Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 Enantioselective aza-Micheal reaction of hydrazide to chalcones through the nonactivated amine moiety conjugated addition Jun Jiang, Yunfei Cai, Weiliang Chen, Lili Lin, Xiaohua Liu and Xiaoming Feng* †Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. China CONTENTS: (A) General information……………………….…….…………………………………….……………….. 1 (B) General procedure for the asymmetric aza-Micheal reaction of hydrazide and chalcone………… 1 (C) Optimization of conditions…………………………………………………………………….…..... ....2 (D) Other substrates for catalytic asymmetric conjugate addition of hydrazides and chalcones…...….3 (E) The discussion for the reactivity and yield issues ……………………………..……...….…............3 (F) The analytical and spectral characterization data of reaction products ………………………..…...4 (G) Copies of NMR and MS spectra for products……………………………………………..………..…17 (H) The information of single crystal X-ray diffraction analysis.…………………………………… .…57 (I) References..……………………………………………………………………………..…………….....58 (A) General information: 1H NMR spectra were recorded at 400 MHz or 600 MHz on commercial instruments. The chemical shifts were recorded in ppm relative to tetramethylsilane and with the solvent resonance as the internal standard. Data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, br = broad), coupling constants (Hz), integration. 13C NMR data were collected at 100 MHz or 150 MHz on commercial instruments with complete proton decoupling. Chemical shifts were reported in ppm from the tetramethylsilane with the solvent resonance as internal standard. All experiments were monitored by analytical thin layer chromatography (TLC). Enantiomeric excesses of products were determined by chiral HPLC analysis on Daicel Chiralcel AD-H/ IA/IB/IC in comparison with the authentic racemates. Optical rotations were reported as follows: [α] T (c: g/100 mL, in D CH Cl ). ESI-HRMS spectra were recorded on a commercial apparatus. The various chalcones were 2 2 mostly prepared according to the literature procedures except standard one. Hydrazide, dichloromethane were commercially available and purified by usual methods before use. Molecular sieve was dryinged at 500 oC for 2.5 hours, and the various lewis acids also were commercially available and directly used without further purification. Catalysts L1-L13 were synthesized according to the previous literatures in our group.1 (B) General procedure for the asymmetric aza-Micheal reaction of hydrazide and chalcone The mixture of ligand L7 (3.7 mg, 0.006 mmol, 6 mol%), Sc(OTf) (2.5 mg, 0.005 mmol, 5 mol%), 3 benzoyl hydrazine 1a (13.6 mg, 0.1 mmol), chalcone 2a (40.2 mg, 0.20 mmol) and 4ǺMS (60 mg) were stirred in CH Cl (2.0 mL) for 16-20 h at 25 oC. The completion of the reaction was monitored by TLC 2 2 and purified by flash chromatography on silica gel (Eluent: petroleum ether /ethyl acetate = 3/1) to give the pure product 3a in 78% yield with 93% ee. Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 (C) Optimization of conditions n n L1:R=2,6-iPrC6H3 n=1 m=1 L2:R=2,6-Et CH n=1 m=1 O 2 O N m N O L3:R=2,6-Me22C66H33 n=1 m=1 Ph NH1 NH2 L-Metal10mol%PhHN O2 R N H O O H N R LLL457:::RRR===tP2B,h6u-iPrC6H3 nnn===211 mmm===111 + 1a O Solvent NH ∗ O LL98::RR==aCdHa2mPh nn==11 mm==11 Ph Ph O N N O L10:R=CHPh2 n=1 m=1 Ph 2a Ph 3a Ar N H O O H N Ar LL1112::RR==22,,66--iiPPrrCC66HH33 nn==11 mm==02 L6:Ar=2,6-iPrC H L13:R=Anthtyl n=1 m=1 6 3 Yieldc Eed Entrya L-Metal（L/M） Add.(Ant.) 1a/2a (mmol) Sov. (mL)b (%) (%) 1 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 58 78 3 2 2 2 L2/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 40 45 3 2 2 3 L3/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 30 18 3 2 2 4 L4/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 55 54 3 2 2 5 L5/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 32 41 3 2 2 6 L6/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 24 75 3 2 2 7 L7/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 72 -37 3 2 2 8 L8/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 28 -19 3 2 2 9 L9/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 78 13 3 2 2 10 L10/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 33 -44 3 2 2 11 L11/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 68 1 3 2 2 12 L12/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 28 34 3 2 2 13 L13/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 21 -9 3 2 2 14 L1/La(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 34 0 2 2 2 15 L1/Y(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 78 3 3 2 2 16 L1/Ca(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 30 1 2 2 2 17 L1/Zn(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.5mL) 22 4 3 2 2 18 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (0.2mL) 82 26 3 2 2 19 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (1.0mL) 51 83 3 2 2 20 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH Cl (2.0mL) 48 88 3 2 2 21 L1/Sc(OTf) (1.0/1.0) 10mol% - 1.0/1.0 CHCl (2.0mL) 31 82 3 3 22 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH ClClCH (2.0mL) 40 85 3 2 2 23 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 EA (2.0mL) 47 68 3 24 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 CH CN (2.0mL) 60 55 3 3 25 L1/Sc(OTf) (1.0/1.0) 10 mol% - 1.0/1.0 THF (2.0mL) 31 60 3 26 L1/Sc(OTf) (1.0/1.0) 10mol% - 1.0/1.0 PhMe (2.0mL) 49 64 3 27 L1/Sc(OTf) (1.2/1.0) 10 mol% - 1.0/1.0 CH Cl (2.0mL) 52 90 3 2 2 28 L1/Sc(OTf) (1.0/1.2) 10 mol% - 1.0/1.0 CH Cl (2.0mL) 49 80 3 2 2 29 L1/Sc(OTf) (1.2/1.0) 10 mol% - 2.0/1.0 CH Cl (2.0mL) 64 91 3 2 2 30 L1/Sc(OTf) (1.2/1.0) 10 mol% - 1.5/1.0 CH Cl (2.0mL) 57 90 3 2 2 31 L1/Sc(OTf) (1.2/1.0) 10 mol% 1.2/1.0 CH Cl (2.0mL) 50 88 3 2 2 2 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 32 L1/Sc(OTf) (1.2/1.0) 10 mol% 1.0/1.5 CH Cl (2.0 mL) 54 84 3 2 2 33 L1/Sc(OTf) (1.2/1.0) 10 mol% 3 Ǻ MS 20 mg 2.0/1.0 CH Cl (2.0 mL) 62 91 3 2 2 34 L1/Sc(OTf) (1.2/1.0) 10 mol% 4 Ǻ MS 20 mg 2.0/1.0 CH Cl (2.0 mL) 66 93 3 2 2 35 L1/Sc(OTf) (1.2/1.0) 10 mol% 5 Ǻ MS 20 mg 2.0/1.0 CH Cl (2.0 mL) 67 92 3 2 2 36 L1/Sc(OTf) (1.2/1.0) 10 mol% 4 Ǻ MS 10 mg 2.0/1.0 CH Cl (2.0 mL) 58 93 3 2 2 37 L1/Sc(OTf) (1.2/1.0) 10 mol% 4 Ǻ MS 40 mg 2.0/1.0 CH Cl (2.0 mL) 69 93 3 2 2 38 L1/Sc(OTf) (1.2/1.0) 10 mol% 4 Ǻ MS 60 mg 2.0/1.0 CH Cl (2.0 mL) 73 93 3 2 2 39e L1/Sc(OTf) (1.2/1.0) 5 mol% 4 Ǻ MS 60 mg 2.0/1.0 CH Cl (2.0 mL) 78 93 3 2 2 a Unless otherwise noted, reactions were carried in one pot, at 25 oC for 12 h. b EA = ethyl acetate, THF = tetrahydrofuran, c Isolated yield. d Determined by HPLC analysis. e Reactions were carried for 20 h. (D) Other substrates for catalytic asymmetric conjugate addition of chalcones and hydrazides Ph O O O 5mL7o-lS%c;(O60Tmf)3g(41:1Ao)MS HN NH2 + NH O Ph NH R1 R2 CH2Cl2(2.0mL);25oC ∗ R1 R2 1a 2 3 Entrya R1 R2 Hydrazide 1 Yieldb (%) Eec (%) 1 3-PhOC6H4 Ph 1a 78 80 2 2-Thienyl Ph 1a 51 71 3 3-NO2C6H4 Ph 1a 90 71 4 4-CNC6H4 Ph 1a 82 72 5 3-ClC6H4 Ph 1a 82 80 6 3-CF3C6H4 Ph 1a 92 70 7 2-ClC6H4 Ph 1a 68 82 8 CCl3 Ph 1a 99 10 9 EtCO2 Ph 1a 95 19 a 10 1a 35 0 11 Ph Ph TsNH-NH trace - 2 12d Ph Ph AcNH-NH2 56 81 a Unless otherwise noted, the reactions were carried out with 5 mol% L7/Sc(OTf) (1.2/1.0), 0.1 mmol hydrazide 1, and 2.0 equiv 3 chalcones 2 in CH Cl (2.0 mL) at 25 oC for 16-20 h. b Isolated yield. c Determined by HPLC analysis. d The reaction was carried 2 2 out with 0.1 mmol acetylhydrazine 1b and 2.0 equiv chalcone 2a, using 10 mol% catalyst. (E) The discussion for the reactivity and yield issues The electronic property and steric hindrance of the O Ph Ph O O substituted groups at the aromatic ring R1 had marked HN NH + NH O N Ph influence on reactivity. In addition, another reaction * Ph Ph Ph phenomenon in this system was found that a little unknow 3a 5a compound was exited and further confirmed to be hydrazone through reverse Mannich reaction.2 Under the alkaline condition or heating, the product 3a 3 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 still existed stably, whereas, it was slowly transformed into 5a in the catalytic environment. Thus, controlling the reaction time was another important factor. (F) The analytical and spectral characterization data of reaction products 1) Product 3a: O Ph solid; 78% yield, 93% ee. [α] 28 = 39.8 (c 0.068 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ = NH O 254 nm, retention time: 17.6 min (minor) and 19.4 min (major); 1H NMR (400 ∗ MHz, CDCl ) δ 7.94 (d, J = 7.4 Hz, 2H, Ar-H and NH-C=O), 7.63 – 7.26 (m, 3 3a 14H, Ar-H), 5.71 (s, 1H, C-NH-N), 4.82 (dd, J = 7.8, 5.1 Hz, 1H, N-CH-Ph), 3.46 (qd, J = 16.9, 6.5 Hz, 2H -CH C=O) ppm; 13C NMR (151 MHz, CDCl ) 198.21, 167.00, 140.84, 2 3 136.69, 133.32, 132.85, 131.71, 128.81, 128.64, 128.59, 128.22, 128.05, 127.72, 126.83, 60.92, 44.40 ppm; HRMS (ESI-TOF) calcd for C H N O ([M+Na+]) = 367.1422, Found: 367.1421. 22 20 2 2 0.06 1 AU00..0024 17.89 9.887 1 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 ?? AU00..2400 17.568 19.424 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 ?? 2) Product 3b: O Ph solid; 81% yield, 95% ee. [α] 23 = 36.3 (c 0.039 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL ADH, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ = NH O 254 nm, retention time: 20.8 min (major) and 23.4 min (minor); 1H NMR (400 ∗ MHz, CDCl ) δ 7.94 (dd, J = 8.6, 5.5 Hz, 2H, Ar-H and NH-C=O), 7.59 – 7.30 3 3b F (m, 11H, Ar-H), 7.08 (t, J = 8.6 Hz, 2H, Ar-H), 5.69 (s, 1H, C-NH-N), 4.81 (dd, J = 7.7, 5.2 Hz, 1H, N-CH-Ph), 3.42 (ddd, J = 21.8, 16.8, 6.5 Hz, 2H, -CH C=O) ppm. 13C NMR 2 (101 MHz, CDCl ) 196.59, 167.06, 164.58, 140.69, 133.14, 132.77, 131.75, 130.92, 130.83, 128.82, 3 128.59, 128.10, 127.69, 126.82, 115.85, 115.63, 60.85, 44.23 ppm. HRMS (ESI-TOF) calcd for C H FN O ([M+Na+]) = 385.1328, Found: 385.1332. 22 19 2 2 AU0.20 20.485 23.078 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 ?? AU0.20 20.789 23.439 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 ?? 4 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 3) Product 3c: O Ph solid; 77% yield, 96% ee. [α] 28 = 41.0 (c 0.016 in CH Cl ). HPLC DAICEL D 2 2 CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ HN NH O = 254 nm, retention time: 22.5 min (major) and 27.3 min (minor); 1H NMR ∗ (400 MHz, CDCl ) δ 7.85 (d, J = 8.5 Hz, 2H, Ar-H and NH-C=O), 7.61 – 7.27 3 3c Cl (m, 13H, Ar-H), 5.68 (s, 1H, C-NH-N), 4.81 (dd, J = 7.6, 5.2 Hz, 1H, N-CH-Ph), 3.42 (ddd, J = 21.8, 16.8, 6.5 Hz, 2H, -CH C=O) ppm. 13C NMR (101 MHz, CDCl ) 196.98, 2 3 167.10, 140.62, 139.80, 134.99, 132.74, 131.77, 129.62, 128.95, 128.83, 128.60, 128.12, 127.69, 126.82, 60.80, 44.25 ppm. HRMS (ESI-TOF) calcd for C H ClN O ([M+Na+]) = 401.1033, Found: 22 19 2 2 401.1032. AU0.50 2.424 288 2 7. 0.00 2 10.00 12.00 14.00 16.00 18.00 20.00 22.00 24.00 26.00 28.00 30.00 32.00 34.00 ?? 7 AU0.20 22.51 7.335 2 0.00 10.00 12.00 14.00 16.00 18.00 20.00 22.00 24.00 26.00 28.00 30.00 32.00 34.00 ?? 4) Product 3d: O Ph solid; 75% yield, 89% ee. [α]D28 = 24.2 (c 0.018 in CH2Cl2). HPLC DAICEL CHIRALCEL IA, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ = HN NH O 254 nm, retention time: 17.1 min (minor) and 19.4 min (major); 1H NMR (600 ∗ Cl MHz, CDCl3) δ 7.87 (s, 1H, NH-C=O), 7.79 (d, J = 7.8 Hz, 1H, Ar-H), 7.63 – 3d 7.54 (m, 3H, Ar-H), 7.48 (dd, J = 26.9, 7.7 Hz, 4H, Ar-H), 7.33 (dt, J = 32.1, 7.4 Hz, 6H, Ar-H), 4.82 (dd, J = 7.4, 5.3 Hz, 1H, N-CH-Ph), 3.71 (dd, J = 12.4, 5.1 Hz, 1H, C-NH-N), 3.43 (ddd, J = 21.8, 16.9, 6.4 Hz, 2H, -CH C=O) ppm. 13C NMR (151 MHz, CDCl3) 196.96, 167.19, 2 140.52, 138.18, 134.98, 133.24, 132.69, 131.80, 129.97, 128.84, 128.61, 128.31, 128.16, 127.72, 126.85, 60.72, 44.31 ppm; HRMS (ESI-TOF) calcd for C H ClN O ([M+Na+]) = 401.1033, Found: 22 19 2 2 401.1039. 2 AU1.00 16.74 8.955 1 0.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 Minutes 4 0 1 6 AU0.10 17. 9.37 1 0.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 Minutes 5 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 5) Product 3e: solid; 82% yield, 91% ee. [α] 20 = 31.6 (c 0.017 in CH Cl ). HPLC DAICEL O Ph D 2 2 CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, HN NH O λ = 254 nm, retention time: 26.7 min (major) and 32.6 min (minor); 1H ∗ NMR (600 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2H, Ar-H and NH-C=O), 7.56 (d, J = 8.3 Hz, 4H, Ar-H), 7.47 (t, J = 7.6 Hz, 3H, Ar-H), 7.41 (s, 1H, 3e Br Ar-H), 7.37 (t, J = 7.1 Hz, 4H, Ar-H), 7.31 (t, J = 7.2 Hz, 1H, Ar-H), 5.68 (s, 1H, C-NH-N), 4.81 (dd, J = 7.8, 5.1 Hz, 1H, N-CH-Ph), 3.41 (ddd, J = 21.7, 16.8, 6.5 Hz, 2H, -CH C=O). ppm. 13C NMR (151 MHz, CDCl ) 197.17, 167.08, 140.62, 135.40, 132.74, 131.96, 131.79, 2 3 129.72, 128.86, 128.62, 128.15, 127.69, 126.81, 60.80, 44.25 ppm;HRMS (ESI-TOF) calcd for C H BrN O ([M+Na+]) = 445.0528, Found: 445.0535. 22 19 2 2 0.15 AU00..0150 26.852 32.976 0.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 Minutes AU00..0024 26.659 32.607 0.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 Minutes 6) Product 3f: O Ph solid; 74% yield, 94% ee. [α] 29 = 27.9 (c 0.034 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, NH O λ = 254 nm, retention time: 28.4 min (minor) and 31.4 min (major); 1H ∗ NMR (600 MHz, CDCl3) δ 7.92 (d, J = 8.8 Hz, 2H, Ar-H and NH-C=O), 3f OMe 7.69 – 7.27 (m, 11H, Ar-H), 6.90 (d, J = 8.8 Hz, 2H, Ar-H), 5.71 (s, 1H, C-NH-N), 4.80 (dd, J = 7.8, 4.9 Hz, 1H, N-CH-Ph), 3.86 (s, 3H, -OCH ), 3.40 (ddd, J = 21.3, 16.5, 6.5 3 Hz, 2H, -CH C=O)ppm. 13C NMR (151 MHz, CDCl ) 196.78, 166.85, 163.67, 141.01, 132.91, 131.67, 2 3 130.56, 129.83, 128.80, 128.58, 128.01, 127.69, 126.82, 113.79, 61.16, 55.49, 44.18. HRMS (ESI-TOF) calcd for C H N O ([M+Na+]) = 397.1528, Found: 397.1522. 23 22 2 3 5 AU0.10 28.01 1.142 0.00 3 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 37.00 ?? 6 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 6 0 3 AU0.10 28.4 1.44 3 0.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 37.00 ?? 7) Product 3g: O Ph solid; 71% yield, 94% ee. [α] 28 = 32.6 (c 0.032 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ NH O ∗ = 254 nm, retention time: 20.2 min (minor) and 22.6 min (major); 1H NMR (600 MHz, CDCl ) δ 7.93 (d, J = 7.6 Hz, 2H, Ar-H and NH-C=O), 7.64 – 7.31 3 3g Me (m, 12H, Ar-H), 7.17 (d, J = 7.5 Hz, 2H, Ar-H and C-NH-N), 4.84 – 4.71 (m, 1H, N-CH-Ph), 3.56 – 3.31 (m, 2H, -CH C=O), 2.34 (s, 3H, -CH ). ppm. 13C NMR (101 MHz, CDCl ) 2 3 3 197.92, 166.96, 144.20, 140.92, 134.24, 132.88, 131.68, 129.33, 128.79, 128.57, 128.36, 128.02, 127.72, 126.85, 61.03, 44.32, 21.66 ppm. HRMS (ESI-TOF) calcd for C H N O ([M+Na+]) = 23 22 2 2 381.1579, Found: 381.1591. 0.10 3 5 0 AU0.05 20.5 3.19 2 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 ?? AU0.20 20.194 22.597 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 ?? 8) Product 3h: O Ph solid; 70% yield, 94% ee. [α] 28 = 28.4 (c 0.031 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL IA, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ = NH O ∗ Me 254 nm, retention time: 13.8 min (minor) and 15.2 min (major); 1H NMR (600 MHz, CDCl ) δ 7.73 (d, J = 1.1 Hz, 2H, Ar-H and NH-C=O), 7.62 – 7.54 (m, 3 3h 3H, Ar-H), 7.46 (dd, J = 15.3, 7.4 Hz, 3H, Ar-H), 7.34 (ddt, J = 15.6, 13.4, 6.8 Hz, 7H, Ar-H), 4.81 (dd, J = 8.0, 4.9 Hz, 1H, N-CH-Ph), 3.72 (s, 1H, C-NH-N), 3.45 (ddd, J = 21.7, 16.8, 6.5 Hz, 2H, -CH C=O), 2.37 (s, 3H, -CH )ppm. 13C NMR (151 MHz, CDCl ) 198.53, 167.00, 2 3 3 140.83, 138.44, 136.70, 134.12, 132.81, 131.71, 128.80, 128.77, 128.58, 128.51, 128.05, 127.73, 126.85, 125.45, 63.76, 60.98, 44.42ppm; HRMS (ESI-TOF) calcd for C H N O ([M+Na+]) = 23 22 2 2 381.1579, Found: 381.1577. 7 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 2.00 2 AU 13.64 5.116 1 0.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 Minutes AU1.00 13.845 15.195 0.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 Minutes 9) Product 3i: O Ph solid; 75% yield, 90% ee. [α] 28 = 21.5 (c 0.021 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ = NH O ∗ S 254 nm, retention time: 22.2 min (minor) and 24.5 min (major); 1H NMR (600 MHz, CDCl ) δ 7.67 (d, J = 3.7 Hz, 1H, NH-C=O), 7.62 (d, J = 4.9 Hz, 1H, Ar-H), 3 3i 7.56 (t, J = 12.9 Hz, 3H, Ar-H), 7.46 (t, J = 8.0 Hz, 3H, Ar-H), 7.34 (dt, J = 13.9, 6.4 Hz, 5H, Ar-H), 5.61 (s, 1H, C-NH-N), 4.80 (dd, J = 7.7, 5.1 Hz, 1H, N-CH-Ph), 3.38 (ddd, J = 20.8, 15.9, 6.5 Hz, 2H, -CH C=O) ppm. 13C NMR (151 MHz, CDCl ) 191.14, 167.07, 144.09, 140.56, 134.25, 2 3 132.74, 132.46, 131.76, 128.83, 128.60, 128.21, 128.15, 127.64, 126.84, 63.75, 61.34, 45.28ppm; HRMS (ESI-TOF) calcd for C H SN O ([M+Na+]) = 373.0987, Found: 373.0981. 20 18 2 2 AU02..0000 22.363 23.902 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 ?? AU00..1200 22.218 24.457 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 ?? 10) Product 3j: O Ph solid; 68% yield, 90% ee. [α] 29 = 20.2 (c 0.030 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, NH O ∗ λ = 220 nm, retention time: 11.3 min (minor) and 14.0 min (major); 1H NMR (600 MHz, CDCl ) δ 8.43 (s, 1H, NH-C=O), 8.02 (d, J = 8.6 Hz, 1H, Ar-H), 3 3j 7.95 – 7.84 (m, 3H, Ar-H), 7.63 – 7.50 (m, 6H, Ar-H), 7.39 (dtt, J = 18.4, 14.8, 7.4 Hz, 8H, Ar-H), 5.76 (s, 1H C-NH-N), 4.93 – 4.80 (m, 1H, N-CH-Ph), 3.60 (ddd, J = 21.4, 16.6, 6.5 Hz, 2H, -CH C=O) ppm. 13C NMR (151 MHz, CDCl ) 199.10, 197.98, 140.92, 138.89, 133.53, 2 3 131.70, 130.07, 129.95, 129.63, 129.30, 128.84, 128.51, 128.07, 128.01, 127.73, 127.46, 126.81, 64.99, 61.10, 44.50ppm; HRMS (ESI-TOF) calcd for C H N O ([M+Na+]) = 417.1579, Found: 417.1568. 26 22 2 2 8 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 0.10 18 5 5 0 AU0.05 27. 30.9 0.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 ?? AU00..1200 7.214 30.375 2 0.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 ?? 11) Product 3k: O Ph solid; 65% yield, 87% ee. [α] 28 = 17.9 (c 0.017 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL IA, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ = NH O ∗ 254nm, retention time: 30.8 min (minor) and 37.3 min (major); 1H NMR (600 O MHz, CDCl ) δ 7.44 (dddd, J = 58.6, 26.1, 14.0, 1.9 Hz, 14H, Ar-H and 3 O 3k NH-C=O), 6.05 (dd, J = 26.7, 1.7 Hz, 2H, -O-CH -O-), 5.71 (s, 1H, C-NH-N), 2 4.79 (s, 1H, N-CH-Ph), 3.60 – 3.14 (m, 2H, -CH C=O) ppm. 13C NMR (151 MHz, CDCl ) 196.28, 2 3 166.94, 151.98, 148.22, 140.86, 132.84, 131.70, 128.80, 128.58, 128.04, 127.69, 126.83, 124.65, 107.98, 107.87, 101.88, 61.08, 44.17ppm; HRMS (ESI-TOF) calcd for C H N O ([M+Na+]) = 23 20 2 4 411.1321, Found: 411.1319. 0.10 AU0.05 30.577 37.732 0.00 16.00 18.00 20.00 22.00 24.00 26.00 28.00 30.00 32.00 34.00 36.00 38.00 40.00 42.00 44.00 Minutes AU 00..0024 30.752 37.263 0.00 16.00 18.00 20.00 22.00 24.00 26.00 28.00 30.00 32.00 34.00 36.00 38.00 40.00 42.00 44.00 Minutes 12) Product 3l: O Ph solid; 87% yield, 86% ee. [α] 21 = 32.5 (c 0.043 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL IB, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ = NH O ∗ 254 nm, retention time: 13.1 min (major) and 17.0 min (minor); 1H NMR (400 MHz, CDCl ) δ 7.60 (d, J = 7.2 Hz, 3H, Ar-H and NH-C=O), 7.51 – 7.43 (m, 3 3l 5H, Ar-H), 7.41 – 7.29 (m, 8H, Ar-H), 6.71 (d, J = 16.1 Hz, 1H, =CH-Ar), 5.60 (s, 1H, C-NH-N), 4.75 (dd, J = 7.8, 5.3 Hz, 1H, N-CH-Ph), 3.73 (s, 1H, CO-CH=), 3.16 (ddd, J = 21.3, 16.1, 6.6 Hz, 2H, -CH C=O) ppm. 13C NMR (101 MHz, CDCl3) 198.23, 167.05, 143.57, 140.67, 2 134.27, 132.78, 131.76, 130.67, 128.94, 128.81, 128.62, 128.42, 128.10, 127.69, 126.86, 125.99, 63.77, 61.03, 46.62.ppm; HRMS (ESI-TOF) calcd for C H N O ([M+Na+]) = 393.1579, Found: 393.1587. 24 22 2 2 9 Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 2 AU0.10 3.10 557 1 6. 1 0.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 ?? AU0.50 13.148 16.982 0.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 ?? 13) Product 3m: O Ph solid; 67% yield, 91% ee. [α] 18 = 33.1 (c 0.027 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ NH O ∗ = 254 nm, retention time: 18.4 min (minor) and 21.5 min (major); 1H NMR (600 MHz, CDCl ) δ 7.92 (d, J = 7.6 Hz, 2H, Ar-H and NH-C=O), 7.61 – 7.31 3 F 3m (m, 11H, Ar-H), 7.04 (t, J = 8.6 Hz, 2H, Ar-H), 4.84 – 4.80 (m, 1H, N-CH-Ph), 3.43 (ddd, J = 22.1, 16.8, 6.5 Hz, 2H-CH C=O) ppm. 13C NMR (151 MHz, CDCl ) 197.97, 167.19, 2 3 163.22, 161.59, 136.63, 136.59, 133.40, 132.70, 131.82, 129.42, 129.36, 128.67, 128.63, 128.18, 126.82, 115.70, 115.56, 60.22, 44.34 ppm; HRMS (ESI-TOF) calcd for C H FN O ([M+Na+]) = 22 19 2 2 385.1328, Found: 385.1331. 1 AU0.05 18.29 1.313 0.00 2 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 ?? AU0.10 18.431 21.463 0.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 ?? 14) Product 3n: O Ph solid; 69% yield, 84% ee. [α] 29 = 41.5 (c 0.051 in CH Cl ). HPLC DAICEL D 2 2 HN CHIRALCEL AD-H, 2-propanol/n-hexane = 20/80, flow rate = 1.0 mL/min, λ NH O ∗ = 254 nm, retention time: 19.7min (minor) and 24.2 min (major); 1H NMR (600 MHz, CDCl ) δ 7.92 (d, J = 7.9 Hz, 2H, Ar-H and NH-C=O), 7.57 (dd, J 3 Cl 3n = 15.9, 7.6 Hz, 3H, Ar-H), 7.50 – 7.33 (m, 10H, Ar-H), 5.62 (s, 1H, C-NH-N), 4.90 – 4.74 (m, 1H, N-CH-Ph), 3.42 (ddd, J = 22.2, 16.8, 6.5 Hz, 2H-CH C=O) ppm. 13C NMR (151 2 MHz, CDCl ) 197.75, 167.21, 139.43, 136.58, 133.74, 133.44, 132.65, 131.87, 129.15, 128.95, 128.69, 3 128.66, 128.18, 126.82, 60.27, 44.23 ppm. HRMS (ESI-TOF) calcd for C H ClN O ([M+Na+]) = 22 19 2 2 401.1033, Found: 401.1023. 10