z 343.155. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 9:1,.8 ml/.]: 9.686 (major), 11.558 (or). diethyl 2-(3-oxo-1-p-tolylbutyl)malonate (12ia) EtOOC COOEt O Prepared according to general procedure. The product was obtained in 91% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.4 (t, J = 7.2 Hz, 3H), 1.26 (t, J = 7.2 Hz, 3H), 2.2 (s, 3H), 2.29 (s, 3H), 2.86-2.96 (m, 2H), 3.68 (d, J = 1 Hz, 1H), 3.91-3.99 (m, 3H), 4.17-4.23 (m, 2H), 7.7 (d, J = 8. Hz, 2H), 7.13 (d, J = 8. Hz, 2H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.7, 14., 2.9, 3.2, 4.1, 47.4, 57.5, 61.2, 61.5, 128., 129.1, 136.6, 137.3, 167.6, 168.2, 26.1. [α] 29.1 D = + 18.48 (c = 1.3 in CHCl 3, 94% ee), literature value reported by Steven 2a for the S enantiomer [α] 2 D = + 14. (c = 1.1 in CHCl 3, 88% ee). HRMS: exact mass calculated for [M+Na] + (C 18 H 24 O 5 Na) requires m/z 343.1521, found m/z 343.1513. The enantiomeric excess was detered by HPLC. [AS-H column, 22 nm, hexane: IPA = 9:1,.8 ml/.]: 11.2 (major), 11.851 (or). diethyl 2-(1-(2-methoxyphenyl)-3-oxobutyl)malonate (12ja) EtOOC COOEt O COOEt O Prepared according to general procedure. The product was obtained in 71% yield, yellow oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1. (t, J = 7. Hz, 3H), 1.25 (t, J = 7. Hz, 3H), 2.5 (s, 3H), 2.91 (dd, J = 4.4, 16.4 Hz, 1H), 3.7 (dd, J = 9.2, 16.4 Hz, 1H), 3.87 (s, 3H), 3.93 (q, J = 7.1 Hz, 2H), 4.5 (d, J = 1. Hz, 1H), 4.14-4.23 (m, 3H), 6.83-6.87 (m, 2H), 7.17-7.21 (m, 2H). OMe 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.7, 14., 29.9, 37.3, 45.7, 55., 55.3, 61., 61.3, 11.9, 12.4, 127.8, 128.4, 13.4, 157.4, 168., 168.6, 26.7. [α] 29.4 D = + 22.38 (c = 1.1 in CHCl 3, 97% ee). HRMS: exact mass calculated for [M+Na] + (C 18 H 24 O 6 Na) requires m/z 359.1471, found m/z 359.1433. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/]: 1.385 (major), 14.38 (or). dimethyl 2-(1-(2-nitrophenyl)-3-oxobutyl)malonate (12eb) MeOOC COOMe Prepared according to general procedure. The product was obtained in 93% O yield, orange oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 2.1 (s, 3H), 3.6-3.19 (m, 2H), 3.6 (s, 3H), 3.71 (s, 3H), 4.3 (d, J = 8.4 Hz, 1H), 4.46-4.51 (m, 1H), 7.35-7.55 (m, 3H), 7.79-7.82 (dd, J = 1.2, 8. Hz, 1H). NO 13 2 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 29.9, 34.5, 45.9, 52.6, 53.5, 55.5, 124.6, 128., 128.9, 132.7, 135.2, 15.2, 167.8, 168.3, 25.5. [α] 29.4 D = - 12.22 (c =.99 in CHCl 3, S7
93% ee). HRMS: exact mass calculated for [M+Na] + (C 15 H 17 NO 7 Na) requires m/z 346.93, found m/z 346.91. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/]: 31.43 (major), 35.23 (or). diethyl 2-(3-oxo-1-(thiophen-2-yl)butyl)malonate (12ka) EtOOC S Prepared according to general procedure. The product was obtained in 83% yield, yellow oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm) 1.14 (t, J = 7. Hz, 3H), 1.26 (t, J = 7. Hz, 3H), 2.1 (s, 3H), 3.1 (d, J = 6.4 Hz, 2H), 3.75 (d, J = 8.8 Hz, 1H), 4.6 (m, 2H), 4.17-4.23 (m, 2H), 4.29-4.34 (m, 1H), 6.88-6.91 (m, 2H), 7.15-7.16 (d, J = 3.2 Hz, 1H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.8, 14., 3.2, 35.7, 47.9, 57.7, 61.5, 61.6, 124.2, 125.7, 126.6, 143.6, 167.5, 167.9, 25.7. [α] 29.4 D = + 18.64 (c = 1.5 in CHCl 3, 9% ee), literature value reported by Steven 2a for the S enantiomer [α] 2 D = + 14.3 (c = 1. in CHCl 3, 88% ee). HRMS: exact mass calculated for [M+Na] + (C 15 H 2 SO 5 Na) requires m/z 335.929, found m/z 335.826. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/]: 14.918 (major), 17.495 (or). diethyl 2-(2-oxoheptan-4-yl)malonate (12la) EtOOC COOEt O COOEt O Prepared according to general procedure. The product was obtained in 91% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm).89 (t, J = 6.8 Hz, 3H), 1.24-1.35 (m, 1H), 2.14 (s, 3H), 2.51 (dd, J = 6., 8.4 Hz,1H), 2.66-2.77 (m, 2H), 3.52 (d, J = 5.6 Hz, 1H), 4.17 (m, 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.9, 14., 2., 3.2, 33.2, 34.4, 45.2, 54., 61.1, 61.2, 168.6, 168.9, 27.4. [α] 27.9 D = + 16.28 (c = 1.5 in CHCl 3, 96% ee). HRMS: exact mass calculated for [M+Na] + (C 14 H 24 O 5 Na) requires m/z 295.1521, found m/z 295.1515. The enantiomeric excess was detered by HPLC. [OD-H column, 22 nm, hexane: IPA = 2:1,.8 ml/]: 6.499 (major), 6.865 (or). diethyl 2-(2-oxooctan-4-yl)malonate (12ma) Prepared according to general procedure. The product was obtained in EtOOC COOEt O 9% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm).87 (t, J = 7. Hz, 3H), 1.21-1.43 (m, 12H), 2.14 (s, 3H), 2.48-2.54 (m, 1H), 2.65-2.69 (m, 1H), 2.72-2.77 (m, 1H), 3.52 (d, J = 5.6 Hz, 1H), 4.15-4.21 (m, 4H). 13 C-NMR (4 MHz, CDCl 3 ): δ (ppm) 13.8, 14., 22.5, 29., 3.2, 31.8, 33.4, 45.2, 54., 61.1, 61.2, 168.6, 168.9, 27.4. [α] 28.1 D = + 13.98 (c = 1.5 in CHCl 3, 97% ee). HRMS: exact mass calculated for [M+Na] + (C 15 H 26 O 5 Na) requires m/z 39.1678, found m/z 39.1652. The enantiomeric excess was detered by HPLC. [OD-H column, 22 nm, hexane: IPA = 2:1,.8 ml/]: 6.15 (major), 6.491 (or). diethyl 2-(3-oxo-1-phenylpentyl)malonate (12na) EtOOC COOEt O Prepared according to general procedure. The product was obtained in 8% yield, colorless oil. 1 H-NMR (4 MHz, CDCl 3 ): δ (ppm).93 (t, J = 7.2 Hz, 3H), 1.2 (t, J = 7.2 Hz, 3H), 1.27 (t, J = 7.2 Hz, 3H), 2.19-2.4 (m, 2H), 2.91 (m, J = 7.2 Hz, 2H), 3.72 (d, J = 1. Hz, 1H), 3.92 (m, 3H), 4.2 (q, J = 7.2 Hz, 2H), 7.22-7.29 (m, 5H). 13 C-NMR (4 MHz, CDCl 3 ): S8
δ (ppm) 7.5, 13.7, 14., 36.4, 4.5, 46.2, 57.4, 61.3, 61.6, 127.2, 128.1, 128.4, 14.5, 167.7, 168.3, 28.8. [α] 13.4 D = + 5.58 (c = 1.1 in CHCl 3, 83% ee). HRMS: exact mass calculated for [M+Na] + (C 18 H 24 O 5 Na) requires m/z 343.1521, found m/z 343.153. The enantiomeric excess was detered by HPLC. [AS-H column, 254 nm, hexane: IPA = 9:1,.8 ml/]: 1.81 (major), 12.36 (or). S9
D: CSP-HPLC or CSP-GC Analysis of Addition Products diethyl 2-(3-oxocyclohexyl)malonate (1aa) pa FID1 A, 前部信号 (D:\CHEM32\1\DATA\LIPF\81128\ 环己烯酮 - 丙二酸酯.D 1 8 6 4 31.376 31.824 峰面积峰面积 : 381 : 39 2 1 2 3 Racemic adduct (sample in CH 2 Cl 2 ) 1 31.376 381.1 27.7.2292 49.415 2 31.824 39.1 31.298 1.36 5.585 pa 1 8 FID1 A, 前部信号 (D:\CHEM32\1\DATA\LIPF\81128\ 环己烯酮 - 丙二酸酯 1.D 31.487 峰面积 : 836 6 4 2 31.773 峰面积 : 14 1 2 3 Asymmetric adduct (sample in CH 2 Cl 2 ) 1 31.487 837 57.2.2439 2.67 98.243 2 31.773 15 1.7.1462.757 1.757 S1
dimethyl 2-(3-oxocyclohexyl)malonate (1ab) pa FID1 A, 前部信号 (D:\CHEM32\1\DATA\LIPF\81128\ 环己烯酮 - 丙二酸酯 2.D 4 35 24.218 23.874 3 25 2 15 5 1 15 2 25 Racemic adduct (sample in CH 2 Cl 2 ) 1 23.874 16 19.9.1117 1.197 49.878 2 24.218 16.8 19.8.1259 1.232 5.122 pa 1 8 FID1 A, 前部信号 (D:\CHEM32\1\DATA\LIPF\81128\ 环己烯酮 - 丙二酸酯 3.D) 23.938 峰面积 : 51.847 6 4 2 24.2 峰面积 : 1.89 5 1 15 2 25 Asymmetric adduct (sample in CH 2 Cl 2 ) 1 23.938 51.8 57.4.1458 2.118 97.892 2 24.2 1.8 1.5.1229.922 2.18 S11
diisopropyl 2-(3-oxocyclohexyl)malonate (1ac) pa FID1 A, 前部信号 (D:\CHEM32\1\DATA\LIPF\81128\ 环己烯酮 - 丙二酸酯 4.D) 22 2 18 48.645 49.552 峰面积 : 59.5916 峰面积 : 6.4533 16 14 2 4 Racemic adduct (sample in CH 2 Cl 2 ) 1 48.645 59.6 2.5.3962.943 49.641 2 49.552 6.5 2.5.498 1.1 5.359 pa 1 8 6 4 2 FID1 A, 前部信号 (D:\CHEM32\1\DATA\LIPF\81128\ 环己烯酮 - 丙二酸酯 5.D) 49.111 49.669 峰面积 : 1459.23 峰面积 : 32.2851 2 4 Asymmetric adduct (sample in CH 2 Cl 2 ) 1 49.111 1459.2 5.1.4854 3.189 97.835 2 49.669 32.3 1.8.2912.938 2.165 S12
diethyl 2-(3-oxocycloheptyl)malonate (1ba) VWD1 A, 波长 =22 nm (LIPF\81127\ 烯酮 - 丙二酸酯 2.D) 25 2 15 1 5 23.299 29.982 峰面积 : 4182.62 1 2 3 Racemic adduct (sample in EtOH) 1 23.299 3877.2 6.2.9584.379 48.15 2 29.982 4182.6 39.4 1.77.375 51.895 6 VWD1 A, 波长 =22 nm (LIPF\81127\ 烯酮 - 丙二酸酯 4.D) 23.553 5 4 3 2 1 1 2 3 28.749 Asymmetric adduct (sample in EtOH) 1 23.553 432.3 62.9.9931.326 96.489 2 28.749 157.2 2.9.751.796 3.511 S13
diethyl 2-(3-oxocyclopentyl)malonate (1ca) VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 39.D) 6 4 55.33 61.869 2-2 2 4 6 Racemic adduct (sample in EtOH) # Time Area Height Width Symmetry Area% 1 55.33 55.7 28.2 2.5858.196 49.714 2 61.869 5563.9 29 2.594.237 5.286 8 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 4.D) 7 6 5 4 56.799 3 2 52.918 1 2 4 6 Asymmetric adduct (sample in EtOH) # Time Area Height Width Symmetry Area% 1 52.918 1495.9 13.2 1.5552.315 18.565 2 56.799 6561.8 37.2 2.3147.233 81.435 S14
diethyl 2-(2,2-dimethyl-5-oxocyclohexyl)malonate (1da) VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 47.D) 2 15 1 15.237 18.438 5 5 1 15 2 Racemic adduct (sample in EtOH) # Time Area Height Width Symmetry Area% 1 15.237 2258.8 113.9.2895.552 48.658 2 18.438 2383.5 92.2.37.445 51.342 16 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 48.D) 15.16 14 12 1 8 6 4 2 18.719 5 1 15 2 Asymmetric adduct (sample in EtOH) # Time Area Height Width Symmetry Area% 1 15.16 3527.4 167.2.314.436 95.444 2 18.719 168.4 7.4.3455 1.12 4.556 S15
diethyl 2-(3-oxo-1-phenylbutyl)malonate (12aa) 8 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 19.D) 1.85 13.219 6 4 2 5 1 15 Racemic adduct (sample in EtOH) 1 1.85 1924.2 96.1.378.434 5.11 2 13.219 1923.3 76.4.3911.591 49.989 6 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 2.D) 1.915 5 4 3 2 1 13.463 峰面积 : 22.7197 5 1 15 Asymmetric adduct (sample in EtOH) 1 1.915 1263.6 67.3.296.56 98.234 2 13.463 22.7 1.2.3112.778 1.766 S16
dimethyl 2-(3-oxo-1-phenylbutyl)malonate (12ab) 3 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 5.D) 15.384 25 2 19.577 15 1 5 5 1 15 2 Racemic adduct (sample in EtOH) 1 15.384 7292 286.3.45.669 49.515 2 19.577 7434.9 22.3.5744.585 5.485 4 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 49.D) 15.135 3 2 1 19.54 5 1 15 2 Asymmetric adduct (sample in EtOH) 1 15.135 12584.9 476.5.4188.552 96.98 2 19.54 391.9 12.5.4824.856 3.2 S17
diisopropyl 2-(3-oxo-1-phenylbutyl)malonate (12ac) 16 VWD1 A, 波长 =254 nm (LIPF\81127\ 烯酮 - 丙二酸酯 5.D) 7.746 14 12 1 9.928 8 6 4 2 2.5 5 7.5 1 Racemic adduct (sample in EtOH) 1 7.746 259.4 151.5.2559.59 5.13 2 9.928 258.1 95.1.482.448 49.987 VWD1 A, 波长 =254 nm (LIPF\81127\ 烯酮 - 丙二酸酯 6.D) 7.678 2 15 1 5 2 4 6 8 1 1.268 Asymmetric adduct (sample in EtOH) 1 7.678 5196.1 254.6.3182.433 97.91 2 1.268 111.4 4.5.387.975 2.99 S18
diethyl 2-(1-(4-chlorophenyl)-3-oxobutyl)malonate (12ba) VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 11.D) 2 15 1 5 12.28 13.231-5 -1 2.5 5 7.5 1 12.5 Racemic adduct (sample in EtOH) 1 12.28 1583.1 46.5.682.529 5.53 2 13.231 1579.7 69.3531.595 49.947 1 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 12.D) 12.4 8 6 4 2 13.463 2.5 5 7.5 1 12.5 Asymmetric adduct (sample in EtOH) 1 12.4 5228.4 15.7.845.395 96.482 2 13.463 19.6 7.2.3875.68 3.518 S19
diethyl 2-(1-(2-bromophenyl)-3-oxobutyl)malonate (12ca) 14 12 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 31.D) 11.426 12.62 1 8 6 4 2 5 1 15 Racemic adduct (sample in EtOH) 1 11.426 3117.3 1474.6.3291.63 49.753 2 12.62 31416.7 1228.3931.56 5.247 35 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 32.D) 11.542 3 25 2 15 1 5 12.763 5 1 15 Asymmetric adduct (sample in EtOH) 1 11.542 7846.1 399.9.361.751 97.186 2 12.763 227.2 1.5.33.942 2.814 S2
diethyl 2-(1-(4-bromophenyl)-3-oxobutyl)malonate (12da) 12 1 8 6 4 2-2 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 43.D) 22.259 23.214 5 1 15 2 25 Racemic adduct (sample in EtOH) 1 22.259 3617.9 18.7.5192.838 5.677 2 23.214 3521.2 96.2.5597.821 49.323 14 12 1 8 6 4 2-2 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 44.D) 22.179 23.15 5 1 15 2 25 Asymmetric adduct (sample in EtOH) 1 22.179 574.7 165.4.5348.759 97.89 2 23.15 171.1 6.2.4156.283 2.911 S21
diethyl 2-(1-(2-nitrophenyl)-3-oxobutyl)malonate (12ea) 17.5 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 53.D) 21.643 22.863 15 12.5 1 7.5 5 2.5-2.5 5 1 15 2 25 Racemic adduct (sample in EtOH) 1 21.643 765.5 21.6.5524.919 48.314 2 22.863 819 2.7.626.743 51.686 8 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 54.D) 21.668 6 4 2 23.295 1 2 3 Asymmetric adduct (sample in EtOH) 1 21.668 4115.1 921.7.6939.529 96.99 2 23.295 1273 27.4.6663.586 3.1 S22
diethyl 2-(1-(4-nitrophenyl)-3-oxobutyl)malonate (12fa) 1 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 14.D) 31.961 35.472 8 6 4 2 1 2 3 4 Racemic adduct (sample in EtOH) 1 31.961 88965 113.4 1.3285.399 49.441 2 35.472 9977.9 145.8 1.3294.413 5.559 4 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 13.D) 32.472 3 2 1 36.585 1 2 3 4 Asymmetric adduct (sample in EtOH) 1 32.472 41613.6 49.7 1.2792.45 96.486 2 36.585 1515.7 21.3 1.574.941 3.514 S23
diethyl 2-(3-oxo-1-o-tolylbutyl)malonate (12ga) 6 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 35.D) 8.16 9.411 5 4 3 2 1 2 4 6 8 1 Racemic adduct (sample in EtOH) 1 8.16 996.5 76.4.2175.671 5.471 2 9.411 9721.4 625.3.244.773 49.529 8 7 6 5 4 3 2 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 36.D) 8.79 1 9.357 2 4 6 8 1 Asymmetric adduct (sample in EtOH) 1 8.79 12332.4 856.6.2233.663 96.516 2 9.357 445.2 23.283 1.25 3.484 S24
diethyl 2-(3-oxo-1-m-tolylbutyl)malonate (12ha) 4 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 33.D) 9.89 11.631 3 2 1 2.5 5 7.5 1 Racemic adduct (sample in EtOH) 1 9.89 792.6 474.9.2582.733 5.253 2 11.631 7822.9 391.8.3116.736 49.747 16 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 34.D) 9.686 14 12 1 8 6 4 2 11.558 2.5 5 7.5 1 Asymmetric adduct (sample in EtOH) 1 9.686 32955.4 175.2.399.53 97.9 2 11.558 987.6 52.5.2923.98 2.91 S25
diethyl 2-(3-oxo-1-p-tolylbutyl)malonate (12ia) 3 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 37.D) 1.918 11.643 25 2 15 1 5 2.5 5 7.5 1 12.5 Racemic adduct (sample in EtOH) 1 1.918 5875 333.4.274.797 46.428 2 11.643 6779 312.4.326.936 53.572 1 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 38.D) 11.2 8 6 4 2 11.851 2.5 5 7.5 1 12.5 Asymmetric adduct (sample in EtOH) 1 11.2 238.9 173.2959.647 97.22 2 11.851 625.6 28.8.3266.853 2.978 S26
diethyl 2-(1-(2-methoxyphenyl)-3-oxobutyl)malonate (12ja) 5 4 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 29.D) 1.383 14.288 3 2 1 5 1 15 Racemic adduct (sample in EtOH) 1 1.383 117.6 59.2.2661.752 49.793 2 14.288 126.1 38.5.4141.749 5.27 5 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 3.D) 1.385 4 3 2 1 14.38 峰面积 : 15.4419 5 1 15 Asymmetric adduct (sample in EtOH) 1 1.385 15.6 58.5.2676.747 98.486 2 14.38 15.5 7.1E-1.364.825 1.514 S27
dimethyl 2-(1-(2-nitrophenyl)-3-oxobutyl)malonate (12eb) VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 55.D) 35 3 25 2 15 1 5 31.719 34.997 1 2 3 Racemic adduct (sample in EtOH) 1 31.719 1275.1 26.2.7534.913 53.43 2 34.997 1111.4 21.2.8238.864 46.57 35 3 25 2 15 1 VWD1 A, 波长 =254 nm (LIPF\8624\ 烯酮 - 丙二酸酯 56.D) 31.43 5 35.23 1 2 3 Asymmetric adduct (sample in EtOH) 1 31.43 21113.4 41.7.8199.658 96.545 2 35.23 755.5 14.8.7931.842 3.455 S28
diethyl 2-(3-oxo-1-(thiophen-2-yl)butyl)malonate (12ka) 12 1 VWD1 A, 波长 =22 nm (LIPF\81127\ 烯酮 - 丙二酸酯.D) 14.788 17.362 8 6 4 2 5 1 15 Racemic adduct (sample in EtOH) 1 14.788 36957.6 126.2.4528.54 5.47 2 17.362 36888.6 141.2.552.53 49.953 6 VWD1 A, 波长 =22 nm (LIPF\81127\ 烯酮 - 丙二酸酯 1.D) 14.918 5 4 3 2 1 17.495 5 1 15 Asymmetric adduct (sample in EtOH) 1 14.918 1799.1 68.5.3952.773 95.29 2 17.495 94.1 3.5.428.898 4.971 S29
diethyl 2-(2-oxoheptan-4-yl)malonate (12la) 5 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 2.D) 6.553 6.87 4 3 2 1 2 4 6 8 Racemic adduct (sample in EtOH) 1 6.553 427.8 52.3.1275.97 49.863 2 6.87 43.2 49.2.1354.888 5.137 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 3.D) 6.499 3 25 2 15 1 5 6.865 2 4 6 8 Asymmetric adduct (sample in EtOH) 1 6.499 3148.1 357.4.1362.66 97.88 2 6.865 68.2 5.4.1798.515 2.12 S3
diethyl 2-(2-oxooctan-4-yl)malonate (12ma) 14 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯.D) 6.155 6.469 12 1 8 6 4 2 2 4 6 8 Racemic adduct (sample in EtOH) 1 6.155 1183.7 146.8.1246.857 5.35 2 6.469 1182 135.2.1355.794 49.965 2 VWD1 A, 波长 =22 nm (LIPF\8624\ 烯酮 - 丙二酸酯 1.D) 6.15 175 15 125 1 75 5 25 6.491 2 4 6 8 Asymmetric adduct (sample in EtOH) 1 6.15 1678.2 26.2.127.761 98.581 2 6.491 24.2 2.5.1441.724 1.419 S31
diethyl 2-(3-oxo-1-phenylpentyl)malonate (12na) 35 3 25 VWD1 A, 波长 =254 nm (LIPF\81127\ 烯酮 - 丙二酸酯 19.D) 1.822 12.272 2 15 1 5 2.5 5 7.5 1 12.5 Racemic adduct (sample in EtOH) 1 1.822 749.9 37.3.385.639 51.123 2 12.272 716.9 28.6.39.564 48.877 4 VWD1 A, 波长 =254 nm (LIPF\81127\ 烯酮 - 丙二酸酯 2.D) 1.81 35 3 25 2 15 1 5 12.36 2.5 5 7.5 1 12.5 Asymmetric adduct (sample in EtOH) 1 1.81 869.3 43.313.694 91.35 2 12.36 82.3 3.6.3548.842 8.65 S32
E: Copies of 1 H, and 13 C NMR spectra of Adducts S33
S34
S35
S36
S37
S38
S39
S4
S41
S42
S43
S44
S45
S46
S47
S48
S49
S5
S51
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E: References 1. Sinisterra, J. V.; Garcia-Raso, A. Synthesis 1984, 6, 52-54. 2. (a) Wascholowski, V.; Knudsen, K. R.; Mitchell, C. E. T.; Ley, S. V. Chem. Eur. J. 28, 14, 6155 6165. (b) Guo, R.; Chen, X.; Elpelt, C.; Song, D.; Morris, R. H. Org. Lett. 25, 7, 1757-1759. (c) Watanabe, M.; Murata, K.; Ikariya, T. J. Am. Chem. Soc. 23, 125, 758-759. (d) Halland, N.; Aburel, P. S.; Jørgensen, K. A. Angew. Chem., Int. Ed. 23, 42, 661-665. S56